FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Kuljis, RO Darvesh, S Greig, NH Geula, C AF Kuljis, Rodrigo O. Darvesh, Sultan Greig, Nigel H. Geula, Changiz TI Tomographic visualization of cholinesterase SO ANNALS OF NEUROLOGY LA English DT Letter ID BUTYRYLCHOLINESTERASE ACTIVITY; DISEASE C1 Brain Mind Project, Miami, FL USA. Univ Miami, Sch Med, Miami, FL USA. Dalhousie Univ, Dept Med, Halifax, NS, Canada. Dalhousie Univ, Dept Anat & Neurobiol, Halifax, NS, Canada. NIA, Drug Design & Dev Sect, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Lab Neurodegenerat & Aging Res, Boston, MA USA. RP Kuljis, RO (reprint author), Brain Mind Project, Miami, FL USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD DEC PY 2006 VL 60 IS 6 BP 745 EP 746 DI 10.1002/ana.20926 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 122BO UT WOS:000243200900016 PM 17111417 ER PT J AU Yian, C Moon, SK Jin, SJ Webster, P Rhim, JS Andalibi, A Lim, DJ AF Yian, Christopher Moon, Sung K. Jin, Sunji Webster, Paul Rhim, Johng S. Andalibi, Ali Lim, David J. TI Characterization of rat spiral ligament cell line immortalized by adenovirus 12-simian virus 40 hybrid virus SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE adenovirus 12-simian virus 40 hybrid virus; cell line; spiral ligament fibrocyte ID EAR EPITHELIAL-CELLS; JUNCTION PROTEIN CONNEXIN43; INNER-EAR; MIDDLE-EAR; NEOPLASTIC TRANSFORMATION; CREATINE-PHOSPHOKINASE; IMMUNOHISTOCHEMICAL LOCALIZATION; SARCOPLASMIC-RETICULUM; MOUSE COCHLEA; EXPRESSION AB Objectives: Spiral ligament fibrocytes play an important role in inner ear ion homeostasis and are classified into several subtypes according to expression of specific enzymes such as Na+,K+-ATPase, Ca++-ATPase, and carbonic anhydrase. Although our understanding of the cell and molecular biology of spiral ligament fibrocytes has increased over time, access to these cells still remains a significant hurdle hindering future studies. In this study, we aimed to establish a rat spiral ligament cell line with minimal disruption of the original characteristics. Methods: The primary spiral ligament fibrocytes were exposed to adenovirus 12-simian virus 40 hybrid virus for immortalization. Karyotypic analysis was performed after stabilization of the infected cells, and the population doubling time was compared to that of the primary cell. The cell line was characterized by immunolabeling and electron microscopy. Results: We describe the establishment and characterization of a line of type I spiral ligament fibrocytes immortalized with an adenovirus 12-simian virus 40 hybrid virus. Conclusions: This cell line can be a useful research tool for investigating the role of spiral ligament fibrocytes in homeostasis and inflammation of the inner ear. C1 Univ So Calif, Gonda Dept Cell & Mol Biol, House Ear Inst, Keck Sch Med, Los Angeles, CA 90057 USA. Univ So Calif, Ctr Adv Electon Microscopy, House Ear Inst, Keck Sch Med, Los Angeles, CA 90057 USA. Univ So Calif, Keck Sch Med, Dept Otolaryngol, Los Angeles, CA 90057 USA. Univ So Calif, Keck Sch Med, Det Cell & Neurobiol, Los Angeles, CA 90057 USA. Uniformed Serv Univ Hlth Sci, Cell Biol Lab, Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD 20814 USA. Uniformed Serv Univ Hlth Sci, Ctr Prostate Dis Res, Dept Surg, Bethesda, MD 20814 USA. RP Lim, DJ (reprint author), Univ So Calif, Gonda Dept Cell & Mol Biol, House Ear Inst, Keck Sch Med, 2100 W 3rd St, Los Angeles, CA 90057 USA. NR 44 TC 5 Z9 5 U1 0 U2 0 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD DEC PY 2006 VL 115 IS 12 BP 930 EP 938 PG 9 WC Otorhinolaryngology SC Otorhinolaryngology GA 120LE UT WOS:000243085400013 PM 17214269 ER PT J AU Wang, PS Patrick, A Avorn, J Azocar, F Ludman, E McCulloch, J Simon, G Kessler, R AF Wang, Philip S. Patrick, Amanda Avorn, Jerry Azocar, Francisca Ludman, Evette McCulloch, Joyce Simon, Gregory Kessler, Ronald TI The costs and benefits of enhanced depression care to employers SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; NATIONAL COMORBIDITY SURVEY; MENTAL-HEALTH-SERVICES; MAJOR DEPRESSION; COLLABORATIVE CARE; UNITED-STATES; HIGH UTILIZERS; ANTIDEPRESSANT TREATMENT; QUALITY IMPROVEMENT; SURVEY REPLICATION AB Context: Although outreach and enhanced treatment interventions improve depression outcomes, uptake has been poor in part because purchasers lack information on their return on investment. Objective: To estimate the costs and benefits of enhanced depression care for workers from the societal and employer-purchaser perspectives. Design: Cost-effectiveness and cost-benefit analyses using state-transition Markov models. Simulated movements between health states were based on probabilities drawn from the clinical literature. Participants: Hypothetical cohort of 40-year-old workers. Intervention: Enhanced depression care consisting of a depression screen and care management for those depressed vs usual care. Main Outcome Measures: Our base-case cost-effectiveness analysis was from the societal perspective; costs and quality-adjusted life-years were used to compute the incremental cost-effectiveness of the intervention relative to usual care. A secondary cost-benefit analysis from the employer's perspective tracked monetary costs and monetary benefits accruing to employers during a 5-year time horizon. Results: From the societal perspective, screening and depression care management for workers result in an incremental cost-effectiveness ratio of $19976 per quality-adjusted life-year relative to usual care. These results are consistent with recent primary care effectiveness trials and within the range for medical interventions usually covered by employer-sponsored insurance. From the employer's perspective, enhanced depression care yields a net cumulative benefit of $2895 after 5 years. In 1-way and probabilistic sensitivity analyses, these findings were robust to a variety of assumptions. Conclusion: If these results can be replicated in effectiveness trials directly assessing effects on work outcomes, they suggest that enhanced treatment quality programs for depression are cost-beneficial to purchasers. C1 NIMH, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. United Behav Hlth, San Francisco, CA USA. Ctr Hlth Studies, Grp Hlth Cooperat, Seattle, WA USA. RP Wang, PS (reprint author), NIMH, 6001 Execut Blvd,Room 7151 MSC 9629, Bethesda, MD 20892 USA. EM wangphi@mail.nih.gov RI Page, Andrew/G-5438-2012 OI Page, Andrew/0000-0003-3133-2844 FU NIMH NIH HHS [R01 MH 61941] NR 93 TC 68 Z9 68 U1 1 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD DEC PY 2006 VL 63 IS 12 BP 1345 EP 1353 DI 10.1001/archpsyc.63.12.1345 PG 9 WC Psychiatry SC Psychiatry GA 111YU UT WOS:000242492600005 PM 17146009 ER PT J AU Schulze, TG Hedeker, D Zandi, P Rietschel, M McMahon, FJ AF Schulze, Thomas G. Hedeker, Donald Zandi, Peter Rietschel, Marcella McMahon, Francis J. TI What is familial about familial bipolar disorder? Resemblance among relatives across a broad spectrum of phenotypic characteristics SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 12th World Congress of Psychiatric Genetics CY OCT 09-13, 2004 CL Dublin, IRELAND SP Int Soc Psychiat Genet ID GENOME-WIDE SCAN; SYMPTOM DIMENSIONS; PSYCHIATRIC-DISORDERS; SUSCEPTIBILITY LOCI; DEPRESSIVE DISORDER; REGRESSION-ANALYSIS; COMPUTER-PROGRAM; MOOD DISORDERS; SIBLING PAIRS; GENETIC RISK AB Context: Current diagnostic criteria for bipolar affective disorder define a phenotype that is highly heritable, yet clinically variable. A more homogeneous definition might facilitate genetic and other studies, but the best approach is unclear. Familial features of bipolar disorder should help define more homogeneous subtypes, but there are few data indicating which clinical features of bipolar disorder are the most familial. Objective: To study the familiality of phenotypic features in families ascertained through individuals with bipolar affective disorder. Design: The study comprises 1246 individuals in 172 multiplex families ascertained for genetic linkage studies of bipolar disorder. The familiality of 40 diverse phenotypic features was studied using mixed-effects regression analysis. Results: Substance abuse, alcoholism, psychosis, history of suicide attempt, and the level of social functioning were all strongly familial in this sample. Several other traits, including clinical subtype, earliest age at onset, and comorbid panic disorder, showed a suggestion of familiality that did not hold up to conservative correction for multiple testing. Conclusions: This is the largest and most comprehensive study to assess the familiality of phenotypic features in bipolar disorder. Our results suggest that comorbid conditions and social functioning should be considered along with other familial clinical features in formulating subtypes of bipolar disorder suitable for further studies. Familial variables may help reduce diagnostic heterogeneity in genetic and other biological studies. C1 Univ Heidelberg, Div Genet Epidemiol Psychiat, Cent Inst Mental Hlth, D-68159 Mannheim, Germany. NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. Univ Illinois, Div Epidemiol & Biostat, Sch Publ Hlth, Chicago, IL USA. Johns Hopkins Univ, Dept Mental Hlth, Bloomberg Sch Publ Hlth, Baltimore, MD USA. RP Schulze, TG (reprint author), Univ Heidelberg, Div Genet Epidemiol Psychiat, Cent Inst Mental Hlth, D-68159 Mannheim, Germany. EM thomas.schulze@zi-mannheim.de RI McMahon, Francis/A-7290-2009; Schulze, Thomas/H-2157-2013; OI McMahon, Francis/0000-0002-9469-305X FU Intramural NIH HHS; NIMH NIH HHS [R01 MH 061613, K01 MH072866, K01 MH072866-01, R01 MH 042243] NR 77 TC 75 Z9 76 U1 4 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD DEC PY 2006 VL 63 IS 12 BP 1368 EP 1376 DI 10.1001/archpsyc.63.12.1368 PG 9 WC Psychiatry SC Psychiatry GA 111YU UT WOS:000242492600007 PM 17146011 ER PT J AU Drabant, EM Hariri, AR Meyer-Lindenberg, A Munoz, KE Mattay, VS Kolachana, BS Egan, MF Weinberger, DR AF Drabant, Emily M. Hariri, Ahmad R. Meyer-Lindenberg, Andreas Munoz, Karen E. Mattay, Venkata S. Kolachana, Bhaskar S. Egan, Michael F. Weinberger, Daniel R. TI Catechol O-methyltransferase val(158)met genotype and neural mechanisms related to affective arousal and regulation SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID TRIDIMENSIONAL PERSONALITY QUESTIONNAIRE; STRUCTURED CLINICAL INTERVIEW; OBSESSIVE-COMPULSIVE DISORDER; ORBITAL FRONTAL-CORTEX; PREFRONTAL CORTEX; HUMAN AMYGDALA; ORBITOFRONTAL CORTEX; RAT-BRAIN; FUNCTIONAL CONNECTIVITY; SEROTONIN TRANSPORTER AB Context: Catechol O-methyltransferase (COMT), the major enzyme determining cortical dopamine flux, has a common functional polymorphism (val(158)met) that affects prefrontal function and working memory capacity and has also been associated with anxiety and emotional dysregulation. Objectives: To examine COMT val(158)met effects on corticolimbic circuitry reactivity and functional connectivity during processing of biologically salient stimuli, as well as the relationship to the temperamental trait of novelty seeking. Design: Within-subject functional magnetic resonance imaging study. Setting: National Institute of Mental Health, Genes, Cognition, and Psychosis Program, Bethesda, Md. Patients: One hundred one healthy subjects of both sexes. Results: We found that the met allele was associated with a dose-dependent increase in hippocampal formation and ventrolateral prefrontal cortex activation during viewing of faces displaying negative emotion. In met/met homozygotes, limbic and prefrontal regions showed increased functional coupling. Moreover, in these same subjects, the magnitude of amygdala-orbitofrontal coupling was inversely correlated with novelty seeking, an index of temperamental inflexibility. Conclusions: Our results indicate that heritable variation in dopamine neurotransmission associated with the met allele of the COMT polymorphism results in heightened reactivity and connectivity in corticolimbic circuits. This may reflect a genetic predisposition for inflexible processing of affective stimuli, a mechanism possibly accounting for aspects of arousal and behavioral control that contribute to emotional dysregulation previously reported in met/met individuals. C1 NIMH, Genes Cognit & Psychosis Program, Intramural Res Program, NIH,US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Weinberger, DR (reprint author), NIMH, Genes Cognit & Psychosis Program, Intramural Res Program, NIH,US Dept Hlth & Human Serv, 10 Ctr Dr,Room 4S-235, Bethesda, MD 20892 USA. EM weinberd@intra.nimh.nih.gov RI Hariri, Ahmad/D-5761-2011; Meyer-Lindenberg, Andreas/H-1076-2011 OI Meyer-Lindenberg, Andreas/0000-0001-5619-1123 FU Intramural NIH HHS NR 90 TC 234 Z9 239 U1 2 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD DEC PY 2006 VL 63 IS 12 BP 1396 EP 1406 DI 10.1001/archpsyc.63.12.1396 PG 11 WC Psychiatry SC Psychiatry GA 111YU UT WOS:000242492600010 PM 17146014 ER PT J AU Kinoshita, Y Uo, T Jayadev, S Garden, GA Conrads, TP Veenstra, TD Morrison, RS AF Kinoshita, Yoshito Uo, Takuma Jayadev, Suman Garden, Gwenn A. Conrads, Thomas P. Veenstra, Timothy D. Morrison, Richard S. TI Potential applications and limitations of proteomics in the study of neurological disease SO ARCHIVES OF NEUROLOGY LA English DT Article ID CEREBROSPINAL-FLUID; MASS-SPECTROMETRY; QUANTITATIVE PROTEOMICS; PROTEIN; MITOCHONDRIA; BIOMARKERS; SCLEROSIS; IDENTIFICATION; PEPTIDES; LIVER AB Proteomics represents the comprehensive study of cellular proteins and is aimed at analyzing their structure, function, expression, interactions, and localization in complex biological systems. The information obtained from these types of analyses can contribute to our understanding of the function of individual proteins by identifying protein X protein interactions and dynamic protein networks found in normal and diseased conditions. Genomic (DNA) or transcriptomic (messenger RNA) approaches alone do not take into account changes in protein stability, localization, and posttranslational modifications that are often critical determinants of protein function and, by extension, cellular behavior. Although proteomic methods still require significant technical advances to provide a truly "global" or "comprehensive" measure of gene expression similar to that achieved by DNA microarrays, recent advances in proteomics are beginning to provide a means to simultaneously characterize the expression of thousands of proteins in a whole cell or bio-fluid proteome and hundreds of proteins in select subcellular structures or protein complexes. The information obtained from these studies should promote a better understanding of disease conditions, help therapeutic decision making, and potentially foster the identification of therapeutic targets by comparing the proteomes of normal and diseased samples. C1 Univ Washington, Sch Med, Dept Neurol Surg, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Ctr Neurogenet & Neurotherapeut, Seattle, WA 98195 USA. NCI, SAIC Frederick Inc, Lab Proteom & Analyt Technol, Frederick, MD USA. RP Morrison, RS (reprint author), Univ Washington, Sch Med, Dept Neurol Surg, Box 356470, Seattle, WA 98195 USA. EM yael@u.washington.edu NR 27 TC 4 Z9 4 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0003-9942 EI 1538-3687 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD DEC PY 2006 VL 63 IS 12 BP 1692 EP 1696 DI 10.1001/archneur.63.12.1692 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 115KK UT WOS:000242733000004 PM 17172608 ER PT J AU Kang, DW Lattimore, SU Latour, LL Warach, S AF Kang, Dong-Wha Lattimore, Susan U. Latour, Lawrence L. Warach, Steven TI Silent ischemic lesion recurrence on magnetic resonance imaging predicts subsequent clinical vascular events SO ARCHIVES OF NEUROLOGY LA English DT Article ID CEREBRAL INFARCTION; MINOR STROKE; RISK; WARFARIN; ASPIRIN; SUBTYPE; ATTACK; TRIAL AB Background: Previous studies identified a high frequency of silent ischemic lesion recurrence on magnetic resonance imaging (MRI) after an index stroke. Objective: To investigate whether ischemic lesion recurrence on MRI predicts subsequent clinical events. Design: Retrospective cohort study. Setting: General community hospital. Patients: We recruited 120 patients who experienced an acute ischemic stroke (IS) and who underwent initial MRI within 24 hours of onset and subsequent MRI on day 5. Of those patients, 68 underwent follow-up MRI up to 90 days after onset. Main Outcome Measures: Early silent lesion recurrence was defined as new asymptomatic ischemic lesions on 5-day MRI, and late silent lesion recurrence was defined as those on 30- or 90-day MRI. Patients were followed up for recurrent vascular events by interviews. Results: Among the 104 patients (86.7%) who had available clinical outcome data, 35 (33.7%) had early silent lesion recurrence; 15 (22.1%) of 68 patients had late silent lesion recurrence. Of the patients, 8 experienced a recurrent IS, 3 experienced a transient ischemic attack, and 3 had vascular deaths during a mean +/- SD follow-up of 19.3 +/- 9.0 months. For recurrent IS as a clinical end point, late silent lesion recurrence independently predicted recurrent IS (odds ratio, 6.55; 95% confidence interval, 1.09-39.55) by the Cox proportional hazards model. For combined clinical end points, early (odds ratio, 3.19; 95% confidence interval, 1.02-10.00) and late (odds ratio, 8.09; 95% confidence interval, 1.29-50.91) silent lesion recurrences independently predicted clinical recurrent IS, transient ischemic attack, or vascular deaths. Conclusion: These data suggest that silent ischemic lesion recurrence on MRI may be a potential surrogate marker of clinical recurrence. C1 Natl Inst Neurol Disorders & Stroke, Sect Stroke Diagnost & Therapeut, Stroke Branch, NIH, Bethesda, MD 20892 USA. Univ Ulsan, Coll Med, Asan Med Ctr, Dept Neurol, Seoul, South Korea. RP Warach, S (reprint author), Natl Inst Neurol Disorders & Stroke, Sect Stroke Diagnost & Therapeut, Stroke Branch, NIH, 10 Ctr Dr,Room B1D733, Bethesda, MD 20892 USA. EM WarachS@ninds.nih.gov FU Intramural NIH HHS NR 14 TC 33 Z9 34 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD DEC PY 2006 VL 63 IS 12 BP 1730 EP 1733 DI 10.1001/archneur.63.12.1730 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 115KK UT WOS:000242733000009 PM 17172612 ER PT J AU Pate, RR Stevens, J Pratt, C Sallis, JF Schmitz, KH Webber, LS Welk, G Young, DR AF Pate, Russell R. Stevens, June Pratt, Charlotte Sallis, James F. Schmitz, Kathryn H. Webber, Larry S. Welk, Gregory Young, Deborah R. TI Objectively measured physical activity in sixth-grade girls SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID CARDIOVASCULAR HEALTH; ACTIVITY GUIDELINES; ADOLESCENT GIRLS; BLOOD-LIPIDS; US CHILDREN; WHITE GIRLS; PREVALENCE; AMERICAN; YOUTH; POPULATION AB Objectives: To describe the objectively measured physical activity characteristics of a diverse sample of sixth-grade girls, to examine influences on physical activity, and to report compliance with physical activity guidelines. Design: Cross-sectional study. Setting: Six locations across the United States. Participants: A total of 1578 sixth-grade girls. Accelerometers were worn for 7 days, and data for 6 days were included in the analyses. Main Exposures: Race/ethnicity, free or reduced-price lunch, and geographic region. Main Outcome Measures: Six operational definitions of adequate activity (60 or 30 minutes of daily moderate to vigorous physical activity at or above 4.6, 3.8, or 3.0 metabolic equivalents) were used to examine whether girls met physical activity guidelines. Results: Average times spent in sedentary, light, moderate, and vigorous activities were 460, 342, 18, and 6 min/d, respectively. White girls were more active than girls in other race/ethnic groups, and girls who did not receive free or reduced-price lunch were more active than girls who did. Girls in western states were most active. Percentages of girls in compliance with the 6 thresholds for adequate activity varied widely and ranged from 0.6% to 100.0%. Conclusions: When physical activity is measured objectively and a 4.6-metabolic equivalents cut point for moderate to vigorous physical activity is used, most sixth-grade girls do not meet guidelines for adequate physical activity. One notable finding was the effect of different accelerometer scoring protocols on estimates of compliance. Conceptual and empirical work is needed to define appropriate physical activity for youth using objective physical activity measures. C1 Univ S Carolina, Dept Exercise Sci, Columbia, SC 29208 USA. Univ N Carolina, Dept Nutr, Chapel Hill, NC USA. Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. NHLBI, Bethesda, MD 20892 USA. San Diego State Univ, Dept Psychol, San Diego, CA 92182 USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Tulane Univ, Dept Biostat, New Orleans, LA 70118 USA. Iowa State Univ, Dept Hlth & Human Performance, Ames, IA USA. Univ Maryland, Dept Kinesiol, College Pk, MD 20742 USA. RP Pate, RR (reprint author), Univ S Carolina, Dept Exercise Sci, 921 Assembly St, Columbia, SC 29208 USA. EM rpate@gwm.sc.edu RI Schmitz, Kathryn/B-7154-2011 FU NHLBI NIH HHS [U01 HL066857-01, 5U01HL066852, U01 HL066845, U01 HL066845-01, U01 HL066852, U01 HL066852-01, U01 HL066853, U01 HL066853-01, U01 HL066855, U01 HL066855-01, U01 HL066856, U01 HL066856-01, U01 HL066857, U01 HL066858-01] NR 40 TC 56 Z9 57 U1 2 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD DEC PY 2006 VL 160 IS 12 BP 1262 EP 1268 DI 10.1001/archpedi.160.12.1262 PG 7 WC Pediatrics SC Pediatrics GA 111YW UT WOS:000242492800009 PM 17146024 ER PT J AU Gerber, LH Hoffman, K Chaudhry, U Augustine, E Parks, R Bernad, M Mackall, C Steinberg, S Mansky, P AF Gerber, Lynn H. Hoffman, Karen Chaudhry, Usha Augustine, Elizabeth Parks, Rebecca Bernad, Martha Mackall, Crystal Steinberg, Seth Mansky, Patrick TI Functional outcomes and life satisfaction in long-term survivors of pediatric sarcomas SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE pediatric; rehabilitation; sarcoma ID YOUNG-ADULT SURVIVORS; QUALITY-OF-LIFE; SOFT-TISSUE SARCOMA; CHILDHOOD-CANCER SURVIVORS; MUSCLE STRENGTH; PINCH STRENGTH; NORMATIVE DATA; HEALTH-STATUS; MORTALITY; GRIP AB Objectives: To describe the inter-relation ships among impairments, performance, and disabilities in survivors of pediatric sarcoma and to identify measurements that profile survivors at risk for functional loss. Design: Prospective, cross-sectional. Setting: Research facility. Participants: Thirty-two participants in National Cancer Institute clinical trials. Interventions: Not applicable. Main Outcome Measures: Range of motion (ROM), strength, limb volume, grip strength, walk velocity, Assessment of Motor and Process Skills (AMPS); Human Activity Profile (HAP), Sickness Impact Profile (SIP), standard form of the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36); and vocational attitudes and leisure satisfaction. Results: Twenty of 30 survivors tested had moderate or severe loss of ROM; 13 of 31 tested had 90% or less of predicted walk velocity; all of whom had trunk or lower-extremity lesions. Women with decreased ROM (r=.50, P=.06) or strength (r=.74, P=.002) had slow gait velocity. Sixteen of 31 tested were more than I standard deviation below normal grip strength. Eighteen had increased limb volume. These 18 had low physical competence (SF-36) (r= -.70, P=.001) and high SIP scores (r=.73, P=.005). AMPS scores were lower than those of the matched normed sample (P<.001). HAP identified 15 of 30 who had moderately or severely reduced activity. Leisure satisfaction was higher in the subjects (P<.001). Eight reported cancer had negatively impacted work and 17 reported that it negatively impacted vocational plans. Conclusions: Survivors with lower-extremity or truncal lesions and women with decreased ROM and strength likely have slow walk velocity, low exercise tolerance, and high risk for functional loss. They should be identified using ROM, strength, limb volume, and walk time measures. C1 NIH, Ctr Clin, Dept Rehabil Med, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Natl Ctr Complementary & Alternat Med, NIH, Bethesda, MD USA. RP Gerber, LH (reprint author), George Mason Univ, Ctr Study Chron Illness & Disabil, 4400 Univ Dr,MSN 5B7, Fairfax, VA 22030 USA. EM ngerber1@gmu.edu NR 49 TC 30 Z9 31 U1 2 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD DEC PY 2006 VL 87 IS 12 BP 1611 EP 1617 DI 10.1016/j.apmr.2006.08.341 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 114OH UT WOS:000242675000009 PM 17141641 ER PT J AU Harris-Love, ML Cohen, LG AF Harris-Love, Michelle L. Cohen, Leonardo G. TI Noninvasive cortical stimulation in neurorehabilitation: A review SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Review DE neuronal plasticity; rehabilitation; transcranial magnetic stimulation ID TRANSCRANIAL MAGNETIC STIMULATION; HUMAN MOTOR CORTEX; INDUCED MOVEMENT THERAPY; LONG-TERM POTENTIATION; LEFT PREFRONTAL CORTEX; CHRONIC STROKE; INTERHEMISPHERIC INHIBITION; BRAIN-STIMULATION; INTRACORTICAL FACILITATION; TRANSCALLOSAL INHIBITION AB The purpose of this special communication is to provide an overview of noninvasive cortical stimulation techniques, the types of mechanistic information they can provide, and the ways their use is contributing to our understanding of current models of neurorehabilitation. The focus is primarily on studies using noninvasive cortical stimulation techniques in the human motor system. Noninvasive cortical stimulation techniques are useful tools in the field of neurorebabilitation that are being actively used to test proposed models of functional recovery after neurologic injury. They can provide insight into the physiologic mechanisms of functional recovery and are under investigation as a possible auxiliary intervention to modulate cortical excitability and enhance training effects. C1 NINDS, Human Cort Physiol Sect, Bethesda, MD 20892 USA. RP Harris-Love, ML (reprint author), NINDS, Human Cort Physiol Sect, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. RI Harris-Love, Michelle/J-1388-2014 OI Harris-Love, Michelle/0000-0001-5571-3858 FU Intramural NIH HHS NR 150 TC 29 Z9 29 U1 3 U2 10 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD DEC PY 2006 VL 87 IS 12 SU 2 BP S84 EP S93 DI 10.1016/j.apmr.2006.08.330 PG 10 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 115ZV UT WOS:000242773200012 PM 17140884 ER PT J AU Hodics, T Cohen, LG Cramer, SC AF Hodics, Timea Cohen, Leonardo G. Cramer, Steven C. TI Functional imaging of intervention effects in stroke motor rehabilitation SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Review DE magnetic resonance imaging; functional; motor skills disorders; positron-emission tomography; rehabilitation; stroke ID INDUCED MOVEMENT THERAPY; TRANSCRANIAL MAGNETIC STIMULATION; INDUCED CORTICAL REORGANIZATION; CONSTRAINT-INDUCED THERAPY; ACUTE ISCHEMIC-STROKE; CORTEX ACTIVATION; ELECTRICAL-STIMULATION; CEREBRAL ACTIVATION; CORTICOSPINAL TRACT; LOCOMOTOR RECOVERY AB Objective: To assess intervention-specific effects on cortical reorganization after stroke as shown by available functional neuroimaging studies. Data Sources: We searched Medline for clinical trials that contained the terms stroke, reorganization, and recovery, as well as either positron-emission tomography and PET, near-infrared spectroscopy and NIRS, single-photon emission tomography and SPECT, or functional magnetic resonance imaging and functional MRI; we reviewed primary and secondary references. Study Selection: Articles that reported neuroimaging findings as a result of a specific treatment involving more than 1 subject were included. Data Extraction: We included clinical trials that contained the terms stroke, reorganization, and recovery, as well as functional neuroiniaging data findings as a result of a specific treatment involving more than 1 subject. Data Synthesis: Included studies differed clearly from one another with regard to patient characteristics, intervention protocol, and outcome measures. Most studies used functional magnetic resonance imaging and a motor paradigm. Studies were limited in size. Conclusions: Despite the methodologic differences, several common features can be identified based on the reviewed studies. Clinical improvements occurred even late after injury, after subjects were deemed to have reached a recovery plateau. This clinical improvement was accompanied by cortical reorganization that depended on the type of intervention as well as other factors. This review also suggests direction for future research studies. C1 Georgetown Univ Hosp, Dept Neurol, Washington, DC 20007 USA. NIH, Physiol Sect, Bethesda, MD 20892 USA. Univ Calif Irvine, Dept Neurol, Irvine, CA 92717 USA. RP Hodics, T (reprint author), Georgetown Univ Hosp, Dept Neurol, PHC Bldg,7th Fl,3800 Reservoir Rd, Washington, DC 20007 USA. EM thodics@hotmail.com FU NICHD NIH HHS [K23 HD050267] NR 84 TC 32 Z9 32 U1 1 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD DEC PY 2006 VL 87 IS 12 SU 2 BP S36 EP S42 DI 10.1016/j.apmr.2006.09.005 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 115ZV UT WOS:000242773200006 PM 17140878 ER PT J AU O'Donnell, CJ Shea, MK Price, PA Gagnon, DR Wilson, PWF Larson, MG Kiel, DP Hoffmann, U Ferencik, M Clouse, ME Williamson, MK Cupples, LA Dawson-Hughes, B Booth, SL AF O'Donnell, Christopher J. Shea, M. Kyla Price, Paul A. Gagnon, David R. Wilson, Peter W. F. Larson, Martin G. Kiel, Douglas P. Hoffmann, Udo Ferencik, Maros Clouse, Melvin E. Williamson, Matthew K. Cupples, L. Adrienne Dawson-Hughes, Bess Booth, Sarah L. TI Matrix Gla protein is associated with risk factors for atherosclerosis but not with coronary artery calcification SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE atherosclerosis; coronary artery calcification; coronary risk factors; matrix Gla protein ID BEAM COMPUTED-TOMOGRAPHY; VASCULAR CALCIFICATION; HEART-DISEASE; REGULATING PROTEINS; QUANTIFICATION; MINERALIZATION; EXPRESSION; SERUM; RAT AB Objectives - Atherosclerotic coronary artery calcification (CAC) is associated with increased coronary heart disease (CHD) risk. Matrix Gla protein (MGP) is an inhibitor of calcification in vivo. However, little is known regarding the distribution of circulating MGP and its associations with CHD risk factors or with CAC in humans. Methods and Results - Serum MGP concentrations were determined in 2 independent populations of men and women free of clinically apparent cardiovascular disease: study A, n = 316, mean age 58 years, and study B, n = 452, mean age 68 years. CAC was determined by computed tomography. Mean MGP concentrations were 98.4 and 198 ng/mL in men, and 97.4 and 201 ng/mL in women, in study A and study B, respectively. In both cohorts, MGP levels were higher with increasing age. In age-adjusted analyses, there was an association of circulating MGP with increasing Framingham CHD risk score (in study A, P = 0.003 in men and P = 0.016 in women, respectively; in study B, a nonsignificant increase in men and P = 0.05 in women, respectively). Significant associations of circulating MGP with high-density lipoprotein and other individual CHD risk factors were also noted in both cohorts. There were no consistent associations between MGP and CAC after adjustment for CHD risk score in the 2 cohorts. Conclusions - MGP is associated with individual CHD risk factors and the Framingham CHD risk score in men and women free of clinically apparent CHD. The relation of MGP with CAC deserves further study in larger populations. C1 Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Beth Israel Deaconess Hosp, Dept Radiol, Boston, MA USA. Hebrew SeniorLife, Inst Aging Res, Boston, MA USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. Tufts Univ, USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. Univ Calif San Diego, Dept Biol, La Jolla, CA 92093 USA. NHLBI, Bethesda, MD 20892 USA. RP O'Donnell, CJ (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM odonnellc@nhlbi.nih.gov OI Gagnon, David/0000-0002-6367-3179; Cupples, L. Adrienne/0000-0003-0273-7965; Larson, Martin/0000-0002-9631-1254; Kiel, Douglas/0000-0001-8474-0310 FU NHLBI NIH HHS [HL58090, HL69272, N01-HC-38038, R01 HL058090, R01 HL069272, T32 HL069772]; NIA NIH HHS [R01 AG019147-05, AG14759, AG19147, R01 AG019147, R01 AG019147-01, R01 AG019147-02, R01 AG019147-03, R01 AG019147-04] NR 27 TC 39 Z9 40 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD DEC PY 2006 VL 26 IS 12 BP 2769 EP 2774 DI 10.1161/01.ATV.0000245793.83158.06 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 127DS UT WOS:000243566100029 PM 16973975 ER PT J AU Illei, GG AF Illei, Gabor G. TI Hematopoietic stem cell transplantation in autoimmune diseases: Is the glass half full or half empty? SO ARTHRITIS AND RHEUMATISM LA English DT Editorial Material ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; HIGH-DOSE CHEMOTHERAPY; RHEUMATOID-ARTHRITIS; MULTIPLE-SCLEROSIS; REPERTOIRE; THERAPY C1 Natl Inst Dent & Craniofacial Res, Sjogrens Syndrome Clin, Gene Therapy & Therapeut Branch, Bethesda, MD 20892 USA. RP Illei, GG (reprint author), Natl Inst Dent & Craniofacial Res, Sjogrens Syndrome Clin, Gene Therapy & Therapeut Branch, 10 Ctr Dr,Room 1N114, Bethesda, MD 20892 USA. EM illeig@mail.nih.gov FU Intramural NIH HHS NR 18 TC 8 Z9 11 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 2006 VL 54 IS 12 BP 3730 EP 3734 DI 10.1002/art.22257 PG 5 WC Rheumatology SC Rheumatology GA 116CS UT WOS:000242780700003 PM 17133534 ER PT J AU Mamyrova, G O'Hanlon, TP Monroe, JB Carrick, DM Malley, JD Adams, S Reed, AM Shamim, EA James-Newton, L Miller, FW Rider, LG AF Mamyrova, Gulnara O'Hanlon, Terrance P. Monroe, Jason B. Carrick, Danielle Mercatante Malley, James D. Adams, Sharon Reed, Ann M. Shamim, Ejaz A. James-Newton, Laura Miller, Frederick W. Rider, Lisa G. CA Childhood Myositis Heterogeneity C TI Immunogenetic risk and protective factors for juvenile dermatomyositis in Caucasians SO ARTHRITIS AND RHEUMATISM LA English DT Article ID IDIOPATHIC INFLAMMATORY MYOPATHIES; DISTINCT HLA-A; RHEUMATOID-ARTHRITIS; AUTOIMMUNE-DISEASES; ALLELIC PROFILES; ASSOCIATION; HLA-DRB1; CHILDREN; GENES; ONSET AB Objective. To define the relative importance (RI) of class II major histocompatibility complex (MHC) alleles and peptide binding motifs as risk or protective factors for juvenile dermatomyositis (DM), and to compare these with HLA associations in adult DM. Methods. DRB1 and DQA1 typing was performed in 142 Caucasian patients with juvenile DM, and the results were compared with HLA typing data from 193 patients with adult DM and 797 race-matched controls. Random Forests classification and multiple logistic regression were used to assess the RI of the HLA associations. Results. The HLA-DRB1*0301 allele was a primary risk factor (odds ratio [OR] 3.9), while DQA1*0301 (OR 2.8), DQA1*0501 (OR 2.1), and homozygosity for DQA1*0501 (OR 3.2) were additional risk factors for juvenile DM. These risk factors were not present in patients with adult DM without defined autoantibodies. DQA1 alleles *0201 (OR 0.37), *0101 (OR 0.38), and *0102 (OR 0.51) were identified as novel protective factors for juvenile DM, the latter 2 also being protective factors in adult DM. The peptide binding motif DRB1 (EYSTS13)-E-9 was a risk factor, and DQA1 motifs F-25, S-26, and (45)(V/A)W(R/K)(47) were protective. Random Forests classification analysis revealed that among the identified risk factors for juvenile DM, DRB1*0301 had a higher RI (100%) than DQA1*0301 (RI 57%), DQA1*0501 (RI 42%), or the peptide binding motifs. In a logistic regression model, DRB1*0301 and DQA1*0201 were the strongest risk and protective factors, respectively, for juvenile DM. Conclusion. DRB1*0301 is ranked higher in RI than DQA1*0501 as a risk factor for juvenile DM. DQA1*0301 is a newly identified HLA risk factor for juvenile DM, while 3 of the DQA1 alleles studied are newly identified protective factors for juvenile DM. C1 Natl Inst Environm Hlth Sci, Environm Autoimmun Grp, NIH, Clin Res Ctr, Bethesda, MD 20892 USA. NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. Mayo Clin, Rochester, MN USA. RP Rider, LG (reprint author), Natl Inst Environm Hlth Sci, Environm Autoimmun Grp, NIH, Clin Res Ctr, Room 4-2352,10 Ctr Dr,MSC 1301, Bethesda, MD 20892 USA. EM riderl@mail.nih.gov OI Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593 FU Intramural NIH HHS [Z01 ES101074-05, Z99 ES999999] NR 31 TC 32 Z9 33 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 2006 VL 54 IS 12 BP 3979 EP 3987 DI 10.1002/art.22216 PG 9 WC Rheumatology SC Rheumatology GA 116CS UT WOS:000242780700033 PM 17133612 ER PT J AU Illei, GG Yarboro, C Shirota, Y Tackey, E Lapteva, L Fleisher, T Balow, J Lipsky, P AF Illei, Gabor G. Yarboro, Cheryl Shirota, Yuko Tackey, Edward Lapteva, Larissa Fleisher, Thomas Balow, James Lipsky, Peter TI Tocilizumab (humanized anti IL-6 receptor monoclonal antibody) in patients with systemic lupus erythematosus (SLE): Safety, tolerability and preliminary efficacy. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIH, NIDCR, Bethesda, MD USA. NIAMS, Bethesda, MD USA. NIDCR, Bethesda, MD USA. CC, Bethesda, MD USA. NIDDK, Bethesda, MD USA. NR 0 TC 7 Z9 7 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 2006 VL 54 IS 12 BP 4043 EP 4043 PG 1 WC Rheumatology SC Rheumatology GA 116CS UT WOS:000242780700071 ER PT J AU Marinescu, LM Collins, CE Aranow, C Mackay, M Martins, DC Kamran, M Kang, J Hardin, JA AF Marinescu, L. Manuela Collins, Christopher E. Aranow, Cindy Mackay, Meggan Martins, Diana C. Kamran, Mohammad Kang, Jane Hardin, John A. TI Corticosteroid dose correlates inversely with vitamin D levels in patients with lupus. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Albert Einstein Coll Med, Bronx, NY 10467 USA. Natl Inst Hlth, Bethesda, MD USA. Columbia Univ, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 2006 VL 54 IS 12 BP 4043 EP 4044 PG 2 WC Rheumatology SC Rheumatology GA 116CS UT WOS:000242780700072 ER PT J AU Chitkara, P Jayamuni, S Athreya, BH Kastner, DL Barron, KS AF Chitkara, Puja Jayamuni, Salini Athreya, Balu H. Kastner, Daniel L. Barron, Karyl S. TI Undifferentiated periodic fever syndrome - A long term follow up study. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Natl Inst Hlth, Bethesda, MD USA. Alfred DuPont Hosp Children, Wilmington, DE USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 2006 VL 54 IS 12 BP 4053 EP 4054 PG 2 WC Rheumatology SC Rheumatology GA 116CS UT WOS:000242780700092 ER PT J AU Chitkara, P Feder, H Salazar, J Barham, B Plass, N Barron, KS Kastner, DL Stojanov, S AF Chitkara, Puja Feder, Henry Salazar, Juan Barham, Beverly Plass, Nicole Barron, Karyl S. Kastner, Daniel L. Stojanov, Silvia TI Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome - Clinical characterization. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 70th Annual Scientific Meeting of the American-College-of-Rheumatology/41st Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 10-15, 2006 CL Washington, DC SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Natl Inst Hlth, Bethesda, MD USA. Univ Connecticut, Hartford, CT 06112 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 2006 VL 54 IS 12 BP 4056 EP 4056 PG 1 WC Rheumatology SC Rheumatology GA 116CS UT WOS:000242780700097 ER PT J AU Balls, M Amcoff, P Bremer, S Casati, S Coecke, S Clothier, R Combes, R Corvi, R Curren, R Eskes, C Fentem, J Gribaldo, L Halder, M Hartung, T Hoffmann, S Schechtman, L Scott, L Spielmann, H Stokes, W Tice, R Wagner, D Zuang, V AF Balls, Michael Amcoff, Patric Bremer, Susanne Casati, Silvia Coecke, Sandra Clothier, Richard Combes, Robert Corvi, Raffaella Curren, Rodger Eskes, Chantra Fentem, Julia Gribaldo, Laura Halder, Marlies Hartung, Thomas Hoffmann, Sebastian Schechtman, Leonard Scott, Laurie Spielmann, Horst Stokes, William Tice, Raymond Wagner, Drew Zuang, Valerie TI The principles of weight of evidence validation of test methods and testing strategies - The report and recommendations of ECVAM Workshop 58(a) SO ATLA-ALTERNATIVES TO LABORATORY ANIMALS LA English DT Article ID EVIDENCE-BASED TOXICOLOGY; TOXICITY TEST PROCEDURES; TEST ACCURACY; METAANALYSIS; DIAGNOSIS; REVIEWS C1 European Commiss Joint Res Ctr, Inst Hlth & Consumer Protect, ECVAM, I-21020 Ispra, VA, Italy. FRAME, Nottingham, England. OECD, Environm Directorate, Paris, France. Univ Nottingham, Sch Biomed Sci, Nottingham NG7 2RD, England. Inst In Vitro Sci, Gaithersburg, MD USA. Unilever, SEAC, Sharnbrook, Beds, England. Natl Ctr Toxicol Res, Food & Drug Adm, Rockville, MD USA. Fed Inst Risk Assessment, ZEBET, Berlin, Germany. Natl Inst Environm Hlth Sci, Natl Toxicol Program, Interagcy Ctr Evaluat Alternat Toxicol Methods, Res Triangle Pk, NC USA. RP Balls, M (reprint author), European Commiss Joint Res Ctr, Inst Hlth & Consumer Protect, ECVAM, I-21020 Ispra, VA, Italy. EM michael.balls@btopenworld.com; valerie.zuang@jrc.it FU Intramural NIH HHS [Z99 ES999999] NR 58 TC 40 Z9 40 U1 0 U2 4 PU FRAME PI NOTTINGHAM PA RUSSELL & BURCH HOUSE 96-98 NORTH SHERWOOD ST, NOTTINGHAM NG1 4EE, NOTTS, ENGLAND SN 0261-1929 J9 ATLA-ALTERN LAB ANIM JI ATLA-Altern. Lab. Anim. PD DEC PY 2006 VL 34 IS 6 BP 603 EP 620 PG 18 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 132MT UT WOS:000243947600022 PM 17266393 ER PT J AU Rajesh, M Mukhopadhyay, P Godlewski, G Batkai, S Hasko, G Liaudet, L Pacher, P AF Rajesh, Mohanraj Mukhopadhyay, Partha Godlewski, Grzegorz Batkai, Sandor Hasko, Gyorgy Liaudet, Lucas Pacher, Pal TI Poly(ADP-ribose)polymerase inhibition decreases angiogenesis SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE poly(ADP-ribose)polymerase (PARP); angiogenesis; proliferation; migration; tube formation; aortic ring assay; HUVEC; 5-aminoisoquinolinone-hydrochloride; (5-AIQ); 1,5-isoquinolinediol (IQD); cancer ID MISMATCH REPAIR-DEFICIENT; POLYMERASE INHIBITORS; CANCER-THERAPY; HEART-FAILURE; TEMOZOLOMIDE; GROWTH; CELLS; MINOCYCLINE; ACTIVATION; AG14361 AB Inhibitors of poly(ADP-ribose)polymerase (PARP), a nuclear enzyme involved in regulating cell death and cellular responses to DNA repair, show considerable promise in the treatment of cancer both in monotherapy as well as in combination with chemotherapeutic agents and radiation. We have recently demonstrated that PARP inhibition with 3-aminobenzamide or PJ-34 reduced vascular endothelial growth factor (VEGF)-induced proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) in vitro. Here, we show dose-dependent reduction of VEGF- and basic fibroblast growth factor (bFGF)-induced proliferation, migration, and tube formation of HUVECs in vitro by two potent PARP inhibitors 5-aminoisoquinolinone-hydrochloride (5-AIQ) and 1,5-isoquinolinediol (IQD). Moreover, PARP inhibitors prevented the sprouting of rat aortic ring explants in an ex vivo assay of angiogenesis. These results establish the novel concept that PARP inhibitors have antiangiogenic effects, which may have tremendous clinical implications for the treatment of various cancers, tumor metastases, and certain retinopathies. (c) 2006 Elsevier Inc. All rights reserved. C1 NIAAA, Lab Physiol Studies, NIH, Bethesda, MD USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, Newark, NJ 07103 USA. Univ Lausanne Hosp, Dept Intens Care Med, CH-1011 Lausanne, Switzerland. RP Pacher, P (reprint author), NIAAA, Lab Physiol Studies, NIH, Bethesda, MD USA. EM pacher@mail.nih.gov RI Batkai, Sandor/G-3889-2010; MUKHOPADHYAY, PARTHA/G-3890-2010; Pacher, Pal/B-6378-2008; Batkai, Sandor/H-7983-2014; Liaudet, Lucas/E-1322-2017 OI MUKHOPADHYAY, PARTHA/0000-0002-1178-1274; Pacher, Pal/0000-0001-7036-8108; Liaudet, Lucas/0000-0003-2670-4930 FU Intramural NIH HHS [Z99 AA999999] NR 33 TC 48 Z9 56 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 1 PY 2006 VL 350 IS 4 BP 1056 EP 1062 DI 10.1016/j.bbrc.2006.09.160 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 100TD UT WOS:000241690800039 PM 17046715 ER PT J AU Beluzic, R Cuk, M Pavkov, T Fumic, K Baric, I Mudd, SH Jurak, I Vugrev, O AF Beluzic, Robert Cuk, Mario Pavkov, Tea Fumic, Ksenija Baric, Ivo Mudd, S. Harvey Jurak, Igor Vugrev, Oliver TI A single mutation at Tyr(143) of human S-adenosylhomocysteine hydrolase renders the enzyme thermosensitive and affects the oxidation state of bound cofactor nicotinamide-adenine dinucleotide SO BIOCHEMICAL JOURNAL LA English DT Article DE CD; 5,5 '-dithiobis-(2-nitrobenzoic acid) (DTNB); hydrogen bond; in vitro mutagenesis; S-adenosylhomocysteine hydrolase (AdoHeyase) deficiency; thermosensitivity ID SITE-DIRECTED MUTAGENESIS; ADENOSYL-L-HOMOCYSTEINE; RAT-LIVER; CRYSTAL-STRUCTURE; PLASMA HOMOCYSTEINE; CATALYTIC MECHANISM; SWISS-MODEL; INACTIVATION; DEFICIENCY; BINDING AB Recently, we have described the first human case of AdoHcyase (S-adenosylhomocysteine hydrolarse) deficiency. Two point mutations in the AdoHcyase gene, the missense mutation p.Y143C (AdoHcyase in which Tyr(143) is replaced by cysteine) and the truncation mutation p.W112stop (AdoHcyase in which Trp(112) is replaced by opal stop codon) were identified [Baric, Fumic, Glenn, Cuk, Schulze, Finkelstein, James, Mejaski-Bosnjak, Pazanin, Pogribny et al. (2004) Proc. Natl. Acad. Sci. U.S.A. 101, 42344239]. To elucidate the molecular and catalytic properties of AdoHcyase, we have made recombinant wild-type and mutant p.Y143C (AdoHcyase in which Tyr(143) is replaced by cysteine) enzymes for a comparative analysis. The catalytic rates of p.Y143C protein in the directions of S-adenosylhomocysteine synthesis or hydrolysis are decreased from 65 % to 75 %. Further, the oxidation states of coenzyme NAD differ between mutant and wild-type protein, with an increased NADH accumulation in the mutant p.Y143C enzyme of 88 % NADH (wild-type contains 18 % NADH). Quantitative binding of NAD is not affected. Native polyacrylamide gel electrophoresis showed, that mutant p.Y143C subunits are able to form the tetrameric complex as is the wild-type enzyme. CD analysis showed that the p.Y143C mutation renders the recombinant protein thermosensitive, with an unfolding temperature significantly reduced by 7 degrees C compared with wild-type protein. Change of Glu(115) to lysine in wild-type protein causes a change in thermosensitivity almost identical with that found in the p.Y143C enzyme, indicating that the thermosensitivity is due to a missing hydrogen bond between Tyr(143) and Glu(115). We emphasize involvement of this particular hydrogen bond for subunit folding and/or holoenyzme stability. In summary, a single mutation in the AdoHcyase affecting both the oxidation state of bound co-factor NAD and enzyme stability is present in a human with AdoHcyase deficiency. C1 Rudjer Boskovic Inst, Div Mol Med, Zagreb 10000, Croatia. Univ Hosp Ctr, Dept Pediat, Sch Med, Zagreb 1000, Croatia. Karl Franzens Univ Graz, Inst Chem Struct Biol, A-8010 Graz, Austria. Univ Hosp Ctr, Clin Inst Lab Diagnosis, Zagreb 10000, Croatia. NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. Robert Koch Inst, Div Viral Infect, D-1000 Berlin, Germany. RP Vugrev, O (reprint author), Rudjer Boskovic Inst, Div Mol Med, Zagreb 10000, Croatia. EM ovugrek@irb.hr RI Pavkov-Keller, Tea/K-9234-2015 OI Pavkov-Keller, Tea/0000-0001-7871-6680 NR 36 TC 11 Z9 11 U1 0 U2 7 PU PORTLAND PRESS LTD PI LONDON PA CHARLES DARWIN HOUSE, 12 ROGER STREET, LONDON WC1N 2JU, ENGLAND SN 0264-6021 EI 1470-8728 J9 BIOCHEM J JI Biochem. J. PD DEC 1 PY 2006 VL 400 BP 245 EP 253 DI 10.1042/BJ20060749 PN 2 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 113YC UT WOS:000242632900004 PM 16872278 ER PT J AU Mahishi, L Usdin, K AF Mahishi, Lata Usdin, Karen TI NF-Y, AP2, Nrf1 and Sp1 regulate the fragile X-related gene 2 (FXR2) SO BIOCHEMICAL JOURNAL LA English DT Article DE chromatin immunoprecipitation; fragile X mental retardation-1 gene (FMR1); fragile X-related gene 2 (FXR2); nuclear factor Y; promoter regulation; transcription factor ID ANDROGEN-BINDING PROTEIN; MENTAL-RETARDATION SYNDROME; FMR1 MESSENGER-RNA; TRANSCRIPTION FACTORS; GLOBULIN GENE; HUMAN GENOME; PROMOTER; IDENTIFICATION; METHYLATION; AP-2-ALPHA AB Fragile X syndrome, the most common heritable form of mental retardation, is caused by silencing of the FMR1 (fragile X mental retardation-1 gene). The protein product of this gene, FMRP (fragile X mental retardation protein), is thought to be involved in the translational regulation of mRNAs important for learning and memory. In mammals, there are two homologues of FMRP, namely FXR1P (fragile X-related protein 1) and FXR2P. Disruption of Fxr2 in mice produces learning and memory deficits, and Fmr1 and Fxr2 double-knockout mice have exaggerated impairments in certain neurobehavioral phenotypes relative to the single gene knockouts. This has led to the suggestion that FMR1 and FXR2 functionally overlap and that increasing the expression of FXR2P may ameliorate the symptoms of an FMRP deficiency. Interestingly, the region upstream of the FXR2 translation start site acts as a bidirectional promoter in rodents, driving transcription of an alternative transcript encoding the ABP (androgen-binding protein) [aABP (alternative ABP promoter)]. To understand the regulation of the human FXR2 gene, we cloned the evolutionarily conserved region upstream of the FXR2 translation start site and showed that it also has bidirectional promoter activity in both neuronal and muscle cells as evidenced by luciferase reporter assay studies. Alignment of the human, mouse, rat, rabbit and dog promoters reveals several highly conserved transcription factor-binding sites. Gel electrophoretic mobility-shift assays, chromatin immunoprecipitation studies and co-transfection experiments with plasmids expressing these transcription factors or dominant-negative versions of these factors showed that NF-YA (nuclear transcription factor Y alpha), AP2 (activator protein 2), Nrf1 (nuclear respiratory factor/alpha-Pal) and Sp1 (specificity protein 1) all bind to the FXR2 promoter both in vitro and in vivo and positively regulate the FXR2 promoter. C1 NIDDKD, Gene Struct & Dis Sect, NIH, Bethesda, MD 20892 USA. RP Usdin, K (reprint author), NIDDKD, Gene Struct & Dis Sect, NIH, Bethesda, MD 20892 USA. EM ku@helix.nih.gov FU Intramural NIH HHS NR 36 TC 6 Z9 6 U1 0 U2 2 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD DEC 1 PY 2006 VL 400 BP 327 EP 335 DI 10.1042/BJ20060734 PN 2 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 113YC UT WOS:000242632900011 PM 16886907 ER PT J AU Lee, YJ Hallenbeck, JM AF Lee, Y. -J. Hallenbeck, J. M. TI Insights into cytoprotection from ground squirrel hibernation, a natural model of tolerance to profound brain oligaemia SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article; Proceedings Paper CT 8th International Symposium on Cytochrome P450 Biodiversity and Biotechnology CY JUL 23-27, 2006 CL Swansea Med Sch, Swansea, WALES HO Swansea Med Sch DE Akt; cytoprotection; hibernation; ischaemia; oligaemia; small ubiquitin-related modifier (SUMO) ID TRANSCRIPTION FACTOR; CAENORHABDITIS-ELEGANS; CELLS; PATHWAY; DAF-16; STROKE; KINASE; SUMO; ISCHEMIA; SIGNALS AB Progression of acute ischaemic brain damage is complex and multifactorial. Also, evidence suggests that participating molecules and signal transduction pathways can function differently in different cellular contexts. Hibernation torpor, a model of natural tolerance to profoundly reduced blood flow and oxygen delivery to brain, along with models of induced ischaemic tolerance can guide efforts to identify cytoprotective mechanisms that are multifactorial and that target multiple mechanisms in multiple cellular contexts. Posttranslational modification of proteins by conjugation with the SUMO (small ubiquitin-related modifier) is massively increased in hibernation and may be such a mechanism. C1 NINDS, NIH, Stroke Branch, Bethesda, MD 20892 USA. RP Hallenbeck, JM (reprint author), NINDS, NIH, Stroke Branch, Bldg 49,Room 2A10,49 Convent Dr MSC 4476, Bethesda, MD 20892 USA. EM Hallenbj@ninds.nih.gov FU Intramural NIH HHS [Z99 NS999999] NR 29 TC 17 Z9 17 U1 0 U2 2 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0300-5127 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD DEC PY 2006 VL 34 BP 1295 EP 1298 PN 6 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 119LJ UT WOS:000243013500070 PM 17073805 ER PT J AU Baird, AE AF Baird, A. E. TI Blood genomic profiling: novel diagnostic and therapeutic strategies for stroke? SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article; Proceedings Paper CT 8th International Symposium on Cytochrome P450 Biodiversity and Biotechnology CY JUL 23-27, 2006 CL Swansea Med Sch, Swansea, WALES HO Swansea Med Sch DE blood genomic profiling; gene expression profiling; ischaemic stroke; leucocyte; peripheral blood; therapeutic strategy ID GENE-EXPRESSION PROFILE; BURKITTS-LYMPHOMA; ISCHEMIC-STROKE; MICROARRAY PLATFORMS; MULTIPLE-SCLEROSIS; CELLS; LYMPHOCYTES; HYPOXIA; DISEASE; PROTEIN AB Findings from gene expression profiling studies are leading to new diagnostic and therapeutic strategies that can be applied in medical practice, especially in the field of oncology. Promising results of gene expression profiling of the peripheral blood in patients with ischaemic stroke have been obtained in recent pilot studies, demonstrating a partially reproducible gene signature of acute cerebral ischaemia. However, questions remain. Given that blood is at least in part a surrogate tissue for ischaemic stroke, the specificity of these signatures needs to be evaluated. Furthermore, it needs to be determined whether standardization of this methodology is required and whether clinical signatures can be identified that are improvements over the tools currently used in clinical practice. Clinically useful signatures would include those of haemorrhagic as well as ischaemic stroke, reclassification of stroke type and prognosis, and vascular disease risk. if these conditions are met, then it should be possible to develop cost-effective and rapid assays. 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 34 TC 3 Z9 5 U1 0 U2 1 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0300-5127 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD DEC PY 2006 VL 34 BP 1313 EP 1317 PN 6 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 119LJ UT WOS:000243013500075 PM 17073810 ER PT J AU Hait, NC Oskeritzian, CA Paugh, SW Milstien, S Spiegel, S AF Hait, Nitai C. Oskeritzian, Carole A. Paugh, Steven W. Milstien, Sheldon Spiegel, Sarah TI Sphingosine kinases, sphingosine 1-phosphate, apoptosis and diseases SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES LA English DT Review DE sphingosine kinase; sphingosine-1-phosphate; apoptosis; cancer; allergy; asthma; development ID NECROSIS-FACTOR-ALPHA; FC-EPSILON-RI; PROTEIN-COUPLED RECEPTOR; CYTOCHROME-C RELEASE; MAST-CELL ACTIVATION; BREAST-CANCER CELLS; SPLENIC T-CELLS; GROWTH-FACTOR; DEPENDENT ACTIVATION; MOLECULAR-CLONING AB Sphingolipids are ubiquitous components of cell membranes and their metabolites ceramide (Cer), sphingosine (Sph), and sphingosine-1-phosphate (S I P) have important physiological functions, including regulation of cell growth and survival. Cer and Sph are associated with growth arrest and apoptosis. Many stress stimuli increase levels of Cer and Sph, whereas suppression of apoptosis is associated with increased intracellular levels of S1P. In addition, extracellular/secreted S1P regulates cellular processes by binding to five specific G protein coupled-receptors (GPCRs). SIP is generated by phosphorylation of Sph catalyzed by two isoforms of sphingosine kinases (SphK), type I and type 2, which are critical regulators of the "sphingolipid rheostat", producing pro-survival SIP and decreasing levels of pro-apoptotic Sph. Since sphingolipid metabolism is often dysregulated in many diseases, targeting SphKs is potentially clinically relevant. Here we review the growing recent literature on the regulation and the roles of SphKs and S I P in apoptosis and diseases. (c) 2006 Elsevier B.V. All rights reserved. C1 Virginia Commonwealth Univ, Sch Med, Dept Biochem, Richmond, VA 23298 USA. NIMH, Lab Cellular Mol & Regulat, Bethesda, MD 20892 USA. RP Spiegel, S (reprint author), Virginia Commonwealth Univ, Sch Med, Dept Biochem, 1101 E Marshall St, Richmond, VA 23298 USA. EM sspiegel@vcu.edu RI Paugh, Steven/A-7739-2008 OI Paugh, Steven/0000-0001-5697-9228 FU Intramural NIH HHS; NCI NIH HHS [CA61774]; NIAID NIH HHS [AI50094]; NIGMS NIH HHS [GM43880] NR 133 TC 276 Z9 290 U1 0 U2 20 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2736 J9 BBA-BIOMEMBRANES JI Biochim. Biophys. Acta-Biomembr. PD DEC PY 2006 VL 1758 IS 12 BP 2016 EP 2026 DI 10.1016/j.bbamem.2006.08.007 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 122IZ UT WOS:000243220800011 PM 16996023 ER PT J AU Zhang, DL Su, D Berczi, A Vargas, A Asard, H AF Zhang, De-liang Su, Dan Berczi, Alajos Vargas, Amy Asard, Han TI An ascorbate-reducible cytochrome b561 is localized in macrophage lysosomes SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS LA English DT Article DE lysosomal cytochrome b561 (LCytb); chromaffin granule cytochrome b561 (CGCytb); duodenal cytochrome b561 (Dcytb); macrophage; Lysosome ID ADRENAL CHROMAFFIN VESICLES; HOMOZYGOUS DELETION REGION; HUMAN-CHROMOSOME 3P21.3; IRON-METABOLISM; TRANSPORT PROTEIN; FERRIC REDUCTASE; EXPRESSION; ENDOSOMES; MEMBRANE; GLYCOPROTEIN AB Cytochromes b561 (Cyts b561) are a family of intrinsic membrane proteins involved in ascorbate-mediated transmembrane electron transport. The chromaffin granule Cyt b561 (CGCytb) is believed to transport electrons donated by extravesicular ascorbate (ASC) across the membrane to intravesicular monodehydroascorbate (MDA) supporting catecholamine synthesis in neurnendocrine tissues. Another isoform, the duodenal Cyt 13561 (Deytb), was reported to have ferric reductase activity, possibly facilitating intestinal iron uptake. Herein, a new Cyt b561 homologue, LCytb (for lysosomal Cytb561) was found expressed in the late endosomal-lysosomal membrane. LCytb shared high sequence similarity with CGCytb (45%, identity) and Dcytb (42% identity). Moreover, four heme-coordinating His residues, and putative ASC and MDA binding sites were highly conserved. Recombinant LCytb exhibited an ASC-reducible b-type Cyt absorbance spectrum with a-band maximum at 561 nm in the spectrum of the reduced protein. Northern blots and Western blots revealed that LCytb was predominantly expressed in lung, spleen, thymus, testis and placenta. In situ hybridization and immunofluorescence studies further demonstrated that the protein was expressed in the alveolar macrophages of the lung, in the white pulp of the spleen, widespread in the thymus, and in the Sertoli cells of the testis. Sequence analysis indicated the presence of a (DE)XXXL(LI)-type signal in the C-terminal of the protein, predicting a late endosomal-lysosomal subcellular localization. This localization was confirmed by double labeling experiments in RAW264.7 and 293 cells, stably transfected with LCytb. (c) 2006 Elsevier B.V. All rights reserved. C1 Univ Antwerp, Dept Biol, B-2020 Antwerp, Belgium. Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. Hungarian Acad Sci, Biol Res Ctr, Inst Biophys, H-6701 Szeged, Hungary. NICHHD, Cell Biol & Metab Branch, NICHD, Bethesda, MD 20892 USA. RP Asard, H (reprint author), Univ Antwerp, Dept Biol, Groenenborgerlaan 171, B-2020 Antwerp, Belgium. EM han.asard@ua.ac.be OI Zhang, Deliang/0000-0001-9478-5344 FU NCRR NIH HHS [1 P20 RR17675] NR 34 TC 36 Z9 39 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-4165 J9 BBA-GEN SUBJECTS JI Biochim. Biophys. Acta-Gen. Subj. PD DEC PY 2006 VL 1760 IS 12 BP 1903 EP 1913 DI 10.1016/j.bbagen.2006.07.019 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 111NN UT WOS:000242459500019 PM 16996694 ER PT J AU Guo, GL Santamarina-Fojo, S Akiyama, TE Amar, MJA Paigen, BJ Brewer, B Gonzalez, FJ AF Guo, Grace L. Santamarina-Fojo, Silvia Akiyama, Taro E. Amar, Marcelo J. A. Paigen, Beverly J. Brewer, Bryan Gonzalez, Frank J. TI Effects of FXR in foam-cell formation and atherosclerosis development SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS LA English DT Article DE FXR; nuclear receptor; atherosclerosis; cholesterol; cytokine ID ACTIVATED RECEPTOR-GAMMA; ORPHAN NUCLEAR RECEPTOR; FARNESOID-X-RECEPTOR; BILE-ACIDS; OXIDIZED LDL; PPAR-GAMMA; MACROPHAGE DIFFERENTIATION; EXPRESSION; MICE; CD36 AB Famesoid X receptor (FXR), a bile-acid-activated member of the nuclear receptor superfamily, is essential in regulating bile-acid, cholesterol, and triglyceride homeostasis. Disruption of the FXR gene in mice results in a proathero sclerotic lipid profile with increased serum cholesterols and triglycerides. However, the role of FXR in foam-cell formation and atherosclerosis development remains unclear. The current study showed that the peritoneal macrophages isolated from FXR-null mice took up less oxidized LDL-cholesterol (oxLDL-C), which was accompanied by a marked reduction in CD36 expression in these cells. This result appears to be FXR-independent, as FXR was not detected in the peritoneal macrophages. To assess to what extent FXR modulates atherosclerosis development, FXR/ApoE double-null mice were generated. Female mice were used for atherosclerosis analysis. Compared to ApoE-null mice, the FXR/ApoE double-null mice were found to have less atherosclerotic lesion area in the aorta, despite a further increase in the serum cholesterols and triglycerides. Our results indicate that disruption of the FXR gene could attenuate atherosclerosis development, most likely resulting from reduced oxLDL-C uptake by macrophages. Our study cautions the use of serum lipid levels as a surrogate marker to determine the efficiency of FXR modulators in treating hyperlipidemia. (c) 2006 Elsevier B.V. All rights reserved. C1 NCI, Metab Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Mol Dis Branch, NIH, Bethesda, MD 20892 USA. Jackson Lab, Bar Harbor, ME 04609 USA. RP Gonzalez, FJ (reprint author), NCI, Metab Lab, NIH, Bldg 37,Rm 3106B,9000 Rockville Pike, Bethesda, MD 20892 USA. EM fjgonz@helix.nih.gov FU Intramural NIH HHS; NCI NIH HHS [Z01 BC005708-14] NR 40 TC 65 Z9 71 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1388-1981 J9 BBA-MOL CELL BIOL L JI Biochim. Biophys. Acta Mol. Cell Biol. Lipids PD DEC PY 2006 VL 1761 IS 12 BP 1401 EP 1409 DI 10.1016/j.bbalip.2006.09.018 PG 9 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 121JL UT WOS:000243153800001 PM 17110163 ER PT J AU Kim, NK Tharakaraman, K Spouge, JL AF Kim, Nak-Kyeong Tharakaraman, Kannan Spouge, John L. TI Adding sequence context to a Markov background model improves the identification of regulatory elements SO BIOINFORMATICS LA English DT Article ID FACTOR-BINDING SITES; DISCOVERY; ALIGNMENT; GENES AB Motivation: Many computational methods for identifying regulatory elements use a likelihood ratio between motif and background models. Often, the methods use a background model of independent bases. At least two different Markov background models have been proposed with the aim of increasing the accuracy of predicting regulatory elements. Both Markov background models suffer theoretical drawbacks, so this article develops a third, context-dependent Markov background model from fundamental statistical principles. Results: Datasets containing known regulatory elements in eukaryotes provided a basis for comparing the predictive accuracies of the different background models. Non-parametric statistical tests indicated that Markov models of order 3 constituted a statistically significant improvement over the background model of independent bases. Our model performed slightly better than the previous Markov background models. We also found that for discriminating between the predictive accuracies of competing background models, the correlation coefficient is a more sensitive measure than the performance coefficient. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Spouge, JL (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM spouge@ncbi.nlm.nih.gov FU Intramural NIH HHS NR 16 TC 7 Z9 7 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD DEC 1 PY 2006 VL 22 IS 23 BP 2870 EP 2875 DI 10.1093/informatics/btl528 PG 6 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 108NK UT WOS:000242246300006 PM 17068091 ER PT J AU Nagasawa, H Uto, Y Kirk, KL Hori, H AF Nagasawa, Hideko Uto, Yoshihiro Kirk, Kenneth Lee Hori, Hitoshi TI Design of hypoxia-targeting drugs as new cancer chemotherapeutics SO BIOLOGICAL & PHARMACEUTICAL BULLETIN LA English DT Review DE tumor hypoxia; angiogenic inhibitor; hypoxia inducible factor (HIF)-1 alpha inhibitor; hypoxic cell radiosensitizer; boron neutron capture therapy; p53 inhibitor ID NEUTRON-CAPTURE THERAPY; TUMOR HYPOXIA; BIOLOGICAL-ACTIVITIES; GENE-THERAPY; NECK-CANCER; 1,2,4-BENZOTRIAZINE 1,4-DIOXIDES; CELL RADIOSENSITIZERS; ACTIVATED PRODRUGS; INDUCIBLE FACTOR-1; HEPARAN-SULFATE AB The tumor microenvironment is now recognized as a major factor that influences not only the response to conventional anti-cancer therapies but also helps define the potential for malignant progression and metastasis. In particular, hypoxia is now considered a fundamentally important characteristic of the tumor microenvironment. Furthermore, discovery of the hypoxia inducible factor 1 alpha (HIF-1 alpha) has led to a rapidly increasing understanding of the molecular mechanisms involved in tumor hypoxia. This in turn has led to the current extensive interest in the signal molecules related to tumor hypoxia as potential molecular targets for cancer therapeutics. In this paper we give an overview of recent advances in hypoxia research, including cancer treatments that target tumor hypoxia. Progress in the development of hypoxia-targeting drugs will be discussed, including antiangiogenic hypoxic cell radiosensitizers and hypoxic cytotoxins, hypoxia targeting boron carriers and p53-inhibiting bifunctional radiosensitizers. We will also review our own recent research results in these areas. For example, we have found that certain of the 2-nitroimidazole radiosensitizers and heterocycle-N-oxide hypoxic cytotoxins we developed have antiangiogenic activity and antimetastatic activity. We propose that these activities are based on the inhibition of signal transcluction mediated by HIF-1 alpha. The anti-tumor activities of hypoxia response are considered to be cytostatic (tumor dormancy-inducing) effects in contrast to cytotoxic DNA damaging effects. The combinaiton of these cytostatic effects that are related to radiosensitization with the cytotoxic effects of radiation should improve the prognosis and QOL of patients receiving radiation and lead to an overall response to treatment. Based on these considerations, we developed the antiangiogenic hypoxic cell radiosensitizers, TX-1877, TX-1898 and the hypoxic cytotoxin TX-402 that inhibits the HIF-1 alpha pathway We will also discuss our research involved with the development of other drugs to exploit tumor hypoxia, including a hypoxia-targeting boron carrier for boron neutron capture therapy (BNCT) and a p53 inhibiting radiosensitizer. C1 Gifu Pharmaceut Univ, Lab Pharmaceut Chem, Gifu 5028585, Japan. Univ Tokushima, Inst Sci & Technol, Dept Life Syst, Tokushima 7708506, Japan. NIDDK, Bioorgan Chem Lab, DHHS, NIH, Bethesda, MD 20892 USA. RP Nagasawa, H (reprint author), Gifu Pharmaceut Univ, Lab Pharmaceut Chem, 5-6-1 Mitahora Higashi, Gifu 5028585, Japan. EM hnagasawa@gifu-pu.ac.jp; hori@bio.tokushima-u.ac.jp FU Intramural NIH HHS NR 71 TC 42 Z9 43 U1 2 U2 32 PU PHARMACEUTICAL SOC JAPAN PI TOKYO PA 2-12-15 SHIBUYA, SHIBUYA-KU, TOKYO, 150-0002, JAPAN SN 0918-6158 J9 BIOL PHARM BULL JI Biol. Pharm. Bull. PD DEC PY 2006 VL 29 IS 12 BP 2335 EP 2342 DI 10.1248/bpb.29.2335 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 121GP UT WOS:000243146400001 PM 17142959 ER PT J AU Buchsbaum, MS Friedman, J Buchsbaum, BR Chu, KW Hazlett, EA Newmark, R Schneiderman, JS Torosjan, Y Tang, C Hof, PR Stewart, D Davis, KL Gorman, J AF Buchsbaum, Monte S. Friedman, Joseph Buchsbaum, Bradley R. Chu, King-Wai Hazlett, Erin A. Newmark, Randall Schneiderman, Jason S. Torosjan, Yuliya Tang, Cheuk Hof, Patrick R. Stewart, Daniel Davis, Kenneth L. Gorman, Jack TI Diffusion tensor imaging in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Article DE schizophrenia; diffusion tensor imaging; magnetic resonance imaging; frontal lobe; white matter; prefrontal function ID WHITE-MATTER MICROSTRUCTURE; AUDITORY HALLUCINATIONS; PREFRONTAL CORTEX; VOLUME REDUCTION; MRI; DISRUPTION; INTEGRITY; DISORDER; ANISOTROPY; DENSITY AB Background: Alignment of white matter axons as inferred from diffusion tensor imaging has indicated changes in schizophrenia in frontal and frontotemperoral white matter. Methods. Diffusion tensor anisotropy and anatomical magnetic resonance images were acquired in 64 patients with schizophrenia and 55 normal volunteers. Anatomical images were acquired with a magnetization prepared rapid gradient echo sequence, and fusion tensor images used a pulsed gradient spin-echo acquisition. Images were aligned and warped to a standard brain, and diffusion tensor images used a pulsed gradient spin-echo acquisition. Images were aligned and warped to a standard brain, and anisotropy in normal volunteers and patients was compared using significance probability mapping. Results: Patients showed widespread areas of reduced anisotropy, including the frontal white matter, the corpus callosum, and the frontal longitudinal fasciculus. Conclusions. These findings, which are consistent with earlier reports of frontal decreases in anisotropy, demonstrate that the effects are most prominent in frontal and callosal areas and are particularly widespread in frontal white matter regions. C1 Mt Sinai Sch Med, Neurosci Positron Emiss Tomog Lab, New York, NY 10029 USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. NIMH, Brain Disorders Branch, Bethesda, MD 20892 USA. RP Buchsbaum, MS (reprint author), Mt Sinai Sch Med, Neurosci Positron Emiss Tomog Lab, Box 1505,1 Gustave Levy Pl, New York, NY 10029 USA. EM monte.buchsbaum@mssm.edu RI Schneiderman, Jason/E-1528-2013 OI Schneiderman, Jason/0000-0002-9313-0415 FU NCRR NIH HHS [M01-RR-00071]; NIMH NIH HHS [P50 MH 66392-01, MH60023] NR 46 TC 92 Z9 92 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD DEC 1 PY 2006 VL 60 IS 11 BP 1181 EP 1187 DI 10.1016/j.biopsych.2005.11.028 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 108ZW UT WOS:000242278700003 PM 16893533 ER PT J AU Tost, H Meyer-Lindenberg, A Klein, S Schmitt, A Hohn, F Tenckhoff, A Ruf, M Encle, G Rietschel, M Henn, FA Braus, DF AF Tost, Heike Meyer-Lindenberg, Andreas Klein, Sabine Schmitt, Andrea Hoehn, Fabian Tenckhoff, Amrei Ruf, Matthias Encle, Gabriele Rietschel, Marcella Henn, Fritz A. Braus, Dieter F. TI D-2 antidopaminergic modulation of frontal lobe function in healthy human subjects SO BIOLOGICAL PSYCHIATRY LA English DT Article DE dopamine; fMRI; haloperidol; sequential finger opposition; executive functioning ID SEQUENTIAL FINGER MOVEMENTS; SPATIAL WORKING-MEMORY; CORTICAL MOTOR AREAS; BLOOD-FLOW CHANGES; PARKINSONS-DISEASE; BASAL GANGLIA; PREFRONTAL CORTEX; DOPAMINE MODULATION; SCHIZOPHRENIA; SUPPLEMENTARY AB Background: Although the major principles of dopamine (DA) signaling have been well described previously, its precise modulatory impact on the prefrontal cortex (PFC) in humans is poorly understood. Two major neurophysiological models propose segregated functional circuits on the systems level as well as D-1 and D-2 receptor-dependent processing states on the cellular level (two-state model). Methods. We examined the predictive validity of these models in 10 healthy male volunteers with a haloperidol challenge (HLP). Coilico-striatal-thalamo-cortical (CSTC) motor loop functions were examined during functional magnetic resonance imaging (fMRI) with a sequential finger opposition task. Neuropsychological implications of the two-state model were evaluated with a test battery of D-1- or D-2-sensitive prefrontal measures. Results. Analysis of fMRI data revealed a significant HLP-induced blood oxygen level dependent-signal decrease in the sensorimotor striatum and a lateralized activation loss of ipsilateral higher order motor cortices and contralateral cerebellum. Neuropsycbological evaluation demonstrated a preferential impairment of D-2-sensitive functions, whereas D-1 or non-dopaminergic domains were unaffected. Conclusions: Our data support the hypothesis that mesocortical D-1 and D-2 receptors exert differential influences in the PFC for cognitive function, but the nigrostriatal CSTC network model for the motor domain could not be confirmed. C1 Univ Heidelberg, Cent Inst Mental Hlth, Fac Clin Med Mannheim, Dept Psychiat & Psychotherapy, D-6800 Mannheim, Germany. Univ Heidelberg, Cent Inst Mental Hlth, Fac Clin Med Mannheim, Dept Addict Behav & Addict Med, D-6800 Mannheim, Germany. Univ Hamburg, Dept Psychiat, NeuroImage Nord, Hamburg, Germany. NIMH, Unit Syst Neurosci Psychiat, Genes Cognit & Psychosis Program, Bethesda, MD 20892 USA. RP Tost, H (reprint author), Cent Inst Mental Hlth, Div Neuroimaging, POB 12 21 20, D-68072 Mannheim, Germany. EM tost@zi-mannheim.de RI Vollstadt-Klein, Sabine/C-6744-2012; Meyer-Lindenberg, Andreas/H-1076-2011 OI Vollstadt-Klein, Sabine/0000-0002-6210-672X; Meyer-Lindenberg, Andreas/0000-0001-5619-1123 NR 80 TC 24 Z9 26 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD DEC 1 PY 2006 VL 60 IS 11 BP 1196 EP 1205 DI 10.1016/j.biopsych.2006.04.014 PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 108ZW UT WOS:000242278700005 PM 16950215 ER PT J AU Bertolino, A Rubino, V Sarnbataro, F Blasi, G Latorre, V Fazio, L Caforio, G Petruzzella, V Kolachana, B Hariri, A Meyer-Lindenberg, A Nardini, M Weinberger, DR Scarabino, T AF Bertolino, Alessandro Rubino, Valeria Sarnbataro, Fabio Blasi, Giuseppe Latorre, Valeria Fazio, Leonardo Caforio, Grazia Petruzzella, Vittoria Kolachana, Bhaskar Hariri, Ahmad Meyer-Lindenberg, Andreas Nardini, Marcello Weinberger, Daniel R. Scarabino, Tommaso TI Prefrontal-hippocampal coupling during memory processing is modulated by COMT Val158met genotype SO BIOLOGICAL PSYCHIATRY LA English DT Article DE COMT Val158met; connectivity; declarative memory; dopamine; hippocampus; prefrontal ID MEDIAL TEMPORAL-LOBE; METHYLTRANSFERASE VAL(158)MET GENOTYPE; VAL(108/158) MET GENOTYPE; LONG-TERM POTENTIATION; DECLARATIVE MEMORY; GENETIC-VARIATION; WORKING-MEMORY; DOPAMINE MODULATION; EXECUTIVE FUNCTIONS; RECOGNITION MEMORY AB Background: Studies in humans and in animals have demonstrated that a network of brain regions is involved in performance of declarative and recognition memory tasks. This network includes the hippocampal formation (HF) as well as the ventrolateral prefrontal cortex (VLPFC). Studies in animals have suggested that the relationship between these brain regions is strongly modulated by dopamine. Methods. Using fMRI in healthy humans matched for a series of demographic and genetic variables, we studied the effect of the COMT val158met polymorphism on function of HF and VLPFC as well as on their functional coupling during recognition memory. Results: The COMT Val allele was associated with: relatively poorer performance at retrieval; reduced recruitment of neuronal resources in HF and increased recruitment in VLPFC during both encoding and retrieval; and unfavorable functional coupling between these two regions at retrieval. Moreover, functional coupling during retrieval was predictive of behavioral accuracy. Conclusions: These results shed new light on individual differences in responsivity and connectivity between HE and VLPFC related to genetic modulation of dopamine, a mechanism accounting at least in pan for individual differences in recognition memory performance. C1 Univ Bari, Psychiat Neurosci Grp, Sect Mental Disorders, Dept Psychiat & Neurol Sci, Bari, Italy. NIMH, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA. Univ Bari, Dept Med Biochem & Med Biol, Bari, Italy. IRCCSS Casa Sollievo Sofferenza, Dept Neuroradiol, San Giovanni Rotondo, Italy. RP Bertolino, A (reprint author), Univ Bari, Dipartimento Sci Neurol & Psichiat, Piazza Giulio Cesare 9, I-70124 Bari, Italy. EM bertolia@psichiat.uniba.it RI Picchioni, Marco/E-3300-2010; Hariri, Ahmad/D-5761-2011; Fazio, Leonardo/J-4570-2012; Sambataro, Fabio/E-3426-2010; Bertolino, Alessandro/O-6352-2016; Meyer-Lindenberg, Andreas/H-1076-2011 OI Picchioni, Marco/0000-0001-6681-147X; Fazio, Leonardo/0000-0003-4000-974X; Sambataro, Fabio/0000-0003-2102-416X; Bertolino, Alessandro/0000-0002-1251-1380; Meyer-Lindenberg, Andreas/0000-0001-5619-1123 NR 68 TC 116 Z9 120 U1 5 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD DEC 1 PY 2006 VL 60 IS 11 BP 1250 EP 1258 DI 10.1016/j.biopsych.2006.03.078 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 108ZW UT WOS:000242278700011 PM 16950222 ER PT J AU Savani, BN Montero, A Srinivasan, R Singh, A Shenoy, A Mielke, S Rezvani, K Karimpour, S Childs, R Barrett, AJ AF Savani, Bipin N. Montero, Aldemar Srinivasan, Ramaprasad Singh, Anurag Shenoy, Aarthi Mielke, Stephan Rezvani, Katayoun Karimpour, Shervin Childs, Richard Barrett, A. John TI Chronic GVHD and pretransplantation abnormalities in pulmonary function are the main determinants predicting worsening pulmonary function in long-term survivors after stem cell transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE pulmonary complications; myeloablative; nonmyeloablative; stem cell transplantation ID BONE-MARROW-TRANSPLANTATION; VERSUS-HOST-DISEASE; TOTAL-BODY IRRADIATION; IDIOPATHIC-PNEUMONIA-SYNDROME; NECROSIS-FACTOR-ALPHA; AIR-FLOW OBSTRUCTION; BRONCHIOLITIS-OBLITERANS; RANDOMIZED-TRIAL; LUNG-FUNCTION; RISK-FACTORS AB Pulmonary function (PF) was studied in 69 consecutive patients with hematologic diseases, with a minimum 5-year (range, 5-13 years) follow-up after allogeneic stem cell transplantation from an HLA-matched sibling. Fifty-six patients (81%) received total body irradiation based myeloablative stem cell transplantation (NIT) and 13 (19%) underwent nonmyeloablative stem cell transplantation (NST). Thirty-one patients (45%) developed a late decrease in PF from baseline, 25 with a restrictive and 6 with an obstructive pattern PF abnormality. Twelve patients (17%) were symptomatic, 8 with a severe restrictive PF defect, but none required supplemental oxygen. The incidence of developing a late PF abnormality was comparable in MT (24 of 56) and NST (5 of 13; P =.51). In multivariate analysis, chronic graft-versus-host disease (relative risk, 16) and pretransplantation diffusion capacity for carbon monoxide or forced expiratory volume in the first second < 80% predicted were independently associated with a late decrease in PF from baseline (relative risk, 7). Our results indicate that late PF abnormality is common after MT and NST. Patients with a low pretransplantation diffusion capacity for carbon monoxide of or forced expiratory volume in the first second who developed chronic graft-versus-host disease were most severely affected. Longer follow-up is needed to determine whether PF will continue to decrease or reach a plateau and whether more patients with PF abnormality will eventually become symptomatic. (C) 2006 American Society for Blood and Marrow Transplantation. C1 NHLBI, Stem Cell Allogeneic Transplantat Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. NCI, Dept Radiat Oncol, NIH, Bethesda, MD 20892 USA. RP Barrett, AJ (reprint author), NHLBI, Stem Cell Allogeneic Transplantat Sect, Hematol Branch, NIH, Bldg 10,Hatfield CRC,Room 3-5330,10 Ctr Dr MSC 12, Bethesda, MD 20892 USA. EM barrettj@nhlbi.nih.gov FU NHLBI NIH HHS [Z01 HL002342-11] NR 31 TC 38 Z9 38 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD DEC PY 2006 VL 12 IS 12 BP 1261 EP 1269 DI 10.1016/j.bbmt.2006.07.016 PG 9 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 119KZ UT WOS:000243012500003 PM 17162207 ER PT J AU Montero, A Savani, BN Shenoy, A Read, EJ Carter, CS Leitman, SF Mielke, S Rezvani, K Childs, R Barrett, AJ AF Montero, Aldemar Savani, Bipin N. Shenoy, Aarthi Read, Elizabeth J. Carter, Charles S. Leitman, Susan F. Mielke, Stephan Rezvani, Katayoun Childs, Richard Barrett, A. John TI T cell depleted peripheral blood stem cell allotransplantation with T cell add back for patients with hematological malignancies: Effect of chronic GVHD on outcome SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE T cell depleted; myeloablative; peripheral blood stem cell transplantation ID BONE-MARROW-TRANSPLANTATION; VERSUS-HOST DISEASE; CHRONIC MYELOGENOUS LEUKEMIA; HLA-IDENTICAL SIBLINGS; CD34(+); RECOVERY; RISK; ENGRAFTMENT; RECIPIENTS; SURVIVAL AB One hundred thirty-eight patients with hematologic malignancies received myeloablative T cell-depleted peripheral blood stem cell transplant (PBSCT) from an HLA-identical sibling donor. The T cell dose was adjusted to 0.2-1 X 10(5) CD3(+) cells/kg. The CD34 dose was 2.7-16 X 10(6) /kg. Patients with acute graft-versus-host disease (GVHD) grade <2 received 1 or 2 donor lymphocyte infusions of 10(7) CD3(+) cells/kg between days 45 and 100. Patients were designated according to relapse probability as standard or high relapse risk (77 and 61, respectively). Overall survival (OS), relapse-free survival, relapse, and transplant-related mortality (TRM) were 58%, 46%, 40%, and 20%, respectively, after a median follow-up of 4 years. Fifty-three (39%) and 21 (15%) patients developed grade 2-4 and 3-4 acute GVHD. Forty-two (36%) had limited and 29 (25%) had extensive chronic GVHD. In multivariate analysis, disease risk was an independent factor for OS and relapse, day-30 lymphocyte count for OS and TRM, and chronic GVHD for OS and relapse. PBSCT with early T cell add back leads to comparable rates of chronic GVHD compared with T cell-replete PBSCT. However, this chronic GVHD after T cell add back is associated with less mortality and retains a protective effect in terms of relapse, at least in the standard-risk patients. (C) 2006 American Society for Blood and Marrow Transplantation. C1 NHLBI, Stem Cell Allotransplantat Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Transfus Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Barrett, AJ (reprint author), NHLBI, Stem Cell Allogeneic Transplantat Sect, Hematol Branch, NIH, Bldg 10,Hatfield CRC,Room 3-5330,10 Ctr Dr MSC 12, Bethesda, MD 20892 USA. EM barrettj@nhlbi.nih.gov NR 25 TC 28 Z9 30 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD DEC PY 2006 VL 12 IS 12 BP 1318 EP 1325 DI 10.1016/j.bbmt.2006.08.034 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 119KZ UT WOS:000243012500010 PM 17162214 ER PT J AU Nam, JM AF Nam, Jun-mo TI Non-inferiority of new procedure to standard procedure in stratified matched-pair design SO BIOMETRICAL JOURNAL LA English DT Article DE likelihood score method; non-inferiority test; restricted maximum likelihood estimators; sample size determinations; stratified matched-pair study ID SAMPLE-SIZE DETERMINATION; UNITY RELATIVE RISK; QUALITATIVE INTERACTIONS; NULL HYPOTHESIS; NONINFERIORITY TRIALS; CLINICAL-TRIALS; MCNEMARS TEST; RATE RATIO; EQUIVALENCE; TESTS AB We consider the statistical testing for non-inferiority of a new treatment compared with the standard one under matched-pair setting in a stratified study or in several trials. A non-inferiority test based on the efficient scores and a Mantel-Haenszel (M-H) like procedure with restricted maximum likelihood estimators (RMLEs) of nuisance parameters and their corresponding sample size formulae are presented. We evaluate the above tests and the M-H type Wald test in level and power. The stratified score test is conservative and provides the best power. The M-H like procedure with RMLEs gives an accurate level. However, the Wald test is anti-conservative and we suggest caution when it is used. The unstratified score test is not biased but it is less powerful than the stratified score test when base-line probabilities related to strata are not the same. This investigation shows that the stratified score test possesses optimum statistical properties in testing noninferiority. A common difference between two proportions across strata is the basic assumption of the stratified tests, we present appropriate tests to validate the assumption and related remarks. C1 NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Nam, JM (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Execut Plaza S,Room 8028,6120 Execut Blvd,MSC 724, Bethesda, MD 20892 USA. EM namj@mail.nih.gov FU Intramural NIH HHS NR 35 TC 8 Z9 8 U1 1 U2 1 PU AKADEMIE VERLAG GMBH PI BERLIN PA PALISADENSTR 40, D-10243 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PD DEC PY 2006 VL 48 IS 6 BP 966 EP 977 DI 10.1002/bimj.200510283 PG 12 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 123SA UT WOS:000243314700008 PM 17243295 ER PT J AU Berger, VW Stefanescu, C Zhou, YY AF Berger, Vance W. Stefanescu, Catalina Zhou, Yan Yan TI The analysis of stratified 2 X 2 contingency tables SO BIOMETRICAL JOURNAL LA English DT Article DE admissibility; binary data; clinical trial; common odds ratio; omnibus test ID ORDERED CATEGORICAL-DATA; EXACT CONDITIONAL TESTS; FISHER EXACT TEST; CLINICAL-TRIALS; STOCHASTIC ORDER; EXACT POWER; RANDOMIZATION; METAANALYSIS; BIAS AB We consider the problem of testing for independence against the consistent superiority of one treatment over another when the response variable is binary and is compared across two treatments in each of several strata. Specifically, we consider the randomized clinical trial setting. A number of issues arise in this context. First, should tables be combined if there are small or zero margins? Second, should one assume a common odds ratio across strata? Third, if the odds ratios differ across strata, then how does the standard test (based on a common odds ratio) perform? Fourth, are there other analyzes that are more appropriate for handling a situation in which the odds ratios may differ across strata? In addressing these issues we find that the frequently used Cochran -Mantel -Haenszel test may have a poor power profile, despite being optimal when the odds ratios are common. We develop novel tests that are analogous to the Smirnov, modified Smirnov, convex hull, and adaptive tests that have been proposed for ordered categorical data. C1 London Business Sch, London NW1 4SA, England. Univ Maryland Baltimore Cty, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. Florida Int Univ, Dept Stat, Miami, FL 33199 USA. RP Stefanescu, C (reprint author), London Business Sch, Regents Pk, London NW1 4SA, England. EM estefanescu@london.edu NR 33 TC 1 Z9 1 U1 2 U2 4 PU AKADEMIE VERLAG GMBH PI BERLIN PA PALISADENSTR 40, D-10243 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PD DEC PY 2006 VL 48 IS 6 BP 992 EP 1007 DI 10.1002/bimj.200610277 PG 16 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 123SA UT WOS:000243314700011 PM 17240657 ER PT J AU Pennell, ML Dunson, DB AF Pennell, Michael L. Dunson, David B. TI Bayesian semiparametric dynamic frailty models for multiple event time data SO BIOMETRICS LA English DT Article DE breast cancer; chemoprevention; Dirichlet process; nonparametric Bayes; palpable tumors; survival analysis; tumor multiplicity data ID MULTIVARIATE SURVIVAL-DATA; GENERALIZED LINEAR-MODELS; PANEL-COUNT DATA; PROPORTIONAL HAZARDS; GAMMA PROCESSES; CARCINOGENESIS; HETEROGENEITY; INFERENCE; TUMOR AB Many biomedical studies collect data on times of occurrence for a health event that can occur repeatedly, such as infection, hospitalization, recurrence of disease, or tumor onset. To analyze such data, it is necessary to account for within-subject dependency in the multiple event times. Motivated by data from studies of palpable tumors, this article proposes a dynamic frailty model and Bayesian semiparametric approach to inference. The widely used shared frailty proportional hazards model is generalized to allow subject-specific frailties to change dynamically with age while also accommodating nonproportional hazards. Parametric assumptions on the frailty distribution are avoided by using Dirichlet process priors for a shared frailty and for multiplicative innovations on this frailty. By centering the semiparametric model on a conditionally conjugate dynamic gamma model, we facilitate posterior computation and lack-of-fit assessments of the parametric model. Our proposed method is demonstrated using data from a cancer chemoprevention study. C1 Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA. Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Pennell, ML (reprint author), Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA. EM pennell@niehs.nih.gov FU Intramural NIH HHS NR 47 TC 17 Z9 18 U1 1 U2 8 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD DEC PY 2006 VL 62 IS 4 BP 1044 EP 1052 DI 10.1111/j.1541-0420.2006.00571.x PG 9 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 115ZH UT WOS:000242771800010 PM 17156278 ER PT J AU Zhang, H Zheng, G Li, Z AF Zhang, H. Zheng, G. Li, Z. TI Statistical analysis for haplotype-based matched case-control studies SO BIOMETRICS LA English DT Article DE conditional logistic regression model; estimating equation; haplotype; matched case-control study; score test; wald test ID UNPHASED GENOTYPE DATA; UNRELATED INDIVIDUALS; GENOMIC CONTROL; LINKAGE PHASE; SCORE TESTS; ASSOCIATION; COHORT; DISEASE; TRAITS; POLYMORPHISMS AB Using unphased genotype data, we studied statistical inference for association between a disease and a haplotype in matched case-control studies. Statistical inference for haplotype data is complicated due to ambiguity of genotype phases. An estimating equation-based method is developed for estimating odds ratios and testing disease-haplotype association. The method potentially can also be applied to testing haplotype-environment interaction. Simulation studies show that the proposed method has good performance. The performance of the method in the presence of departures from Hardy-Weinberg equilibrium is also studied. C1 Univ Sci & Technol China, Dept Stat & Finance, Anhua 230026, Peoples R China. George Washington Univ, Dept Stat, Washington, DC 20052 USA. NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. RP Zhang, H (reprint author), Univ Sci & Technol China, Dept Stat & Finance, 96 Jinzhai Rd, Anhua 230026, Peoples R China. EM zli@agwu.edu FU NEI NIH HHS [EY014478] NR 38 TC 3 Z9 4 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD DEC PY 2006 VL 62 IS 4 BP 1124 EP 1131 DI 10.1111/j.1541-0420.2006.00568.x PG 8 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 115ZH UT WOS:000242771800019 PM 17156287 ER PT J AU Lu, SE Shih, JH AF Lu, Shou-En Shih, Joanna H. TI Case-cohort designs and analysis for clustered failure time data SO BIOMETRICS LA English DT Article DE cost-effective design; proportional hazards; pseudo-likelihood ID TRANSLATING RESEARCH; REGRESSION-MODELS; DIABETES TRIAD; VARIANCE; HAZARDS AB Case-cohort design is an efficient and economical design to study risk factors for infrequent disease in a large cohort. It involves the collection of covariate data from all failures ascertained throughout the entire cohort, and from the members of a random subcohort selected at the onset of follow-up. In the literature, the case-cohort design has been extensively studied, but was exclusively considered for univariate failure time data. In this article, we propose case-cohort designs adapted to multivariate failure time data. An estimation procedure with the independence working model approach is used to estimate the regression parameters in the marginal proportional hazards model, where the correlation structure between individuals within a cluster is left unspecified. Statistical properties of the proposed estimators are developed. The performance of the proposed estimators and comparisons of statistical efficiencies are investigated with simulation studies. A data example from the Translating Research into Action for Diabetes (TRIAD) study is used to illustrate the proposed methodology. C1 Univ Med & Dent New Jersey, Dept Biostat, New Brunswick, NJ 08903 USA. NCI, Biometr Res Branch, Div Canc Treatment & Diagnosis, Bethesda, MD 20892 USA. RP Lu, SE (reprint author), Univ Med & Dent New Jersey, Dept Biostat, New Brunswick, NJ 08903 USA. EM lus2@umdnj.edu FU PHS HHS [04005] NR 24 TC 14 Z9 15 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD DEC PY 2006 VL 62 IS 4 BP 1138 EP 1148 DI 10.1111/j.1541-0420.2006.00584.x PG 11 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 115ZH UT WOS:000242771800021 PM 17156289 ER PT J AU Follmann, D AF Follmann, Dean TI Augmented designs to assess immune response in vaccine trials SO BIOMETRICS LA English DT Article DE AIDS; causal inference; correlate of protection; counterfactual; HIV; missing data; principal stratification; surrogate endpoint ID BAYESIAN-INFERENCE; CAUSAL INFERENCE; VIRAL LOAD; RISK AB This article introduces methods for use in vaccine clinical trials to help determine whether the immune response to a vaccine is actually causing a reduction in the infection rate. This is not easy because immune response to the (say HIV) vaccine is only observed in the HIV vaccine arm. If we knew what the HIV-specific immune response in placebo recipients would have been, had they been vaccinated, this immune response could be treated essentially like a baseline covariate and an interaction with treatment could be evaluated. Relatedly, the rate of infection by this baseline covariate could be compared between the two groups and a causative role of immune response would be supported if infection risk decreased with increasing HIV immune response only in the vaccine group. We introduce two methods for inferring this HIV-specific immune response. The first involves vaccinating everyone before baseline with an irrelevant vaccine, for example, rabies. Randomization ensures that the relationship between the immune responses to the rabies and HIV vaccines observed in the vaccine group is the same as what would have been seen in the placebo group. We infer a placebo volunteer's response to the HIV vaccine using their rabies response and a prediction model from the vaccine group. The second method entails vaccinating all unifected placebo patients at the closeout of the trial with the HIV vaccine and recording immune response. We pretend this immune response at closeout is what they would have had at baseline. We can then infer what the distribution of immune response among placebo infecteds would have been. Such designs may help elucidate the role of immune response in preventing infections. More pointedly, they could be helpful in the decision to improve or abandon an HIV vaccine with mediocre performance in a phase III trial. C1 NIAID, Biostat Res Branch, Bethesda, MD 20892 USA. RP Follmann, D (reprint author), NIAID, Biostat Res Branch, 6700B Rockledge Dr MSC 7609, Bethesda, MD 20892 USA. EM dfollmann@niaid.nih.gov FU Intramural NIH HHS [Z99 AI999999] NR 21 TC 45 Z9 46 U1 0 U2 9 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD DEC PY 2006 VL 62 IS 4 BP 1161 EP 1169 DI 10.1111/j.1541-0420.2006.00569.x PG 9 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 115ZH UT WOS:000242771800023 PM 17156291 ER PT J AU Liu, AY Schisterman, EF Wu, CQ AF Liu, Aiyi Schisterman, Enrique F. Wu, Chengqing TI Multistage evaluation of measurement error in a reliability study SO BIOMETRICS LA English DT Article DE interim analysis; intraclass correlation; measurement error; power and sample size ID CLINICAL-TRIALS; DESIGN; TESTS AB We introduce sequential testing procedures for the planning and analysis of reliability studies to assess an exposure's measurement error. The designs allow repeated evaluation of reliability of the measurements and stop testing if early evidence shows the measurement error is within the level of tolerance. Methods are developed and critical values tabulated for a number of two-stage designs. The methods are exemplified using an example evaluating the reliability of biomarkers associated with oxidative stress. C1 NICHHD, Div Epidemiol Stat & Prevent Res, NIH, DHHS, Rockville, MD 20852 USA. RP Liu, AY (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, NIH, DHHS, 6100 Execut Blvd, Rockville, MD 20852 USA. EM liua@mail.nih.gov OI Liu, Aiyi/0000-0002-6618-5082; Schisterman, Enrique/0000-0003-3757-641X FU Intramural NIH HHS NR 17 TC 6 Z9 6 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD DEC PY 2006 VL 62 IS 4 BP 1190 EP 1196 DI 10.1111/j.1541-0420.2006.00572.x PG 7 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 115ZH UT WOS:000242771800026 PM 17156294 ER PT J AU Huang, CY Wang, MC Zhang, Y AF Huang, Chiung-Yu Wang, Mei-Cheng Zhang, Ying TI Analysing panel count data with informative observation times SO BIOMETRIKA LA English DT Article DE dependent censoring; frailty; Poisson process; rate function; serial events AB In this paper, we study panel count data with informative observation times. We assume nonparametric and semiparametric proportional rate models for the underlying event process, where the form of the baseline rate function is left unspecified and a subject-specific frailty variable inflates or deflates the rate function multiplicatively. The proposed models allow the event processes and observation times to be correlated through their connections with the unobserved frailty; moreover, the distributions of both the frailty variable and observation times are considered as nuisance parameters. The baseline rate function and the regression parameters are estimated by maximising a conditional likelihood function of observed event counts and solving estimation equations. Large-sample properties of the proposed estimators are studied. Numerical studies demonstrate that the proposed estimation procedures perform well for moderate sample sizes. An application to a bladder tumour study is presented. C1 NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA. Univ Iowa, Dept Biostat, Iowa City, IA 52242 USA. RP Huang, CY (reprint author), NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. EM huangchi@niaid.nih.gov; ncwang@jhsph.edu; ying-j-zhang@uiowa.edu FU Intramural NIH HHS [Z99 AI999999] NR 12 TC 42 Z9 42 U1 1 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-3444 J9 BIOMETRIKA JI Biometrika PD DEC PY 2006 VL 93 IS 4 BP 763 EP 775 DI 10.1093/biomet/93.4.763 PG 13 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 120CM UT WOS:000243061200002 PM 23729818 ER PT J AU Auh, S Sampson, AR AF Auh, Sungyoung Sampson, Allan R. TI Isotonic logistic discrimination SO BIOMETRIKA LA English DT Article DE Bayes rule; isotonic discrimination; isotonic regression; logistic discrimination AB We propose an isotonic logistic discrimination procedure which generalises linear logistic discrimination by allowing linear boundaries to be more flexibly shaped as monotone functions of the discriminant variables. Under each of three familiar sampling schemes for obtaining a training dataset, namely prospective, mixture and retrospective, we provide the corresponding likelihood-based inference. An application to a cancer study is given. In addition, we consider theoretical comparisons of our method with two recent algorithmic monotone discrimination procedures. C1 Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Dept Stat, Pittsburgh, PA 15260 USA. RP Auh, S (reprint author), Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20892 USA. EM auhs@ninds.nih.gov; asampson@stat.pitt.edu NR 11 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-3444 J9 BIOMETRIKA JI Biometrika PD DEC PY 2006 VL 93 IS 4 BP 961 EP 972 DI 10.1093/biomet/93.4.961 PG 12 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 120CM UT WOS:000243061200014 ER PT J AU Zhao, XZ Semenova, EA Liao, CZ Nicklaus, M Pommier, Y Burke, TR AF Zhao, Xue Zhi Semenova, Elena A. Liao, Chenzhong Nicklaus, Marc Pommier, Yves Burke, Terrence R., Jr. TI Biotinylated biphenyl ketone-containing 2,4-dioxobutanoic acids designed as HIV-1 integrase photoaffinity ligands SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE HIV-1 integrase; inhibitor; biotin; photoaffinity ID SOLID-PHASE SYNTHESIS; VIRAL REPLICATION; STRAND TRANSFER; DRUG DESIGN; INHIBITORS; BINDING; PROBES; SITES; CELLS; PROTEINS AB The diketo acid (DKA) class of HIV-1 integrase inhibitors are thought to function by chelating divalent metal ions within the enzyme catalytic center. However, differences in mutations conferring resistance among sub-families of DKA inhibitors suggest that multiple binding orientations may exist. In order to facilitate identification of DKA-binding sites, biotin-tagged biphenyl ketone-containing 2,4-dioxobutanoic acids were prepared as DKA photoaffinity probes. Introduction of biotin was obtained by means of Huisgen [3+2] cycloaddition 'click chemistry.' Two photoprobes, 5a and 5b, were prepared bearing short and long linker segments, respectively, between the biotin and DKA nucleus. The greatest inhibitory potency was shown by 5b, which inhibited 3'-processing and strand transfer reactions with IC50 values of > 333 mu M and 12.4 mu M, respectively. In cross-linking assays designed to measure disruption of substrate DNA binding, the photoprobes behaved similarly to a reference DKA inhibitor. Analogues 5a and 5b represent novel photoaffinity ligands, which may be useful in clarifying the HIV-1 binding interactions of DKA inhibitors. Published by Elsevier Ltd. C1 NCI, NIH, Med Chem Lab, CCR, Frederick, MD 21702 USA. NCI, Mol Pharmacol Lab, CCR, NIH, Bethesda, MD 20892 USA. RP Burke, TR (reprint author), NCI, NIH, Med Chem Lab, CCR, Frederick, MD 21702 USA. EM tburke@helix.nih.gov RI Zhao, Xue Zhi/N-9594-2014; Burke, Terrence/N-2601-2014; OI Zhao, Xue Zhi/0000-0003-1006-6364; Nicklaus, Marc/0000-0002-4775-7030 FU Intramural NIH HHS NR 37 TC 15 Z9 15 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD DEC 1 PY 2006 VL 14 IS 23 BP 7816 EP 7825 DI 10.1016/j.bmc.2006.07.064 PG 10 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 105WR UT WOS:000242063500015 PM 16908168 ER PT J AU Zhou, LH Thakur, CS Molinaro, RJ Paranjape, JM Hoppes, R Jeang, KT Silverman, RH Torrence, PF AF Zhou, Longhu Thakur, Chandar S. Molinaro, Ross J. Paranjape, Jayashree M. Hoppes, Rieuwert Jeang, Kuan-Teh Silverman, Robert H. Torrence, Paul F. TI Delivery of 2-5A cargo into living cells using the Tat cell penetrating peptide: 2-5A-tat SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE ribonuclease L; interferon; cycloaddition; sulfhydryl alkylation; RNA; 2 ',5 '-oligoadenylate ID HIV-INFECTION; RNASE-L; GENE-EXPRESSION; DOWN-REGULATION; INHIBITION; PROTEIN; ANTISENSE; TARGET; VIRUS; TRANSACTIVATION AB 2',5'-Oligoadenylate tetramer (2-5A) has been chemically conjugated to short HIV-1 Tat peptides to provide 2-5A-tat chimeras. Two different convergent synthetic approaches have been employed to provide such 2-5A-tat bioconjugates. One involved generation of a bioconjugate through reaction of a cysteine terminated Tat peptide with a alpha-chloroacetyl derivative of 2-5A. The second synthetic strategy was based upon a cycloaddition reaction of an azide derivative of 2-5A with a Tat peptide bearing an alkyne function. Either bioconjugate of 2-5A-tat was able to activate human RNase L. The union of 2-5A and Tat peptide provided an RNase L-active chimeric nucleopeptide with the ability to be taken up by cells by virtue of the Tat peptide and to activate RNase L in intact cells. This strategy provides a valuable vehicle for the entry of the charged 2-5A molecule into cells and may provide a means for targeted destruction of HIV RNA in vivo. (c) 2006 Elsevier Ltd. All rights reserved. C1 No Arizona Univ, Dept Chem & Biochem, Flagstaff, AZ 86011 USA. Cleveland Clin, Lerner Res Inst, Dept Canc Biol, Cleveland, OH 44195 USA. NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. Cleveland State Univ, Dept Chem, Cleveland, OH 44115 USA. RP Torrence, PF (reprint author), No Arizona Univ, Dept Chem & Biochem, Flagstaff, AZ 86011 USA. EM Paul.Torrence@nau.edu RI Jeang, Kuan-Teh/A-2424-2008 FU NIAID NIH HHS [5 R03 AI054184-02] NR 64 TC 8 Z9 10 U1 0 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD DEC 1 PY 2006 VL 14 IS 23 BP 7862 EP 7874 DI 10.1016/j.bmc.2006.07.058 PG 13 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 105WR UT WOS:000242063500020 PM 16908165 ER PT J AU Koushik, SV Chen, H Thaler, C Puhl, HL Vogel, SS AF Koushik, Srinagesh V. Chen, Huanmian Thaler, Christopher Puhl, Henry L., III Vogel, Steven S. TI Cerulean, Venus, and Venus(Y67C) FRET reference standards SO BIOPHYSICAL JOURNAL LA English DT Article ID IMAGING MICROSCOPY FLIM; FLUORESCENT PROTEIN; EFFICIENCY; VARIANT; CELLS AB Forster's resonance energy transfer (FRET) can be used to study protein- protein interactions in living cells. Numerous methods to measure FRET have been devised and implemented; however, the accuracy of these methods is unknown, which makes interpretation of FRET efficiency values difficult if not impossible. This problem exists due to the lack of standards with known FRET efficiencies that can be used to validate FRET measurements. The advent of spectral variants of green fluorescent protein and easy access to cell transfection technology suggests a simple solution to this problem: the development of genetic constructs with known FRET efficiencies that can be replicated with high fidelity and freely distributed. In this study, fluorescent protein constructs with progressively larger separation distances between donors and acceptors were generated and FRET efficiencies were measured using fluorescence lifetime spectroscopy, sensitized acceptor emission, and spectral imaging. Since the results from each method were in good agreement, the FRET efficiency value of each construct could be determined with high accuracy and precision, thereby justifying their use as standards. C1 NIAAA, Lab Mol Physiol, Bethesda, MD USA. RP Vogel, SS (reprint author), NIAAA, Lab Mol Physiol, Bethesda, MD USA. EM stevevog@mail.nih.gov RI Vogel, Steven/A-3585-2012; OI Puhl, Henry/0000-0003-3095-7201; Vogel, Steven/0000-0002-3005-2667 FU Intramural NIH HHS NR 15 TC 100 Z9 100 U1 0 U2 12 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD DEC PY 2006 VL 91 IS 12 BP L99 EP L101 DI 10.1529/biophysj.106.096206 PG 3 WC Biophysics SC Biophysics GA 109WF UT WOS:000242339600001 PM 17040988 ER PT J AU Singh, JB Zarate, CA AF Singh, Jaskaran B. Zarate, Carlos A., Jr. TI Pharmacological treatment of psychiatric comorbidity in bipolar disorder: a review of controlled trials SO BIPOLAR DISORDERS LA English DT Review DE bipolar disorder; comorbidity; treatment ID OBSESSIVE-COMPULSIVE DISORDER; PLACEBO-CONTROLLED TRIAL; BORDERLINE PERSONALITY-DISORDER; POSTTRAUMATIC-STRESS-DISORDER; SEROTONIN REUPTAKE INHIBITORS; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DOUBLE-BLIND; COCAINE DEPENDENCE; ALCOHOL-DEPENDENCE; DIVALPROEX SODIUM AB Objective: Little is known about the treatment of psychiatric comorbidities in bipolar disorder. The aim of this review was to summarize the literature on controlled pharmacological trials that have been conducted in psychiatric conditions that commonly co-occur in bipolar disorder. Methods: A Medline search (1980-October 2005) using the terms bipolar disorder and randomized controlled trials, comorbidity, anxiety disorders, alcohol abuse or dependence, substance abuse or dependence, eating disorder, impulse control disorders, attention-deficit disorder, lithium, anticonvulsants, atypical antipsychotic drugs, antidepressants, stimulants was used. Results: The literature establishes a strong association between bipolar disorder and substance abuse/dependence, anxiety disorders, impulse control disorders, eating disorders and attention-deficit hyperactivity disorder. Comorbidity often complicates the diagnosis and the treatment of bipolar disorder and worsens its course of illness and prognosis. Few controlled pharmacological studies have examined the treatment of comorbid conditions in patients with bipolar disorder. Conclusions: Treatment of psychiatric comorbidities in bipolar disorder is not based on controlled data but is largely empirically based. Controlled trials in patients with bipolar disorder and comorbidity are urgently needed. C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RP Zarate, CA (reprint author), NIMH, Mood & Anxiety Disorders Program, 10 Ctr Dr,Mark O HAtfield CRC,Unit 7 SE,Rm 7-3445, Bethesda, MD 20892 USA. EM zaratec@mail.nih.gov FU Intramural NIH HHS NR 69 TC 33 Z9 35 U1 5 U2 12 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD DEC PY 2006 VL 8 IS 6 BP 696 EP 709 DI 10.1111/j.1399-5618.2006.00371.x PG 14 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 110IZ UT WOS:000242373200006 PM 17156156 ER PT J AU Rozman, KK Bhatia, J Calafat, AM Chambers, C Culty, M Etzel, RA Flaws, JA Hansen, DK Hoyer, PB Jeffery, EH Kesner, JS Marty, S Thomas, JA Umbach, D AF Rozman, Karl K. Bhatia, Jatinder Calafat, Antonia M. Chambers, Christina Culty, Martine Etzel, Ruth A. Flaws, Jodi A. Hansen, Deborah K. Hoyer, Patricia B. Jeffery, Elizabeth H. Kesner, James S. Marty, Sue Thomas, John A. Umbach, David TI NTP-CERHR expert panel report on the reproductive and developmental toxicity of genistein SO BIRTH DEFECTS RESEARCH PART B-DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY LA English DT Review ID SPRAGUE-DAWLEY RATS; MAMMARY-GLAND DEVELOPMENT; CHROMATOGRAPHY-MASS SPECTROMETRY; LUTEINIZING-HORMONE SECRETION; NATURALLY-OCCURRING ESTROGENS; TYROSINE KINASE INHIBITORS; SEXUALLY DIMORPHIC NUCLEUS; MATERNAL DIETARY EXPOSURE; PURIFIED SOY ISOFLAVONES; EPIDERMAL-GROWTH-FACTOR C1 Univ Kansas, Med Ctr, Dept Pharmacol & Toxicol, Kansas City, KS 66103 USA. Med Coll Georgia, Dept Pediat, Div Neonatol, Augusta, GA 30912 USA. Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA. Univ Calif San Diego, Med Ctr, Dept Pediat, San Diego, CA 92103 USA. Univ Calif San Diego, Med Ctr, Dept Family & Prevent Med, San Diego, CA 92103 USA. Georgetown Univ, Med Ctr, Dept Biochem & Mol Biol, Washington, DC 20007 USA. George Washington Univ, Sch Publ Hlth & Hlth Sci, Washington, DC USA. Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. Univ Arizona, Dept Physiol, Tucson, AZ USA. Univ Illinois, Dept Food Sci & Human Nutr, Urbana, IL 61801 USA. NIOSH, Cincinnati, OH 45226 USA. Dow Chem Co USA, Toxicol Res Lab, Midland, MI 48674 USA. Indiana Univ, Sch Med, Dept Pharmacol & Toxicol, Indianapolis, IN 46202 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Rozman, KK (reprint author), NIEHS EC-32,POB 12233, Res Triangle Pk, NC 27709 USA. FU Intramural NIH HHS [Z01 ES045002-12] NR 235 TC 42 Z9 43 U1 1 U2 8 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1542-9733 J9 BIRTH DEFECTS RES B JI Birth Defects Res. Part B-Dev. Reprod. Toxicol. PD DEC PY 2006 VL 77 IS 6 BP 485 EP 638 DI 10.1002/bdrb.20087 PG 154 WC Oncology; Genetics & Heredity; Toxicology SC Oncology; Genetics & Heredity; Toxicology GA 119AD UT WOS:000242983700001 PM 17186522 ER PT J AU Romero, R Espinoza, J Kusanovic, JP Gotsch, F Hassan, S Erez, O Chaiworapongsa, T Mazor, M AF Romero, R. Espinoza, J. Kusanovic, J. P. Gotsch, F. Hassan, S. Erez, O. Chaiworapongsa, T. Mazor, M. TI The preterm parturition syndrome SO BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY LA English DT Article; Proceedings Paper CT 3rd International Preterm Labour Congress CY APR 27-29, 2006 CL Montreaux, SWITZERLAND DE allergy; cervical insufficiency; inflammation; intrauterine infection; multiple aetiology; prematurity; preterm birth; preterm labour; uterine ischaemia; uterine overdistension ID TUMOR-NECROSIS-FACTOR; AMNIOTIC-FLUID INTERLEUKIN-6; SMOOTH-MUSCLE-CELLS; CORTICOTROPIN-RELEASING HORMONE; FACTOR-KAPPA-B; FETAL INFLAMMATORY RESPONSE; DECAY-ACCELERATING FACTOR; COLONY-STIMULATING FACTOR; POLYMERASE-CHAIN-REACTION; MESSENGER-RIBONUCLEIC-ACID AB The implicit paradigm that has governed file Study and clinical management of preterm labour is that term and preterm parturition arc the same processes, except for the gestational age at which they occur. Indeed, both share a common pathway composed of uterine contractility, cervical dilatation and activation of the membranes/decidua. This review explores the concept that while term labour results front physiological activation of the components of the common pathway, preterm labour crises from pathological signalling and activation of one or more components of the common pathway of parturition. The term 'great obstetrical syndromes' has been coined to reframe the concept of obstetrical disease. Such syndromes arc characterised by: (1) Multiple aetiology; (2) long preclinical stage; (3) frequent fetal involvement; (4) clinical manifestations that are often adaptive in nature; and (5) gene-environment interactions that may predispose to the syndromes. This article reviews the evidence indicating that the pathological processes implicated in the preterm parturition syndrome include: (1) intrauterine infection/inflammation; (2) uterine ischaemia; (3) uterine overdistension; (4) abnormal allograft reaction; (5) allergy; (6) cervical insufficiency; and (7) hormonal disorders (progesterone related and corticotrophin-releasing factor related). The implications of this conceptual framework for the prevention, diagnosis, and treatment of preterm labour arc discussed. C1 Hutzel Hosp, Perinatol Res Branch, NICHD, NIH,DHHS, Detroit, MI 48201 USA. Hutzel Hosp, Perinatol Res Branch, NICHD, NIH,DHHS, Bethesda, MD USA. Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI 48202 USA. Ben Gurion Univ Negev, Soroka Med Ctr, Dept Obstet & Gynecol, IL-84105 Beer Sheva, Israel. RP Romero, R (reprint author), Hutzel Hosp, Perinatol Res Branch, NICHD, NIH,DHHS, Box 4,3990 John R, Detroit, MI 48201 USA. EM awarfiel@med.wayne.edu NR 433 TC 468 Z9 479 U1 3 U2 35 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1470-0328 J9 BJOG-INT J OBSTET GY JI BJOG PD DEC PY 2006 VL 113 SU 3 BP 17 EP 42 DI 10.1111/j.1471-0528.2006.01120.x PG 26 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 122ZS UT WOS:000243266700005 PM 17206962 ER PT J AU Klebanoff, M Searle, K AF Klebanoff, M. Searle, K. TI The role of inflammation in preterm birth - focus on periodontitis SO BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY LA English DT Article; Proceedings Paper CT 3rd International Preterm Labour Congress CY APR 27-29, 2006 CL Montreaux, SWITZERLAND DE inflammation; periodontitis; preterm birth ID DISEASE; INFECTION; RISK; ASSOCIATION; PREGNANCY; DELIVERY; WEIGHT AB It is universally accepted that acute inflammation is responsible for a substantial fraction of preterm births, particularly early cases. Much of this inflammation is caused by intrauterine infection. There is also evidence that infection and perhaps inflammation remote From the genitourinary tract call trigger preterm tabour. Several studies have Suggested that periodontitis during pregnancy increases the risk of preterin birth. Periodontitis may cause preterin birth by causing low-grade bacteraema, which lodges in the decidua, chorion and aminion or by releasing endotoxin into the maternal circulation, which triggers intrauterine inflammation and preterm birth. Alternatively, it may release cytokines and other inflammatory products, which then trigger preterin tabour. It is also conceivable that periodontitis might serve as a marker for other uuhealthy behaviours, or immune hyperresponsiveness and that hyperresponsiveness to low-grade intrauterine infection itself might cause preterm birth. Currently, there are few data available to distinguish these possibilities. Such distinctions are important since they have clear implications for whether treatment of periodontitis might reduce the incidence of preterm birth. Several clinical trials of treatment of periodontitis are continuing, but until their results are known there is Currently little evidence that treatment of periodontitis during pregnancy reduces the incidence of preterm birth. C1 NICHHD, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Klebanoff, M (reprint author), NICHHD, Dept Hlth & Human Serv, NIH, Bldg 6100,Room 7B05, Bethesda, MD 20892 USA. EM klebanom@exchange.nih.gov NR 15 TC 24 Z9 26 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1470-0328 J9 BJOG-INT J OBSTET GY JI BJOG PD DEC PY 2006 VL 113 SU 3 BP 43 EP 45 DI 10.1111/j.1471-0528.2006.01121.x PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 122ZS UT WOS:000243266700006 PM 17206963 ER PT J AU Romero, R Espinoza, J Gotsch, F Kusanovic, JP Friel, LA Erez, O Mazaki-Tovi, S Than, NG Hassan, S Tromp, G AF Romero, R. Espinoza, J. Gotsch, F. Kusanovic, J. P. Friel, L. A. Erez, O. Mazaki-Tovi, S. Than, N. G. Hassan, S. Tromp, G. TI The use of high-dimensional biology (genomics, transcriptomics, proteomics, and metabolomics) to understand the preterm parturition syndrome SO BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY LA English DT Article; Proceedings Paper CT 3rd International Preterm Labour Congress CY APR 27-29, 2006 CL Montreux, SWITZERLAND DE analytical tools; genetics; high-throughput; omics; predisposing factors; preterm birth; preterm labour; systems biology ID TUMOR-NECROSIS-FACTOR; FLUID MATRIX METALLOPROTEINASE-8; FACTOR-KAPPA-B; SUPPRESSION SUBTRACTIVE HYBRIDIZATION; GENE-EXPRESSION SIGNATURE; THAN-G POLYMORPHISM; FACTOR-ALPHA GENE; PREMATURE-RUPTURE; AMNIOTIC-FLUID; FETAL MEMBRANES AB High-dimensional biology (HDB) refers to the simultaneous study of the genetic variants (DNA variation), transcription (messenger RNA [mRNA]), peptides and proteins, and metabolites of an organ, tissue, or an organism in health and disease. The fundamental premise is that the evolutionary complexity of biological systems renders them difficult to comprehensively understand using only a reductionist approach. Such complexity can become tractable with the use of 'omics' research. This term refers to the study of entities in aggregate. The current nomenclature of 'omics' sciences includes genomics for DNA variants, transcriptomics for mRNA, proteomics for proteins, and metabolomics for intermediate products of metabolism. Another discipline relevant to medicine is pharmacogenomics. The two major advances that have made HDB possible are technological breakthroughs that allow simultaneous examination of thousands of genes, transcripts, and proteins, etc., with high-throughput techniques and analytical tools to extract information. What is conventionally considered hypothesis-driven research and discovery-driven research (through 'omic' methodologies) are complementary and synergistic. Here we review data which have been derived from: 1) genomics to examine predisposing factors for preterm birth; 2) transcriptomics to determine changes in mRNA in reproductive tissues associated with preterm labour and preterm prelabour rupture of membranes; 3) proteomics to identify differentially expressed proteins in amniotic fluid of women with preterm labour; and 4) metabolomics to identify the metabolic footprints of women with preterm labour likely to deliver preterm and those who will deliver at term. The complementary nature of discovery science and HDB is emphasised. C1 Hutzel Hosp, Perinatol Res Branch, Intramural Div, NICHD,NIH,DHHS, Bethesda, MD USA. Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48202 USA. Wayne State Univ, Hutzel Womens Hosp, Dept Obstet & Gynecol, Detroit, MI 48202 USA. RP Romero, R (reprint author), Hutzel Hosp, Perinatol Res Branch, Intramural Div, NICHD,NIH,DHHS, Box 44,3990 John R, Detroit, MI 48201 USA. EM warfiela@mail.nih.gov RI Tromp, Gerard/B-2677-2017 OI Tromp, Gerard/0000-0002-7761-0806 FU Intramural NIH HHS NR 204 TC 95 Z9 100 U1 2 U2 12 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1470-0328 J9 BJOG-INT J OBSTET GY JI BJOG PD DEC PY 2006 VL 113 SU 3 BP 118 EP 135 DI 10.1111/j.1471-0528.2006.01150.x PG 18 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 122ZS UT WOS:000243266700023 PM 17206980 ER PT J AU Biggar, RJ Jaffe, ES Goedert, JJ Chaturvedi, A Pfeiffer, R Engels, EA AF Biggar, Robert J. Jaffe, Elaine S. Goedert, James J. Chaturvedi, Anil Pfeiffer, Ruth Engels, Eric A. TI Hodgkin lymphoma and immunodeficiency in persons with HIV/AIDS SO BLOOD LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; B-CELL LYMPHOMA; AIDS-DEFINING CANCERS; REED-STERNBERG CELLS; SWISS HIV COHORT; HOMOSEXUAL MEN; SAN-FRANCISCO; UNITED-STATES; RHEUMATOID-ARTHRITIS; INFECTION AB In persons with HIV/AIDS (PWHAs), Hodgkin lymphoma (HL) risk is increased. However, HL incidence in PWHAs has unexpectedly increased since highly active antiretroviral therapy (HAART) was introduced. We linked nationwide HIV/AIDS and cancer registry data from 1980 through 2002. Immunity was assessed by CD4 T-lymphocyte counts at AIDS onset. Annual HL incidence rates were calculated for 4 through 27 months after AIDS onset. During 477 368 person years (py's) of follow-up in 317 428 persons with AIDS (PWAS), 173 HL cases occurred (36.2 per 105 py's). Incidence was significantly higher in 1996 to 2002 than earlier. Incidence in PWAs with 150 to 199 CD4 cells/mu L was 53.7 per 10(5) py's, whereas in PWAs with fewer than 50 CD4 cells/mu L, it was 20.7 per 10(5) py's (P-trend = .002). For each HL subtype, incidence decreased with declining CD4 counts, but nodular sclerosing decreased more precipitously than mixed cellularity, thereby increasing the proportion of mixed cellularity HL seen in PWAs. We conclude that HL incidence is lower with severe immunosuppression than with moderate immunosuppression, and HAART-related improvements in CD4 counts likely explain the increasing HL incidence in PWHAS observed since 1996. With more severe immunosuppression, nodular sclerosing HL becomes infrequent, explaining the higher proportion of mixed cellularity HL found in PWAs. Pathogenesis implications are discussed. C1 NCI, Biostat Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Lab Pathol,NIH,Dept Hlth & Human Serv, Bethesda, MD USA. RP Biggar, RJ (reprint author), Natl Canc Inst, Viral Epidemiol Branch, 6120 Executive Blvd,Rm EPS 7074, Rockville, MD 20852 USA. EM biggarb@mail.nih.gov RI Pfeiffer, Ruth /F-4748-2011; Chaturvedi, Anil/J-2024-2015 OI Chaturvedi, Anil/0000-0003-2696-8899 FU Intramural NIH HHS NR 39 TC 214 Z9 217 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 1 PY 2006 VL 108 IS 12 BP 3786 EP 3791 DI 10.1182/blood-2006-05-024109 PG 6 WC Hematology SC Hematology GA 109LO UT WOS:000242309800032 PM 16917006 ER PT J AU Nilsson, J Boasso, A Velilla, PA Zhang, R Vaccari, M Franchini, G Shearer, GM Andersson, J Chougnet, C AF Nilsson, Jakob Boasso, Adriano Velilla, Paula Andrea Zhang, Rui Vaccari, Monica Franchini, Genoveffa Shearer, Gene M. Andersson, Jan Chougnet, Claire TI HIV-1-driven regulatory T-cell accumulation in lymphoid tissues is associated with disease progression in HIV/AIDS SO BLOOD LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-INFECTED PATIENTS; IN-VIVO EXPANSION; LOW VIRAL LOAD; TGF-BETA; CUTTING EDGE; ENVELOPE GLYCOPROTEIN; IMMUNE-RESPONSES; TYPE-1 INFECTION; FOXP3 INDUCTION AB Regulatory T (Treg) cells accumulate in the lymphoid tissues of human immunodeficiency virus (HIV)-infected individuals, contributing to the inability of the immune System to control virus replication. We investigate here Treg-cell numbers and functional markers (FOXP3, CTLA-4, IDO, and TGF-beta 1) in lymphoid tissues from untreated infected hosts with progressive or nonprogressive disease (HIV-infected humans and simian immunodeficiency virus [SIV]-infected macaques). We found that increased numbers of FOXP3(+) T cells as well as increased expression of Treg-cell-associated functional markers were detected only during progressive disease. Such increases were not correlated with immune activation. Of importance, a high-perforin/FOXP3 ratio was associated with nonprogressive disease, suggesting that the immune control of virus replication represents a balance between cell-mediated immune responses and Treg-cell-mediated counter regulation of such responses. Furthermore, using an in vitro model of Treg-cell-HIV interactions, we showed that exposure of Treg cells to HIV selectively promoted their survival via a CD4-gp120-dependent pathway, thus providing an underlying mechanism for the accumulation of Treg cells in infected hosts with active viral replication. Considered together, our findings imply that therapeutic manipulation of Treg-cell number and/or function could improve immune control of HIV infection. C1 Karolinska Univ Hosp, Karolinska Inst, Div Infect Dis, Ctr Infect Med, Stockholm, Sweden. Natl Canc Inst, Expt Immunol Branch, NIH, Bethesda, MD USA. Univ Cincinnati, Dept Pediat, Cincinnati, OH 45221 USA. Univ Cincinnati, Div Mol Immunol, Cincinnati Childrens Hosp Res Fdn, Coll Med, Cincinnati, OH 45221 USA. Univ Antioquia, Immunovirol Grp, Medellin, Colombia. Natl Canc Ctr, Anim Modes & Retroviral Vaccine Sect, Bethesda, MD USA. RP Chougnet, C (reprint author), Childrens Hosp, Ctr Med, Div Mol Immunol, 3333 Burnet Ave, Cincinnati, OH 45229 USA. EM claire.chougnet@cchmc.org OI Nilsson, Jakob/0000-0001-5091-8133; Boasso, Adriano/0000-0001-9673-6319 FU NIAID NIH HHS [AI068524, R01 AI068524] NR 67 TC 209 Z9 228 U1 2 U2 8 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 1 PY 2006 VL 108 IS 12 BP 3808 EP 3817 DI 10.1182/blood-2006-05-021576 PG 10 WC Hematology SC Hematology GA 109LO UT WOS:000242309800035 PM 16902147 ER PT J AU Gattinoni, L Ranganathan, A Surman, DR Palmer, DC Antony, PA Theoret, MR Heimann, DM Rosenberg, SA Restifo, NP AF Gattinoni, Luca Ranganathan, Anju Surman, Deborah R. Palmer, Douglas C. Antony, Paul A. Theoret, Marc R. Heimann, David M. Rosenberg, Steven A. Restifo, Nicholas P. TI CTLA-4 dysregulation of self/tumor-reactive CD8(+) T-cell function is CD4(+) T-cell dependent SO BLOOD LA English DT Article ID ANTIGEN 4 CTLA-4; IN-VIVO; LYMPHOCYTE ANTIGEN-4; COMBINATION IMMUNOTHERAPY; METASTATIC MELANOMA; TUMOR-REGRESSION; BLOCKADE; IMMUNITY; AUTOIMMUNITY; ACTIVATION AB Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) maintains peripheral tolerance by suppressing T-cell activation and proliferation but its precise role in vivo remains unclear. We sought to elucidate the impact of CTLA-4 expression on self/tumor-reactive CD8(+) T cells by using the glycoprotein (gp) 100-specific T-cell receptor (TCR) transgenic mouse, pmel-1. pmel-1 CLTA-4(-/-) mice developed profound, accelerated autoimmune vitiligo. This enhanced autoimmunity was associated with a small but highly activated CD8(+) T-cell population and large numbers of CD4(+) T cells not expressing the transgenic TCR. Adoptive transfer of pmel-1 CLTA-4(-/-) CD8(+) T cells did not mediate superior antitumor immunity in the settings of either large established tumors or tumor challenge, suggesting that the mere absence of CTLA-4-mediated inhibition on CD8(+) T cells did not directly promote enhancement of their effector functions. Removal of CD4(+) T cells by crossing the pmel-1 CLTA-4(-/-) mouse onto a Rag-1(-/-) background re-suited in the complete abrogation of CD8+ T-cell activation and autoimmune manifestations. The effects of CD4(+) lLTA-4(-/-) cells were dependent on the absence of CTLA-4 on CD8(+) T cells. These results indicated that CD8(+) CLTA-4(-/-) T-cell-mediated autoimmunity and tumor immunity required CD4(+) T cells in which the function was dysregulated by the absence of CTLA-4-mediated negative co-stimulation. C1 NCI, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Natl Inst Hlth Res Scholars Program, Howard Hughes Med Inst, Bethesda, MD USA. RP Restifo, NP (reprint author), NCI, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. EM restifo@nih.gov RI Gattinoni, Luca/A-2281-2008; Palmer, Douglas/B-9454-2008; Restifo, Nicholas/A-5713-2008; OI Gattinoni, Luca/0000-0003-2239-3282; Palmer, Douglas/0000-0001-5018-5734; Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999] NR 45 TC 34 Z9 34 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 1 PY 2006 VL 108 IS 12 BP 3818 EP 3823 DI 10.1182/blood-2006-07-034066 PG 6 WC Hematology SC Hematology GA 109LO UT WOS:000242309800036 PM 16882704 ER PT J AU Hryniewicz, A Boasso, A Edghill-Smith, Y Vaccari, M Fuchs, D Venzon, D Nacsa, J Betts, MR Tsai, WP Heraud, JM Beer, B Blanset, D Chougnet, C Lowy, I Shearer, GM Franchini, G AF Hryniewicz, Anna Boasso, Adriano Edghill-Smith, Yvette Vaccari, Monica Fuchs, Dietmar Venzon, David Nacsa, Janos Betts, Michael R. Tsai, Wen-Po Heraud, Jean-Michel Beer, Brigitte Blanset, Diann Chougnet, Claire Lowy, Israel Shearer, Gene M. Franchini, Genoveffa TI CTLA-4 blockade decreases TGF-beta, IDO, and viral RNA expression in tissues of SIVmac251-infected macaques SO BLOOD LA English DT Article ID REGULATORY T-CELLS; HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-INFECTED PATIENTS; INDOLEAMINE 2,3-DIOXYGENASE; TRYPTOPHAN CATABOLISM; LYMPHOCYTE ANTIGEN-4; METASTATIC MELANOMA; IMMUNE-RESPONSES; IN-VIVO; CD4(+) AB Regulatory T (T-reg) cells are a subset of CD25(+)CD4(+) T cells that constitutively express high levels of cytotoxic T lymphocyte antigen-4 (CTLA-4) and suppress T-cell activation and effector functions. Treg cells are increased in tissues of individuals infected with HIV-1 and macaques infected with simian immunodeficiency virus (SIVmac251). In HIV-1 infections T-reg cells could exert contrasting effects: they may limit viral replication by decreasing immune activation, or they may increase viral replication by suppressing virus-specific immune response. Thus, the out-come of blocking T-reg function in HIW/SIV should be empirically tested. Here, we demonstrate that CD25(+) T cells inhibit virus-specific T-cell responses in cultured T cells from blood and lymph nodes of SIV-infected macaques. We investigated the impact of CTLA-4 blockade using the anti-CTLA-4 human antibody MDX-010 in SIV-infected macaques treated with antiretroviral therapy (ART). CTLA-4 blockade decreased expression of the tryptophan-depleting enzyme IDO and the level of the suppressive cytokine transforming growth factor-beta (TGF-beta) in tissues. CTLA-4 blockade was associated with decreased viral RNA levels in lymph nodes and an increase in the effector function of both SIV-specific CD4(+) and CD8(+) T cells. Therefore, blunting T,g function in macaques infected with SIV did not have detrimental virologic effects and may provide a valuable approach to complement ART and therapeutic vaccination in the treatment of HIV-1 infection. C1 NCI, Anim Models & Retroviral Vaccines Sect Expt Immun, Bethesda, MD 20892 USA. NCI, Biostat & data Management Sect, Bethesda, MD 20892 USA. Med Univ Bialystok, Dept Gen & Expt Pathol, Bialystok, Poland. So Res Inst, Frederick, MD USA. Innsbruck Med Univ, Bioctr, Div Biol Chem, Innsbruck, Austria. Ludwig Boltzmann Inst AIDS Res, Innsbruck, Austria. Medarex, Bloomsbury, NJ USA. Univ Penn, Dept Microbiol, Philadelphia, PA USA. Univ Cincinnati, Childrens Hosp Res Fdn, Mol Immunol Sect, Cincinnati, OH 45221 USA. RP Franchini, G (reprint author), NCI, Anim Models & Retroviral Vaccines Sect Expt Immun, Bldg 41,Rm D-804, Bethesda, MD 20892 USA. EM franchig@mail.nih.gov RI HERAUD, Jean-Michel/O-1464-2013; OI HERAUD, Jean-Michel/0000-0003-1107-0859; Boasso, Adriano/0000-0001-9673-6319 FU Intramural NIH HHS; NIAID NIH HHS [N01-AI-15451, N01AI15451] NR 52 TC 91 Z9 99 U1 2 U2 12 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 1 PY 2006 VL 108 IS 12 BP 3834 EP 3842 DI 10.1182/blood-2006-04-010637 PG 9 WC Hematology SC Hematology GA 109LO UT WOS:000242309800038 PM 16896154 ER PT J AU Raju, R Rakocevic, G Chen, ZW Hoehn, G Semino-Mora, C Shi, W Olsen, R Dalakas, MC AF Raju, Raghavan Rakocevic, Goran Chen, Ziwei Hoehn, Gerard Semino-Mora, Cristina Shi, Wei Olsen, Richard Dalakas, Marinos C. TI Autoimmunity to GABA(A)-receptor-associated protein in stiff-person syndrome SO BRAIN LA English DT Article ID GLUTAMIC-ACID DECARBOXYLASE; GAMMA-AMINOBUTYRIC-ACID; PASSIVE TRANSFER; AUTOANTIBODIES; ANTIBODIES; GEPHYRIN; AMPHIPHYSIN; AUTOANTIGEN; RECEPTORS; MEMBRANE AB Stiff-person syndrome (SPS) is an autoimmune neurological disorder characterized by autoantibodies to glutamic acid decarboxylase (GAD), the enzyme responsible for the synthesis of inhibitory neurotransmitter GABA. To search for biomarkers that distinguish SPS from other neurological disorders (OND), we used surface enhanced laser desorption/ionization-time of flight (SELDI-TOF) mass spectrometry to obtain proteomic profile of sera from 25 GAD-positive SPS patients and 25 controls. A significant decrease was found in the level of a protein corresponding to GABA(A)-receptor-associated protein (GABARAP), which is responsible for the stability and surface expression of the GABA(A)-receptor. Up to 70% of the SPS sera examined, compared with 10% of the controls, immunoprecipitated GABARAP protein. Antibodies raised against GABARAP immunostained neuronal cell bodies as well as axonal and dendritic processes, as visualized by confocal microscopy. In vitro experiments demonstrated that the IgG from GABARAP antibody-positive patients, but not control IgG, significantly inhibited the surface expression of GABA(A)-receptor. We conclude that GABARAP is a new autoantigen in SPS. Because the patients' IgG inhibits the expression of GABA(A)-receptors, the circulating antibodies could impair GABAergic pathways and play a role in the clinical symptomatology of SPS patients. C1 Uniformed Serv Univ Hlth Sci, Neuromuscular Dis Sect, NINDS, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Crit Care Med, NIH, Ctr Clin, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Gastrointestinal & Liver Studies Lab, Div Digest Dis, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Dept Mol Pharmacol, Los Angeles, CA USA. RP Dalakas, MC (reprint author), Uniformed Serv Univ Hlth Sci, Neuromuscular Dis Sect, NINDS, 10-4N252,10 Ctr Dr, Bethesda, MD 20892 USA. EM dalakasm@ninds.nih.gov RI Raju, Raghavan/E-9219-2011 FU Intramural NIH HHS NR 25 TC 64 Z9 66 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD DEC PY 2006 VL 129 BP 3270 EP 3276 DI 10.1093/brain/awl245 PN 12 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 111RE UT WOS:000242471100019 PM 16984900 ER PT J AU DeGiorgis, JA Galbraith, JA Dosemeci, A Chen, XB Reese, TS AF DeGiorgis, Joseph A. Galbraith, James A. Dosemeci, Ayse Chen, Xiaobing Reese, Thomas S. TI Distribution of the scaffolding proteins PSD-95, PSD-93, and SAP97 in isolated PSDs SO BRAIN CELL BIOLOGY LA English DT Article ID TANDEM MASS-SPECTROMETRY; POSTSYNAPTIC DENSITY; AMPA RECEPTORS; PROTEOMIC ANALYSIS; CEREBRAL-CORTEX; RAT FOREBRAIN; KINASE-II; IDENTIFICATION; PLASTICITY; COMPLEXES AB We compared the distribution of three scaffolding proteins, all belonging to a family of membrane-associated guanylate kinases, thought to have key roles in the organization of the postsynaptic density (PSD). Isolated PSDs readily adhered to treated glass coverslips where they were labeled with immunogold and rotary shadowed for analysis by EM. The distribution of proteins within individual PSDs were measured by counting and mapping individual immunogold particles. PSD-95, as previously described, is distributed evenly throughout the PSD. We find here that PSD-93 has a nearly identical distribution suggesting that PSD-95 and PSD-93 could perform similar roles. SAP97, in contrast, is concentrated near edges of cleft sides of the PSDs, and in small clumps on their cytoplasmic sides. The homogenous distribution of PSD-95 and PSD-93 throughout the PSD is consistent with their being part of a backbone that stabilizes their various binding partners within the PSD. The distribution of SAP97 confirms that this protein is actually an integral component of the PSD, and suggests that it may have a role in inserting or stabilizing its main binding partner, Glu-R1, at the edge of the PSD. C1 [DeGiorgis, Joseph A.; Galbraith, James A.; Dosemeci, Ayse; Chen, Xiaobing; Reese, Thomas S.] NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. [DeGiorgis, Joseph A.; Galbraith, James A.; Dosemeci, Ayse; Chen, Xiaobing; Reese, Thomas S.] Marine Biol Lab, Woods Hole, MA 02543 USA. RP DeGiorgis, JA (reprint author), NINDS, Neurobiol Lab, NIH, Bldg 49,Room 3A60,49 Convent Dr, Bethesda, MD 20892 USA. EM degiorgj@mail.nih.gov NR 32 TC 26 Z9 26 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1559-7105 EI 1559-7113 J9 BRAIN CELL BIOL JI Brain Cell Biol. PD DEC PY 2006 VL 35 IS 4-6 BP 239 EP 250 DI 10.1007/s11068-007-9017-0 PG 12 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA 322SA UT WOS:000257394400003 PM 18392731 ER PT J AU Lundquist, JJ Dudek, SM AF Lundquist, Joseph J. Dudek, Serena M. TI Differential activation of extracellular signal-regulated kinase 1 and a related complex in neuronal nuclei SO BRAIN CELL BIOLOGY LA English DT Article ID LONG-TERM POTENTIATION; PROTEIN-KINASE; TISSUE-TRANSGLUTAMINASE; MAP-KINASE; GROWTH-FACTOR; IN-VIVO; CREB PHOSPHORYLATION; HIPPOCAMPAL-NEURONS; GENE-EXPRESSION; CROSS-LINKING AB The extracellular signal-regulated kinases 1 and 2 ( ERKs 1/2) are known to participate in regulating transcription in response to moderate depolarization, such as synaptic stimulation, but how the same active enzyme can differentially regulate distinct transcriptional programs induced with abnormal depolarization (high potassium) is unknown. We hypothesized that ERK1 or 2 accomplishes this differential nuclear response through close association with other proteins in stable complexes. In support of this hypothesis, we have found that immunoreactivity for an apparent high molecular weight complex containing phospho-ERK1 increased in response to synaptic stimulation, but decreased in response to high potassium; p-ERK immunoreactivity at 44/42 kDa increased in both cases. Evidence supporting the conclusion that the band of interest contained ERK1 in a complex, as opposed to it being an unrelated protein crossreacting with antibodies against p-ERK, is that ERK1 (p44 MAPK) and 14-3-3 protein were electroeluted from the 160-kDa band cut from a gel. We also found the nuclear complexes to be exceptionally durable, suggesting a role for the crosslinking enzyme, transglutaminase, in its stabilization. In addition, we found other components of the ERK pathway, including MEK, ERK2, p90RSK, and Elk-1, migrating at higher-than-expected weights in brain nuclei. These results describe a novel stable complex of ERK1 in neuronal nuclei that responds differentially to synaptic and depolarizing stimulation, and thus may be capable of mediating gene transcription in a way distinct from the monomeric protein. C1 [Lundquist, Joseph J.; Dudek, Serena M.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Dudek, SM (reprint author), NIEHS, NIH, MD F2-04,POB 12233, Res Triangle Pk, NC 27709 USA. EM dudek@niehs.nih.gov OI Dudek, Serena M./0000-0003-4094-8368 FU Intramural NIH HHS [Z01 ES100221-06] NR 54 TC 3 Z9 3 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1559-7105 J9 BRAIN CELL BIOL JI Brain Cell Biol. PD DEC PY 2006 VL 35 IS 4-6 BP 267 EP 281 DI 10.1007/s11068-008-9018-7 PG 15 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA 322SA UT WOS:000257394400005 PM 18392730 ER PT J AU Sakurai, T Kojima, C Kobayashi, Y Hirano, S Sakurai, MH Waalkes, MP Himeno, S AF Sakurai, T. Kojima, C. Kobayashi, Y. Hirano, S. Sakurai, M. H. Waalkes, M. P. Himeno, S. TI Toxicity of a trivalent organic arsenic compound, dimethylarsinous glutathione in a rat liver cell line (TRL 1215) SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE arsenic; arsenite; dimethylarsenic; dimethylarsinous glutathione; dimethylarsinic acid; trivalent methylarsenic; trivalent dimethylarsenic; GSH; methylation; acute promyelocytic leukemia ID PROMYELOCYTIC LEUKEMIA APL; MONOMETHYLARSONIC ACID; TRIOXIDE AS2O3; METABOLITES; CYTOLETHALITY; MACROPHAGES; MECHANISMS; SPECIATION; EXCRETION; APOPTOSIS AB Background and purpose: Although inorganic arsenite (As-III) is toxic in humans, it has recently emerged as an effective chemotherapeutic agent for acute promyelocytic leukemia (APL). In humans and most animals, As-III is enzymatically methylated in the liver to weakly toxic dimethylarsinic acid (DMAsV) that is a major pentavalent methylarsenic metabolite. Recent reports have indicated that trivalent methylarsenicals are produced through methylation of As-III and participate in arsenic poisoning. Trivalent methylarsenicals may be generated as arsenical-glutathione conjugates, such as dimethylarsinous glutathione (DMAs(III)G), during the methylation process. However, less information is available on the cytotoxicity of DMAsIIIG. Experimental approach: We synthesized and purified DMAs(III)G using high performance TLC (HPTLC) methods and measured its cytotoxicity in rat liver cell line (TRL 1215 cells). Key results: DMAs(III)G was highly cytotoxic in TRL 1215 cells with a LC50 of 160 nM. We also found that DMAs(III)G molecule itself was not transported efficiently into the cells and was not cytotoxic; however it readily became strongly cytotoxic by dissociating into trivalent dimethylarsenicals and glutathione (GSH). The addition of GSH in micromolar physiological concentrations prevented the breakdown of DMAs(III)G, and the DMAs(III)G-induced cytotoxicity. Physiological concentrations of normal human serum (HS), human serum albumin (HSA), and human red blood cells (HRBC) also reduced both the cytotoxicity and cellular arsenic uptake induced by exposure to DMAs(III)G. Conclusions and implications: These findings suggest that the significant cytotoxicity induced by DMAs(III)G may not be seen in healthy humans, even if DMAs(III)G is formed in the body from As-III. C1 Tokushima Bunri Univ, Fac Pharmaceut Sci, Lab Mol Nutr & Toxicol, Tokushima 7708514, Japan. Natl Inst Environm Studies, Environm Hlth Sci Div, Tsukuba, Ibaraki, Japan. Azabu Univ, Dept Environm Hlth, Lab Environm Hyg, Sagamihara, Kanagawa, Japan. NIEHS, NCI, Comparat Carcinogenesis Lab, Inorgan Carcinogenesis Sect,NIH, Res Triangle Pk, NC 27709 USA. RP Sakurai, T (reprint author), Tokushima Bunri Univ, Fac Pharmaceut Sci, Lab Mol Nutr & Toxicol, Yamashiro Cho, Tokushima 7708514, Japan. EM teruaki@ph.bunri-u.ac.jp NR 32 TC 29 Z9 32 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD DEC PY 2006 VL 149 IS 7 BP 888 EP 897 DI 10.1038/sj.bjp.0706899 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 115OC UT WOS:000242742600009 PM 17043674 ER PT J AU Unno, T Matsuyama, H Izumi, Y Yamada, M Wess, J Komori, S AF Unno, T. Matsuyama, H. Izumi, Y. Yamada, M. Wess, J. Komori, S. TI Roles of M-2 and M-3 muscarinic receptors in cholinergic nerve-induced contractions in mouse ileum studied with receptor knockout mice SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE M-2 receptors; M-3 receptors; knockout mice; intestinal smooth muscle; electrical field stimulation; cholinergic contraction; noncholinergic contraction; pertussis toxin ID LONGITUDINAL SMOOTH-MUSCLE; PIG GASTROINTESTINAL-TRACT; INTERSTITIAL-CELLS; ACETYLCHOLINE-RECEPTOR; STOMACH FUNDUS; NEURONS; CAJAL; NK1; NONPEPTIDE; CARBACHOL AB Background and purpose: The functional roles of M-2 and M-3 muscarinic receptors in neurogenic cholinergic contractions in gastrointestinal tracts remain to be elucidated. To address this issue, we studied cholinergic nerve-induced contractions in the ileum using mutant mice lacking M-2 or M-3 receptor subtypes. Experimental approach: Contractile responses to transmural electrical (TE) stimulation were isometrically recorded in ileal segments from M-2-knockout (KO), M-3-KO, M-2/M-3-double KO, and wild-type mice. Key results: TE stimulation at 2-50 Hz frequency-dependently evoked a fast, brief contraction followed by a slower, longer one in wild-type, M-2-KO or M-3-KO mouse preparations. Tetrodotoxin blocked both the initial and later contractions, while atropine only inhibited the initial contractions. The initial cholinergic contractions were significantly greater in wild-type than M-2-KO or M-3-KO mice; the respective mean amplitudes at 50 Hz were 91, 74 and 68% of 70mM K+ -induced contraction. Pretreatment with pertussis toxin blocked the cholinergic contractions in M-3-KO but not in M-2-KO mice. Cholinergic contractions also remained in wild-type preparations, but their sizes were reduced by 20-30% at 10-50 Hz. In M-2/M-3-double KO mice, TE stimulation evoked only slow, noncholinergic contractions, which were significantly greater in sizes than in any of the other three mouse strains. Conclusion and Implications: These results demonstrate that M-2 and M-3 receptors participate in mediating cholinergic contractions in mouse ileum with the latter receptors assuming a greater role. Our data also suggest that the lack of both M-2 and M-3 receptors causes upregulation of noncholinergic excitatory innervation of the gut smooth muscle. C1 Gifu Univ, Fac Appl Biol Sci, Dept Vet Med, Pharmacol Lab, Gifu 5011193, Japan. RIKEN, Brain Sci Inst, Neurogenet Lab, Saitama, Japan. NIDDKD, Bioorgan Chem Lab, Bethesda, MD 20892 USA. RP Komori, S (reprint author), Gifu Univ, Fac Appl Biol Sci, Dept Vet Med, Pharmacol Lab, 1-1 Yanagido, Gifu 5011193, Japan. EM skomori@gifu-u.ac.jp NR 34 TC 28 Z9 29 U1 1 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD DEC PY 2006 VL 149 IS 8 BP 1022 EP 1030 DI 10.1038/sj.bjp.0706955 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 119EC UT WOS:000242994000006 PM 17099717 ER PT J AU Hurst, SA Danis, M AF Hurst, SA Danis, M TI Indecent coverage? Protecting the goals of health insurance from the impact of co-payments SO CAMBRIDGE QUARTERLY OF HEALTHCARE ETHICS LA English DT Editorial Material ID MEDICAL-CARE; EXPENDITURE; EMERGENCY; DEMAND; RISK C1 Univ Geneva, Fac Med, Bioeth Res & Teaching Unit, CH-1211 Geneva 4, Switzerland. Natl Inst Hlth, Ctr Clin, Dept Clin Bioeth, Sect Eth & Hlth Policy, Bethesda, MD USA. RP Hurst, SA (reprint author), Univ Geneva, Fac Med, Bioeth Res & Teaching Unit, CH-1211 Geneva 4, Switzerland. RI Hurst, Samia/A-9661-2008 OI Hurst, Samia/0000-0002-1980-5226 NR 39 TC 1 Z9 1 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 0963-1801 J9 CAMB Q HEALTHC ETHIC JI Camb. Q. Healthc. Ethics PD WIN PY 2006 VL 15 IS 1 BP 107 EP 113 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Social Sciences, Biomedical SC Health Care Sciences & Services; Biomedical Social Sciences GA 006VT UT WOS:000234926500012 PM 16529313 ER PT J AU Kurup, SK Buggage, RR Clarke, GL Ursea, R Lim, WK Nussenblatt, RB AF Kurup, Shree K. Buggage, Ronald R. Clarke, Grace L. Ursea, Roxana Lim, Wee Kiak Nussenblatt, Robert B. TI Gamma interferon assay as an alternative to PPD skin testing in selected patients with granulomatous intraocular inflammatory disease SO CANADIAN JOURNAL OF OPHTHALMOLOGY-JOURNAL CANADIEN D OPHTALMOLOGIE LA English DT Article DE uveitis; QuantiFERON; gamma interferon; tuberculosis; TB ID OCULAR TUBERCULOSIS; EYE; MANAGEMENT; INFECTION; DIAGNOSIS AB Background: To evaluate the QuantiFERON-TB test (gamma interferon assay), approved by the Centers for Disease Control and Prevention for the detection of latent tuberculosis (LTB), in patients who potentially may require immunosuppressive therapy for ocular inflammatory disease. Methods: Blood samples from 12 consecutive patients with granulomatous ocular inflammatory disease were evaluated first with the purified protein derivative (PPD) skin test and then with the QuantiFERON-TB test (I I of 12 patients, I declined). The results of the 2 tests in both U.S.- and non-U.S.-born patients were compared with their Bacillus Calmette-Guerin (BCG) vaccination status and chest x-rays. Results: In our small series there was a high degree of concordance between the QuantiFERON-TB assay and the PPD skin test. Interpretation: The QuantiFERON-TB test did not demonstrate intrinsic merit over IPPD skin testing for screening for LTB in selected patients when immunosuppressive therapy is considered. The confounding effect of BCG vaccination renders interpretation of both tests difficult. Early reports suggest the second-generation tests that are now available may hold promise for use in the uveitis clinic and should be formally evaluated. C1 NEI, NIH, Lab Immunol, Bethesda, MD 20892 USA. RP Kurup, SK (reprint author), NEI, NIH, Lab Immunol, Bethesda, MD 20892 USA. EM kurups@nei.nih.gov NR 32 TC 25 Z9 27 U1 0 U2 0 PU CANADIAN OPHTHAL SOC PI OTTAWA PA 1525 CARLING AVE SUITE 610, OTTAWA, ONTARIO K1Z 8R9, CANADA SN 0008-4182 J9 CAN J OPHTHALMOL JI Can. J. Opthalmol.-J. Can. Opthalmol. PD DEC PY 2006 VL 41 IS 6 BP 737 EP 740 DI 10.1139/I06-068 PG 4 WC Ophthalmology SC Ophthalmology GA 158LV UT WOS:000245793900011 PM 17224956 ER PT J AU Bogdanova, TI Zurnadzhy, LY Greenebaum, E McConnell, RJ Robbins, J Epstein, OV Olijnyk, VA Hatch, M Zablotska, LB Tronko, MD AF Bogdanova, Tetyana I. Zurnadzhy, Ludmyla Y. Greenebaum, Ellen McConnell, Robert J. Robbins, Jacob Epstein, Ovsiy V. Olijnyk, Valery A. Hatch, Maureen Zablotska, Lydia B. Tronko, Mykola D. TI A Cohort Study of thyroid cancer and other thyroid diseases after the Chornobyl accident - Pathology analysis of thyroid cancer cases in Ukraine detected during the first screening (1998-2000) SO CANCER LA English DT Article DE Chornobyl accident; Chernobyl; thyroid cancer; pathology; papillary carcinoma; radiation; latency ID CARCINOMA; CHILDREN AB BACKGROUND. The Ukrainian American Cohort Study evaluated the risk of thyroid disorders in a group of individuals who were younger than age 18 years at the time of the Chornobyl (Chernobyl) accident. In this article, the authors describe the pathology of thyroid carcinomas detected in the first screening. METHODS. From 1998 to 2000, 13,243 individuals completed the first cycle of screening examinations. Eighty patients underwent surgery between 1998 and 2004. Intraoperative and postoperative pathologic studies were performed at the Institute of Endocrinology and Metabolism, Kyiv. RESULTS. Pathologic analysis revealed 45 thyroid carcinomas, including 43 papillary thyroid carcinomas (PTCs) (95.6%) and 2 follicular thyroid carcinomas (FTCs) (4.4%). TNM classification (5th edition) of the PTCs included 8 T1 tumors (18.6%), 16 T2 tumors (37.2%), and 19 T4 tumors (44.2%). Fifteen PTCs (34.9%) were N1a,N1b, and 3 PTCs (7.0%) were M1. Among the PTCs, 8 exhibited the classical papillary histologic pattern (18.6%), 14 exhibited a follicular histologic pattern (32.6%), 5 exhibited a solid histologic pattern (11.6%), and 16 exhibited a mixed histologic pattern (37.2%). Both FTCs had a microfollicular-solid structure. Eleven of 20 cohort members who underwent surgery before the first screening had PTCs. Regional metastases (63.6%) and distant metastases (18.2%) were more common in this group. CONCLUSIONS. Multifocal growth, lymphatic and blood vessel invasion, extrathyroid spread, and regional and distant metastases were more frequent in less differentiated PTCs (> 30% solid structure). Small carcinomas (<= 10 mm) comprised 23.3% of PTCs, and most of those (8 of 10 small carcinomas; 80%) were of the papillary-follicular subtype and therefore were more differentiated. The solid subtype of PTC was associated with shorter latency, especially in individuals who were diagnosed before the first screening. The histology of post-Chornobyl cancers is changing with time. C1 Columbia Univ, Coll Phys & Surg, Dept Pathol, New York, NY 10032 USA. Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY 10032 USA. Inst Endocrinol & Metab, Endocrine Syst, Lab Morphol, Kiev, Ukraine. NIDDKD, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Inst Endocrinol & Metab, Dept Funct Dis, Kiev, Ukraine. Inst Endocrinol & Metab, Dept Gen Endocrine Pathol, Kiev, Ukraine. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10027 USA. Inst Endocrinol & Metab, Endocrine Syst, Dept Pathophysiol, Kiev, Ukraine. RP Greenebaum, E (reprint author), Columbia Univ, Coll Phys & Surg, Dept Pathol, VC14-215,630 W 168th St, New York, NY 10032 USA. EM eg39@columbia.edu FU Intramural NIH HHS; NCI NIH HHS [N01 CP021178, N01CP21178] NR 24 TC 22 Z9 23 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD DEC 1 PY 2006 VL 107 IS 11 BP 2559 EP 2566 DI 10.1002/cncr.22321 PG 8 WC Oncology SC Oncology GA 108UG UT WOS:000242264100006 PM 17083123 ER PT J AU Brown, LM Howard, RA Travis, LB AF Brown, Linda Morris Howard, Regan A. Travis, Lois B. TI The risk of secondary malignancies over 30 years after the treatment of non-hodgkin lymphoma SO CANCER LA English DT Letter C1 NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Brown, LM (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NR 2 TC 6 Z9 6 U1 1 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD DEC 1 PY 2006 VL 107 IS 11 BP 2741 EP 2742 DI 10.1002/cncr.22309 PG 2 WC Oncology SC Oncology GA 108UG UT WOS:000242264100029 PM 17039496 ER PT J AU Ockers, S Price, DK Figg, WD AF Ockers, Sandra Price, Douglas K. Figg, William D. TI DNA microarrays - Tissue removal and processing affects gene expression SO CANCER BIOLOGY & THERAPY LA English DT Editorial Material DE microarrays; cancer; ischemia; prostate; surgery; Jun Kinase Activity; gene expression C1 NCI, Mol Pharmacol Sect, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Canc Therapeut Branch, 9000 Rockville Pike,Bldg 10,Room 5A01,MSC 1910, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Figg Sr, William/M-2411-2016 NR 3 TC 0 Z9 0 U1 0 U2 3 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD DEC PY 2006 VL 5 IS 12 BP 1608 EP 1609 DI 10.4161/cbt.5.12.3547 PG 2 WC Oncology SC Oncology GA 160DK UT WOS:000245919000013 PM 17172817 ER PT J AU Mariotto, AB Yabroff, KR Feuer, EJ De Angelis, R Brown, M AF Mariotto, Angela B. Yabroff, K. Robin Feuer, Eric J. De Angelis, Roberta Brown, Martin TI Projecting the number of patients with colorectal carcinoma by phases of care in the US: 2000-2020 SO CANCER CAUSES & CONTROL LA English DT Article DE colorectal cancer; prevalence; projection ID CANCER PREVALENCE; SURVIVAL AB Objective This study provides projections of colorectal cancer prevalence by phases of care (initial, monitoring, and last year of life) to the year 2020 and describes the estimation method. Methods Cancer prevalence by phase of care was estimated from colorectal cancer incidence and survival from the Surveillance, Epidemiology, and End Results (SEER) Program data, population estimates and projections from the US Census Bureau, and all cause mortality data from the Human Mortality Life Tables. Assumptions of constant incidence and survival were used for projections from 2000 to 2020. Modeled and directly observed patient months by phase of care were compared for 1996 -1998 to provide validation of estimates. Results Prevalence of colorectal cancer is estimated to increase from 1,002,786 (0.36%) patients to 1,522,348 (0.46%) patients between 2000 and 2020. The estimated number of person-months in the initial and last year of life phases of care will increase 43%, while the monitoring phase of care will increase 54%. Modeled person-months by phase of care were consistent with directly observed measures of person months by phase of care in 1996-1998. Conclusions Under assumptions of current cancer control strategies we project that colorectal cancer prevalence will increase more rapidly than the US population, largely due to the aging of the US population. This suggests that considerable resources will be needed in the future for initial, continuing and last year of life treatment of colorectal cancer patients unless notable breakthroughs in primary prevention occur in the future years. C1 NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Mariotto, AB (reprint author), NCI, Div Canc Control & Populat Sci, 6116 Execut Blvd, Bethesda, MD 20892 USA. EM mariotta@mail.nih.gov OI Yabroff, K. Robin/0000-0003-0644-5572 NR 16 TC 37 Z9 37 U1 1 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD DEC PY 2006 VL 17 IS 10 BP 1215 EP 1226 DI 10.1007/s10552-006-0072-0 PG 12 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 107BM UT WOS:000242145700001 PM 17111252 ER PT J AU Wang, LH Yang, XY Zhang, XH An, P Kim, HJ Huang, JQ Clarke, R Osborne, CK Inman, JK Appella, E Farrar, WL AF Wang, Li Hua Yang, Xiao Yi Zhang, Xiaohu An, Ping Kim, Han-Jong Huang, Jiaqiang Clarke, Robert Osborne, C. Kent Inman, John K. Appella, Ettore Farrar, William L. TI Disruption of estrogen receptor DNA-binding domain and related intramolecular communication restores tamoxifen sensitivity in resistant breast cancer SO CANCER CELL LA English DT Article ID EPIDERMAL-GROWTH-FACTOR; ACTIVATED PROTEIN-KINASE; N-TERMINAL REGION; FACTOR-I; TRANSACTIVATION FUNCTIONS; MOLECULAR DETERMINANTS; ENDOCRINE-THERAPY; GENE-EXPRESSION; LIGAND-BINDING; PPAR-GAMMA AB A serious obstacle to successful treatment of estrogen receptor (ER)-positive human breast cancer is cell resistance to tamoxifen (TAM) therapy. Here we show that the electrophile disulfide benzamide (DIBA), an ER zinc finger inhibitor, blocks ligand-dependent and -independent cell growth of TAM-resistant breast cancer in vitro and in vivo. Such inhibition depends on targeting disruption of the ER DNA-binding domain and its communication with neighboring functional domains, facilitating ER alpha dissociation from its coactivator AIB1 and concomitant association with its corepressor NCoR bound to chromatin. DIBA does not affect phosphorylation of HER2, MAPK, AKT, and AIB1, suggesting that DIBA-modified ER alpha may induce a switch from agonistic to antagonistic effects of TAM on resistant breast cancer cells. C1 NCI, Basic Res Program, SAIC Frederick, Frederick, MD 21702 USA. NCI, Canc Stem Cell Sect, Lab Canc Prevent, Frederick, MD 21702 USA. Georgetown Univ, Dept Oncol, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. Methodist Hosp, Houston, TX 77030 USA. Baylor Coll Med, Breast Ctr, Houston, TX 77030 USA. NIAID, Bioorgan Chem Sect, Immunol Lab, Bethesda, MD 20892 USA. NCI, Cell Biol Lab, Bethesda, MD 20892 USA. RP Wang, LH (reprint author), NCI, Basic Res Program, SAIC Frederick, Frederick, MD 21702 USA. EM lhwang@ncifcrf.gov; farrar@ncifcrf.gov RI Clarke, Robert/A-6485-2008; Messier, Claude/A-2322-2008 OI Clarke, Robert/0000-0002-9278-0854; Messier, Claude/0000-0002-4791-1763 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 66 TC 52 Z9 53 U1 1 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD DEC PY 2006 VL 10 IS 6 BP 487 EP 499 DI 10.1016/j.ccr.2006.09.015 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 118PA UT WOS:000242953000007 PM 17157789 ER PT J AU Landgren, O Zhang, YW Zahm, SH Inskip, P Zheng, TZ Baris, D AF Landgren, Ola Zhang, Yawei Zahm, Sheila Hoar Inskip, Peter Zheng, Tongzhang Baris, Dalsu TI Risk of multiple myeloma following medication use and medical conditions: A case-control study in Connecticut women SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID NON-HODGKIN-LYMPHOMA; UNITED-STATES; CANCER-RISK; POLYMYALGIA-RHEUMATICA; MALIGNANT-LYMPHOMA; COLORECTAL-CANCER; FAMILY-HISTORY; SAN-FRANCISCO; DRUG-USE; LEUKEMIA AB Certain commonly used drugs and medical conditions characterized by chronic immune dysfunction and/or antigen stimulation have been suggested to affect important pathways in multiple myeloma tumor cell growth and survival. We conducted a population-based case-control study to investigate the role of medical history in the etiology of multiple myeloma among Connecticut women. Methods: A total of 179 incident multiple myeloma cases (2184 years, diagnosed 1996-2002) and 691 population-based controls was included in this study. Information on medical conditions, medications, and medical radiation was obtained by in-person interviews. We calculated odds ratios (OR) as measures of relative risks using logistic regression models. Results: A reduced multiple myeloma risk was found among women who had used antilipid statin therapy [OR, 0.4; 95% confidence interval (95% CI), 0.2-0.8] or estrogen replacement therapy (OR, 0.6; 95% Cl, 0.4-0.99) or who had a medical history of allergy (OR, 0.4; 95% Cl, 0.3-0.7), scarlet fever (OR, 0.5; 95% Cl, 0.2-0.9), or bursitis (OR, 0.4; 95% CI, 0.2-0.7). An increased risk of multiple myeloma was found among women who used prednisone (OR, 5.1; 95% Cl, 1.8-14.4), insulin (OR, 3.1; 95% CI, 1.1-9.0), or gout medication (OR, 6.7; 95% CI, 1.2-38.0). Conclusions: If our results are confirmed, mechanistic studies examining how prior use of insulin, prednisone, and, perhaps, gout medication might promote increased occurrence of multiple myeloma and how antilipid statins, estrogen replacement therapy, and certain medical conditions might protect against multiple myeloma may provide insights to the as yet unknown, etiology of multiple myeloma. C1 NCI, Div Canc Epidemiol & Genet, Genet Epidemiol Branch, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. RP Landgren, O (reprint author), NCI, Div Canc Epidemiol & Genet, Genet Epidemiol Branch, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,Bldg EPS Room 7110, Bethesda, MD 20892 USA. EM landgreo@mail.nih.gov RI Zahm, Shelia/B-5025-2015 FU Intramural NIH HHS NR 66 TC 35 Z9 35 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 2006 VL 15 IS 12 BP 2342 EP 2347 DI 10.1158/1055-9965.EPI-06-0097 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 119AK UT WOS:000242984400005 PM 17132770 ER PT J AU Chow, HHS Hakim, IA Vining, DR Crowell, JA Cordova, CA Chew, WM Xu, MJ Hsu, CH Ranger-Moore, J Alberts, DS AF Chow, H-H. Sherry Hakim, Iman A. Vining, Donna R. Crowell, James A. Cordova, Catherine A. Chew, Wade M. Xu, Min-Jian Hsu, Chiu-Hsieh Ranger-Moore, James Alberts, David S. TI Effects of repeated green tea catechin administration on human cytochrome P450 activity SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; DRUG-METABOLISM; HEALTHY-INDIVIDUALS; CAMELLIA-SINENSIS; POLYPHENON-E; INDUCTION; CYP1A2; RAT; PHARMACOKINETICS; DEXTROMETHORPHAN AB Purpose: Preclinical studies suggested that green tea or green tea catechins can modulate the activities of drug-metabolizing enzymes. We conducted this clinical study to determine the effect of repeated green tea catechin administration on human cytochrome P450 (CYP) enzyme activities. Methods: Forty-two healthy volunteers underwent a 4-week washout period by refraining from tea or tea-related products. At the end of the washout period, study participants received a cocktail of CYP metabolic probe drugs, including caffeine, dextromethorphan, losartan, and buspirone for assessing the activity of CYP1A2, CYP2D6, CYP2C9, and CYP3A4, respectively. Blood and urine samples before and 8 h after probe drug administration were collected to determine parent drug and metabolite concentrations for measurements of baseline CYP enzyme activities. Following the baseline evaluation, study participants underwent 4 weeks of green tea catechin intervention at a dose that contains 800 mg epigallocatechin gallate (EGCG) daily. The green tea catechin product was taken on an empty stomach to optimize the p.o. bioavailability of EGCG. The EGCG dose given in this study exceeded the amounts provided by average green tea consumption. Upon completion of the green tea catechin intervention, the postintervention CYP enzyme activities were evaluated as described above. Results: There are large between-subject variations in CYP enzyme activities in healthy individuals. Four weeks of green tea catechin intervention did not alter the phenotypic indices of CYP1A2, CYP12D6, and CYP12C9, but resulted in a 20% increase (P = 0.01) in the area under the plasma buspirone concentration-time profile, suggesting a small reduction in CYP3A4 activity. Conclusions: We conclude that repeated green tea catechin administration is not likely to result in clinically significant effects on the disposition of drugs metabolized by CYP enzymes. C1 Univ Arizona, Arizona Canc Ctr, Tucson, AZ 85724 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Chow, HHS (reprint author), Univ Arizona, Arizona Canc Ctr, Tucson, AZ 85724 USA. EM schow@azcc.arizona.edu FU NCI NIH HHS [N01-CN-25119] NR 25 TC 73 Z9 80 U1 2 U2 18 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 2006 VL 15 IS 12 BP 2473 EP 2476 DI 10.1158/1055-9965.EPI-06-0365 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 119AK UT WOS:000242984400025 PM 17164372 ER PT J AU Reed, GA Arneson, DW Putnam, WC Smith, HJ Gray, JC Sullivan, DK Mayo, MS Crowell, JA Hurwitz, A AF Reed, Gregory A. Arneson, Dora W. Putnam, William C. Smith, Holly J. Gray, John C. Sullivan, Debra K. Mayo, Matthew S. Crowell, James A. Hurwitz, Aryeh TI Single-dose and multiple-dose administration of indole-3-carbinol to women: Pharmacokinetics based on 3,3 '-diindolylmethane SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GASTRIC-ACID-SECRETION; DIETARY INDOLE-3-CARBINOL; BREAST-CANCER; MAMMARY CARCINOGENESIS; RAINBOW-TROUT; RATS; MICE; CHEMOPREVENTION; INHIBITION; METABOLISM AB We have completed a phase I trial in women of the proposed chemopreventive natural product indole-3-carbinol (I3C). Women received oral doses of 400, 600, 800, 1,000, and 1,200 mg I3C. Serial plasma samples were analyzed by high-performance liquid chromatography-mass spectrometry for I3C and several of its condensation products. I3C itself was not detectable in plasma. The only detectable I3C-derived product was 3,3'-diindolylmethane (DIM). Mean C-max for DIM increased from 61 ng/mL at the 400-mg I3C dose to 607 ng/mL following a 1,000-mg dose. No further increase was observed following a 1,200-mg dose. A similar result was obtained for the area under the curve, which increased from 329 h ng/mL at the 400-mg dose to 3,376 h ng/mL after a 1,000-mg dose of I3C. Significant interindividual quantitative variation was seen in plasma DIM values within each dosing group, but the overall profiles were qualitatively similar, with no quantifiable DIM before dosing, t(max) at similar to 2 h, and DIM levels near or below 15 ng/mL (the limit of quantitation), by 24 h. Different results were obtained for 14 subjects who received a 400-mg dose of I3C after 8 weeks of twice-daily I3C dosing. Although the predose sampling occurred at least 12 h after the last known ingestion of I3C, 6 of 14 subjects exhibited C-max for DIM in their predose plasma. Despite this high initial value, plasma DIM for all subjects decreased to near or below the limit of quantitation within the 12-h sampling period. Possible reasons for this disparity between apparent t(1/2) of DIM and the high predose values are discussed. C1 Univ Kansas, Med Ctr, Dept Internal Med, Kansas City, KS 66160 USA. Univ Kansas, Med Ctr, Dept Pharmacol, Kansas City, KS 66160 USA. Univ Kansas, Med Ctr, Dept Toxicol, Kansas City, KS 66160 USA. Univ Kansas, Med Ctr, Dept Therapeut, Kansas City, KS 66160 USA. Univ Kansas, Med Ctr, Dept Nutr & Dietet, Kansas City, KS 66160 USA. Univ Kansas, Med Ctr, Ctr Biostat & Adv Informat, Kansas City, KS 66160 USA. Univ Kansas, Med Ctr, Kansas Mason Ctr, Res Inst, Kansas City, KS 66160 USA. Midw Res Inst, Kansas City, MO USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Reed, GA (reprint author), Univ Kansas, Med Ctr, Dept Internal Med, MS 1018,3901 Rainbow Blvd, Kansas City, KS 66160 USA. EM greed@kumc.edu RI Mayo, Matthew/E-3774-2015 FU NCI NIH HHS [N01-CN-55121] NR 31 TC 81 Z9 86 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 2006 VL 15 IS 12 BP 2477 EP 2481 DI 10.1158/1055-9655.EPI-06-0396 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 119AK UT WOS:000242984400026 PM 17164373 ER PT J AU Mahabir, S Baer, DJ Johnson, LL Hartman, TJ Dorgan, JF Campbell, WS Clevidence, BA Taylor, PR AF Mahabir, Somdat Baer, David J. Johnson, Laura L. Hartman, Terry J. Dorgan, Joanne F. Campbell, William S. Clevidence, Beverly A. Taylor, Philip R. TI Usefulness of body mass index as a sufficient adiposity measurement for sex hormone concentration associations in postmenopausal women SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BREAST-CANCER RISK; STEROID-HORMONES; ENDOGENOUS HORMONES; CIRCULATING LEVELS; FAT DISTRIBUTION; HEALTHY WOMEN; IGF-I; ESTROGEN; DIET; OBESITY AB Background: Both obesity and sex hormones are known risk factors for postmenopausal breast cancer. Although adiposity and sex hormones have been studied in the past, previous reports in postmenopausal women have not been conducted under carefully controlled dietary conditions. In this study, we investigated the usefulness of body mass index (BMI) as a sufficient adiposity measurement to assess associations with sex hormone levels. Methods: This study was conducted as a cross-sectional analysis within the control segment (0 g alcohol group) of a randomized, crossover design, in which 51 postmenopausal women consumed 0 (control), 15 (one drink), and 30 (two drinks) g alcohol (ethanol)/d for 8 weeks each as part of a controlled diet. Dual-energy X-ray absorptiometry scans were administered to the women during the control (0 g alcohol) segment, and a blood sample was drawn at the end of that diet period for hormone analysis. Results: In multivariate analysis (adjusted for age, race, family history of breast cancer, parity, and menarche < 12 years), women who were overweight or obese had significantly higher serum concentrations of estradiol, bioavailable estradiol, estrone, and estrone sulfate and lower sex hormone-binding globulin than normal weight women (all P < 0.05). In models adjusted for BMI and the covariates above, none of the dual-energy X-ray absorptiometry adiposity measures added further information (all P > 0.10) for these five analytes beyond that of BMI alone. Conclusions: In this population of postmenopausal women, under carefully controlled dietary conditions, we confirmed previous findings that higher levels of adiposity were associated with higher concentrations of estrogens and lower sex hormone-binding globulin, and we found that the use of the epidemiology-friendly BMI seems sufficient to assess associations with these hormone levels. C1 Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. USDA ARS, Beltsville, MD USA. NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. NIH, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Penn State Univ, Dept Nutr, University Pk, PA 16802 USA. Fox Chase Canc Ctr, Div Populat Sci, Philadelphia, PA 19111 USA. RP Mahabir, S (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, 1155 Pressler Blvd,CPB4-3247, Houston, TX 77030 USA. EM smahabir@mdanderson.org RI Mahabir, Somdat/A-9788-2008 FU Intramural NIH HHS; NCI NIH HHS [Y1-SC-8012] NR 38 TC 36 Z9 36 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 2006 VL 15 IS 12 BP 2502 EP 2507 DI 10.1158/1055-9965.EPI-06-0499 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 119AK UT WOS:000242984400030 PM 17164376 ER PT J AU Rajaraman, P Stewart, PA Samet, JM Schwartz, BS Linet, MS Zahm, SH Rothman, N Yeager, M Fine, HA Black, PM Loeffler, J Shapiro, WR Selker, RG Inskip, PD AF Rajaraman, Preetha Stewart, Patricia A. Samet, Jonathan M. Schwartz, Brian S. Linet, Martha S. Zahm, Shelia Hoar Rothman, Nathaniel Yeager, Meredith Fine, Howard A. Black, Peter M. Loeffler, Jay Shapiro, William R. Selker, Robert G. Inskip, Peter D. TI Lead, genetic susceptibility, and risk of adult brain tumors SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID AMINOLEVULINIC-ACID DEHYDRATASE; SMELTER WORKERS; BLOOD LEAD; 5-AMINOLEVULINIC ACID; ALAD POLYMORPHISM; NERVOUS-SYSTEM; OCCUPATIONAL EXPOSURES; HUMAN ERYTHROCYTES; CANCER-MORTALITY; UNITED-STATES AB Background: Although few etiologic factors for brain tumors have been identified, limited data suggest that lead may increase the risk of brain tumors, particularly meningioma. The ALAD G177C polymorphism affects the toxicokinetics of lead and may confer genetic susceptibility to adverse effects of lead exposure. Methods: We examined occupational exposure to lead and risk of brain tumors in a multisite, hospital-based, case-control study of 489 patients with glioma, 197 with meningioma, and 799 non-cancer controls frequency matched on hospital, age, sex, race/ethnicity, and residential proximity to hospital. ALAD genotype was assessed by a Taqman assay for 355 glioma patients, 151 meningioma patients, and 505 controls. Exposure to lead was estimated using a rigorous questionnaire-based exposure assessment strategy incorporating lead measurement and other occupational data abstracted from published articles and reports. Results: Increased risk of meningioma with occupational lead exposure (estimated by odds ratios and 95% confidence intervals) was most apparent in individuals with the ALAD2 variant allele, for whom risk increased from 1.1 (0.3-4.5) to 5.6 (0.7-45.5) and 12.8 (1.4-120.8) for estimated cumulative lead exposures of 1 to 49 mu g/m(3)-y, 50 to 99 mu g/m(3)-y, and >= 100 mu g/m(3)-y, respectively, compared with unexposed individuals (two-sided P trend = 0.06). This relationship became stronger after excluding occupational lead exposures characterized by a low confidence level or occurring in the 10 years before meningioma diagnosis. Occupational lead exposure was not associated with glioma risk. Conclusions: Although our results indicate that lead may be implicated in meningioma risk in genetically susceptible individuals, these results need to be interpreted with caution given the small numbers of exposed cases with a variant genotype. C1 NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NCI, Core Genotyping Facil, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NCI, NeuroOncol Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. St Josephs Hosp, Barrow Neurol Inst, Phoenix, AZ USA. Western Penn Hosp, Pittsburgh, PA 15224 USA. RP Rajaraman, P (reprint author), NCI, Radiat Epidemiol Branch, NIH, Dept Hlth & Human Serv, 6120 Execut Blvd,EPS Room 7085, Bethesda, MD 20892 USA. EM rajarama@mail.nih.gov RI Zahm, Shelia/B-5025-2015 NR 54 TC 38 Z9 40 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 2006 VL 15 IS 12 BP 2514 EP 2520 DI 10.1158/1055-9965.EPI-06-0482 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 119AK UT WOS:000242984400032 PM 17164378 ER PT J AU Touillaud, MS Thiebaut, ACM Niravong, M Boutron-Ruault, MC Clavel-Chapelon, F AF Touillaud, Marina S. Thiebaut, Anne C. M. Niravong, Maryvonne Boutron-Ruault, Marie-Christine Clavel-Chapelon, Francoise TI No association between dietary phytoestrogens and risk of premenopausal breast cancer in a french cohort study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material ID SOY INTAKE; SERUM ENTEROLACTONE; WOMEN; CONSUMPTION; POPULATION; SINGAPORE; VALIDITY; LIGNANS; CHINESE C1 Inst Gustave Roussy, INSERM ERI 20, F-94805 Villejuif, France. NCI, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Clavel-Chapelon, F (reprint author), Inst Gustave Roussy, INSERM ERI 20, E3N,39 Rue Camille Desmoulins, F-94805 Villejuif, France. EM clavel@igr.fr RI Boutron Ruault, Marie-Christine/G-3705-2013; Boutron, Marie-Christine/K-8168-2013; Clavel-Chapelon, Francoise/G-6733-2014; Boutron-Ruault, Marie-Christine/H-3936-2014 NR 25 TC 29 Z9 29 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 2006 VL 15 IS 12 BP 2574 EP 2576 DI 10.1158/1055-9965.EPI-06-0543 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 119AK UT WOS:000242984400045 PM 17164390 ER PT J AU Norris, JS Bielawska, A Day, T El-Zawahri, A ElOjeimy, S Hannun, Y Holman, D Hyer, M Landon, C Lowe, S Dong, JY McKillop, J Norris, K Obeid, L Rubinchik, S Tavassoli, M Tomlinson, S Voelkel-Johnson, C Liu, X AF Norris, J. S. Bielawska, A. Day, T. El-Zawahri, A. ElOjeimy, S. Hannun, Y. Holman, D. Hyer, M. Landon, C. Lowe, S. Dong, J. Y. McKillop, J. Norris, K. Obeid, L. Rubinchik, S. Tavassoli, M. Tomlinson, S. Voelkel-Johnson, C. Liu, X. TI Combined therapeutic use of AdGFPFasL and small molecule inhibitors of ceramide metabolism in prostate and head and neck cancers: a status report SO CANCER GENE THERAPY LA English DT Review DE FasL; HNSCC; ceramide; prostate; adenovirus; bystander effect ID FAS-MEDIATED APOPTOSIS; PROTEIN PHOSPHATASE-1; ADENOVIRAL VECTOR; GENE-EXPRESSION; CELL-LINES; IN-VITRO; ACTIVATION; SPHINGOSINE-1-PHOSPHATE; TRAIL; GFP AB As of January 2005, there were 1020 gene therapy clinical trials ongoing worldwide with 675 or 66.2% devoted to cancer gene therapy. The majority are occurring in the US and Europe (http://www.wiley.co.uk/genetherapy/clinical/). At the present time, to our knowledge there are no trials that employ gene delivery of Fas Ligand (FasL). As an important note, and in contrast to somatic cell therapy trials, there are no reported deaths due to therapeutic vector administration in any cancer gene therapy trial. That said, from our studies and from the published literature, the issue of gene delivery remains the major obstacle to successfully employing gene therapy for cancer treatment. Numerous laboratories are studying this with many different approaches. My co-workers and I have focused on the delivery issue by using various approaches that address tumor targeting and transgene expression. In addition, we are focusing on enhancing tumor cell killing via the bystander effect and through use of small molecules to enhance bystander activity. C1 Med Univ S Carolina, Dept Microbiol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Immunol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. Burnham Inst, Reed Lab, La Jolla, CA 92037 USA. NINDS, Surg Neurol Branch, Porter Neurosci Res Ctr, Bethesda, MD USA. Univ London, Guys Kings & St Thomas Coll London, Oral Pathol Dent Inst, London, England. RP Norris, JS (reprint author), Dept Microbiol & Immunol, POB 250504,173 Ashley Ave, Charleston, SC 29425 USA. EM norrisjs@musc.edu OI obeid, lina/0000-0002-0734-0847 FU NCI NIH HHS [1R24 CA82933, P01 CA97132] NR 37 TC 40 Z9 43 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD DEC PY 2006 VL 13 IS 12 BP 1045 EP 1051 DI 10.1038/sj.cgt.7700965 PG 7 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 105GN UT WOS:000242018500001 PM 16763610 ER PT J AU Castellone, MD Teramoto, H Gutkind, JS AF Castellone, Maria Domenica Teramoto, Hidemi Gutkind, J. Silvio TI Cyclooxygenase-2 and colorectal cancer chemoprevention: The beta-catenin connection SO CANCER RESEARCH LA English DT Review ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; INTESTINAL ADENOMA GROWTH; ACTIVATED-RECEPTOR-DELTA; PROSTAGLANDIN E-2; MOLECULAR TARGET; CELL-GROWTH; PPAR-DELTA; PREVENTION; INHIBITION; PATHWAY AB Colorectal cancer poses a major clinical challenge in the developed world where this disease is common. Recent findings suggest that the prostaglandin E-2, the proinflammatory product of elevated cyclooxygenase-2 activity in colon cancer, stimulates cancer cell growth through a G protein-dependent signaling pathway coupling the prostaglandin EP2 receptor to beta-catenin control. These findings provide new insights into the molecular framework needed to evaluate chemopreventive strategies for colorectal cancer. C1 NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. Kojin Hosp, Nagoya, Aichi, Japan. RP Gutkind, JS (reprint author), NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bldg 30,Room 211, Bethesda, MD 20892 USA. EM sg39v@nih.gov RI Gutkind, J. Silvio/A-1053-2009; OI CASTELLONE, MARIADOMENICA/0000-0003-0507-8037 FU Intramural NIH HHS NR 41 TC 63 Z9 67 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 2006 VL 66 IS 23 BP 11085 EP 11088 DI 10.1158/0008-5472.CAN-06-2233 PG 4 WC Oncology SC Oncology GA 113RF UT WOS:000242614300001 PM 17145847 ER PT J AU Cao, C Albert, JM Geng, L Ivy, PS Sandler, A Johnson, DH Lu, B AF Cao, Carolyn Albert, Jeffrey M. Geng, Ling Ivy, Percy S. Sandler, Alan Johnson, David H. Lu, Bo TI Vascular endothelial growth factor tyrosine kinase inhibitor AZD2171 and fractionated radiotherapy in mouse models of lung cancer SO CANCER RESEARCH LA English DT Article ID IONIZING-RADIATION; TUMOR RESPONSE; THERAPEUTIC IMPLICATIONS; ANTITUMOR-ACTIVITY; POTENT INHIBITOR; ANGIOGENESIS; RECEPTOR; VEGF; NORMALIZATION; BEVACIZUMAB AB The vascular endothelial growth factor receptor (VEGFR) tyrosine kinases are being explored as targets for antiangio-genic cancer therapy. Radiotherapy also inhibits tumor growth and affects vasculature. We investigated the combination of the potent VEGFR tyrosine kinase inhibitor AZD2171 and ionizing radiation in cell culture and mouse models of lung cancer. We show that ionizing radiation induces expression of phosphorylated VEGFR-2 (Flk-1) in endothelial cells and that this phosphorylation is inhibited by AZD2171. Human umbilical vascular endothelial cells become more sensitive to radiation after treatment with AZD2171 as determined by clonogenic assay. Matrigel assay showed a decrease in in vitro endothelial tubule formation with AZD2171/radiation combination treatment. When similar combination was applied to the H460 lung cancer xenograft model in nude mice, loss of radiation-induced phosphorylated Flk-1 was observed in the combination treatment group, which also showed a large decrease in tumor vascular density by staining of the von Willebrand factor. H460 tumor growth delay was enhanced in the combination treatment group compared with the groups treated with AZD2171 or radiation alone. Additionally, after therapy, Ki67 index showed > 4-fold reduction of tumor proliferation in the combination therapy group, which also showed increased intratumoral apoptotic index by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining. In conclusion, AZD2171 sensitizes lung tumor xenografts to radiation and inhibits angiogenesis both in vitro and in vivo. When used as a radiation enhancer, AZD2171 has the potential to improve tumor growth delay by inhibiting tumor proliferation and promoting apoptosis. Clinical trials are needed to determine the potential of this combination therapy in patients with locally advanced lung cancer. C1 Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Sch Med, Nashville, TN 37232 USA. NCI, Bethesda, MD 20892 USA. RP Lu, B (reprint author), Vanderbilt Univ, Dept Radiat Oncol, 1301 22nd Ave S,B-902 Vanderbilt Clin, Nashville, TN 37232 USA. EM bo.lu@vauderbilt.edu RI Johnson, David/A-7437-2009; lu, bo/G-4573-2010 NR 33 TC 41 Z9 43 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 2006 VL 66 IS 23 BP 11409 EP 11415 DI 10.1158/0008-5472.CAN-06-2414 PG 7 WC Oncology SC Oncology GA 113RF UT WOS:000242614300043 PM 17145887 ER PT J AU Sudheendra, D Neeman, Z Kam, A Locklin, J Libutti, SK Wood, BJ AF Sudheendra, Deepak Neeman, Ziv Kam, Anthony Locklin, Julia Libutti, Steven K. Wood, Bradford J. TI Intermittent hepatic vein balloon occlusion during radiofrequency ablation in the liver SO CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article DE hyperthermia; liver neoplasms; oncology; radiofrequency ((RF) ablation; vascular occlusion ID TISSUE ABLATION; BLOOD-FLOW; ELECTRODE; TUMORS; PERFUSION; DIAMETER; LESION AB The purpose of the study was to assess the feasibility of intermittent hepatic vein balloon occlusion during percutaneous radiofrequency (RF) ablation. Eight non-anticoagulated patients who had primary (n = 2) and metastatic (n = 6) liver tumors with a mean diameter of 4.2 cm (range 2.4-6.5 cm) were treated, resulting in a mean ablation diameter of 6.3 cm (range 4.3-9.3 cm). Six of 9 (67%) of the balloon-occluded hepatic veins were patent. No clinical sequelae of thrombosis were noted. Mean length of follow-up with CT and/or MRI was 12 months. Local tumor control was achieved in 5 of 8 patients. Intermittent hepatic vein balloon occlusion could potentially be a low-risk adjunctive maneuver for thermal ablation therapy in the treatment of large tumors and tumors adjacent to large vessels. C1 Warren G Magnuson Clin Ctr, Dept Radiol, NIH, Bethesda, MD 20892 USA. Warren G Magnuson Clin Ctr, Dept Surg, NIH, Bethesda, MD 20892 USA. RP Wood, BJ (reprint author), Warren G Magnuson Clin Ctr, Dept Radiol, NIH, Bldg 10,Room 1C660, Bethesda, MD 20892 USA. EM bwood@cc.nih.gov FU Intramural NIH HHS [Z99 CL999999] NR 21 TC 7 Z9 7 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0174-1551 J9 CARDIOVASC INTER RAD JI Cardiovasc. Interv. Radiol. PD DEC PY 2006 VL 29 IS 6 BP 1088 EP 1092 DI 10.1007/s00270-006-0040-9 PG 5 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 099OY UT WOS:000241606000025 PM 16967215 ER PT J AU Chen, EA Neeman, Z Lee, FT Kam, A Wood, B AF Chen, Enn Alexandria Neeman, Ziv Lee, Fred T. Kam, Anthony Wood, Brad TI Thermal protection with 5% dextrose solution blanket during radiofrequency ablation SO CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article DE radiofrequency ablation ID GASTROINTESTINAL-TRACT; LIVER-TUMORS; COMPLICATIONS; CARCINOMA; EFFICACY AB A serious complication for any thermal radiofrequency ablation is thermal injury to adjacent structures, particularly the bowel, which can result in additional major surgery or death. Several methods using air, gas, fluid, or thermometry to protect adjacent structures from thermal injury have been reported. In the cases presented in this report, 5% dextrose water (D5W) was instilled to prevent injury to the bowel and diaphragm during radiofrequency ablation. Creating an Insulating envelope or moving organs with D5W might reduce risk for complications such as bowel perforation. C1 NIH, Warren G Magnuson Clin Ctr, Dept Radiol, Bethesda, MD 20892 USA. RP Chen, EA (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Radiol, Bethesda, MD 20892 USA. EM echen@cc.nih.gov FU Intramural NIH HHS [Z99 CL999999] NR 12 TC 23 Z9 26 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0174-1551 J9 CARDIOVASC INTER RAD JI Cardiovasc. Interv. Radiol. PD DEC PY 2006 VL 29 IS 6 BP 1093 EP 1096 DI 10.1007/s00270-004-6216-2 PG 4 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 099OY UT WOS:000241606000026 PM 16802079 ER PT J AU Matoba, S Kang, JG Patino, WD Wragg, A Boehm, M Gavrilova, O Hurley, PJ Bunz, F Hwang, PM AF Matoba, Satoaki Kang, Ju-Gyeong Patino, Willmar D. Wragg, Andrew Boehm, Manfred Gavrilova, Oksana Hurley, Paula J. Bunz, Fred Hwang, Paul M. TI p53 regulates mitochondrial respiration SO CARDIOVASCULAR DRUGS AND THERAPY LA English DT Meeting Abstract C1 NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Radiat Oncol & Mol Radiat Sci, Baltimore, MD 21231 USA. NR 0 TC 0 Z9 0 U1 4 U2 9 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0920-3206 J9 CARDIOVASC DRUG THER JI Cardiovasc. Drugs Ther. PD DEC PY 2006 VL 20 IS 6 BP 415 EP 415 PG 1 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 124JT UT WOS:000243364800041 ER PT J AU Pagel, I Mantell, B Sack, MN AF Pagel, Ines Mantell, Benjamin Sack, Michael N. TI PPAR gamma agonist pioglitazone restores impaired mitochondrial biogenesis and function in insulin resistant C2C12 myotubes SO CARDIOVASCULAR DRUGS AND THERAPY LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0920-3206 J9 CARDIOVASC DRUG THER JI Cardiovasc. Drugs Ther. PD DEC PY 2006 VL 20 IS 6 BP 418 EP 418 PG 1 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 124JT UT WOS:000243364800046 ER PT J AU Kang, SW Rane, NS Kim, SJ Garrison, JL Taunton, J Hegde, RS AF Kang, Sang-Wook Rane, Neena S. Kim, Soo Jung Garrison, Jennifer L. Taunton, Jack Hegde, Ramanujan S. TI Substrate-specific translocational attenuation during ER stress defines a pre-emptive quality control pathway SO CELL LA English DT Article ID ENDOPLASMIC-RETICULUM MEMBRANE; SIGNAL SEQUENCE RECOGNITION; UNFOLDED PROTEIN RESPONSE; PRION PROTEIN; COTRANSLATIONAL TRANSLOCATION; CHANNEL; CYTOSOL; PRP; NEURODEGENERATION; DEGRADATION AB Eukaryotic proteins entering the secretory pathway are translocated into the ER by signal sequences that vary widely in primary structure. We now provide a functional rationale for this long-observed sequence diversity by demonstrating that differences among signals facilitate substrate-selective modulation of protein translocation. We find that during acute ER stress, translocation of secretory and membrane proteins is rapidly and transiently attenuated in a signal sequence-selective manner. Their cotranslational rerouting to the cytosol for degradation reduces the burden of misfolded substrates entering the ER and represents a pathway for pre-emptive quality control (pQC). Bypassing the pQC pathway for the prion protein increases its rate of aggregation in the ER lumen during prolonged stress and renders cells less capable of viable recovery. Conversely, pharmacologically augmenting pQC during ER stress proved protective. Thus, protein translocation is a physiologically regulated process that is utilized for pQC as part of the ER stress response. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. Korea Res Inst Biosci & Biotechnol, Funct Genom Res Ctr, Taejon 305333, South Korea. Univ Calif San Francisco, Dept Mol & Cellular Pharmacol, San Francisco, CA 94107 USA. RP Hegde, RS (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, 18 Lib Dr,Bldg 18T,Room 101, Bethesda, MD 20892 USA. EM hegder@mail.nih.gov OI Hegde, Ramanujan/0000-0001-8338-852X FU Intramural NIH HHS; NIGMS NIH HHS [R01 GM071434-04] NR 32 TC 143 Z9 144 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD DEC 1 PY 2006 VL 127 IS 5 BP 999 EP 1013 DI 10.1016/j.cell.2006.10.032 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 113RA UT WOS:000242613800016 PM 17129784 ER PT J AU Chen, L Zhang, H Shi, Y Chin, KL Tang, DC Rodgers, GP AF Chen, Ling Zhang, Hong Shi, Ying Chin, Kyung L. Tang, Delia C. Rodgers, Griffin P. TI Identification of key genes responsible for cytokine-induced erythroid and myeloid differentiation and switching of hematopoietic stem cells by RAGE SO CELL RESEARCH LA English DT Article DE lineage switching; hematopoietic stem cells; erythroid/myeloid differentiation; co-expression; biological processes; cytokines ID AGE-RELATED-CHANGES; HUMAN BONE-MARROW; PROGENITOR CELLS; LINEAGE PROMISCUITY; C/EBP-ALPHA; B-CELLS; EXPRESSION; BLOOD; COMMITMENT; ONCOGENE AB We utilized a unique culture system to analyze the expression patterns of gene, protein, and cell surface antigen, and the biological process of the related genes in erythroid and myeloid differentiation and switching of hematopoietic stem cells (HSCs) in response to cytokine alterations. Gene-specific fragments (266) identified from five populations of cytokine-stimulated HSCs were categorized into three groups: (1) expressed specifically in a single cell population; (2) expressed in two cell populations, and (3) expressed in three or more populations. Of 145 defined cDNAs, three (2%) were novel genes. Protein two-dimensional gel electrophoresis and flow cytometry analyses showed overlapped and distinguished protein expression profiles in the cell populations studied. Biological process mapping of mRNAs expressed in erythroid and myeloid lineages indicated that mRNAs shared by both lineages attended `core processes,' whereas genes specifically expressed in either lineage alone were related to specific processes or cellular maturation. Data from this study support the hypothesis that committed HSCs (E14 or G14) cells can still be redirected to develop into myeloid or erythroid cells when erythropoietin (EPO) is replaced with granulocyte-colony stimulating factor (G-CSF) under erythroid-cultured condition or G-CSF with EPO in myeloid-cultured environment, respectively. Our results suggest that genes or proteins co-expressed in erythroid and myeloid lineages may be essential for the lineage maintenance and switching in hematopoiesis. C1 NIDDK, MCHB, NIH, Bethesda, MD 20892 USA. Z BioMed Inc, Rockville, MD 20855 USA. First Affiliated Hosp, Zunyi Med Coll, Dept Med, Zunyi 563003, Peoples R China. RP Rodgers, GP (reprint author), NIDDK, MCHB, NIH, Bethesda, MD 20892 USA. EM gprod@helix.nih.gov NR 41 TC 1 Z9 1 U1 0 U2 0 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYAND ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 J9 CELL RES JI Cell Res. PD DEC PY 2006 VL 16 IS 12 BP 923 EP 939 DI 10.1038/sj.cr.7310115 PG 17 WC Cell Biology SC Cell Biology GA 130CP UT WOS:000243777300003 PM 17146449 ER PT J AU Chen, X Yang, L Howard, OMZ Oppenheim, JJ AF Chen, Xin Yang, Lu Howard, O. M. Zack Oppenheim, Joost J. TI Dendritic Cells as a Pharmacological Target of Traditional Chinese Medicine SO CELLULAR & MOLECULAR IMMUNOLOGY LA English DT Review DE dendritic cell; traditional Chinese medicine AB Dendritic cells (DCs) represent a heterogeneous population of professional antigen-presenting cells (APCs) that play a central role in the initiation and regulation of immune responses. There is considerable evidence that DCs can be used as therapeutic targets for pharmacological modulation of immune responses. Traditional Chinese medicine (TCM) has a long-standing history of using herbal medicine in the treatment of variety of human diseases. Many of the clinical effects of TCM have reportedly been attributed to the up- or down-regulation of immune responses. Accumulating evidence indicates that TCM and its components can interfere with immune responses at the earliest stage by targeting key functions of DCs. Here, we review those published studies of TCM with respect to their effects on immunobiological functions of DCs. Investigations based on both chemical entities derived from TCM as well as TCM herbal mixtures are presented. These studies suggest that various TCM herbal medicines have the capacity to inhibit or promote major functions of DCs, such as differentiation, maturation, cytokine production, survival, antigen uptake and presentation as well as trafficking. These studies have revealed novel biological effects of TCM and documented the utility of this approach to discover novel biological modifier of DC functions derived from natural sources. C1 [Chen, Xin] NCI, SAIC Frederick Inc, Basic Res Program, Frederick, MD 21701 USA. [Yang, Lu] ImQuest BioSci Inc, Frederick, MD 21704 USA. [Howard, O. M. Zack; Oppenheim, Joost J.] NCI, Ctr Canc Res, Mol Immunoregulat Lab, Ft Detrick, MD 21702 USA. RP Chen, X (reprint author), NCI, BRP, SAIC Frederick, Mol Immunoregulat Lab,Canc Inflammat Program,CCR, POB B,Bldg 560,Rm 31-19, Frederick, MD 21702 USA. EM chenxin@mail.nih.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 NR 106 TC 15 Z9 18 U1 0 U2 0 PU CHIN SOCIETY IMMUNOLOGY PI BEING PA 5 DONGDAN SANTIAO, DONGCHEN DISTRICT, BEING, 100005, PEOPLES R CHINA SN 1672-7681 EI 2042-0226 J9 CELL MOL IMMUNOL JI Cell. Mol. Immunol. PD DEC PY 2006 VL 3 IS 6 BP 401 EP 410 PG 10 WC Immunology SC Immunology GA V32BN UT WOS:000208926800001 PM 17257493 ER PT J AU Liu, XF Xie, XZ Miki, T AF Liu, Xiu Fen Xie, Xiaozhen Miki, Toru TI Inhibition of protein kinase C zeta blocks the attachment of stable microtubules to kinetochores leading to abnormal chromosome alignment SO CELLULAR SIGNALLING LA English DT Article DE chromosome separation; mitosis; Par3; Par6; stable microtubules ID EXCHANGE FACTOR ECT2; SPINDLE CHECKPOINT; PKC-ZETA; MEIOTIC-SPINDLE; CELL-POLARITY; MOUSE EGGS; CDC42; ROLES; ACTIVATION; METAPHASE AB The attachment of spindle microtubules to kinetochores is crucial for accurate segregation of chromosomes to daughter cells during mitosis. While a growing number of proteins involving this step are being identified, its molecular mechanisms are still not clear. Here we show that protein kinase C xi (PKC xi) is localized at the mitotic spindle during mitosis and plays a role in stable kinetochore-microtubule attachment. Striking staining for PKC was observed at the mitotic spindle and spindle poles in cells at prometaphase and metaphase. PKC xi molecules at these stages were phosphorylated at Thr-410, as detected by a phosphospecific antibody. PKC xi was also detected at the spindle midzone and the midbody during anaphase and telophase, respectively, and PKC xi at these stages was no longer phosphorylated at Thr-410. The polarity determinants Par3 and Par6, which are known to associate with PKC xi, were also localized to the spindles and spindle poles at prometaphase and metaphase. Knockdown of PKC xi by RNA interference affected normal chromosome alignment leading to generation of cells with aberrant nuclei. A specific PKC xi inhibitor strongly blocked the formation of cold-sensitive stable kinetochore micrombules, and thus prevented microtubule-kinetochore attachment. Treatment of cells with the PKC xi inhibitor also dislocated the minus-end directed motor protein dynein from kinetochores, but not the mitotic checkpoint proteins Mad2 and CENP-E. Prolonged exposure to the PKC xi inhibitor eventually resulted in cell death. These results suggest a critical role of PKC xi in spindle microtubule-kinetochore attachment and subsequent chromosomal separation. (c) 2006 Elsevier Inc. All rights reserved. C1 NCI, Mol Tumor Biol Sect, Cell Biol Lab, Bethesda, MD 20892 USA. RP Miki, T (reprint author), NCI, Mol Tumor Biol Sect, Cell Biol Lab, Bldg 37,Room 2144,37 Convent Dr,MSC 4256, Bethesda, MD 20892 USA. EM toru@helix.nih.gov FU Intramural NIH HHS NR 32 TC 10 Z9 10 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD DEC PY 2006 VL 18 IS 12 BP 2314 EP 2323 DI 10.1016/j.cellsig.2006.05.017 PG 10 WC Cell Biology SC Cell Biology GA 108VD UT WOS:000242266400025 PM 16820280 ER PT J AU Pohl, LR AF Pohl, Lance R. TI Role of reactive metabolites and other risk factors in determining susceptibility to drug-induced liver disease. SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Meeting Abstract CT Meeting of the Division of Chemical Toxicology of the American-Chemical-Society held at the 232nd ACS National Meeting CY SEP 10-14, 2006 CL San Francisco, CA SP Amer Chem Soc, Div Chem Toxicol C1 NIH, NHLBI, Mol & Cell Toxicol Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD DEC PY 2006 VL 19 IS 12 MA 23 BP 1680 EP 1681 PG 2 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 119FD UT WOS:000242997300037 ER PT J AU Tannenbaum, SR AF Tannenbaum, Steven R. TI Role of nitric oxide in the carcinogenic process. SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Meeting Abstract CT Meeting of the Division of Chemical Toxicology of the American-Chemical-Society held at the 232nd ACS National Meeting CY SEP 10-14, 2006 CL San Francisco, CA SP Amer Chem Soc, Div Chem Toxicol C1 NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD DEC PY 2006 VL 19 IS 12 MA 20 BP 1680 EP 1680 PG 1 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 119FD UT WOS:000242997300034 ER PT J AU Rodriguez, FA Tang, YJ Sayer, JM Jerina, DM Geacintov, NE AF Rodriguez, Fabian A. Tang, Yijin Sayer, Jane M. Jerina, Donald M. Geacintov, Nicholas E. TI Conformation of a 14S(-)-trans-anti-Dibenzo[a,l]pyrene diol epoxide-dG adduct in an 11-mer DNA duplex investigated by NMR methods. SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Meeting Abstract CT Meeting of the Division of Chemical Toxicology of the American-Chemical-Society held at the 232nd ACS National Meeting CY SEP 10-14, 2006 CL San Francisco, CA SP Amer Chem Soc, Div Chem Toxicol C1 NYU, Dept Chem, New York, NY 10003 USA. NIH, NIDDK, Bioorgan Chem Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD DEC PY 2006 VL 19 IS 12 MA 51 BP 1687 EP 1687 PG 1 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 119FD UT WOS:000242997300065 ER PT J AU Salnikow, K AF Salnikow, Konstantin TI Metal-induced carcinogenesis: The role of ascorbate. SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Meeting Abstract CT Meeting of the Division of Chemical Toxicology of the American-Chemical-Society held at the 232nd ACS National Meeting CY SEP 10-14, 2006 CL San Francisco, CA SP Amer Chem Soc, Div Chem Toxicol C1 NIH, Natl Canc Inst, Comparat Carcinogenesis Lab, Bldg 538, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD DEC PY 2006 VL 19 IS 12 MA 104 BP 1699 EP 1700 PG 2 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 119FD UT WOS:000242997300118 ER PT J AU Gonzalez, FJ AF Gonzalez, Frank J. TI Mouse metabolomics. SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Meeting Abstract CT Meeting of the Division of Chemical Toxicology of the American-Chemical-Society held at the 232nd ACS National Meeting CY SEP 10-14, 2006 CL San Francisco, CA SP Amer Chem Soc, Div Chem Toxicol C1 NCI, Lab Metab, Bethesda, MD 20892 USA. Charles Univ Prague, Inst Pharmacol, Fac Med 1, Prague, Czech Republic. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD DEC PY 2006 VL 19 IS 12 MA 110 BP 1701 EP 1701 PG 1 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 119FD UT WOS:000242997300124 ER PT J AU Kapetanovic, IM Krishnaraj, R Martin-Jimenez, T Yuan, L van Breemen, RB Lyubimov, A AF Kapetanovic, I. M. Krishnaraj, R. Martin-Jimenez, T. Yuan, L. van Breemen, R. B. Lyubimov, A. TI Effects of oral dosing paradigms (gavage versus diet) on pharmacokinetics and pharmacodynamics SO CHEMICO-BIOLOGICAL INTERACTIONS LA English DT Article; Proceedings Paper CT 45th SOT Annual Meeting CY 2006 CL San Diego, CA SP SOT DE oral gavage; diet dosing; pharmacokinetics; pharmacodynamics; sulindac; PGE2 ID DOSED FEED; RAT; CHEMOPREVENTION; TOXICOKINETICS; METABOLISM; CYCLOOXYGENASE-2; CARCINOGENESIS; ABSORPTION; SULINDAC; SPARSE AB In cancer chemopreventive studies, test agents are typically administered via diet, while the preclinical safety studies normally employ oral gavage dosing. Correspondence in pharmacokinetic and pharmacodynamic profiles between the two dosing approaches cannot be assumed a priori. Sulindac, a non-steroidal anti-inflammatory agent with potential chemopreventive activity, was used to assess effects of the two oral dosing paradigms on its pharmacokinetics and pharmacodynamics. Time-dependent concentrations of sulindac and its sulfone metabolite were determined in plasma and potential target organ, mammary gland. Prostaglandin E-2 was used as a pharmacodynamic biomarker and measured in mammary gland. An inverse linear relationship was detected between pharmacodynamic and pharmacokinetic markers, area under the curve for prostaglandin E, levels and sulindac sulfone concentrations, respectively, in the mammary tissue. Marked differences in pharmacokinetics and pharmacodynamics were observed after administration of sulindac by the two oral dosing paradigms. In general, oral gavage resulted in higher peak and lower trough concentrations of sulindac in plasma and mammary tissue, higher area under concentration-time curve in plasma and mammary tissue, and greater effect on prostaglandin E-2 levels than the corresponding diet dosing. This study illustrates potential pitfalls and limitations in trying to generalize based on data obtained with different oral dosing schemes and their extrapolation to potential efficacy and health risks in humans. Published by Elsevier Ireland Ltd. C1 NCI, Chemoprevent Agent Dev Res Grp, Div Canc Prevent, Bethesda, MD 20892 USA. Univ Illinois, Dept Pharmacol, Toxicol Res Lab, Chicago, IL 60612 USA. Univ Tennessee, Dept Comparat Med, Knoxville, TN 37996 USA. Univ Illinois, Coll Pharm, Chicago, IL 60612 USA. RP Kapetanovic, IM (reprint author), NCI, Chemoprevent Agent Dev Res Grp, Div Canc Prevent, Bethesda, MD 20892 USA. EM kapetani@mail.nih.gov RI Yuan, Long/H-9552-2013 OI Yuan, Long/0000-0003-1863-2308 FU NCI NIH HHS [N01-CN-25134] NR 20 TC 14 Z9 14 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0009-2797 J9 CHEM-BIOL INTERACT JI Chem.-Biol. Interact. PD DEC 1 PY 2006 VL 164 IS 1-2 BP 68 EP 75 DI 10.1016/j.cbi.2006.08.019 PG 8 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA 114ET UT WOS:000242650200007 PM 17027946 ER PT J AU Arumugam, TV Magnus, T Woodruff, TM Proctor, LM Shiels, IA Taylor, SM AF Arumugam, Thiruma V. Magnus, Tim Woodruff, Trent M. Proctor, Lavinia M. Shiels, Ian A. Taylor, Stephen M. TI Complement mediators in ischemia-reperfusion injury SO CLINICA CHIMICA ACTA LA English DT Review DE ischemia-reperfusion; complement; C5a; membrane attack complex; inflammation ID C5A RECEPTOR ANTAGONIST; MEMBRANE ATTACK COMPLEX; ACUTE MYOCARDIAL-INFARCTION; REMOTE ORGAN INJURY; RESPIRATORY-DISTRESS-SYNDROME; INFLAMMATORY-BOWEL-DISEASE; HUMAN ENDOTHELIAL-CELLS; MANNOSE-BINDING LECTIN; C1 ESTERASE INHIBITOR; LOWER TORSO ISCHEMIA AB Background: Ischemia-reperfusion (I/R) injury occurs when a tissue is temporarily deprived of blood supply and the return of the blood supply triggers an intense inflammatory response. Pathologically, increased complement activity can cause substantial damage to blood vessels, tissues and also facilitate leukocyte activation and recruitment following I/R injury. Herein, previously published studies are reported and critically reviewed. Methods: Medline and the World Wide Web were searched and the relevant literature was classified under the following categories: (1) Complement pathways; (2) The complement system and the inflammatory response; (3) Complement in ischemia-reperfusion injuries; and (4) Therapeutic approaches against complement in I/R injuries. Results and conclusions: I/R injury is a common clinical event with the potential to seriously affect, and sometimes kill, the patient and is a potent inducer of complement activation that results in the production of a number of inflammatory mediators. Complement activation leads to the release of biologically active potent inflammatory complement substances including the anaphylatoxins (C3a and C5a) and the cytolytic terminal membrane attack complement complex C5b-9 (MAC). The use of specific complement inhibitors to block complement activation at various levels of the cascade has been shown to prevent or reduce local tissue injury after I/R. Several agents that inhibit all or part of the complement system, such as soluble complement receptor type I (sCRI), CI inhibitor (Cl-INH), C5a monoclonal antibodies, a C5a receptor antagonist and soluble CD59 (sCD59) have been shown to reduce I/R injury of various organs. The novel inhibitors of complement products may eventually find wide clinical application because there are no effective drug therapies currently available to treat I/R injuries. (c) 2006 Elsevier B.V. All rights reserved. C1 Univ Queensland, Dept Physiol & Pharmacol, Sch Biomed Sci, Brisbane, Qld 4072, Australia. NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Taylor, SM (reprint author), Univ Queensland, Dept Physiol & Pharmacol, Sch Biomed Sci, Brisbane, Qld 4072, Australia. EM s.taylor@uq.edu.au RI Arumugam, Thiruma/C-7969-2009; Shiels, Ian/C-8046-2009; Arumugam, Thiruma/B-4898-2011; Woodruff, Trent/B-4861-2009 OI Woodruff, Trent/0000-0003-1382-911X NR 155 TC 70 Z9 82 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD DEC PY 2006 VL 374 IS 1-2 BP 33 EP 45 DI 10.1016/j.cca.2006.06.010 PG 13 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 105OL UT WOS:000242040100004 PM 16872589 ER PT J AU Fouda, GG Leke, RFG Long, C Druilhe, P Zhou, AN Taylor, DW Johnson, AH AF Fouda, Genevieve G. Leke, Rose F. G. Long, Carole Druilhe, Pierre Zhou, Ainong Taylor, Diane Wallace Johnson, Armead H. TI Multiplex assay for simultaneous measurement of antibodies to multiple Plasmodium falciparum antigens SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID FLOW-CYTOMETRIC ASSAY; SUSPENSION ARRAY TECHNOLOGY; LINKED-IMMUNOSORBENT-ASSAY; SIMULTANEOUS QUANTITATION; MICROSPHERE IMMUNOASSAY; CYTOKINES; SERUM AB Antibodies to Plasmodium falciparum are classically measured using the enzyme-linked immunosorbent assay (ELISA). Although highly sensitive, this technique is labor-intensive when large numbers of samples must be screened against multiple antigens. The suspension array technology (SAT) might be an alterative to ELISA, as it allows measurement of antibodies against multiple antigens simultaneously with a small volume of sample. This study sought to adapt the new SAT multiplex system for measuring antibodies against nine malarial vaccine candidate antigens, including recombinant proteins from two variants of merozoite surface protein 1, two variants of apical merozoite antigen 1, erythrocyte binding antigen 175, merozoite surface protein 3, and peptides from the circumsporozoite protein, ring erythrocyte surface antigen, and liver-stage antigen 1. Various concentrations of the antigens were coupled to microspheres with different spectral addresses, and plasma samples from Cameroonian adults were screened by SAT in mono- and multiplex formats and by ELISA. Optimal amounts of protein required to perform the SAT assay were 10- to 100-fold less than that needed for ELISA. Excellent agreement was found between the single and multiplex formats (R >= 0.96), even when two variants of the same antigen were used. The multiplex assay was rapid, reproducible, required less than 1 mu l of plasma, and had a good correlation with ELISA. Thus, SAT provides an important new tool for studying the immune response to malaria rapidly and efficiently in large populations, even when the amount of plasma available is limited, e.g., in studies of neonates or finger-prick blood. C1 Georgetown Univ, Dept Biol, Washington, DC 20057 USA. Univ Yaounde, Fac Med & Biomed Sci, Yaounde, Cameroon. NIAID, NIH, Malaria Vaccine Dev Branch, Rockville, MD 20852 USA. Inst Pasteur, Paris, France. AZ DataClin Inc, Rockville, MD 20850 USA. Georgetown Univ, Sch Med, Dept Pediat, Washington, DC 20007 USA. RP Taylor, DW (reprint author), Univ Hawaii, Dept Trop Med, Asia Pacific Inst Trop Med & Infect Dis, John A Burns Sch Med, 651 Ilalo St, Honolulu, HI 96813 USA. EM taylordw@georgetown.edu FU NIAID NIH HHS [R21 AI053798, R21AI53798, U01 AI043888, U01 AI43888] NR 17 TC 39 Z9 40 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD DEC PY 2006 VL 13 IS 12 BP 1307 EP 1313 DI 10.1128/CVI.00183-06 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 118ZM UT WOS:000242982000002 PM 17035513 ER PT J AU Imrich, R Goldstein, DS Jacobowitz, DM AF Imrich, Richard Goldstein, David S. Jacobowitz, David M. TI Prevalence of anti-locus coeruleus immunoreactivity in CSF of patients with autonomic failure SO CLINICAL AUTONOMIC RESEARCH LA English DT Article DE autonomic failure; multiple system atrophy; Parkinson's disease; antibody; locus coeruleus; autonomic nervous system ID ACETYLCHOLINE-RECEPTORS; AUTOANTIBODIES; DISEASE AB In this study we evaluated by indirect immunohistochemistry the prevalence of cerebrospinal fluid (CSF) antibodies reacting with structures of rat pons/medulla in patients with multiple system atrophy (MSA) (n = 29), Parkinson disease with neurogenic orthostatic hypotension (n = 13), or pure autonomic failure (n = 11) and in control subjects without autonomic failure (n = 33). About 10-20% of CSF samples had positive immunoreactivity to rat locus coeruleus (LC), regardless of clinical diagnosis. The results failed to confirm the previously reported high prevalence of immune binding to rat LC in CSF from patients with MSA. C1 NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. USUHS, Dept Anat Physiol & Genet, Bethesda, MD USA. RP Imrich, R (reprint author), NINDS, Clin Neurocardiol Sect, NIH, Bldg 10,Room 6N252,10 Ctr Dr, Bethesda, MD 20892 USA. EM imrichr@ninds.nih.gov FU Intramural NIH HHS; NIMH NIH HHS [1ZDI MH00382-31 LCS] NR 11 TC 1 Z9 1 U1 0 U2 0 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY SN 0959-9851 J9 CLIN AUTON RES JI Clin. Auton. Res. PD DEC PY 2006 VL 16 IS 6 BP 401 EP 405 DI 10.1007/s10286-006-0366-z PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 125GN UT WOS:000243430500009 PM 16977375 ER PT J AU Mamounas, EP Lembersky, B Jeong, JH Cronin, W Harkins, B Geyer, C Wickerham, DL Paik, S Costantino, J Wolmark, N AF Mamounas, Eleftherios P. Lembersky, Barry Jeong, Jong-Hyeon Cronin, Walter Harkins, Barbara Geyer, Charles Wickerham, Donald Lawrence Paik, Soonmyung Costantino, Joseph Wolmark, Norman TI NSABP B-42: A clinical trial to determine the efficacy of five years of letrozole compared with placebo in patients completing five years of hormonal therapy consisting of an aromatase inhibitor (AI) or tamoxifen followed by an AI in prolonging disease-free survival in postmenopausal women with hormone receptor-positive breast cancer SO CLINICAL BREAST CANCER LA English DT Article DE arterial thrombotic events; duration of therapy; early-stage disease; osteoporotic fracture ID FIRST-LINE THERAPY; EXTENDED ADJUVANT THERAPY; PHASE-III TRIALS; RANDOMIZED-TRIAL; MEGESTROL-ACETATE; DOUBLE-BLIND; UPDATED FINDINGS; ANASTROZOLE; EXEMESTANE; SUPERIOR C1 Aultman Hlth Fdn, Ctr Canc, Canton, OH 44710 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. Allegheny Gen Hosp, Ctr Canc, Pittsburgh, PA 15212 USA. RP Mamounas, EP (reprint author), Aultman Hlth Fdn, Ctr Canc, 2600 6th St SW, Canton, OH 44710 USA. EM tmamounas@aultman.com FU NCI NIH HHS [U10CA-69651, U10CA-12027, U10CA-37377, U10CA-69974] NR 34 TC 23 Z9 23 U1 1 U2 1 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1526-8209 J9 CLIN BREAST CANCER JI Clin. Breast Cancer PD DEC PY 2006 VL 7 IS 5 BP 416 EP 421 DI 10.3816/CBC.2006.n.061 PG 6 WC Oncology SC Oncology GA 123WP UT WOS:000243327200010 PM 17239269 ER PT J AU Hortin, GL Seam, N Hoehn, GT AF Hortin, Glen L. Seam, Nitin Hoehn, Gerard T. TI Bound homocysteine, cysteine, and cysteinylglycine distribution between albumin and globulins SO CLINICAL CHEMISTRY LA English DT Article ID PLASMA HOMOCYSTEINE; MIXED DISULFIDES; GENETIC-VARIANTS; RISK FACTOR; DISEASE; TRANSTHYRETIN; PROTEINS; MILANO; SERUM; HYPERHOMOCYSTEINEMIA AB Background: Major portions of homocysteine (Hcy), cysteine (Cys), cysteinylglycine (CysGly), and glutathione in serum are covalently bound to proteins via disulfides. Albumin has been considered the dominant binding protein. Methods: Pooled serum and plasma from healthy adults were fractionated into albumin and globulins by affinity columns. Content of Hcy, Cys, CysGly, and glutathione was determined for serum and plasma fractions and purified proteins by an HPLC method before and after incubation with excess CysGly, Hcy, or glutathione Results: Of protein-bound amino acids in pooled serum, 12% of Hcy, 21% of Cys, and 33% of CysGly were bound to globulins, with the remainder bound to albumin. Slightly higher proportions were bound to globulins in pooled plasma. Globulins had similar to 16% of total exchangeable disulfide and thiol groups in serum based on results of loading with CysGly. These results agree with expected abundance of unpaired Cys residues in globulins relative to albumin. Significant amounts of disulfide-linked amino acids were detected for HDL and alpha(1)-acid glycoprotein but not for transferrin. Exchange of disulfide-linked amino acids on exposure to excess Hcy or glutathione was much faster for albumin than for alpha(1)-acid glycoprotein. Conclusions: Approximately 10%-30%, of protein-bound Hcy, Cys, and CysGly are disulfide-linked to globulins. Amino acids disulfide-linked to albumin are rapidly exchangeable, while exchange of disulfide-linked amino acids from globulins, such as alpha(1)-acid glycoprotein, is much slower. Consequently, the pools of Hcy, Cys, and CysGly bound to albumin and globulin may represent kinetically and functionally distinct pools. Plasma concentrations of total Hcy and Cys, which are dominated by albumin-bound pools, may not reflect the abundance of functionally significant modifications of globulins. (c) 2006 American Association for Clinical Chemistry. C1 NIH, Warren G Magnuson Clin Ctr, Dept Lab Med, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Hortin, GL (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Lab Med, Bethesda, MD 20892 USA. EM ghortin@mail.cc.nih.gov FU Intramural NIH HHS NR 37 TC 29 Z9 33 U1 1 U2 7 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD DEC PY 2006 VL 52 IS 12 BP 2258 EP 2264 DI 10.1373/clinchem.2006.074302 PG 7 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 116RM UT WOS:000242820000014 PM 17068168 ER PT J AU Limburg, PJ Stolzenberg-Solomon, RZ Vierkant, RA Roberts, K Sellers, TA Taylor, PR Virtamo, J Cerhan, JR Albanes, D AF Limburg, Paul J. Stolzenberg-Solomon, Rachael Z. Vierkant, Robert A. Roberts, Katherine Sellers, Thomas A. Taylor, Philip R. Virtamo, Jarmo Cerhan, James R. Albanes, Demetrius TI Insulin, glucose, insulin resistance, and incident colorectal cancer in male smokers SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID HOMEOSTASIS MODEL ASSESSMENT; GROWTH-FACTOR-I; SENSITIVITY CHECK INDEX; CASE-COHORT DESIGN; C-PEPTIDE; FOLLOW-UP; CARDIOVASCULAR-DISEASE; PLASMA-INSULIN; FACTOR (IGF)-I; BLOOD-GLUCOSE AB Background & Aims: Hyperinsulinemia is a putative colorectal cancer (CRC) risk factor. Insulin resistance (IR) commonly precedes hyperinsulinemia and can be quantitatively measured by using the homeostasis model assessment-insulin resistance (HOMA-IR) index. To date, few studies have directly examined serum insulin as an indicator of CRC risk, and none have reported associations on the basis of HOMA-IR. Methods: We performed a case-cohort study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study (n = 29,133). Baseline exposure and fasting serum biomarker data were available for 134 incident CRC case and 399 non-case subjects. HOMA-IR was derived as fasting insulin X fasting glucose/22.5. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by using age-adjusted and multivariable-adjusted Cox proportional hazards regression models. Results: Median (interquartile range) values for serum insulin, glucose, and HOMA-IR were 4.1 (2.9-7.2) mIU/L, 101 (94-108) mg/dL, and 0.99 (0.69-1.98) for case subjects and 4.1 (2.7-6.1) mIU/L, 99 (93-107) mg/dL, and 1.02 (0.69-1.53) for non-case subjects, respectively. On the basis of comparison of the highest versus lowest quartiles for each biomarker, insulin (HR, 1.84; 95% CI, 1.03-3.30) and HOMA-IR (HR, 1.85; 95% CI, 1.06-3.24) were significantly associated with incident CRC, whereas glucose was marginally associated with incident CRC (HR, 1.70; 95% CI, 0.92-3.13) in age-adjusted risk models. However, trends across biomarker quartiles were somewhat inconsistent (P trend = .12, .04, and .12, respectively), and multivariable adjustment generally attenuated the observed risk estimates. Conclusions: Data from this prospective study of male smokers provide limited support for hyperinsulinemia, hyperglycemia, and/or insulin resistance as CRC risk factors. C1 Mayo Clin Coll Med, Rochester, MN USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Helsinki, Finland. RP Limburg, PJ (reprint author), Mayo Clin & Mayo Fdn, Div Gastroenterol & Hepatol, 200 1st St SW, Rochester, MN 55905 USA. EM limburg.paul@mayo.edu RI Albanes, Demetrius/B-9749-2015; Bowers, Katherine/N-5226-2015; OI Cerhan, James/0000-0002-7482-178X; Vierkant, Robert/0000-0001-6242-5221 FU CCR NIH HHS [N01RC37004]; NCI NIH HHS [K07 CA092216, N01 CN045165] NR 57 TC 41 Z9 42 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD DEC PY 2006 VL 4 IS 12 BP 1514 EP 1521 DI 10.1016/j.cgh.2006.09.014 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 119CN UT WOS:000242989900018 PM 17162243 ER PT J AU Almyroudis, NG Kontoyiannis, DP Sepkowitz, KA DePauw, BE Walsh, TJ Segal, BH AF Almyroudis, Nikolaos G. Kontoyiannis, Dimitrios P. Sepkowitz, Kent A. DePauw, Ben E. Walsh, Thomas J. Segal, Brahm H. TI Issues related to the design and interpretation of clinical trials of salvage therapy for invasive mold infection SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID CELL TRANSPLANT RECIPIENTS; LIPOSOMAL AMPHOTERICIN-B; CARE CANCER CENTER; EXPERIMENTAL PULMONARY ASPERGILLOSIS; BONE-MARROW-TRANSPLANTATION; AIR CRESCENT SIGN; BETA-D-GLUCAN; FUNGAL-INFECTIONS; ACUTE-LEUKEMIA; GALACTOMANNAN ANTIGENEMIA AB Invasive mold infection is a major cause of morbidity and mortality among severely immunocompromised individuals. We discuss the challenges involved in the design and interpretation of salvage antifungal trials, focusing on mold infection. We suggest that patients with refractory fungal infection be analyzed separately from those with intolerance to standard regimens because of the poorer prognosis of the former group. We propose a composite outcome assessment in which refractory infection is defined as infection associated with the worsening of at least 2 of the following 3 types of criteria: clinical, radiologic, and mycologic. Confounding variables, including heterogeneity in host factors, initial antifungal therapy, and selection bias, are discussed. Although randomized studies would provide the most credible results, the lack of an adequate number of patients to meet prespecified stratification criteria for all confounding variables makes such studies impractical. Given that randomized studies are unrealistic, studies involving carefully selected, matched, contemporaneous control subjects are likely to be the most useful alternative. C1 Roswell Pk Canc Inst, Div Infect Dis, Rochester, NY 14623 USA. Cornell Univ, Med Ctr, Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. Univ Texas, Dept Infect Dis Infect Control & Employee Hlth, Houston, TX 77030 USA. NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. Univ Nijmegen, Med Ctr St Radboud, Dept Haematol, Nijmegen, Netherlands. RP Almyroudis, NG (reprint author), Roswell Pk Canc Inst, Div Infect Dis, Elm & Carlton St, Rochester, NY 14623 USA. EM Nick.Almyroudis@roswellpark.org NR 67 TC 26 Z9 26 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 1 PY 2006 VL 43 IS 11 BP 1449 EP 1455 DI 10.1086/508455 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 102CF UT WOS:000241787700013 PM 17083020 ER PT J AU Powers, JH AF Powers, John H. TI Salvage therapy trials in invasive fungal disease: Challenges and opportunities SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID CLINICAL-TRIALS C1 NIAID, NIH, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. George Washington Univ, Sch Med, Dept Med, Washington, DC 20052 USA. RP Powers, JH (reprint author), 18511 Fiddleleaf Ter, Olney, MD 20832 USA. EM JPowers3@aol.com NR 13 TC 3 Z9 3 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 1 PY 2006 VL 43 IS 11 BP 1456 EP 1460 DI 10.1086/508468 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 102CF UT WOS:000241787700014 PM 17083021 ER PT J AU Nelson, KB AF Nelson, Karin B. TI Thrombophilias, perinatal stroke, and cerebral palsy SO CLINICAL OBSTETRICS AND GYNECOLOGY LA English DT Article DE thrombophilia; perinatal stroke; cerebral palsy ID FETAL THROMBOTIC VASCULOPATHY; RISK-FACTORS; ARTERIAL STROKE; PREGNANCY; PLACENTA; CHILDREN; INFANTS AB Perinatal ischemic stroke has become recognized as a not-rare adverse outcome of pregnancy and a common cause of chronic neurologic disability in children. This review discusses the clinical entity, perinatal stroke, and its relationship to thrombophilias, inherited and acquired, and to maternal and pregnancy factors. C1 NINDS, NIH, NEB, Bldg 10,Room 5S221, Bethesda, MD 20892 USA. RP Nelson, KB (reprint author), NINDS, NIH, NEB, Bldg 10,Room 5S221, Bethesda, MD 20892 USA. EM knelson@helix.nih.gov FU Intramural NIH HHS NR 21 TC 13 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-9201 J9 CLIN OBSTET GYNECOL JI Clin. Obstet. Gynecol. PD DEC PY 2006 VL 49 IS 4 BP 875 EP 884 DI 10.1097/01.grf.0000211956.61121.e0 PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 102QO UT WOS:000241828000015 PM 17082682 ER PT J AU Jain, L Raju, TNK AF Jain, Lucky Raju, Tonse N. K. TI Late preterm pregnancy and the newborn - Preface SO CLINICS IN PERINATOLOGY LA English DT Editorial Material C1 Emory Univ, Sch Med, Div Neonatol, Dept Pediat & Physiol, Atlanta, GA 30322 USA. NICHD, Pregnancy & Perinatol Branch, CDBPM, NIH, Bethesda, MD 20892 USA. RP Jain, L (reprint author), Emory Univ, Sch Med, Div Neonatol, Dept Pediat & Physiol, 2015 Uppergate Dr NE, Atlanta, GA 30322 USA. EM ljain@emory.edu; rajut@mail.nih.gov NR 0 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0095-5108 J9 CLIN PERINATOL JI Clin. Perinatol. PD DEC PY 2006 VL 33 IS 4 BP XV EP XVI DI 10.1016/j.clp.2006.10.002 PG 2 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 121EI UT WOS:000243140500001 ER PT J AU Raju, TNK AF Raju, Tonse N. K. TI Epidemiology of late preterm (near-term) births SO CLINICS IN PERINATOLOGY LA English DT Article ID LAST MENSTRUAL PERIOD; GESTATIONAL-AGE; UNITED-STATES; RISK-FACTORS; MORTALITY; LABOR; RATES; STILLBIRTH; ULTRASOUND; PREGNANCY AB The preterm birth rate (births before 37 completed weeks of gestation) has been increasing in the United States, largely driven by an increase in infants delivered between 34 and 36 weeks, often called near-term, but referred to as late preterm in this article. In 2004, the preterm birth rate was 12.5%, the highest rate since the National Center for Health Statistics began tracking such data. This article reviews the epidemiology of late preterm births and proposes a research agenda. C1 NICHHD, NIH, Bethesda, MD 20892 USA. RP Raju, TNK (reprint author), NICHHD, NIH, 6100 Execut Blvd,4B03, Bethesda, MD 20892 USA. EM rajut@mail.nih.gov NR 52 TC 69 Z9 74 U1 1 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0095-5108 J9 CLIN PERINATOL JI Clin. Perinatol. PD DEC PY 2006 VL 33 IS 4 BP 751 EP + DI 10.1016/j.clp.2006.09.009 PG 14 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 121EI UT WOS:000243140500002 PM 17148002 ER PT J AU Solomon, J Butman, JA Sood, A AF Solomon, Jeffrey Butman, John A. Sood, Arun TI Segmentation of brain tumors in 4D MR images using the hidden Markov model SO COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE LA English DT Article DE brain tumor; expectation-maximization; hidden Markov model; software ID PRIORS; ATLAS AB Tumor size is an objective measure that is used to evaluate the effectiveness of anticancer agents. Responses to therapy are categorized as complete response, partial response, stable disease and progressive disease. Implicit in this scheme is the change in the tumor over time; however, most tumor segmentation algorithms do not use temporal information. Here we introduce an automated method using probabilistic reasoning over both space and time to segment brain tumors from 4D spatio-temporal MRI data. The 3D expectation-maximization method is extended using the hidden Markov model to infer tumor classification based on previous and subsequent segmentation results. Spatial coherence via a Markov Random Field was included in the 3D spatial model. Simulated images as well as patient images from three independent sources were used to validate this method. The sensitivity and specificity of tumor segmentation using this spatio-temporal model is improved over commonly used spatial or temporal models alone. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 NIH, Dept Radiol, Bethesda, MD 20854 USA. Med Numer Inc, Sterling, VA USA. George Mason Univ, Ctr Image Anal, Fairfax, VA 22030 USA. RP Solomon, J (reprint author), NIH, Dept Radiol, Bldg 10,Room 1C543,10 Ctr Dr, Bethesda, MD 20854 USA. EM jsolomon@cc.nih.gov RI Butman, John/A-2694-2008; OI Butman, John/0000-0002-1547-9195 NR 16 TC 14 Z9 14 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-2607 J9 COMPUT METH PROG BIO JI Comput. Meth. Programs Biomed. PD DEC PY 2006 VL 84 IS 2-3 BP 76 EP 85 DI 10.1016/j.cmpb.2006.09.007 PG 10 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Engineering, Biomedical; Medical Informatics SC Computer Science; Engineering; Medical Informatics GA 111YK UT WOS:000242491600003 PM 17050032 ER PT J AU Meert, KL Eggly, S AF Meert, Kathleen L. Eggly, Susan TI Parents' perspectives on a physician-parent conference after their child's death in the PICU. SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 36th Critical Care Congress of the Society-of-Critical-Care-Medicine CY FEB 18-21, 2007 CL Orlando, FL SP Soc Crit Care Med C1 Wayne State Univ, Detroit, MI USA. NIH, NICHHD, Collaborat Pediat Crit Care Res Network, Dept Hlth & Human Serv, 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 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2006 VL 34 IS 12 SU S SI SI MA 45 BP A12 EP A12 DI 10.1097/00003246-200612002-00045 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 112PZ UT WOS:000242540400046 ER PT J AU Zimmerman, FJ Barker, R Cantini, C AF Zimmerman, Ferry J. Barker, Ruch Cantini, Cheri TI Effect of adjunctive corticosteroids on clinical outcomes in pediatric sepsis syndrome. SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 36th Critical Care Congress of the Society-of-Critical-Care-Medicine CY FEB 18-21, 2007 CL Orlando, FL SP Soc Crit Care Med C1 Seattle Childrens Hosp, Crit Care Med, Seattle, WA USA. Collaborat Pediat Crit Care Res Network, CPCCRN, DHHS NIH, NICHD, Bethesda, 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 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2006 VL 34 IS 12 SU S SI SI MA 461 BP A129 EP A129 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 112PZ UT WOS:000242540400440 ER PT J AU Fulwood, R Guyton-Krishnan, J Wallace, M Sommer, E AF Fulwood, Robinson Guyton-Krishnan, Jeanette Wallace, Madeleine Sommer, Ellen TI Role of community programs in controlling blood pressure SO CURRENT HYPERTENSION REPORTS LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; HEALTH-WORKERS; UNITED-STATES; HYPERTENSION; DISEASE; RISK; CARE AB Despite more than 30 years of intense activity to improve control-and more recently prevention-high blood pressure continues to be a major public health problem. Evidence-based reviews have identified best practices and quality improvement strategies to address prevention and control. Since the 1970s, community-based programs have been instrumental in raising awareness, increasing knowledge, and promoting changes in health behavior to improve blood pressure control. Most of these programs have emphasized the use of partnerships and involvement of community residents in conducting screening and referral activities, implementing clinical practice guidelines, and increasing healthy eating and physical activity. Many also have used health care team approaches, including the use of trained community health workers to deliver targeted, culturally sensitive heart health education, particularly related to the prevention of cardiovascular disease risk factors in general and high blood pressure in particular. Increased focus on implementation of evidence-based lifestyle and clinical management strategies coupled with community-based approaches may help increase blood pressure control rates within communities. C1 NHLBI, Off Prevent Educ & Control, NIH, Bethesda, MD 20892 USA. RP Fulwood, R (reprint author), NHLBI, Off Prevent Educ & Control, NIH, Bldg 31,Room 4A10,31 Ctr Dr,MSC 2480, Bethesda, MD 20892 USA. EM fulwoodr@nhlbi.nih.gov NR 31 TC 7 Z9 7 U1 0 U2 5 PU CURRENT SCIENCE INC PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1522-6417 J9 CURR HYPERTENS REP JI Curr. Hypertens. Rep. PD DEC PY 2006 VL 8 IS 6 BP 512 EP 520 DI 10.1007/s11906-006-0031-x PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 105BI UT WOS:000242003900014 PM 17087861 ER PT J AU Masters, SL Lobito, AA Chae, JJ Kastner, DL AF Masters, Seth L. Lobito, Adrian A. Chae, JaeJin Kastner, Daniel L. TI Recent advances in the molecular pathogenesis of hereditary recurrent fevers SO CURRENT OPINION IN ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Review DE cryopyrin-associated periodic syndromes; familial Mediterranean fever; hereditary recurrent fever syndromes; hyperimmunoglobulinemia D with periodic fever syndrome; tumor necrosis factor receptor associated periodic syndrome ID FAMILIAL MEDITERRANEAN FEVER; ENCODING MEVALONATE KINASE; NF-KAPPA-B; AUTOINFLAMMATORY DISEASES; HYPERIMMUNOGLOBULINEMIA-D; ACTIVATE CASPASE-1; PERIODIC SYNDROME; TNF-RECEPTOR; PYRIN; MUTATIONS AB Purpose of review To discuss recent developments in the molecular basis of several hereditary recurrent fever syndromes, specifically the cryopyrin-associated periodic syndromes, familial Mediterranean fever and the tumor necrosis factor receptor associated periodic syndrome. Recent findings Mutations of CIAS1, the gene encoding cryopyrin/NALP3, lead to a spectrum of disease states termed the cryopyrinopathies. Recently, cryopyrin-deficient mice have been used to show that the protein is a key regulator of interleukin-1 beta production that functions by recognizing stimuli such as bacterial RNA and infectious agents. Tumor necrosis factor receptor-associated periodic syndrome was initially thought to be caused by deficient metalloprotease-induced tumor necrosis factor receptor shedding, however new findings suggest that mutations in this receptor may result in inappropriate protein folding, leading to a host of other functional abnormalities that may cause inflammatory disease. Finally, data are emerging that address the possible function of the C-terminal B30.2 domain of pyrin, the familial Mediterranean fever protein. This motif has recently been shown to interact with and inhibit caspase-1, and the modeled structure of this complex highlights how mutations may affect the binding interface. Summary Recent reports have advanced our understanding of the structural and functional biology underlying the hereditary recurrent fevers, and are beginning to suggest possible mechanisms by which specific mutations cause disease. C1 NIAMSD, NIH, Bethesda, MD 20892 USA. RP Masters, SL (reprint author), NIAMSD, NIH, Rm 9N210 Bldg 10,9000 Rockville Pike, Bethesda, MD 20892 USA. EM masterss@mail.nih.gov RI Masters, Seth/N-2886-2013 OI Masters, Seth/0000-0003-4763-576X NR 35 TC 41 Z9 44 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1528-4050 J9 CURR OPIN ALLERGY CL JI Curr. Opin. Allergy Clin. Immunol. PD DEC PY 2006 VL 6 IS 6 BP 428 EP 433 DI 10.1097/ACI.0b013e3280109b57 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA 115XQ UT WOS:000242767500005 PM 17088647 ER PT J AU Antignani, A Youle, RJ AF Antignani, Antonella Youle, Richard J. TI How do Bax and Bak lead to permeabilization of the outer mitochondrial membrane? SO CURRENT OPINION IN CELL BIOLOGY LA English DT Article ID PHOSPHOLIPID-BILAYER MEMBRANES; CHANNEL-FORMING ACTIVITY; BCL-2 FAMILY PROTEINS; CYTOCHROME-C RELEASE; TOXIN T-DOMAIN; DIPHTHERIA-TOXIN; ION-CHANNEL; CELL-DEATH; ANTIAPOPTOTIC BCL-2; DROSOPHILA CELLS AB Bcl-2 family members, like the structurally similar translocation domain of diphtheria toxin, can form ion-selective channels and larger-diameter pores in artificial lipid bilayers. Recent studies show how Bcl-2 family members change topology in membranes during apoptosis and that these different states may either promote or inhibit apoptosis. Binding of BH3-only proteins alters the subcellular localization and/or membrane topology and probably affects the channel formation of Bcl-2, Bcl-xL and Bcl-w. However, it remains unclear how the pore-forming activity functions in cells to regulate mitochondrial membrane permeabilization and cell death. Bcl-2 family members in flies and worms regulate apoptosis by mechanisms seemingly unrelated to membrane permeabilization, leaving a unifying model for the biochemical activity of this protein family unknown. Work linking Bcl-2 family members to mitochondrial morphogenesis in worms and mammals suggests some common functions of Bcl-2 family proteins may exist. C1 NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Youle, RJ (reprint author), NINDS, Biochem Sect, Surg Neurol Branch, NIH, 35 Convent Dr MSC 3704, Bethesda, MD 20892 USA. EM ry2i@nih.gov FU Intramural NIH HHS NR 58 TC 184 Z9 194 U1 2 U2 10 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD DEC PY 2006 VL 18 IS 6 BP 685 EP 689 DI 10.1016/j.ceb.2006.10.004 PG 5 WC Cell Biology SC Cell Biology GA 110TE UT WOS:000242402500013 PM 17046225 ER PT J AU Chew, EY AF Chew, Emily Y. TI Screening options for diabetic retinopathy SO CURRENT OPINION IN OPHTHALMOLOGY LA English DT Article DE macular edema; nonmydriatic camera; proliferative retinopathy ID EYE DISEASE; DIRECT OPHTHALMOSCOPY; PHOTOGRAPHY; PHOTOCOAGULATION; CARE; SPECIFICITY; SENSITIVITY; PATTERNS; PROGRAM AB Purpose of review This review assesses the current status of the different methods used in screening for diabetic retinopathy. This update is particularly timely because the incidence of diabetes is rising rapidly and the number of patients with vison threatening diabetic retinopathy is increasing. Recent findings We evaluate the different methods used and their results in improving the delivery of eye care to patients with diabetic retinopathy in populations with poor access to ophthalmic care, screening techniques such as the nonmydriatic camera used in offices of primary care physicians may be useful in identifying lesions of diabetic retinopathy requiring treatment. One of the limitations is the lack of dilation and cataract formation,which may result in ungradable photographs. Patients with treatable lesions as well as those with ungradable photographs should be referred for comprehensive ocular examination. Summary Screening techniques do not replace the eye examination. Ophthalmologists can play an important role in diabetic care apart from treating eye disease. Counseling can be provided to patients regarding the importance of blood glucose and blood pressure control and may motivate patients to achieve strict glucose and blood pressure control. C1 NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA. RP Chew, EY (reprint author), NEI, Div Epidemiol & Clin Res, NIH, Bldg 10,CRC,Room 3-2531,10 Ctr Dr,MSC 1204, Bethesda, MD 20892 USA. EM echew@nei.nih.gov FU Intramural NIH HHS [Z99 EY999999] NR 26 TC 9 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8738 EI 1531-7021 J9 CURR OPIN OPHTHALMOL JI Curr. Opin. Ophthalmol. PD DEC PY 2006 VL 17 IS 6 BP 519 EP 522 DI 10.1097/ICU.0b013e328010948d PG 4 WC Ophthalmology SC Ophthalmology GA 106HL UT WOS:000242091500006 PM 17065919 ER PT J AU Kakuk, A Friedlander, E Vereb, G Kasa, A Balla, A Balla, T Heilmeyer, LMG Gergely, P Vereb, G AF Kakuk, Annamaria Friedlander, Elza Vereb, Gyorgy, Jr. Kasa, Anita Balla, Andras Balla, Tamas Heilmeyer, Ludwig M. G., Jr. Gergely, Pal Vereb, Gyorgy TI Nucleolar localization of phosphatidylinositol 4-kinase PI4K230 in various mammalian cells SO CYTOMETRY PART A LA English DT Article DE phosphatidylinositol 4-kinase isoforms; PI4K230; nucleolus; epitope masking; immunofluorescence; rat brain; cell lines HCN; B50; COS-7 ID RAT-LIVER NUCLEI; PHOSPHOINOSITIDE KINASES; SIGNAL-TRANSDUCTION; LIPIDS; PROTEIN; METABOLISM; EXPRESSION; ISOFORMS; 3-KINASE; DOMAINS AB Background: Previous immunohistochemical investigations could not detect PI4K230, an isoform of mammalian phosphatidylinositol 4-kinases (also called type III alpha), in the nucleus and nucleolus of cells in spite of its predicted nuclear localization signals. Methods: Immunofluorescent detection of PI4K230 and other PI4K isoforms was performed on formaldehyde (PFA) or ethanol fixed cells and rat brain cryosections. Costaining with nucleolin and the effect of siRNA, Triton X-100, DNase, and RNase treatments were also tested to determine the localization of PI4K230. Results: PI4K230 gives a prominent signal in the nucleolus of ethanol fixed rat brain cryosections and of several cell types in addition to its presence in the nucleus and cytoplasm. The PI4K230 immunoreactivity of the nucleolus is masked in PFA fixed cells, but it can be restored by treatment of PFA fixed cells with hot wet citrate buffer or by washing the cryosections with PBS prior to PFA fixation. Nucleolar PI4K230 occurs in a Triton X-100 resistant complex. Treatment of COS-7 cells with siRNA targeting PI4K230 and permeabilized B50 cells with DNase or RNase results in the loss of PI4K230 signal from the nucleolus. Conclusion: These experiments suggest the participation of PI4K230 in a DNase and RNase sensitive complex with a unique localization and function in the nucleolus. (c) 2006 International Society for Analytical Cytology C1 Univ Debrecen, Med & Hlth Sci Ctr, Dept Med Chem, H-4032 Debrecen, Hungary. Univ Debrecen, Med & Hlth Sci Ctr, Dept Biophys & Cell Biol, H-4032 Debrecen, Hungary. NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. Ruhr Univ Bochum, Inst Physiol Chem, Abt Biochem Supramol Syst, Bochum, Germany. RP Vereb, G (reprint author), Univ Debrecen, Med & Hlth Sci Ctr, Dept Med Chem, Life Sci Bldg,Nagyerdei Krt 98, H-4032 Debrecen, Hungary. EM vgyorgy@jaguar.unideb.hu RI Vereb, Gyorgy/A-4241-2008; Gergely, Pal/A-5547-2008; OI Vereb, Gyorgy/0000-0003-2157-3265; Balla, Tamas/0000-0002-9077-3335; Balla, Andras/0000-0002-6450-2793 NR 42 TC 13 Z9 13 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4922 EI 1552-4930 J9 CYTOM PART A JI Cytom. Part A PD DEC 1 PY 2006 VL 69A IS 12 BP 1174 EP 1183 DI 10.1002/cyto.a.20347 PG 10 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 117KI UT WOS:000242871600003 PM 17131383 ER PT J AU Yoon, BS Pogue, R Ovchinnikov, DA Yoshii, I Mishina, Y Behringer, RR Lyons, KM AF Yoon, Byeong S. Pogue, Robert Ovchinnikov, Dmitri A. Yoshii, Isaac Mishina, Yuji Behringer, Richard R. Lyons, Karen M. TI BMPs regulate multiple aspects of growth-plate chondrogenesis through opposing actions on FGF pathways SO DEVELOPMENT LA English DT Article DE bone morphogenetic protein; cartilage; chondrogenesis; fibroblast growth factor; indian hedgehog; BMP receptors; mouse ID BONE MORPHOGENETIC PROTEIN; INDIAN-HEDGEHOG; CHONDROCYTE PROLIFERATION; ENDOCHONDRAL SKELETON; FACTOR-BETA; CONSTITUTIVE ACTIVATION; CARTILAGE DEVELOPMENT; TRANSGENIC MICE; MOUSE LIMB; I RECEPTOR AB Bone morphogenetic protein (BMP) signaling pathways are essential regulators of chondrogenesis. However, the roles of these pathways in vivo are not well understood. Limb-culture studies have provided a number of essential insights, including the demonstration that BMP pathways are required for chondrocyte proliferation and differentiation. However, limb-culture studies have yielded contradictory results; some studies indicate that BMPs exert stimulatory effects on differentiation, whereas others support inhibitory effects. Therefore, we characterized the skeletal phenotypes of mice lacking Bmpr1a in chondrocytes (Bmpr1a(CKO)) and Bmpr1a(CKO); Bmpr1b(+/-) (Bmpr1a(CKO); 1b(+/-)) in order to test the roles of BMP pathways in the growth plate in vivo. These mice reveal requirements for BMP signaling in multiple aspects of chondrogenesis. They also demonstrate that the balance between signaling outputs from BMP and fibroblast growth factor (FGF) pathways plays a crucial role in the growth plate. These studies indicate that BMP signaling is required to promote Ihh expression, and to inhibit activation of STAT and ERK1/2 MAPK, key effectors of FGF signaling. BMP pathways inhibit FGF signaling, at least in part, by inhibiting the expression of FGFR1. These results provide a genetic in vivo demonstration that the progression of chondrocytes through the growth plate is controlled by antagonistic BMP and FGF signaling pathways. C1 Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Orthopaed Surg, Los Angeles, CA 90095 USA. Univ Texas, MD Anderson Canc Ctr, Dept Mol Genet, Houston, TX 77030 USA. Natl Inst Environm Hlth Sci, Lab Reprod & Dev Toxicol, Res Triangle Pk, NC 27709 USA. RP Lyons, KM (reprint author), Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA. EM klyons@mednet.ucla.edu RI Lyons, Karen/P-1843-2014; Pogue, Robert/C-3860-2016; Ovchinnikov, Dmitry/J-7963-2014 OI Lyons, Karen/0000-0001-9420-5813; Pogue, Robert/0000-0002-8789-3512; Ovchinnikov, Dmitry/0000-0001-9603-8385 FU NIAMS NIH HHS [R01 AR044528] NR 75 TC 103 Z9 106 U1 1 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD DEC 1 PY 2006 VL 133 IS 23 BP 4667 EP 4678 DI 10.1242/dev.02680 PG 12 WC Developmental Biology SC Developmental Biology GA 103BA UT WOS:000241857600007 PM 17065231 ER PT J AU Ronsaville, DS Municchi, G Laney, C Cizza, G Meyer, SE Haim, A Radke-Yarrow, M Chrousos, G Gold, PW Martinez, PE AF Ronsaville, DS Municchi, G Laney, C Cizza, G Meyer, SE Haim, A Radke-Yarrow, M Chrousos, G Gold, PW Martinez, PE TI Maternal and environmental factors influence the hypothalamic-pituitary-adrenal axis response to corticotropin-releasing hormone infusion in offspring of mothers with or without mood disorders SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Article ID CEREBROSPINAL-FLUID CONCENTRATIONS; AVOIDANT PERSONALITY-DISORDER; SALIVARY CORTISOL-LEVELS; MAJOR DEPRESSION; STIMULATION TEST; PUBERTAL DEVELOPMENT; ATYPICAL DEPRESSION; REPEATED RESTRAINT; STRESS REACTIVITY; NONHUMAN-PRIMATES AB Individuals with melancholic major depression exhibit basal hypercortisolism and an attenuated ACTH response to exogenous corticotropin-releasing hormone (CRH) infusion. Given the greater incidence of depression in children of depressed parents, we examined the ACTH and cortisol responses to ovine CRH (oCRH) infusion in 63 adolescent offspring of mothers with major depression, bipolar illness, or no Psychiatric illness. Psychiatric and observational assessments of these families had been conducted over the course of 10 years preceding this Study. We examined the children's responses to CRH in relation to maternal characteristics and family environment and found the following: (a) cortisol responses were negatively related to chronic family stress and (b) offspring of depressed mothers with an avoidant personality disorder showed an exaggerated ACTH response. In addition, adolescents in late puberty (Tanner 4 and 5) had lower ACTH and cortisol responses to oCRH infusion than those in early puberty. Further, offspring with early histories of mood problems, and those who developed major depressive disorder as young adults, did not exhibit basal hypercortisolism but did show an attenuated ACTH response to CRH. Our results add to the growing body of literature showing the influence of maternal characteristics and environmental factors on hypothalamic-pituitary-adrenal axis patterns in children. C1 NIMH, Behav Endocrinol Branch, Bethesda, MD 20892 USA. NICHD, Bethesda, MD 20892 USA. NIDDK, Bethesda, MD 20892 USA. RP Martinez, PE (reprint author), NIMH, Behav Endocrinol Branch, Bldg 10,Room 3N242,10 Ctr Dr,MSC 1277, Bethesda, MD 20892 USA. EM martinep@mail.nih.gov NR 100 TC 27 Z9 27 U1 1 U2 7 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0954-5794 EI 1469-2198 J9 DEV PSYCHOPATHOL JI Dev. Psychopathol. PD WIN PY 2006 VL 18 IS 1 BP 173 EP 194 DI 10.1017/S095457940606010X PG 22 WC Psychology, Developmental SC Psychology GA 019ZA UT WOS:000235876100010 PM 16478558 ER PT J AU Lapraz, F Rottinger, E Duboc, V Range, R Duloquin, L Walton, K Wu, SY Bradham, C Loza, MA Hibino, T Wilson, K Poustka, A McClay, D Angerer, L Gache, C Lepage, T AF Lapraz, Francois Rottinger, Eric Duboc, Veronique Range, Ryan Duloquin, Louise Walton, Katherine Wu, Shu-Yu Bradham, Cynthia Loza, Mariano A. Hibino, Taku Wilson, Karen Poustka, Albert McClay, Dave Angerer, Lynne Gache, Christian Lepage, Thierry TI RTK and TGF-beta signaling pathways genes in the sea urchin genome SO DEVELOPMENTAL BIOLOGY LA English DT Review DE receptor tyrosine kinase; signaling; TGF-beta; sea urchin; genome; deuterostome; FGFR; nodal; TGF-beta receptors; Smad ID GROWTH-FACTOR-BETA; DEVELOPMENTALLY RELEVANT GENES; RECEPTOR TYROSINE KINASES; SMAD PROTEINS; SPEMANNS ORGANIZER; XENOPUS-EMBRYOS; TRANSCRIPTIONAL COACTIVATOR; FUNCTIONAL COOPERATION; DROSOPHILA DEVELOPMENT; MORPHOGENETIC PROTEIN AB The Receptor Tyrosine kinase (RTK) and TGF-beta signaling pathways play essential roles during development in many organisms and regulate a plethora of cellular responses. From the genome sequence of Strongylocentrotus purpuratus, we have made an inventory of the genes encoding receptor tyrosine kinases and their ligands, and of the genes encoding cytokines of the TGF-beta superfamily and their downstream components. The sea urchin genome contains at least 20 genes coding for canonical receptor tyrosine kinases. Seventeen of the nineteen vertebrate RTK families are represented in the sea urchin. Fourteen of these RTK among which ALK, CCK4/PTK7, DDR, EGFR, EPH, LMR, MET/RON, MUSK, RET, ROR, ROS, RYK, TIE and TRK are present as single copy genes while pairs of related genes are present for VEGFR, FGFR and INSR. Similarly, nearly all the subfamilies of TGF-beta ligands identified in vertebrates are present in the sea urchin genome including the BMP, ADMP, GDF, Activin, Myostatin, Nodal and Lefty, as well as the TGF-beta sensu stricto that had not been characterized in invertebrates so far. Expression analysis indicates that the early expression of nodal, BMP2/4 and lefty is restricted to the oral ectoderm reflecting their role in providing positional information along the oral-aboral axis of the embryo. The coincidence between the emergence of TGF-beta-related factors such as Nodal and Lefty and the emergence of the deuterostome lineage strongly suggests that the ancestral function of Nodal could have been related to the secondary opening of the mouth which characterizes this clade, a hypothesis supported by functional data in the extant species. The sea urchin genome contains 6 genes encoding TGF-beta receptors and 4 genes encoding prototypical Smad proteins. Furthermore, most of the transcriptional activators and repressors shown to interact with Smads in vertebrates have orthologues in echinoderms. Finally, the sea urchin genome contains an almost complete repertoire of genes encoding extracellular modulators of BMP signaling including Chordin, Noggin, Sclerotin, SFRP, Gremlin, DAN and Twisted gastrulation. Taken together, these findings indicate that the sea urchin complement of genes of the RTK and TGF-beta signaling pathways is qualitatively very similar to the repertoire present in vertebrates, and that these genes are part of the common genetool kit for intercellular signaling of deuterostomes. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Paris 06, CNRS, UMR 7009, Observ Oceanol, F-06230 Villefranche Sur Mer, France. Duke Univ, Dev Mol & Cellular Biol Grp, Durham, NC USA. Univ Toronto, Dept Phys Med, Toronto, ON M4N 3M5, Canada. Sunnybrook & Womens Res Inst, Toronto, ON M4N 3M5, Canada. Kristineberg Marine Res Stn, S-45034 Fiskebackskil, Sweden. Max Planck Inst Mol Genet, Evolut & Dev Grp, D-14195 Berlin, Germany. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. RP Lepage, T (reprint author), Univ Paris 06, CNRS, UMR 7009, Observ Oceanol, F-06230 Villefranche Sur Mer, France. EM lepage@obs-vlfr.fr RI 拓, 日比野/D-8115-2013; OI Lapraz, Francois/0000-0001-9209-2018; Walton, Katherine/0000-0001-9108-5617; Rottinger, Eric/0000-0002-2938-6774 NR 113 TC 83 Z9 86 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 0012-1606 EI 1095-564X J9 DEV BIOL JI Dev. Biol. PD DEC 1 PY 2006 VL 300 IS 1 BP 132 EP 152 DI 10.1016/j.ydbio.2006.08.048 PG 21 WC Developmental Biology SC Developmental Biology GA 117KZ UT WOS:000242873300013 PM 17084834 ER PT J AU Angerer, L Hussain, S Wei, Z Livingston, BT AF Angerer, Lynne Hussain, Sofia Wei, Zheng Livingston, Brian T. TI Sea urchin metalloproteases: A genomic survey of the BMP-1/tolloid-like, MMP and ADAM families SO DEVELOPMENTAL BIOLOGY LA English DT Article DE annotation; microarray; evolution; gene expression; embryo ID ANIMAL-VEGETAL AXIS; BONE MORPHOGENETIC PROTEIN-1; HATCHING ENZYME GENE; BETA-CATENIN; MATRIX METALLOPROTEINASES; EXTRACELLULAR-MATRIX; MONOCLONAL-ANTIBODY; TISSUE INHIBITORS; ASTACIN FAMILY; GROWTH-FACTOR AB Analysis of the Strongylocentrotus purpuratus genome has revealed approximately 240 metalloprotease genes, and they represent all 23 families expressed in vertebrates. EST/cDNA sequencing and microarray analysis show that nearly 70% are represented in embryo RNA. Among them are many metalloproteases with demonstrated developmental roles in other system s-BMP-1/TLD (tolloid) (astacins), MMPs (matrix metalloproteases) and the ADAMs (disintegrin/metalloproteases). The developmental functions of these kinds of metalloproteases include modifying the extracellular matrix, regulating signaling pathways or modulating cellular adhesive properties. The unexpectedly large number of BMP-1/TLD-like protease genes (23) results primarily from expansion of a set encoding an unusual domain conserved in structure and primary sequence only in nematode astacins. Such proteases may have interesting developmental functions because the expression patterns of several are highly regulated along the primary axis at times when cell differentiation and morphogenesis begin. The size of the sea urchin MMP family and the clustered arrangement of many of its members are similar to vertebrates, but phylogenetic analyses suggest that different ancestral genes were independently amplified in sea urchins and vertebrates. One expansion appears to be genes encoding MMPs that have putative transmembrane domains and may be membrane-tethered (MT). Interestingly, the genes encoding TIMPs, inhibitors of MMPs, have also been amplified and the 10 genes are tandemly arranged in a single cluster. In contrast, there are fewer ADAM and ADAMTS genes in sea urchins, but they represent all but one of the chordate-specific groups. The genome sequence now opens the door to experimental manipulations designed to understand how modulation of the extracellular environment affects development. (c) 2006 Elsevier Inc. All rights reserved. C1 Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20815 USA. Univ S Florida, Dept Biol, Tampa, FL 33620 USA. RP Angerer, L (reprint author), Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20815 USA. EM langerer@mail.nih.gov FU Intramural NIH HHS NR 48 TC 30 Z9 32 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD DEC 1 PY 2006 VL 300 IS 1 BP 267 EP 281 DI 10.1016/j.ydbio.2006.07.046 PG 15 WC Developmental Biology SC Developmental Biology GA 117KZ UT WOS:000242873300021 PM 17059814 ER PT J AU Livingston, BT Killian, CE Wilt, F Cameron, A Landrum, MJ Ermolaeva, O Sapojnikov, V Maglott, DR Buchanan, AM Ettensohn, CA AF Livingston, B. T. Killian, C. E. Wilt, F. Cameron, A. Landrum, M. J. Ermolaeva, O. Sapojnikov, V. Maglott, D. R. Buchanan, A. M. Ettensohn, C. A. TI A genorne-wide analysis of biomineralization-related proteins in the sea urchin Strongylocentrotus purpuratus SO DEVELOPMENTAL BIOLOGY LA English DT Article DE biomineralization; genome; echinoderm ID SPICULE MATRIX PROTEIN; CARBONIC-ANHYDRASE ACTIVITY; PRIMARY MESENCHYME CELLS; SKELETON FORMATION; POSTTRANSLATIONAL MODIFICATIONS; DEVELOPMENTAL EXPRESSION; SIBLING PROTEINS; EARLY EVOLUTION; EMBRYO SPICULE; GENETIC-BASIS AB Biomineralization, the biologically controlled formation of mineral deposits, is of widespread importance in biology, medicine, and engineering. Mineralized structures are found in most metazoan phyla and often have supportive, protective, or feeding functions. Among deuterostomes, only echinoderms and vertebrates produce extensive biomineralized structures. Although skeletons appeared independently in these two groups, ancestors of the vertebrates and echinoderms may have utilized similar components of a shared genetic "toolkit" to carry out biomineralization. The present study had two goals. First, we sought to expand our understanding of the proteins involved in biomineralization in the sea urchin, a powerful model system for analyzing the basic cellular and molecular mechanisms that underlie this process. Second, we sought to shed light on the possible evolutionary relationships between biomineralization in echinoderms and vertebrates. We used several computational methods to survey the genome of the purple sea urchin Strongylocentrotus purpuratus for gene products involved in biomineralization. Our analysis has greatly expanded the collection of biomineralization-related proteins. We have found that these proteins are often members of small families encoded by genes that are clustered in the genome. Most of the proteins are sea urchin-specific; that is, they have no apparent homologues in other invertebrate deuterostomes or vertebrates. Similarly, many of the vertebrate proteins that mediate mineral deposition do not have counterparts in the S. purpuratus genome. Our findings therefore reveal substantial differences in the primary sequences of proteins that mediate biomineral formation in echinoderms and vertebrates, possibly reflecting loose constraints on the primary structures of the proteins involved. On the other hand, certain cellular and molecular processes associated with earlier events in skeletogenesis appear similar in echinoderms and vertebrates, leaving open the possibility of deeper evolutionary relationships. (c) 2006 Elsevier Inc. All rights reserved. C1 Carnegie Mellon Univ, Dept Biol Sci, Pittsburgh, PA 15213 USA. Univ S Florida, Dept Biol, Tampa, FL 33620 USA. Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. CALTECH, Div Biol, Pasadena, CA 91125 USA. NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. RP Ettensohn, CA (reprint author), Carnegie Mellon Univ, Dept Biol Sci, 4400 5th Ave, Pittsburgh, PA 15213 USA. EM ettensohn@andrew.cmu.edu FU NCRR NIH HHS [RR15044] NR 87 TC 120 Z9 122 U1 1 U2 15 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD DEC 1 PY 2006 VL 300 IS 1 BP 335 EP 348 DI 10.1016/j.ydbio.2006.07.047 PG 14 WC Developmental Biology SC Developmental Biology GA 117KZ UT WOS:000242873300026 PM 16987510 ER PT J AU Hibino, T Loza-Coll, M Messier, C Majeske, AJ Cohen, AH Terwilliger, DP Buckley, KM Brockton, V Nair, SV Berney, K Fugmann, SD Anderson, MK Pancer, Z Cameron, RA Smith, LC Rast, JP AF Hibino, Taku Loza-Coll, Mariano Messier, Cynthia Majeske, Audrey J. Cohen, Avis H. Terwilliger, David P. Buckley, Katherine M. Brockton, Virginia Nair, Sham V. Berney, Kevin Fugmann, Sebastian D. Anderson, Michele K. Pancer, Zeev Cameron, R. Andrew Smith, L. Courtney Rast, Jonathan P. TI The immune gene repertoire encoded in the purple sea urchin genome SO DEVELOPMENTAL BIOLOGY LA English DT Review DE hematopoiesis; developmental immunology; innate immunity; TLR; RAG; NOD; echinoderm; scavenger receptor; complement; cytokine ID TOLL-LIKE RECEPTORS; VARIABLE LYMPHOCYTE RECEPTORS; MIGRATION INHIBITORY FACTOR; COMPLEMENT FACTOR-B; INNATE IMMUNITY; PATHOGEN RECOGNITION; STRONGYLOCENTROTUS-PURPURATUS; SOMATIC DIVERSIFICATION; CAENORHABDITIS-ELEGANS; BACTERIAL-INFECTION AB Echinoderms occupy a critical and largely unexplored phylogenetic vantage point from which to infer both the early evolution of bilaterian immunity and the underpinnings of the vertebrate adaptive immune system. Here we present an initial survey of the purple sea urchin genome for genes associated with immunity. An elaborate repertoire of potential immune receptors, regulators and effectors is present, including unprecedented expansions of innate pathogen recognition genes. These include a diverse array of 222 Toll-like receptor (TLR) genes and a coordinate expansion of directly associated signaling adaptors. Notably, a subset of sea urchin TLR genes encodes receptors with structural characteristics previously identified only in protostomes. A similarly expanded set of 203 NOD/NALP-like cytoplasmic recognition proteins is present. These genes have previously been identified only in vertebrates where they are represented in much lower numbers. Genes that mediate the alternative and lectin complement pathways are described, while gene homologues of the terminal pathway are not present. We have also identified several homologues of genes that function in jawed vertebrate adaptive immunity. The most striking of these is a gene cluster with similarity to the jawed vertebrate Recombination Activating Genes 1 and 2 (RAG1/2). Sea urchins are long-lived, complex organisms and these findings reveal an innate immune system of unprecedented complexity. Whether the presumably intense selective processes that molded these gene families also gave rise to novel immune mechanisms akin to adaptive systems remains to be seen. The genome sequence provides immediate opportunities to apply the advantages of the sea urchin model toward problems in developmental and evolutionary immunobiology. (c) 2006 Elsevier Inc. All rights reserved. C1 George Washington Univ, Dept Biol Sci, Washington, DC 20052 USA. Univ Toronto, Sunnybrook Res Inst, Toronto, ON M4N 3M5, Canada. Univ Toronto, Dept Med Biophys, Toronto, ON M4N 3M5, Canada. Univ Maryland, Dept Biol, College Pk, MD 20742 USA. Univ Maryland, Inst Syst Res, College Pk, MD 20742 USA. Macquarie Univ, Dept Biol Sci, Sydney, NSW 2109, Australia. CALTECH, Div Biol, Pasadena, CA 91125 USA. NIA, Cellular & Mol Biol Lab, Baltimore, MD 21224 USA. Univ Toronto, Dept Immunol, Toronto, ON M4N 3M5, Canada. UMBI, Ctr Marine Biotechnol, Columbus Ctr, Baltimore, MD 21202 USA. RP Smith, LC (reprint author), George Washington Univ, Dept Biol Sci, 340 Lisner Hall,2023 G St NW, Washington, DC 20052 USA. EM csmith@gwu.edu; jrast@sri.utoronto.ca RI 拓, 日比野/D-8115-2013; OI Buckley, Katherine/0000-0002-6585-8943; Anderson, Michele/0000-0002-8820-5910; Cameron, R. Andrew/0000-0003-3947-6041 FU Intramural NIH HHS NR 109 TC 292 Z9 305 U1 9 U2 51 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 EI 1095-564X J9 DEV BIOL JI Dev. Biol. PD DEC 1 PY 2006 VL 300 IS 1 BP 349 EP 365 DI 10.1016/j.ydbio.2006.08.065 PG 17 WC Developmental Biology SC Developmental Biology GA 117KZ UT WOS:000242873300027 PM 17027739 ER PT J AU Goldstone, JV Hamdoun, A Cole, BJ Howard-Ashby, M Nebert, DW Scally, M Dean, M Epel, D Hahn, ME Stegeman, JJ AF Goldstone, J. V. Hamdoun, A. Cole, B. J. Howard-Ashby, M. Nebert, D. W. Scally, M. Dean, M. Epel, D. Hahn, M. E. Stegeman, J. J. TI The chemical defensome: Environmental sensing and response genes in the Strongylocentrotus purpuratus genome SO DEVELOPMENTAL BIOLOGY LA English DT Review DE defense; toxicity; P450; nuclear receptor; MRP; PGP; AHR; coregulation; oxidative stress; detoxification ID ARYL-HYDROCARBON RECEPTOR; SEA-URCHIN EMBRYOS; OXIDATIVE-STRESS-RESPONSE; MULTIPLE SEQUENCE ALIGNMENT; ABC TRANSPORTER SUPERFAMILY; HEAT-SHOCK PROTEINS; PREGNANE-X-RECEPTOR; CAENORHABDITIS-ELEGANS; MULTIDRUG-RESISTANCE; TRANSCRIPTION FACTOR AB Metazoan genomes contain large numbers of genes that participate in responses to environmental stressors. We surveyed the sea urchin Strongylocentrotus purpuratus genome for homologs of gene families thought to protect against chemical stressors; these genes collectively comprise the 'chemical defensome.' Chemical defense genes include cytochromes P450 and other oxidases, various conjugating enzymes, ATP-dependent efflux transporters, oxidative detoxification proteins, and transcription factors that regulate these genes. Together such genes account for more than 400 genes in the sea urchin genome. The transcription factors include homologs of the aryl hydrocarbon receptor, hypoxia-inducible factor, nuclear factor erythroid-derived 2, heat shock factor, and nuclear hormone receptors, which regulate stress-response genes in vertebrates. Some defense gene families, including the ABCC, the UGT, and the CYP families, have undergone expansion in the urchin relative to other deuterostome genomes, whereas the stress sensor gene families do not show such expansion. More than half of the defense genes are expressed during embryonic or larval life stages, indicating their importance during development. This genome-wide survey of chemical defense genes in the sea urchin reveals evolutionary conservation of this network combined with lineage-specific diversification that together suggest the importance of these chemical stress sensing and response mechanisms in early deuterostomes. These results should facilitate future studies on the evolution of chemical defense gene networks and the role of these networks in protecting embryos from chemical stress during development. (c) 2006 Elsevier Inc. All rights reserved. C1 Woods Hole Oceanog Inst, Dept Biol, Woods Hole, MA 02543 USA. Stanford Univ, Hopkins Marine Stn, Pacific Grove, CA 93950 USA. CALTECH, Dept Biol, Pasadena, CA 91125 USA. Univ Cincinnati, Med Ctr, Dept Environm Hlth, Cincinnati, OH 45267 USA. NCI, Human Genet Sect, Lab Genom Divers, Frederick, MD 21702 USA. RP Goldstone, JV (reprint author), Woods Hole Oceanog Inst, Dept Biol, Redfield 3-52,MS 32, Woods Hole, MA 02543 USA. EM jgoldstone@whoi.edu; hamdoun@stanford.edu OI Goldstone, Jared/0000-0002-9618-4961; Dean, Michael/0000-0003-2234-0631; Hahn, Mark/0000-0003-4358-2082 FU Intramural NIH HHS; NICHD NIH HHS [F32 HD047136-02, F32 HD047136, F32 HD047136-03, F32-HD47136]; NIEHS NIH HHS [2-P42-ES07381, F32 ES012794, F32-ES012794, P30 ES006096, P30-ES06096, P42 ES007381, R01 ES006272, R01 ES006272-13, R01ES006272] NR 168 TC 115 Z9 119 U1 2 U2 24 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 EI 1095-564X J9 DEV BIOL JI Dev. Biol. PD DEC 1 PY 2006 VL 300 IS 1 BP 366 EP 384 DI 10.1016/j.ydbio.2006.08.066 PG 19 WC Developmental Biology SC Developmental Biology GA 117KZ UT WOS:000242873300028 PM 17097629 ER PT J AU Burke, RD Angerer, LM Elphick, MR Humphrey, GW Yaguchi, S Kiyama, T Liang, S Mu, X Agca, C Klein, WH Brandhorst, BP Rowe, M Wilson, K Churcher, AM Taylor, JS Chen, N Murray, G Wang, D Mellott, D Olinski, R Hallbook, F Thorndyke, MC AF Burke, R. D. Angerer, L. M. Elphick, M. R. Humphrey, G. W. Yaguchi, S. Kiyama, T. Liang, S. Mu, X. Agca, C. Klein, W. H. Brandhorst, B. P. Rowe, M. Wilson, K. Churcher, A. M. Taylor, J. S. Chen, N. Murray, G. Wang, D. Mellott, D. Olinski, R. Hallbook, F. Thorndyke, M. C. TI A genomic view of the sea urchin nervous system SO DEVELOPMENTAL BIOLOGY LA English DT Review DE genomics; neurobiology; neural development; deurerostome; evolution; echnioderm ID RETINAL GANGLION-CELL; VERTEBRATE EYE DEVELOPMENT; SYNAPTIC VESICLE CYCLE; STRONGYLOCENTROTUS-PURPURATUS; TRANSCRIPTION FACTOR; CIONA-INTESTINALIS; HOMEOBOX GENE; EVOLUTIONARY ORIGIN; PLUTEUS LARVA; NEURAL CREST AB The sequencing of the Strongylocentrotus purpuratus genome provides a unique opportunity to investigate the function and evolution of neural genes. The neurobiology of sea urchins is of particular interest because they have a close phylogenetic relationship with chordates, yet a distinctive pentaradiate body plan and unusual neural organization. Orthologues of transcription factors that regulate neurogenesis in other animals have been identified and several are expressed in neurogenic domains before gastrulation indicating that they may operate near the top of a conserved neural gene regulatory network. A family of genes encoding voltage-gated ion channels is present but, surprisingly, genes encoding gap junction proteins (connexins and pannexins) appear to be absent. Genes required for synapse formation and function have been identified and genes for synthesis and transport of neurotransmitters are present. There is a large family of G-protein-coupled receptors, including 874 rhodopsin-type receptors, 28 metabotropic glutamate-like receptors and a remarkably expanded group of 161 secretin receptor-like proteins. Absence of cannabinoid, lysophospholipid and melanocortin receptors indicates that this group may be unique to chordates. There are at least 37 putative G-protein-coupled peptide receptors and precursors for several neuropeptides and peptide hormones have been identified, including SALMFamides, NGFFFamide, a vasotocin-like peptide, glycoprotein hormones and insulin/insulin-like growth factors. Identification of a neurotrophin-like gene and Trk receptor in sea urchin indicates that this neural signaling system is not unique to chordates. Several hundred chemoreceptor genes have been predicted using several approaches, a number similar to that for other animals. Intriguingly, genes encoding homologues of rhodopsin, Pax6 and several other key mammalian retinal transcription factors are expressed in tube feet, suggesting tube feet function as photosensory organs. Analysis of the sea urchin genome presents a unique perspective on the evolutionary history of deuterostome nervous systems and reveals new approaches to investigate the development and neurobiology of sea urchins. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Victoria, Dept Biol, Dept Biochem Microbiol, Victoria, BC V8W 3N5, Canada. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. Queen Mary Univ London, Sch Biol & Chem Sci, London, England. NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Louisiana State Univ, Dept Cell Biol & Anat, Hlth Sci Ctr, New Orleans, LA USA. Univ Victoria, Dept Biol, Victoria, BC V8W 2Y2, Canada. Simon Fraser Univ, Dept Mol Biol & Biochem, Burnaby, BC V5A 1S6, Canada. Uppsala Univ, Dept Neurosci, Uppsala, Sweden. Royal Swedish Acad Sci, Fiskebackskil Marine Res Stn, S-45034 Fiskebackskil, Sweden. RP Burke, RD (reprint author), Univ Victoria, Dept Biol, Dept Biochem Microbiol, POB 3020,STN CSC, Victoria, BC V8W 3N5, Canada. EM rburke@uvic.ca RI Brandhorst, Bruce/A-3157-2008; Chen, Nansheng/E-6450-2012; Churcher, Allison/M-6169-2013; Mu, Xiuqian/I-9146-2014; OI Churcher, Allison/0000-0003-1902-3002; Mu, Xiuqian/0000-0002-8003-7529; Elphick, Maurice/0000-0002-9169-0048; Burke, Robert/0000-0001-5527-4410; Yaguchi, Shunsuke/0000-0002-8326-5762; Hallbook, Finn/0000-0001-7552-187X FU Biotechnology and Biological Sciences Research Council [S19916]; Intramural NIH HHS [Z01 DE000712-02]; NEI NIH HHS [EY11930, R01 EY011930]; NICHD NIH HHS [HD22619, R01 HD022619] NR 201 TC 123 Z9 124 U1 4 U2 23 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 EI 1095-564X J9 DEV BIOL JI Dev. Biol. PD DEC 1 PY 2006 VL 300 IS 1 BP 434 EP 460 DI 10.1016/j.ydbio.2006.08.007 PG 27 WC Developmental Biology SC Developmental Biology GA 117KZ UT WOS:000242873300032 PM 16965768 ER PT J AU Wei, Z Angerer, RC Angerer, LM AF Wei, Zheng Angerer, Robert C. Angerer, Lynne M. TI A database of mRNA expression patterns for the sea urchin embryo SO DEVELOPMENTAL BIOLOGY LA English DT Article DE gene prediction; microarray; genscan ID GENE-EXPRESSION; STRONGYLOCENTROTUS-PURPURATUS; MATERNAL RNA; DNA; HYBRIDIZATION; PREDICTION; SEQUENCES; FAMILIES; NETWORK AB We present an initial characterization of a database that contains temporal expression profiles of sequences found in 35,282 gene predictions within the sea urchin genome. The relative RNA abundance for each sequence was determined at 5 key stages of development using high-density oligonucleotide microarrays that were hybridized with populations of polyA+ RNA sequence. These stages were two-cell, which represents maternal RNA, early blastula, the time at which major tissue territories are specified, early and late gastrula, during which important morphogenetic events occur, and the pluteus larva, which marks the culmination of pre-feeding embryogenesis. We provide evidence that the microarray reliably reports the temporal profiles for the large majority of predicted genes, as shown by comparison to data for many genes with known expression patterns. The sensitivity of this assay allows detection of mRNAs whose concentration is only several hundred copies/embryo. The temporal expression profiles indicate that 5% of the gene predictions encode mRNAs that are found only in the maternal population while 24% are embryo-specific. Further, we find that the concentration of > 80% of different mRNAs is modulated by more than a factor of 3 during development. Along with the annotated sea urchin genome sequence and the whole-genome tiling array (the transcriptome, Samanta, M., Tongprasit, W., Istrrail, S., Cameron, R., Tu, Q., Davidson, E., Stolc, V, in press. A high-resolution transcriptome map of the sea urchin embryo. Science), this database proves a valuable resource for designing experiments to test the function of specific genes during development. Published by Elsevier Inc. C1 Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. RP Angerer, LM (reprint author), Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. EM langerer@mail.nih.gov FU Intramural NIH HHS [Z01 DE000712-02] NR 30 TC 49 Z9 49 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD DEC 1 PY 2006 VL 300 IS 1 BP 476 EP 484 DI 10.1016/j.ydbio.2006.08.034 PG 9 WC Developmental Biology SC Developmental Biology GA 117KZ UT WOS:000242873300034 PM 17007833 ER PT J AU Lee, JS Yu, C Shin, JT Sebzda, E Bertozzi, C Chen, M Mericko, P Stadtfeld, M Zhou, D Cheng, L Graf, T MacRae, CA Lepore, JJ Lo, CW Kahn, ML AF Lee, John S. Yu, Cing Shin, Jordan T. Sebzda, Eric Bertozzi, Cara Chen, Mei Mericko, Patti Stadtfeld, Matthias Zhou, Diane Cheng, Lan Graf, Thomas MacRae, Calum A. Lepore, John J. Lo, Cecilia W. Kahn, Mark L. TI KIf2 is an essential regulator of vascular hemodynamic forces in vivo SO DEVELOPMENTAL CELL LA English DT Article ID NONIMMUNE HYDROPS-FETALIS; KRUPPEL-LIKE FACTOR-2; BLOOD-FLOW; GENE-EXPRESSION; MOUSE EMBRYO; MICE LACKING; MECHANISMS; RECEPTOR; KLF2; DIFFERENTIATION AB Hemodynamic responses that control blood pressure and the distribution of blood flow to different organs are essential for survival. Shear forces generated by blood flow regulate hemodynamic responses, but the molecular and genetic basis for such regulation is not known. The transcription factor KLF2 is activated by fluid shear stress in cultured enclothelial cells, where it regulates a large number of vasoactive endothelial genes. Here, we show that KIf2 expression during development mirrors the rise of fluid shear forces, and that enclothelial loss of KIf2 results in lethal embryonic heart failure due to a high-cardiac-output state. KIf2 deficiency does not result in anemia or structural vascular defects, and it can be rescued by administration of phenylephrine, a catecholamine that raises vessel tone. These findings identify KIf2 as an essential hemodynamic regulator in vivo and suggest that hemodynamic regulation in response to fluid shear stress is required for cardiovascular development and function. C1 Univ Penn, Dept Med, Philadelphia, PA 19104 USA. NHLBI, NIH, Dev Biol Lab, Bethesda, MD 20824 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Dev & Mol Biol, Bronx, NY 10461 USA. RP Kahn, ML (reprint author), Univ Penn, Dept Med, Philadelphia, PA 19104 USA. EM markkahn@mail.med.upenn.edu RI Graf, Thomas/B-4252-2015 OI Graf, Thomas/0000-0003-2774-4117 FU NHLBI NIH HHS [HL081084, HL081654, K08 HL068711]; NIGMS NIH HHS [R21 GM075946] NR 46 TC 126 Z9 132 U1 1 U2 10 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD DEC PY 2006 VL 11 IS 6 BP 845 EP 857 DI 10.1016/j.devcel.2006.09.006 PG 13 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 114KK UT WOS:000242664900013 PM 17141159 ER PT J AU Gray, J Yeo, GSH Cox, JJ Morton, J Adlam, ALR Keogh, JM Yanovski, JA El Gharbawy, A Han, JC Tung, YCL Hodges, JR Raymond, FL O'Rahilly, S Farooqi, IS AF Gray, Juliette Yeo, Giles S. H. Cox, James J. Morton, Jenny Adlam, Anna-Lynne R. Keogh, Julia M. Yanovski, Jack A. El Gharbawy, Areeg Han, Joan C. Tung, Y. C. Loraine Hodges, John R. Raymond, F. Lucy O'Rahilly, Stephen Farooqi, I. Sadaf TI Hyperphagia, severe obesity, impaired cognitive function, and hyperactivity associated with functional loss of one copy of the brain-derived neurotrophic factor (BDNF) gene SO DIABETES LA English DT Article ID ACTIVITY-DEPENDENT SECRETION; HIPPOCAMPAL FUNCTION; ENERGY-BALANCE; DELETION; MICE; NEURONS; COMPLEX; LEPTIN; SYSTEM; MEMORY AB The neurotrophin brain-derived neurotrophic factor (BDNF) inhibits food intake, and rodent models of BDNF disruption all exhibit increased food intake and obesity, as well as hyperactivity. We report an 8-year-old girl with hyperphagia and severe obesity, impaired cognitive function, and hyperactivity who harbored a de novo chromosomal inversion, 46,XX,inv(11)(p13p15.3), a region encompassing the BDNF gene. We have identified the proximal inversion breakpoint that lies 850 kb telomeric the 5' end of the BDNF gene. The patient's genomic DNA was heterozygous for a common coding polymorphism in BDNF, but monoallelic expression was seen in peripheral lymphocytes. Serum concentration of BDNF protein was reduced compared with age- and BMI-matched subjects. Haploinsufficiency for BDNF was associated with increased ad libitum food intake, severe early-onset obesity, hyperactivity, and cognitive impairment. These findings provide direct evidence for the role of the neurotrophin BDNF in human energy homeostasis, as well as in cognitive function, memory, and behavior. C1 Univ Cambridge, Addenbrookes Hosp, Dept Clin Biochem, Cambridge Inst Med Res, Cambridge CB2 2XY, England. Univ Cambridge, Addenbrookes Hosp, Dept Med Genet, Cambridge Inst Med Res, Cambridge CB2 2XY, England. Birmingham Womens Hosp, W Midlands Reg Genet Serv, Birmingham, W Midlands, England. Univ Cambridge, Addenbrookes Hosp, MRC, Cognit & Brain Sci Unit, Cambridge CB2 2XY, England. NICHHD, Unit Growth & Obes, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Farooqi, IS (reprint author), Univ Cambridge, Addenbrookes Hosp, Dept Clin Biochem, Cambridge Inst Med Res, Cambridge CB2 2XY, England. EM isf20@cam.ac.uk RI Adlam, Anna/F-8400-2010; Cox, James/R-1910-2016; OI Adlam, Anna/0000-0001-7212-4051; Farooqi, Sadaf/0000-0001-7609-3504 FU Intramural NIH HHS [Z01 HD000641-12, Z99 HD999999]; Medical Research Council [G9724461, G9824984, MC_U105559861]; NICHD NIH HHS [Z01 HD000641]; Wellcome Trust [068086] NR 26 TC 142 Z9 146 U1 1 U2 11 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD DEC PY 2006 VL 55 IS 12 BP 3366 EP 3371 DI 10.2337/db06-0550 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 111JG UT WOS:000242446800020 PM 17130481 ER PT J AU Potenza, MA Marasciulo, FL Tarquinio, M Quon, MJ Montagnani, M AF Potenza, Maria A. Marasciulo, Flora L. Tarquinio, Mariela Quon, Michael J. Montagnani, Monica TI Treatment of spontaneously hypertensive rats with rosiglitazone and/or enalapril restores balance between vasodilator and vasoconstrictor actions of insulin with simultaneous improvement in hypertension and insulin resistance SO DIABETES LA English DT Article ID VASCULAR ENDOTHELIAL-CELLS; ACTIVATED PROTEIN-KINASE; LOWERS BLOOD-PRESSURE; SMOOTH-MUSCLE-CELLS; NITRIC-OXIDE; PPAR-GAMMA; ADHESION MOLECULE-1; SIGNALING PATHWAYS; TYPE-1 RECEPTOR; ACE-INHIBITION AB Spontaneously hypertensive rats (SHRs) exhibit endothelial dysfunction and insulin resistance. Reciprocal relationships between endothelial dysfunction and insulin resistance may contribute to hypertension by causing imbalanced regulation of endothelial-derived vasodilators (e.g., nitric oxide) and vasoconstrictors (e.g., endothelin-1 [ET-1]). Treatment of SHRs with rosiglitazone (insulin sensitizer) and/or enalapril (ACE inhibitor) may simultaneously improve hypertension, insulin resistance, and endothelial dysfunction by rebalancing insulin-stimulated production of vasoactive mediators. When compared with WKY control rats, 12-week-old vehicle-treated SHRs were hypertensive, overweight, and insulin resistant, with elevated fasting levels of insulin and ET-1 and reduced serum adiponectin levels. In mesenteric vascular beds (MVBs) isolated from vehicle-treated SHRs and preconstricted with norepinephrine (NE) ex vivo, vasodilator responses to insulin were significantly impaired, whereas the ability of insulin to oppose vasoconstrictor actions of NE was absent (versus WKY controls). Three-week treatment of SHRs with rosiglitazone and/or enalapril significantly reduced blood pressure, insulin resistance, fasting insulin, and ET-1 levels and increased adiponectin levels to values comparable with those observed in vehicle-treated WKY controls. By restoring phosphatidylinositol 3-kinase-dependent effects, rosiglitazone and/or enalapril therapy of SHRs also significantly improved vasodilator responses to insulin in MXVB preconstricted with NE ex vivo. Taken together, our data provide strong support for the existence of reciprocal relationships between endothelial dysfunction and insulin resistance that may be relevant for developing novel therapeutic strategies for the metabolic syndrome. C1 Univ Bari, Sch Med, Pharmacol Sect, Dept Pharmacol & Human Physiol, I-70124 Bari, Italy. NIH, Diabet Unit, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. RP Montagnani, M (reprint author), Univ Bari, Sch Med, Pharmacol Sect, Dept Pharmacol & Human Physiol, Policlin Piazza G Cesare 11, I-70124 Bari, Italy. EM monica@farmacol.umba.it RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915; Potenza, Maria Assunta/0000-0002-9995-1468; montagnani, monica/0000-0002-5697-8185; Quon , Michael /0000-0002-5289-3707 FU Intramural NIH HHS NR 64 TC 64 Z9 68 U1 1 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD DEC PY 2006 VL 55 IS 12 BP 3594 EP 3603 DI 10.2337/db06-0667 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 111JG UT WOS:000242446800048 PM 17130509 ER PT J AU Guo, Y Traurig, M Ma, LJ Kobes, S Harper, I Infante, AM Bogardus, C Baier, LJ Prochazka, M AF Guo, Yan Traurig, Michael Ma, Lijun Kobes, Sayuko Harper, Inge Infante, Aniello M. Bogardus, Clifton Baier, Leslie J. Prochazka, Michal TI CHRM3 gene variation is associated with decreased acute insulin secretion and increased risk for early-onset type 2 diabetes in Pima Indians SO DIABETES LA English DT Article ID MUSCARINIC ACETYLCHOLINE-RECEPTOR; RAT PANCREATIC-ISLETS; EXPRESSION; SUBTYPES; RELEASE; MICE AB The muscarinic acetylcholine receptor subtype M3 (CHRM3) gene is expressed in islet P-cells and has a role in stimulating insulin secretion; therefore, CHRM3 was analyzed as a candidate gene for type 2 diabetes in Pima Indians. Ten variants were genotyped in a family-based sample (n = 1,037), and 1 variant (rs3738435) located in the 5' untranslated region of an alternative transcript was found to be modestly associated with both early-onset type 2 diabetes and the acute insulin response in a small subset of these subjects. To better assess whether this variant has a role in acute insulin secretion, which could affect risk for early-onset type 2 diabetes, rs3738435 was genotyped in a larger group of normal glucose-tolerant Pima Indians who had measures of acute insulin secretion (n = 282) and a larger case-control group of Pima Indians selected for early-onset type 2 diabetes (n = 348 case subjects with age of onset < 25 years; n = 392 nondiabetic control subjects aged > 45 years). Genotyping in these larger sets of subjects confirmed that the C allele of rs3738435 was associated with a reduced acute insulin response (adjusted P = 0.00006) and was also modestly associated with increased risk of early-onset type 2 diabetes (adjusted P = 0.02). C1 NIDDKD, Diabet Mol Genet Sect, NIH, Phoenix, AZ 85004 USA. RP Baier, LJ (reprint author), NIDDKD, Diabet Mol Genet Sect, NIH, 445 N 5th St,Suite 210, Phoenix, AZ 85004 USA. EM lbaier@phx.niddk.nih.gov FU Intramural NIH HHS NR 19 TC 20 Z9 22 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 DEC PY 2006 VL 55 IS 12 BP 3625 EP 3629 DI 10.2337/db06-0379 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 111JG UT WOS:000242446800052 PM 17130513 ER PT J AU Shultis, WA Leary, SD Ness, AR Scott, J Martin, RM Whincup, PH Smith, GD AF Shultis, W. A. Leary, S. D. Ness, A. R. Scott, J. Martin, R. M. Whincup, P. H. Smith, G. Davey CA ALSPAC Study Team TI Haemoglobin A(1c) is not a surrogate for glucose and insulin measures for investigating the early life and childhood determinants of insulin resistance and Type 2 diabetes in healthy children. An analysis from the Avon Longitudinal Study of Parents and Children (ALSPAC) SO DIABETIC MEDICINE LA English DT Article DE body composition; children; HbA(1c); insulin resistance; Type 2 diabetes ID HOMEOSTASIS MODEL ASSESSMENT; NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; FAT-FREE MASS; PLASMA-GLUCOSE; GLYCOSYLATED HEMOGLOBIN; GLYCATED HEMOGLOBIN; BODY-COMPOSITION; GLYCEMIC CONTROL; INDIAN CHILDREN AB Aims Research into early life and childhood determinants of insulin resistance and Type 2 diabetes are complicated by requirements for fasting blood samples and glucose tolerance tests. We investigated haemoglobin A(1c) (HbA(1c)), a marker of glycaemia measured in non-fasting blood, as an alternative. Methods HbA(1c) was measured in 1645 children aged 9-11 years without diabetes from the Avon Longitudinal Study of Parents and Children. Thirty-nine children had two HbA(1c) measurements. Data on parental, child and potential confounding factors were collected prospectively from questionnaires, medical records and direct examination. Data from a shortened 30-min oral glucose tolerance test were available for 431 children at age 8 years. Body composition was measured by dual-energy X-ray absorptiometry. Results Mean (SD) HbA(1c) was 4.91(0.29)%. HbA(1c) increased with age and was higher in boys compared with girls, non-white compared with white children, and in children with anaemia. Mean difference between repeated HbA(1c) measurements was 0.01%. HbA(1c) was weakly positively associated with fasting glucose (beta = 0.066%/mmol/l, P = 0.05), but was not associated with 30-min glucose, fasting or 30-min insulin, or homeostasis model assessment-insulin resistance. HbA(1c) was weakly inversely associated with weight SD score -0.02%/unit, P = 0.004), body mass index SD score (beta = -0.02%/unit, P = 0.002), and total body fat (beta = -0.003%/kg, P = 0.06) and lean mass (beta = -0.011 %/kg, P = 0.01), but was not associated with birthweight or breastfeeding. Conclusions HbA(1c) is not a good marker of fasting or post-load glucose and insulin measures in healthy children, and is not a viable alternative to these measures for investigating the determinants of insulin resistance and Type 2 diabetes in children. C1 Univ Bristol, Dept Social Med, Bristol, Avon, England. Univ Bristol, Dept Community Based Med, Bristol, Avon, England. United Bristol Healthcare NHS Trust, Dept Clin Biochem, Bristol, Avon, England. St Georges Hosp Med Sch, Div Community Hlth Serv, London, England. RP Shultis, WA (reprint author), NIH, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. EM shultisw@mail.nih.gov RI Ness, Andy/M-7612-2013; Leary, Sam/B-4456-2016; Davey Smith, George/A-7407-2013 OI Ness, Andy/0000-0003-3548-9523; Davey Smith, George/0000-0002-1407-8314 FU Medical Research Council [G9815508]; Wellcome Trust NR 51 TC 6 Z9 6 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0742-3071 J9 DIABETIC MED JI Diabetic Med. PD DEC PY 2006 VL 23 IS 12 BP 1357 EP 1363 DI 10.1111/j.1464-5491.2006.01990.x PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 121CM UT WOS:000243135700014 PM 17116188 ER PT J AU Chung, JY Braunschweig, T Hewitt, SM AF Chung, Joon-Yong Braunschweig, Till Hewitt, Stephen M. TI Optimization of recovery of RNA from formalin-fixed, paraffin-embedded tissue SO DIAGNOSTIC MOLECULAR PATHOLOGY LA English DT Article DE RNA; formalin-fixed paraffin-embedded tissue; multiplex RT-PCR; RNAlater ID POLYMERASE CHAIN-REACTION; MESSENGER-RNA; PCR AMPLIFICATION; REVERSE TRANSCRIPTION; EXPRESSION ANALYSIS; HOUSEKEEPING GENE; EXTRACTION; RNALATER; FIXATION; PURIFICATION AB Formalin-fixed, paraffin-embedded (FFPE) tissue is the most common specimen available for application of diagnostic assays on tissue after microscopic examination. Not only is there a substantial archive of tissue available, but FFPE tissue remains the best method of preparation for microscopic examination in a routine clinical environment. Molecular assays, especially reverse transcription and polymerase chain reaction and expression array-based assays, offer significant potential as diagnostic, prognostic, and predictive tools, but require high quality RNA. Herein, we have optimized a reliable RNA extraction method for FFPE tissue. It is based on deparaffinization at high temperature coupled with a 3-day lysis at 65 degrees C. The average total RNA yield is 4.5 to 5.5 pg per 1 mu m(3) of archival FFPE tissue, and 260/280 ratios are between 1.80 and 1.95. The extracted RNA has a modal fragment length between 100 and 200 nt by the Bioanalyzer analysis. Although modal lengths of RNA fragments were shorter, reverse transcription and polymerase chain reaction was able to amplify amplicons in range of 300 bp. Pretreatment with RNA later followed by formalin fixation did not result in improving the RNA quality, but did improve RNA yield. Our method improves the utility of FFPE tissue for molecular profiling studies. C1 NCI, TARP Lab, Ctr Adv Technol, Lab Pathol,NIH, Bethesda, MD 20892 USA. Inje Univ, Coll Med, Pharmaco Genom Res Ctr, Pusan 614735, South Korea. RP Hewitt, SM (reprint author), NCI, TARP Lab, Ctr Adv Technol, Lab Pathol,NIH, MSC 4605, Bethesda, MD 20892 USA. EM genejock@helix.nih.gov OI Hewitt, Stephen/0000-0001-8283-1788; Chung, Joon-Yong/0000-0001-5041-5982 FU Intramural NIH HHS NR 32 TC 50 Z9 53 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1052-9551 J9 DIAGN MOL PATHOL JI Diagn. Mol. Pathol. PD DEC PY 2006 VL 15 IS 4 BP 229 EP 236 DI 10.1097/01.pdm.0000213468.91139.2d PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology GA 114KI UT WOS:000242664700006 PM 17122651 ER PT J AU Biasco, G Nobili, E Calabrese, C Sassatelli, R Camellini, L Pantaleo, MA Bertoni, G De Vivo, A De Leon, MP Poggioli, G Bedogni, G Venesio, T Varesco, L Risio, M Di Febo, G Brandi, G AF Biasco, G. Nobili, E. Calabrese, C. Sassatelli, R. Camellini, L. Pantaleo, M. A. Bertoni, G. De Vivo, A. De Leon, M. Ponz Poggioli, G. Bedogni, G. Venesio, T. Varesco, L. Risio, M. Di Febo, G. Brandi, G. TI Impact of surgery on the development of duodenal cancer in patients with familial adenomatous polyposis SO DISEASES OF THE COLON & RECTUM LA English DT Article DE duodenal cancer; familial adenomatous polyposis; spigelman score; ileoanal anastomosis; ileorectal anastomosis; ileostomy ID POUCH-ANAL ANASTOMOSIS; APC GENE-MUTATIONS; BILE-ACIDS; ILEOANAL ANASTOMOSIS; ULCERATIVE-COLITIS; CELL-PROLIFERATION; TOTAL COLECTOMY; ABSORPTION; CHROMOENDOSCOPY; CHOLESTEROL AB PURPOSE: Precancerous duodenal lesions in patients with familial adenomatous polyposis can be detected with duodenoscopy and treatment may prevent the development of cancer. We proposed to determine the frequency, natural history, cumulative risk, and risk factors of the precancerous duodenal lesions in a series of patients diagnosed in northern Italy. METHODS: A prospective, endoscopic, follow-up protocol was performed in 50 patients examined by gastroduodenoscopy at two years of interval or less. The presence and severity of precancerous lesions of the duodenal mucosa were evaluated by Spigelman score. Twenty-five patients (50 percent) had proctocolectomy and ileoanal anastomosis, 15 (30 percent) had colectomy and ileorectal anastomosis, and 5 (10 percent) had proctocolectomy and definitive ileostomy from 0 to 3 years before the admission to the surveillance program. All patients showed more than a thousand adenomas in the colorectal mucosa. No patients with attenuated polyposis were found. RESULTS: At the first endoscopy, duodenal adenomas could be detected in 19 of 50 patients (38 percent), whereas at the end of the follow-up, 43 (86 percent) had duodenal lesions. The final mean Spigelman score increased during the follow-up period (P < 0.001 respect to baseline values). No duodenal cancer could be detected. Eleven patients had or developed severe precancerous duodenal lesions (Stage IV) treated with endoscopic or surgical resection. The distribution of patients with Stage IV according to the surgery of the colon was: 2 of 25 treated with ileoanal anastomosis and 8 of 15 with ileorectal anastomosis (P=0.0024, Fisher's exact test). CONCLUSIONS: Patients with familial adenomatous polyposis are at risk of significant neoplasia. The natural history of precancerous lesions might be related to surgical treatment of colorectal neoplasms. C1 Inst Haemathol & Med Oncol L & A Seragnoli, I-40138 Bologna, Italy. Univ Bologna, Dept Gastroenterol & Internal Med, Bologna, Italy. Santa Maria Nuova Hosp, Gastrointestinal Endoscopy Unit, Reggio Emilia, Italy. Univ Modena, Dept Internal Med, I-41100 Modena, Italy. Natl Canc Inst, Turin, Italy. Natl Canc Inst, Genoa, Italy. RP Biasco, G (reprint author), Inst Haemathol & Med Oncol L & A Seragnoli, Via Massarenti 9, I-40138 Bologna, Italy. EM gbiasco@med.unibo.it RI Ponz de Leon, Maurizio/A-9356-2015 OI PANTALEO, MARIA ABBONDANZA/0000-0002-0177-6957; Calabrese, Carlo/0000-0003-3657-4463; Ponz de Leon, Maurizio/0000-0003-4465-1043 NR 29 TC 3 Z9 3 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-3706 J9 DIS COLON RECTUM JI Dis. Colon Rectum PD DEC PY 2006 VL 49 IS 12 BP 1860 EP 1866 DI 10.1007/s10350-006-0723-y PG 7 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 111AK UT WOS:000242422600008 PM 17103055 ER PT J AU Elkashef, A Fudala, PJ Gorgon, L Li, SH Kahn, R Chiang, N Vocci, F Collins, J Jones, K Boardman, K Sather, M AF Elkashef, Ahmed Fudala, Paul J. Gorgon, Liza Li, Shou-Hua Kahn, Roberta Chiang, Nora Vocci, Frank Collins, Joseph Jones, Karen Boardman, Kathy Sather, Mike TI Double-blind, placebo-controlled trial of selegiline transdermal system (STS) for the treatment of cocaine dependence SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE cocaine; dependence; selegiline; transdermal ID L-DEPRENYL SELEGILINE; MONOAMINE-OXIDASE INHIBITORS; LONGITUDINAL DATA-ANALYSIS; BETA-PHENYLETHYLAMINE; BRAIN; DRUGS; ABUSE AB Background: Cocaine dependence is a major public health problem for which there is no FDA-approved pharmacological treatment. Selegiline is an irreversible selective inhibitor of monoamine oxidase type B (MAO-B) which may affect cocaine addiction through several potential mechanisms. In this study, selegiline transdermal system (STS) was compared to placebo as a treatment for cocaine dependence. This multi-site, double-blind trial of 300 subjects with cocaine dependence assessed the efficacy of selegiline using subject self-reported cocaine use substantiated by urine benzoylecgonine (BE) as the primary outcome measure. Analysis of the data did not show a significant effect for selegiline over placebo. This study does not support a role for selegiline in treating cocaine dependence. The contrast of this result to earlier, promising preclinical and human pilot data could be due to factors associated with sample size, patient characteristics, dose, or poor predictive validity of preclinical models. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 NIDA, DPMCDA, Bethesda, MD 20892 USA. Behav Hlth Serv, Ctr Med, DVA, Philadelphia, PA 19104 USA. DVA, Cooperat Studies Program Coordinating Ctr 151E, Perry Point, MD 21902 USA. Dept Vet Affairs, Clin Res Pharm Coordinating Ctr, Cooperat Studies Program, Albuquerque, NM 87106 USA. RP Elkashef, A (reprint author), NIDA, DPMCDA, Execut Blvd,Rm 4123,MSC 9551, Bethesda, MD 20892 USA. EM aega@nih.gov FU NIDA NIH HHS [Y1-DA1001] NR 28 TC 22 Z9 23 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD DEC 1 PY 2006 VL 85 IS 3 BP 191 EP 197 DI 10.1016/j.drugalcdep.2006.04.010 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 114LN UT WOS:000242667800003 PM 16730924 ER PT J AU Wang, MZ Saulter, JY Usuki, E Cheung, YL Hall, M Bridges, AS Loewen, G Parkinson, OT Stephens, CE Allen, JL Zeldin, DC Boykin, DW Tidwell, RR Parkinson, A Paine, MF Hall, JE AF Wang, Michael Zhuo Saulter, Janelle Y. Usuki, Etsuko Cheung, Yen-Ling Hall, Michael Bridges, Arlene S. Loewen, Greg Parkinson, Oliver T. Stephens, Chad E. Allen, James L. Zeldin, Darryl C. Boykin, David W. Tidwell, Richard R. Parkinson, Andrew Paine, Mary F. Hall, James Edwin TI CYP4F enzymes are the major enzymes in human liver microsomes that catalyze the O-demethylation of the antiparasitic prodrug DB289 [2,5-bis(4-amidinophenyl)furan-bis-O-methylamidoxime] SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID ARACHIDONIC-ACID; PLASMODIUM-FALCIPARUM; HUMAN CYTOCHROME-P450; OMEGA-HYDROXYLASES; DRUG-INTERACTION; EXPRESSION; METABOLISM; INHIBITION; CYP2J2; RAT AB DB289 [2,5-bis(4-amidinophenyl)furan-bis-O-methylamidoxime] is biotransformed to the potent antiparasitic diamidine DB75 [2,5-bis(4-amidinophenyl) furan] by sequential oxidative O-demethylation and reductive N-dehydroxylation reactions. Previous work demonstrated that the N-dehydroxylation reactions are catalyzed by cytochrome b(5)/NADH-cytochrome b(5) reductase. Enzymes responsible for catalyzing the DB289 O-demethylation pathway have not been identified. We report an in vitro metabolism study to characterize enzymes in human liver microsomes (HLMs) that catalyze the initial O-demethylation of DB289 (M1 formation). Potent inhibition by 1-aminobenzotriazole confirmed that M1 formation is catalyzed by P450 enzymes. M1 formation by HLMs was NADPH-dependent, with a K-m and V-max of 0.5 mu M and 3.8 nmol/min/mg protein, respectively. Initial screening showed that recombinant CYP1A1, CYP1A2, and CYP1B1 were efficient catalysts of M1 formation. However, none of these three enzymes was responsible for M1 formation by HLMs. Further screening showed that recombinant CYP2J2, CYP4F2, and CYP4F3B could also catalyze M1 formation. An antibody against CYP4F2, which inhibited both CYP4F2 and CYP4F3B, inhibited 91% of M1 formation by HLMs. Two inhibitors of P450-mediated arachidonic acid metabolism, HET0016 (N-hydroxy-N'-(4-n-butyl-2-methylphenyl)formamidine) and 17-octadecynoic acid, effectively inhibited M1 formation by HLMs. Inhibition studies with ebastine and antibodies against CYP2J2 suggested that CYP2J2 was not involved in M1 formation by HLMs. Additionally, ketoconazole preferentially inhibited CYP4F2, but not CYP4F3B, and partially inhibited M1 formation by HLMs. We conclude that CYP4F enzymes (e.g., CYP4F2, CYP4F3B) are the major enzymes responsible for M1 formation by HLMs. These findings indicate that, in human liver, members of the CYP4F subfamily biotransform not only endogenous compounds but also xenobiotics. C1 Univ N Carolina, Sch Pharm, Div Mol Pharmaceut, Chapel Hill, NC 27599 USA. XenoTech LLC, Lenexa, KS USA. Georgia State Univ, Dept Chem, Atlanta, GA 30303 USA. Huntingdon Life Sci Ltd, Dept In Vitro Metab, Huntingdon, Cambs, England. Immtech Pharmaceut Inc, Vernon Hills, IL USA. NIEHS, Lab Resp Biol, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. RP Hall, JE (reprint author), Univ N Carolina, Sch Pharm, Div Mol Pharmaceut, 3312 Kerr Hall,CB 7360, Chapel Hill, NC 27599 USA. EM je_hall@unc.edu RI BRIDGES, ARLENE/N-4534-2013 FU Intramural NIH HHS [Z01 ES025034-13] NR 40 TC 52 Z9 54 U1 0 U2 8 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD DEC PY 2006 VL 34 IS 12 BP 1985 EP 1994 DI 10.1124/dmd.106.010587 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 110JN UT WOS:000242374700007 PM 16997912 ER PT J AU Jackson, JP Ferguson, SS Negishi, M Goldstein, JA AF Jackson, Jonathan P. Ferguson, Stephen S. Negishi, Masahiko Goldstein, Joyce A. TI Phenytoin induction of the Cyp2c37 gene is mediated by the constitutive androstane receptor SO DRUG METABOLISM AND DISPOSITION LA English DT Article; Proceedings Paper CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut ID PREGNANE-X-RECEPTOR; CYTOCHROME-P450 CYP GENES; DISTAL ENHANCER MODULE; NUCLEAR RECEPTORS; TRANSCRIPTIONAL REGULATION; GLUCOCORTICOID-RECEPTOR; HUMAN HEPATOCYTES; ACID; CAR; EXPRESSION AB The CYP2C subfamily of cytochrome P450 monooxygenases is responsible for the metabolism of approximately 20% of therapeutic drugs and many endogenous compounds in humans. These enzymes can be induced by prior treatment with drugs, resulting in changes in drug efficacy. Induction of human CYP2C enzymes by xenobiotics occurs at the transcriptional level and is reported to involve the constitutive androstane receptor (CAR) and the pregnane X receptor (PXR). In the present study, we report that murine CYP2C37 mRNA is induced by phenobarbital and phenytoin. In contrast, the mouse PXR agonist 5-pregnen-3 beta-ol-20-one-16 alpha-carbonitrile did not induce CYP2C37 mRNA, suggesting that PXR does not regulate this gene. The induction of CYP2C37 mRNA by phenobarbital and phenytoin is essentially abolished in CAR-null mice; thus, induction of Cyp2c37 by these xenobiotics is CAR-dependent. A functional CAR response element (CAR-RE) was identified at -2791 base pairs from the translation start site of the Cyp2c37 gene. Mutation of this CAR-RE abolished mouse CAR transactivation of a Cyp2c37 -2.9-kilobase pair luciferase reporter construct in HepG2 cells. C1 NIEHS, Pharmacogenet Sect, Lab Reprod & Dev Toxicol, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Dept Environm & Mol Toxicol, Raleigh, NC 27695 USA. RP Negishi, M (reprint author), NIEHS, Pharmacogenet Sect, Lab Reprod & Dev Toxicol, POB 12233, Res Triangle Pk, NC 27709 USA. EM negishi@niehs.nih.gov RI Goldstein, Joyce/A-6681-2012 FU Intramural NIH HHS [Z99 ES999999] NR 33 TC 23 Z9 24 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD DEC PY 2006 VL 34 IS 12 BP 2003 EP 2010 DI 10.1124/dmd.106.012005 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 110JN UT WOS:000242374700009 PM 16936065 ER PT J AU Kim, D Ghanayem, BI AF Kim, Dojung Ghanayem, Burhan I. TI Comparative metabolism and disposition of trichloroethylene in Cyp2e1-/- and wild-type mice SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID TISSUE-DEPENDENT DIFFERENCES; TRICHLOROACETIC-ACID; SPECIES-DIFFERENCES; GLUTATHIONE CONJUGATION; PHARMACOKINETIC MODELS; DICHLOROACETIC ACID; CHLORAL HYDRATE; MOUSE-LIVER; RAT-LIVER; TOXICITY AB Trichloroethylene (TCE) 1 is an important environmental contaminant, a well established rodent carcinogen, and a "probable human carcinogen". Metabolism of TCE occurs primarily via cytochrome P450 (P450)-dependent oxidation. In vitro studies suggested that CYP2E1 is the principal high-affinity enzyme responsible for TCE metabolism. The objective of the present work is to more directly assess the role of CYP2E1 in the metabolism and disposition of 1,2-C-14-TCE administered at 250 or 1000 mg/kg (gavage) using Cyp2e1-/- [knockout(KO)] versus wild-type (WT) mice. After dosing, animals were individually placed in glass metabolism cages that allowed the collection of expired air, urine, and feces. Exhalation of TCE-derived (CO2)-C-14 increased in a dose-dependent manner in mice of both genotypes and was significantly higher in WT versus KO mice. A significantly greater percentage of the dose was exhaled in KO versus WT mice as organic volatiles (mainly as TCE). Urinary excretion was the major route of TCE metabolism in WT mice, and the percentage of dose eliminated in urine was significantly higher at the 250 versus 1000 mg/kg dose. Furthermore, urinary excretion and CO2 exhalation significantly decreased in KO versus WT mice. Pretreatment with 1-aminobenzotriazole clearly inhibited TCE metabolism as evident from increased exhalation of parent TCE, and decreased urinary excretion and CO2 exhalation in mice of both genotypes. In conclusion, these data showed that whereas CYP2E1 plays an important role in TCE metabolism and disposition, other P450s also play a significant role and may explain earlier results showing that TCE causes lung damage in KO and WT mice. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Ghanayem, BI (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233 MD B3-10,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM ghanayem@niehs.nih.gov FU Intramural NIH HHS NR 40 TC 12 Z9 12 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD DEC PY 2006 VL 34 IS 12 BP 2020 EP 2027 DI 10.1124/dmd.106.010538 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 110JN UT WOS:000242374700011 PM 16959879 ER PT J AU Brown, P McShane, LM Zanusso, G Detwiler, L AF Brown, Paul McShane, Lisa M. Zanusso, Gianluigi Detwiler, Linda TI On the question of sporadic or atypical bovine spongiform encephalopathy and Creutzfeldt-Jakob disease SO EMERGING INFECTIOUS DISEASES LA English DT Article ID PRION PROTEIN; BSE AB Strategies to investigate the possible existence of sporadic bovine spongiform encephalopathy (BSE) require systematic testing programs to identify cases in countries considered to have little or no risk for orally acquired disease or to detect a stable occurrence of atypical cases in countries in which orally acquired disease is disappearing. To achieve 95% statistical confidence that the prevalence of sporadic BSE is no greater than 1 per million (i.e., the annual incidence of sporadic Creutzfeldt-Jakob disease [CJD] in humans) would require negative tests in 3 million randomly selected older cattle. A link between BSE and sporadic CJD has been suggested on the basis of laboratory studies but is unsupported by epidemiologic observation. Such a link might yet be established by the discovery of a specific molecular marker or of particular combinations of trends over time of typical and atypical BSE and various subtypes of sporadic CJD, as their numbers are influenced by a continuation of current public health measures that exclude high-risk bovine tissues from the animal and human food chains. C1 NIH, Bethesda, MD 20892 USA. Univ Verona, I-37100 Verona, Italy. Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA. RP Brown, P (reprint author), 7815 Exeter Rd, Bethesda, MD 20814 USA. EM paulwbrown@comcast.net OI ZANUSSO, Gianluigi/0000-0001-5199-6264 NR 16 TC 36 Z9 36 U1 0 U2 0 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD DEC PY 2006 VL 12 IS 12 BP 1816 EP 1821 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 109IR UT WOS:000242301900002 PM 17326930 ER PT J AU Hewitt, SC AF Hewitt, Sylvia C. TI The five W's of progesterone receptors A and B: Now we know where and when SO ENDOCRINOLOGY LA English DT Editorial Material ID MAMMARY-GLAND DEVELOPMENT; TRANSGENIC MICE; EXPRESSION; ENDOMETRIUM; BREAST; ISOFORM C1 Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. RP Hewitt, SC (reprint author), Natl Inst Environm Hlth Sci, 111 Alexander Dr,MD E4-01, Res Triangle Pk, NC 27709 USA. EM curtiss@niehs.nih.gov NR 17 TC 1 Z9 1 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 2006 VL 147 IS 12 BP 5501 EP 5502 DI 10.1210/en.2006-1314 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 105QK UT WOS:000242047200001 PM 17107971 ER PT J AU Yakar, S Nunez, NP Pennisi, P Brodt, P Sun, H Fallavollita, L Zhao, H Scavo, L Novosyadlyy, R Kurshan, N Stannard, B East-Palmer, J Smith, NCP Perkins, SN Fuchs-Young, R Barrett, JC Hursting, SD LeRoith, D AF Yakar, Shoshana Nunez, Nomeli P. Pennisi, Patricia Brodt, Pnina Sun, Hui Fallavollita, Lucia Zhao, Hong Scavo, Louis Novosyadlyy, Ruslan Kurshan, Naamit Stannard, Bethel East-Palmer, Joyce Smith, Nicole C. P. Perkins, Susan N. Fuchs-Young, Robin Barrett, J. Carl Hursting, Stephen D. LeRoith, Derek TI Increased tumor growth in mice with diet-induced obesity: Impact of ovarian hormones SO ENDOCRINOLOGY LA English DT Article ID WESTERN-STYLE DIET; FACTOR-I LEVELS; INSULIN-RECEPTOR ISOFORM; PROSTATE-CANCER CELLS; BREAST-CANCER; GENE-EXPRESSION; ADIPOSE-TISSUE; CALORIC RESTRICTION; COLORECTAL-CANCER; GASTRIC-CARCINOMA AB Obesity increases the risk of many cancers in both males and females. This study describes a link between obesity, obesity-associated metabolic alterations, and the risk of developing cancer in male and female mice. The goal of this study was to evaluate the relationship between gender and obesity and to determine the role of estrogen status in obese females and its effect on tumor growth. We examined the susceptibility of C57BL/6 mice to diet-induced obesity, insulin resistance/glucose intolerance, and tumors. Mice were injected sc with one of two tumorigenic cell lines, Lewis lung carcinoma, or mouse colon 38-adenocarcinoma. Results show that tumor growth rate was increased in obese mice vs. control mice irrespective of the tumor cell type. To investigate the effect of estrogen status on tumor development in obese females, we compared metabolic parameters and tumor growth in ovariectomized (ovx) and intact obese female mice. Obese ovx female mice developed insulin resistance and glucose intolerance similar to that observed in obese males. Our results demonstrate that body adiposity increased in ovx females irrespective of the diet administered and that tumor growth correlated positively with body adiposity. Overall, these data point to more rapid tumor growth in obese mice and suggest that endogenous sex steroids, together with diet, affect adiposity, insulin sensitivity, and tumor growth in female mice. C1 CUNY Mt Sinai Sch Med, Dept Med, Div Endocrinol Diabet & Bone Dis, New York, NY 10029 USA. NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. NCI, Nutr & Mol Carcinogenesis Sect, Lab Biosyst & Canc, NIH, Bethesda, MD 20892 USA. McGill Univ, Royal Victoria Hosp, Ctr Hlth, Dept Med, Montreal, PQ H3A 1A1, Canada. McGill Univ, Royal Victoria Hosp, Ctr Hlth, Dept Surg, Montreal, PQ H3A 1A1, Canada. NCI, Basic Res Program, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21702 USA. Univ Texas, MD Anderson Canc Ctr, Dept Carcinogenesis, Smithville, TX 78957 USA. RP Yakar, S (reprint author), CUNY Mt Sinai Sch Med, Dept Med, Div Endocrinol Diabet & Bone Dis, 1 Gustave L Levy Pl, New York, NY 10029 USA. EM shoshana.yakar@mssm.edu FU NCI NIH HHS [N01-CO-12400] NR 63 TC 78 Z9 81 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 2006 VL 147 IS 12 BP 5826 EP 5834 DI 10.1210/en.2006-0311 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 105QK UT WOS:000242047200036 PM 16959846 ER PT J AU Brouwers, FM Eisenhofer, G Lenders, JWM Pacak, K AF Brouwers, Frederieke M. Eisenhofer, Graeme Lenders, Jacques W. M. Pacak, Karel TI Emergencies caused by pheochromocytoma, neuroblastoma, or ganglioneuroma SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA LA English DT Review ID CATECHOLAMINE-INDUCED CARDIOMYOPATHY; ACUTE-RENAL-FAILURE; NONCARDIOGENIC PULMONARY-EDEMA; ADRENALINE-SECRETING PHAEOCHROMOCYTOMA; RESPIRATORY-DISTRESS-SYNDROME; ACUTE MYOCARDIAL-INFARCTION; PROTEIN-LOSING ENTEROPATHY; HEART-TRANSPLANT CANDIDATE; IV-S NEUROBLASTOMA; DILATED CARDIOMYOPATHY AB Pheochromocytoma may lead to important emergency situations, ranging from cardiovascular emergencies to acute abdomen and multiorgan failure. It is vital to think about this disease in any emergency situation when conventional therapy fails to achieve control or symptoms occur that do not fit the initial diagnosis. The importance of keeping this diagnosis in mind is underscored by the fact that, in 50% of pheochromocytoma patients, the diagnosis is initially overlooked. Two other tumors of the sympathetic nervous system, neuroblastoma and ganglioneuroma, are less commonly associated with emergency conditions. If they occur, they are often linked to catecholamine excess, paraneoplastic phenomena, or local tumor mass effect. C1 NICHHD, Sect Med Neuroendocrinol, Reprod Biol & Med Branch, Bethesda, MD 20892 USA. NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. Radboud Univ Nijmegen, Dept Internal Med, Div Gen Internal Med, Med Ctr, NL-6500 HB Nijmegen, Netherlands. RP Pacak, K (reprint author), NICHHD, Sect Med Neuroendocrinol, Reprod Biol & Med Branch, 10 Ctr Dr MSC 1109,Bldg 10,CRC,Room 1E-3140, Bethesda, MD 20892 USA. EM karel@mail.nih RI Lenders, J.W.M./L-4487-2015 FU Intramural NIH HHS NR 230 TC 22 Z9 24 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8529 J9 ENDOCRIN METAB CLIN JI Endocrinol. Metabol. Clin. North Amer. PD DEC PY 2006 VL 35 IS 4 BP 699 EP + DI 10.1016/j.ecl.2006.09.014 PG 27 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 120UR UT WOS:000243112200005 PM 17127142 ER PT J AU Guettier, JM Gorden, P AF Guettier, Jean-Marc Gorden, Phillip TI Hypoglycemia SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA LA English DT Review ID GROWTH-HORMONE DEFICIENCY; NONINSULINOMA PANCREATOGENOUS HYPOGLYCEMIA; PERSISTENT HYPERINSULINEMIC HYPOGLYCEMIA; ETHANOL-INDUCED HYPOGLYCEMIA; SURGICALLY TREATED PATIENTS; ECTOPIC INSULIN PRODUCTION; GASTRIC-BYPASS-SURGERY; ISLET-CELL TUMOR; REACTIVE HYPOGLYCEMIA; FACTOR-II AB Under physiologic conditions, glucose plays a critical role in providing energy to the central nervous system. A precipitous drop in the availability of this substrate results in dramatic symptoms that signal a medical emergency and warrant immediate therapy aimed at restoring plasma glucose to normal levels. A systemic approach to the differential diagnosis is useful in identifying the cause of hypoglycemia. Once established, a specific and/or definitive intervention that addresses that underlying problem can be implemented. In most cases, this systemic approach to diagnosis and therapy is rewarded with a good outcome for the patient. C1 NIDDKD, NIH, Bethesda, MD 20892 USA. RP Guettier, JM (reprint author), NIDDKD, NIH, 9600 Rockville Pike, Bethesda, MD 20892 USA. EM guettierj@mail.nih.gov NR 101 TC 29 Z9 31 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8529 J9 ENDOCRIN METAB CLIN JI Endocrinol. Metabol. Clin. North Amer. PD DEC PY 2006 VL 35 IS 4 BP 753 EP + DI 10.1016/j.ecl.2006.09.005 PG 16 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 120UR UT WOS:000243112200007 PM 17127144 ER PT J AU Craft, ES Donnelly, KC Neamtiu, I McCarthy, KM Bruce, E Surkova, I Kim, D Uhnakova, I Gyorffy, E Tesarova, E Anderson, B AF Craft, Elena S. Donnelly, Kirby C. Neamtiu, Iulia McCarthy, Kathleen M. Bruce, Erica Surkova, Irina Kim, David Uhnakova, Iveta Gyorffy, Erika Tesarova, Eva Anderson, Beth TI Prioritizing environmental issues around the world: Opinions from an international Central and Eastern European environmental health conference SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE Eastern Europe; environmental health; environmental pollutants; international health concerns ID ASTHMA; DISEASE; COUNTRIES; DRINKING; EXPOSURE; CHILDREN; CULTURE; OBESITY; BURDEN AB BACKGROUND: As the next generation of scientists enters the field of environmental health, it is imperative that they view their contributions in the context of global environmental stewardship. In this commentary, a group of international graduate students facilitated by three experienced environmental health scientists present their views on what they consider to be the global environmental health concerns of today. This group convened initially in October 2004 at an international health conference in Prague, Czech Republic. OBJECTIVES: In this report we identify perceived environmental health concerns that exist around the world, with a focus on Central and Eastern Europe. Additionally, we address these perceived problems and offers some potential solutions. DISCUSSION: At the meeting, students were invited to participate in two panel discussions. One group of young international scientists identified several significant global environmental health concerns, including air pollution, occupational hazards, and risk factors that may exacerbate current environmental health issues. The second panel determined that communication, education, and regulation were the mechanisms for addressing current environmental challenges. CONCLUSIONS: In this commentary we expand on the views presented at the meeting and represent the concerns of young investigators from nine different countries. We provide ideas about and support the exchange of information between developed and developing countries on how to handle the environmental health challenges that face the world today. C1 Duke Univ, Nicholas Sch Environm, Durham, NC USA. NIEHS, Mol Toxicol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. Texas A&M Univ, Dept Vet Anat & Publ Hlth, College Stn, TX USA. Environm Hlth Ctr, Cluj Napoca, Cluj County, Romania. Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. Texas A&M Univ, Dept Civil Engn, Environm & Water Resources Div, College Stn, TX USA. Sechenov Moscow Med Acad, Dept Med Genet, Moscow, Russia. Univ N Carolina, Sch Publ Hlth, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA. Slovak Med Univ, Dept Environm Med, Res Base, Bratislava, Slovakia. Natl Inst Environm Hlth, Fodor Jozsef Natl Ctr Publ Hlth, Budapest, Hungary. Charles Univ, Fac Sci, Dept Phys & Macromol Chem, Prague, Czech Republic. RP Craft, ES (reprint author), 3420 Execut Ctr Dr, Austin, TX 78731 USA. EM esc5@duke.edu RI Bruce, Erica D./H-2194-2015 OI Bruce, Erica D./0000-0002-4900-0496 NR 36 TC 4 Z9 5 U1 3 U2 8 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 DEC PY 2006 VL 114 IS 12 BP 1813 EP 1817 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 112BN UT WOS:000242500200024 PM 17185268 ER PT J AU Mahajan, R Blair, A Lynch, CF Schroeder, P Hoppin, JA Sandler, DP Alavanja, MCR AF Mahajan, Raieev Blair, Aaron Lynch, Charles F. Schroeder, Paul Hoppin, Jane A. Sandler, Dale P. Alavanja, Michael C. R. TI Fonofos exposure and cancer incidence in the Agricultural Health Study SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE agriculture; fonofos; insecticides; neoplasms; occupational exposure; organophosphorus compounds; organothiophosphorus compounds; pesticides ID NON-HODGKINS-LYMPHOMA; RISK-FACTORS; PESTICIDE USE; MEN; TESTOSTERONE; METABOLISM; ACTIVATION; MINNESOTA; LEUKEMIA; FARMERS AB BACKGROUND: The Agricultural Health Study (AHS) is a prospective cohort study of licensed pesticide applicators from Iowa and North Carolina enrolled 1993-1997 and followed for incident cancer through 2002. A previous investigation in this cohort linked exposure to the organophosphate fonofos with incident prostate cancer in subjects with family history of prostate cancer. OBJECTIVES: This finding along with findings of associations between organophosphate pesticides and cancer more broadly led to this study of fonofos and risk of any cancers among 45,372 pesticide applicators enrolled in the AHS. METHODS: Pesticide exposure, and other data were collected using self-administered questionnaires. Poisson regression was used to calculate rate ratios (RRs) and 95% confidence intervals (CIs) while controlling for potential confounders. RESULTS: Relative to the unexposed, leukemia risk was elevated in the highest category of lifetime (RR = 2.24; 95% CI, 0.94-5.34, p(trend) = 0.07) and intensity-weighted exposure-days (RR = 2.67; 95% CI, 1.06-6.70, p(trend) = 0.04), a measure that takes into account factors that modify pesticide exposure. Although prostate cancer risk was unrelated to fonofos use overall, among applicators with a family history of prostate cancer, we observed a significant dose-response trend for lifetime exposure-days (p(trend) = 0.02, RR highest tertile vs. unexposed = 1.77, 95% CI, 1.03-3.05; RRinteraction = 1.28, 95% CI, 1.07-1.54). Intensity-weighted results were similar. No associations were observed with other examined cancer sites. CONCLUSIONS: Further study is warranted to confirm findings with respect to leukemia and determine whether genetic susceptibility modifies prostate cancer risk from pesticide exposure. C1 NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA. Univ Iowa, Dept Epidemiol, Iowa City, IA USA. Westat Corp, Rockville, MD USA. Natl Inst Environm Hlth Sci, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC USA. RP Alavanja, MCR (reprint author), NCI, Occupat Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 8000,MSC 7240, Rockville, MD 20852 USA. EM Alavanjm@mail.nih.gov OI Sandler, Dale/0000-0002-6776-0018 FU Intramural NIH HHS NR 24 TC 36 Z9 42 U1 1 U2 4 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 DEC PY 2006 VL 114 IS 12 BP 1838 EP 1842 DI 10.1289/ehp.9301 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 112BN UT WOS:000242500200028 PM 17185272 ER PT J AU Schwartz, DA AF Schwartz, David A. TI Environmental justice and the NIEHS SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Schwartz, DA (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 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 DEC PY 2006 VL 114 IS 12 BP A686 EP A686 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 112BN UT WOS:000242500200001 PM 17185249 ER PT J AU Galperin, MY AF Galperin, Michael Y. TI The fuzzy border between a cell and an organelle SO ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID LEPTOSPIRA-INTERROGANS; GENOME SEQUENCE; CYANOBACTERIUM TRICHODESMIUM; SHEWANELLA-ONEIDENSIS; BACTERIUM; REVEALS; ENDOSYMBIONT; CAULOBACTER; ADAPTATION; EXPRESSION C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Galperin, MY (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM galperin@ncbi.nlm.nih.gov RI Galperin, Michael/B-5859-2013 OI Galperin, Michael/0000-0002-2265-5572 FU Intramural NIH HHS NR 37 TC 1 Z9 1 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1462-2912 J9 ENVIRON MICROBIOL JI Environ. Microbiol. PD DEC PY 2006 VL 8 IS 12 BP 2062 EP 2067 DI 10.1111/j.1462-2920.2006.01178.x PG 6 WC Microbiology SC Microbiology GA 104IY UT WOS:000241953300002 PM 17107547 ER PT J AU Cannell, JJ Vieth, R Umhau, JC Holick, MF Grant, WB Madronich, S Garland, CF Giovannucci, E AF Cannell, J. J. Vieth, R. Umhau, J. C. Holick, M. F. Grant, W. B. Madronich, S. Garland, C. F. Giovannucci, E. TI Epidemic influenza and vitamin D SO EPIDEMIOLOGY AND INFECTION LA English DT Review ID A H5N1 VIRUSES; D DEFICIENCY; ANTIMICROBIAL PEPTIDES; SEASONAL-VARIATION; ULTRAVIOLET-IRRADIATION; UNITED-STATES; NUTRITIONAL RICKETS; INNATE IMMUNITY; D INSUFFICIENCY; CHILDREN AB In 1981, R. Edgar Hope-Simpson proposed that a 'seasonal stimulus' intimately associated with solar radiation explained the remarkable seasonality of epidemic influenza. Solar radiation triggers robust seasonal vitamin D production in the skin; vitamin D deticiency is common in the winter, and activated vitamin D, 1,25(OH)(2)D, a steroid hormone, has profound effects on human immunity. 1,25(OH)(2)D acts as an immune system modulator, preventing excessive expression of inflammatory cytokines and increasing the 'oxidative burst' potential of macrophages. Perhaps most importantly, it dramatically stimulates the expression of potent anti-microbial peptides, which exist in neutrophils, monocytes, natural killer cells, and in epithelial cells lining the respiratory tract where they play a major role in protecting the lung from infection. Volunteers inoculated with live attenuated influenza virus are more likely to develop fever and serological evidence of an immune response in the winter. Vitamin D deficiency predisposes children to respiratory infections. Ultraviolet radiation (either from artificial sources or from sunlight) reduces the incidence of viral respiratory infections, as does cod liver oil (which contains vitamin D). An interventional study showed that vitamin D reduces the incidence of respiratory infections in children. We conclude that vitamin D, or lack of it, may be Hope-Simpson's 'seasonal stimulus'. C1 Atascadero State Hosp, Atascadero, CA 93422 USA. Mt Sinai Hosp, Dept Med, Toronto, ON M5G 1X5, Canada. NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD USA. Boston Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Physiol, Boston, MA 02215 USA. SUNARC, San Francisco, CA USA. Natl Ctr Atmospher Res, Atmospher Chem Div, Boulder, CO 80307 USA. Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Cannell, JJ (reprint author), Atascadero State Hosp, 10333 El Camino Real, Atascadero, CA 93422 USA. EM jcannell@dmhash.state.ca.us RI Grant, William/B-8311-2009; Madronich, Sasha/D-3284-2015; OI Grant, William/0000-0002-1439-3285; Madronich, Sasha/0000-0003-0983-1313; Holick, Michael/0000-0001-6023-9062; Cannell, John/0000-0001-9748-8740 NR 119 TC 373 Z9 391 U1 3 U2 40 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0950-2688 J9 EPIDEMIOL INFECT JI Epidemiol. Infect. PD DEC PY 2006 VL 134 IS 6 BP 1129 EP 1140 DI 10.1017/S0950268806007175 PG 12 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 108HV UT WOS:000242231800001 PM 16959053 ER PT J AU Vines, AI Baird, DD McNeilly, M Hertz-Picciotto, F Light, KC Stevens, J AF Vines, AI Baird, DD McNeilly, M Hertz-Picciotto, F Light, KC Stevens, J TI Social correlates of the chronic stress of perceived racism among black women SO ETHNICITY & DISEASE LA English DT Article DE perceived racism; racism; racial discrimination; stress ID AFRICAN-AMERICAN WOMEN; BLOOD-PRESSURE; SOCIOECONOMIC-STATUS; BIRTH-WEIGHT; DISCRIMINATION; HEALTH; RESPONSES; RACE AB Objectives: This study describes the perceptions of racism, passive and active responses to this psychosocial stressor, and it examines socioeconomic correlates of perceived racism in an economically diverse population of Black women. Methods: The Telephone-Administered Perceived Racism Scale was administered to 476 Black women, aged 36 to 53 years, who were randomly selected from a large health plan. Results: The percentage of respondents who reported personally experiencing racism in the past five years ranged from 66% to 93%, depending on the specific item asked. When respondents were asked about racism toward Blacks as a group, perceptions of racism were even higher. For example, 68% "agreed" or "strongly agreed" that. they had personally experienced being followed or watched while shopping because of their race, and 93%, reported that Blacks in general experience this form of discrimination. Strong emotional responses to racism were often reported, and though more respondents (41%) reported experiencing very strong active emotions including anger, a substantial group (16%) reported experiencing very strong passive emotions such as powerlessness. Higher education was associated with higher perceived racism, while growing up in a middle-income or well-off family was associated with lower perceived racism and reduced likelihood of passive responses to racism. Conclusions: The high prevalence of perceived racism ill this Study population warrants further examination of this stressor as a potential determinant of racial health disparities. Higher education and income do not appear to protect women from experiencing racism and feeling hopeless or powerless in response. C1 Univ N Carolina, Dept Epidemiol, Sch Publ Hlth, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Publ Hlth, Dept Psychiat, Chapel Hill, NC USA. Univ N Carolina, Sch Publ Hlth, Dept Nutr, Chapel Hill, NC USA. Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA. Duke Univ, Dept Psychiat, Durham, NC 27706 USA. Duke Univ, Dept Psychol, Durham, NC 27706 USA. Univ Calif Davis, Dept Epidemiol & Prevent Med, Davis, CA 95616 USA. RP Vines, AI (reprint author), Univ N Carolina, Dept Epidemiol, Sch Publ Hlth, 267 Rosenau Hall CB 7435, Chapel Hill, NC 27599 USA. EM avines@email.unc.edu OI Baird, Donna/0000-0002-5544-2653 FU Intramural NIH HHS; NIMH NIH HHS [1-R03-MH61057-01, R03 MH061057-01] NR 36 TC 25 Z9 25 U1 4 U2 9 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 WIN PY 2006 VL 16 IS 1 BP 101 EP 107 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 005RH UT WOS:000234841000016 PM 16599356 ER PT J AU Gonzales, JJ Moten, C AF Gonzales, JJ Moten, C TI Commentary: Community partnered research: Driving sensemaking, managing knowledge, and moving mental health care to new heights SO ETHNICITY & DISEASE LA English DT Editorial Material C1 Abt Associates Inc, Bethesda, MD 20814 USA. NIMH, Ctr Neurosci, Bethesda, MD 20892 USA. RP Gonzales, JJ (reprint author), Abt Associates Inc, 4550 Montgomery Ave,Suite 800 N, Bethesda, MD 20814 USA. NR 6 TC 1 Z9 1 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 WIN PY 2006 VL 16 IS 1 SU 1 BP 156 EP 158 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 010EW UT WOS:000235170700017 ER PT J AU Moolchan, ET Franken, FH Jaszyna-Gasior, M AF Moolchan, ET Franken, FH Jaszyna-Gasior, M TI Adolescent nicotine metabolism: Ethnoracial differences among dependent smokers SO ETHNICITY & DISEASE LA English DT Article DE adolescent; ethnicity; metabolisin; nicotine; smoking ID CIGARETTE CONSUMPTION; DISPOSITION KINETICS; CESSATION TREATMENT; TOBACCO SMOKING; WHITE WOMEN; C-OXIDATION; CYP2A6; COTININE; AGE; TRANS-3'-HYDROXYCOTININE AB Variations in nicotine metabolism are thought to contribute to differences in cigarette consumption between African Americans and Caucasian adult smokers. To investigate the potential mechanism of previously documented lower smoking rates among African American adolescent snickers seeking cessation treatment, we measured nicotine metabolite ratios as markers of the metabolic disposition of nicotine, which is generally considered to be Under the influence of cylochrome P450 (CYP) 2A6. Plasma ratios of trans-3'-hydroxycotinine (3HC) to cotinine (COT) were examined in 92 cessation treatment-seeking adolescents (mean age 15.2 years, standard deviation [SD] 1.3, 69% female, 31% African American, mean Fagerstrom Test for Nicotine Dependence [FTND] 6.5, SD 1.6, mean years smoked 2.6, SD 1.6). Groups were similar in age, gender distribution, and mean FTND score. Analysis with independent t tests revealed significantly lower number of cigarettes per clay (CPD) (15.1, SD 7.6 vs 19.6, SD 8.0, P=.013) and nicotine metabolite ratios (0.27, SD 0.15 vs 0.35, SD 0.16, P=.026) in African-American compared to Caucasian adolescent smokers. Consistent with metabolic variation, mean COT/CPD ratio was significantly higher in African-American compared to Caucasian adolescents. Results remained statistically significant when comparing menthol smokers by ethnicity. These findings are consistent with those found among adult smokers and provide a putative mechanism for reported ethnoracial differences in adolescent cigarette consumption. Our results Underscore the need for measures independent Of consumption for determining degree of nicotine dependence and treatment selection across ethnicities, even among youths. C1 NIDA, Teen Tobacco Addict Treatment Res Clin, Addict Treatment Res Clin, Intramural Res Program,NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. RP Moolchan, ET (reprint author), NIDA, Teen Tobacco Addict Treatment Res Clin, Addict Treatment Res Clin, Intramural Res Program,NIH,Dept Hlth & Human Serv, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM etmoolcha@intra.nida.nih.gov FU Intramural NIH HHS NR 40 TC 34 Z9 34 U1 1 U2 3 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 WIN PY 2006 VL 16 IS 1 BP 239 EP 243 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 005RH UT WOS:000234841000037 PM 16599377 ER PT J AU Rice, MM Jablonski, KA Fowler, SE Domanski, MJ Braunwald, E AF Rice, Madeline Murguia Jablonski, Kathleen A. Fowler, Sarah E. Domanski, Michael J. Braunwald, Eugene TI The dangers of categorizing BMI: reply SO EUROPEAN HEART JOURNAL LA English DT Letter C1 George Washington Univ, Ctr Biostat, Rockville, MD 20852 USA. NHLBI, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Rice, MM (reprint author), George Washington Univ, Ctr Biostat, Rockville, MD 20852 USA. EM mrice@biostat.bsc.gwu.edu NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2006 VL 27 IS 23 BP 2904 EP 2904 DI 10.1093/eurheartj/ehl331 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 111RN UT WOS:000242472100032 ER PT J AU Roth, MJ Qiao, YL Abnet, CC Zhang, YH Dawsey, SM Dong, ZW Taylor, PR AF Roth, Mark J. Qiao, You-Lin Abnet, Christian C. Zhang, You-Hui Dawsey, Sanford M. Dong, Zhi-Wei Taylor, Philip R. TI Cellular immune response is not associated with incident cancer or total mortality: a prospective follow-up SO EUROPEAN JOURNAL OF CANCER PREVENTION LA English DT Article DE cancer; immunology; nutrition; prospective study; stimulation index AB The objective of this study was to determine whether immunologic competence, as measured by lymphocyte stimulation indices from three different ex vivo challenges, is associated with subsequent risk of cancer or total mortality in Linzhou, China, a population at high risk for upper gastrointestinal cancers. Cellular immune function tests were conducted on a subgroup of 381 trial participants after 5.25 years of intervention to evaluate whether nutrient supplementation affected the cellular immune system and found significantly higher T-lymphocyte mitogenic responsiveness to phytohemagglutinin-M among men receiving daily supplementation of P-carotene (15 mg) plus selenium (50 mu g) plus a-tocopherol (30mg) (supplementation factor D) compared with those who did not receive this supplement (P < 0.05). The current analysis reports 10 years of post-trial prospective follow-up of these 381 trial participants and identifies 53 incident cancers, 48 (92%) of which were upper gastrointestinal cancers, including 22 esophageal cancers, 22 gastric cardia cancers, and four noncardia gastric cancers. Ninety-one deaths occurred among the 381 participants, including 33 upper gastrointestinal cancer deaths, 23 heart disease deaths, 16 stroke deaths, and seven fatal accidents. Multivariate Cox proportional hazards models including variables for age at time of tests, sex, tobacco smoking, alcohol drinking, and original trial treatment group showed no significant associations between phytohemagglutinin-M, concanavalin-A, or anti-CD3 stimulation indices and subsequent cancer incidence or total mortality. This implies that immune competence, as measured by these stimulation indices, is not associated with incident cancer or total mortality in this population. C1 NCI, NIH, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, Bethesda, MD 20892 USA. Genet Epidemiol Branch, Bethesda, MD USA. Chinese Acad Med Sci, Dept Canc Epidemiol, Inst Canc, Beijing 100037, Peoples R China. Chinese Acad Med Sci, Dept Immunol, Inst Canc, Beijing 100037, Peoples R China. RP Roth, MJ (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, EPS,Suite 320,MSC 7232, Rockville, MD 20852 USA. EM mr166i@nih.gov RI Qiao, You-Lin/B-4139-2012; Abnet, Christian/C-4111-2015 OI Qiao, You-Lin/0000-0001-6380-0871; Abnet, Christian/0000-0002-3008-7843 FU Intramural NIH HHS NR 9 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-8278 J9 EUR J CANCER PREV JI Eur. J. Cancer Prev. PD DEC PY 2006 VL 15 IS 6 BP 548 EP 550 DI 10.1097/01.cej.0000220632.93104.2d PG 3 WC Oncology SC Oncology GA 114UF UT WOS:000242690400014 PM 17106336 ER PT J AU Sarma, A Horne, MK AF Sarma, Anita Horne, McDonald K., III TI Venlafaxine-induced ecchymoses and impaired platelet aggregation SO EUROPEAN JOURNAL OF HAEMATOLOGY LA English DT Article DE platelets; platelet inhibitory drugs; serotonin reuptake inhibitors ID SEROTONIN REUPTAKE INHIBITORS; FLUOXETINE; DISPOSITION; ASSOCIATION; RISK AB Objective: To describe a case of venlafaxine-induced ecchymoses.Methods: A patient with a history of ecchymoses coincident with venlafaxine therapy was rechallenged with the drug. Her platelet function was assessed with aggregation and ATP release studies before the rechallenge and after she developed ecchymoses. In addition, the effect of venlafaxine on platelet aggregation and ATP release was studied in vitro by adding the drug to platelet-rich plasma from normal donors. Results: After 4 wk of treatment with venlafaxine our patient developed extensive ecchymoses. At that time her platelet aggregation and release responses to epinephrine, ADP, collagen, and arachidonic acid were markedly suppressed. Adding venlafaxine to normal platelet-rich plasma also dramatically reduced the aggregation and release responses to the same agonists as well as to serotonin, but the concentrations of venlafaxine required were 1000-fold greater than those normally achieved clinically. Conclusions: Our patient demonstrated an idiosyncratic hypersensitivity to the platelet inhibitory effects of venlafaxine. Because venlafaxine is an inhibitor of serotonin uptake by platelets and neurons, this mechanism may contribute to the impact of this drug on platelet function. However, our in vitro studies suggest that this hypothesis is inadequate to explain the observations completely. C1 NIH, Hematol Serv, Dept Lab Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Horne, MK (reprint author), NIH, Hematol Serv, Dept Lab Med, Warren G Magnuson Clin Ctr, Rm 2C306,Bldg 10, Bethesda, MD 20892 USA. EM mhorne@mail.cc.nih.gov FU Intramural NIH HHS NR 16 TC 10 Z9 10 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0902-4441 J9 EUR J HAEMATOL JI Eur. J. Haematol. PD DEC PY 2006 VL 77 IS 6 BP 533 EP 537 DI 10.1111/j.0902-4441.2006.t01-1-EJH2919.x PG 5 WC Hematology SC Hematology GA 101IR UT WOS:000241735000013 PM 16978240 ER PT J AU Wu, WH Weigand, L Belkaid, Y Mendez, S AF Wu, Wenhui Weigand, Luise Belkaid, Yasmine Mendez, Susana TI Immunomodulatory effects associated with a live vaccine against Leishmania major containing CpG oligodeoxynucleotides SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE CpG; IL-6; latency; Leishmania major; T-reg ID REGULATORY T-CELLS; CUTANEOUS LEISHMANIASIS; DENDRITIC CELLS; TOLL-LIKE; IN-VIVO; RECEPTOR ANTIBODY; NATURAL MODEL; INFECTION; INDUCTION; IMMUNITY AB The inoculation of live Leishmania major to produce a lesion that heals (leishmanization) is to date the only vaccine against cutaneous leishmaniasis that has proven effective in humans, but it still has an unacceptable frequency of large ulcerating lesions that are slow to heal or, in rare cases, non-healing. We have previously shown that C57BL/6 mice vaccinated intradermally with 10(4) L. major/50 mu g CpG oligodeoxynucleotides develop little or no dermal lesions and show early containment of parasite growth in the vaccination site, eliminating safety concerns related to the inoculation of live organisms. The addition of CpG to the live vaccine resulted in early activation of dermal dendritic cells and increased IL-6 production, as well as in a reduction in the accumulation of Foxp3(+)CD4(+)CD25(+) regulatory T (T-reg) cells that naturally occurs in the skin following Leishmania infection. Neutralization of IL-6 caused the development of larger lesions and increased local Treg cell numbers. Transfer of vaccine-primed dendritic cells into IL-6-deficient mice mitigated lesion development, indicating that IL-6 reconstitution limited pathology in the vaccination site. C1 George Washington Univ, Dept Microbiol Immunol & Trop Med, Washington, DC USA. NIAID, Mucosal Immunol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Mendez, S (reprint author), Cornell Univ, Coll Vet Med, James A Baker Inst Anim Hlth, Ithaca, NY 14853 USA. EM sm457@cornell.edu FU NIAID NIH HHS [R01AI057992-01, R21AI61379] NR 43 TC 33 Z9 33 U1 0 U2 0 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 DEC PY 2006 VL 36 IS 12 BP 3238 EP 3247 DI 10.1002/eji.200636472 PG 10 WC Immunology SC Immunology GA 120IQ UT WOS:000243078600015 PM 17109471 ER PT J AU Scholz, S Mandel, RJ Fernandez, HH Foote, KD Rodriguez, RL Barton, E Munson, S Singleton, A Okun, MS AF Scholz, S. Mandel, R. J. Fernandez, H. H. Foote, K. D. Rodriguez, R. L. Barton, E. Munson, S. Singleton, A. Okun, M. S. TI LRRK2 mutations in a clinic-based cohort of Parkinson's disease SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Article DE dardarin; G2019S; LRRK2; Parkinson's disease ID AUTOSOMAL-DOMINANT PARKINSONISM; GENE; ONSET AB In the last decade, major breakthroughs in the understanding of genetic contributions to Parkinson's disease (PD) have been achieved. Recently, mutations in LRRK2, encoding dardarin, have been found to be responsible for an autosomal dominant parkinsonism (OMIM 607060). We screened 311 subjects (cases: n = 202, controls: n = 109) for the three previously reported LRRK2 mutations. Our investigation revealed a sporadic case of PD with a heterozygous mutation G2019S (c.6055G > A). Here, we present the clinical phenotype of this patient and discuss the implications of genetic testing for the G2019S mutation in patients with sporadic PD. C1 Univ Florida, Dept Neurol, Movement Disorders Ctr, Gainesville, FL 32610 USA. Univ Florida, Dept Neurosurg, Movement Disorders Ctr, Gainesville, FL 32610 USA. NIA, Mol Genet Unit, NIH, Bethesda, MD 20892 USA. RP Okun, MS (reprint author), Univ Florida, Dept Neurol, Movement Disorders Ctr, POB 100235, Gainesville, FL 32610 USA. EM okun@neurology.ufl.edu RI Singleton, Andrew/C-3010-2009; OI Okun, Michael/0000-0002-6247-9358; Scholz, Sonja/0000-0002-6623-0429 FU Intramural NIH HHS NR 13 TC 3 Z9 3 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD DEC PY 2006 VL 13 IS 12 BP 1298 EP 1301 DI 10.1111/j.1468-1331.2006.01472.x PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 104IW UT WOS:000241953100009 PM 17116211 ER PT J AU Malkova, L Heuer, E Saunders, RC AF Malkova, L. Heuer, E. Saunders, R. C. TI Longitudinal magnetic resonance imaging study of rhesus monkey brain development SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE Macaca mulatta; MRI; myelination; T1-weighted white matter; total brain volume; volumetric analysis ID MACACA-NEMESTRINA; INFANT MONKEYS; PIGTAILED MACAQUES; RECOGNITION MEMORY; SOCIAL-DEVELOPMENT; COGNITIVE FUNCTION; SEX-DIFFERENCES; WHITE-MATTER; IN-VIVO; MATURATION AB To examine early brain development, T1-weighted structural MRI scans of seven rhesus monkeys (Macaca mulatta) were obtained longitudinally between the ages of 1 week and 4 years at 12 age points. Total brain volume, calculated at each age point, increased significantly, by 56%, between 1 week and 4 years. The greatest increase of 22% occurred between 1 week and 1 month, followed by further significant increases between 1 and 2 months, and 3 and 4 months. Gradually smaller increases continued up to 3 years with no further significant changes thereafter. A robust maturation of white matter occurred between 1 week, at which the only easily identifiable fibre tracts were internal capsule and optic radiations, and 3 months, at which most large fibre tracts were visible; only at this age reproducible measurements were possible for all cases. White matter volume increased by 126% between 3 months and 4 years, with the biggest increase between 3 and 4 months (32%) followed by smaller but significant increases up to 4 years. The macaque brain development parallels that of humans by reaching the maximum in total brain volume around the age of sexual maturity (in macaques 3-4 years) and by the increases in white matter continuing beyond this age. The most rapid growth in both total brain volume and white matter from birth to approximately 4 months is consistent with the emergence of various cognitive abilities in macaques at that age. C1 Georgetown Univ, Dept Pharmacol, Washington, DC 20007 USA. NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Malkova, L (reprint author), Georgetown Univ, Dept Pharmacol, 900 Reservoir Rd, Washington, DC 20007 USA. EM malkoval@georgetown.edu FU Intramural NIH HHS; NICHD NIH HHS [HD39937, K02 HD42269] NR 74 TC 43 Z9 43 U1 3 U2 9 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 DEC PY 2006 VL 24 IS 11 BP 3204 EP 3212 DI 10.1111/j.1460-9568.2006.05175.x PG 9 WC Neurosciences SC Neurosciences & Neurology GA 124IO UT WOS:000243361700024 PM 17156381 ER PT J AU Barrett, T Kobayashi, H Brechbiel, M Choyke, PL AF Barrett, Tristan Kobayashi, Hisataka Brechbiel, Martin Choyke, Peter L. TI Macromolecular MRI contrast agents for imaging tumor angiogenesis SO EUROPEAN JOURNAL OF RADIOLOGY LA English DT Review DE angiogenesis; MRI; contrast media; macromolecular contrast; cancer; dendrimers; liposomes; dextrans ID SUPERPARAMAGNETIC IRON-OXIDE; MAGNETIC-RESONANCE ANGIOGRAPHY; EXPERIMENTAL BREAST-TUMORS; DTPA-LABELED DEXTRAN; GD-DTPA; IN-VIVO; POLYAMIDOAMINE DENDRIMERS; MOLECULAR-WEIGHT; COLON-CARCINOMA; CANCER-CELLS AB Angiogenesis has long been accepted as a vital process in the growth and metastasis of tumors. As a result it is the target of several novel anti-cancer medications. Consequently, there is an urgent clinical need to develop accurate, non-invasive imaging techniques to improve the characterization of tumor angiogenesis and the monitoring of the response to anti-angiogenic therapy. Macromolecular MR contrast media (MMCM) offer this diagnostic potential by preferentially exploiting the inherent hyperpermeable nature of new tumor vessels compared with normal vessels. Over the last 10-15 years many classes of MMCM have been developed. When evaluated with dynamic contrast enhanced (DCE) MRI, a number of MMCM have demonstrated in vivo imaging properties that correlate with ex vivo histological features of angiogenesis. The enhancement patterns with some MMCM have been reported to correlate with tumor grade, as well as show response to anti-angiogenic and anti-vascular drugs. Future applications of MMCM include targeted angiogenesis imaging and drug delivery of anti-cancer `payloads'. Herein we discuss the best known MMCMs along with their advantages and disadvantages. (C) 2006 Elsevier Ireland Ltd. All rights reserved. C1 NCI, Mol Imaging Program, Bethesda, MD 20892 USA. NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, Bethesda, MD 20892 USA. RP Choyke, PL (reprint author), NCI, Mol Imaging Program, Bldg 10,Room 1B40, Bethesda, MD 20892 USA. EM pchoyke@nih.gov FU Intramural NIH HHS NR 102 TC 101 Z9 104 U1 4 U2 18 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0720-048X J9 EUR J RADIOL JI Eur. J. Radiol. PD DEC PY 2006 VL 60 IS 3 BP 353 EP 366 DI 10.1016/j.ejrad.2006.06.025 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 118YA UT WOS:000242978200007 PM 16930905 ER PT J AU Qu, Y Chang, L Klaff, J Seemann, R Greenstein, D Rapoport, SI AF Qu, Ying Chang, Lisa Klaff, Justin Seemann, Ruth Greenstein, Deanna Rapoport, Stanley I. TI Chronic fluoxetine upregulates arachidonic acid incorporation into the brain of unanesthetized rats SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Article DE serotonin; phospholipase A(2); arachidonic; ftuoxetine; rat; 5-HT2A/2C; receptor; depression ID OBSESSIVE-COMPULSIVE DISORDER; PHOSPHOLIPASE A(2) ACTIVATION; SEROTONIN UPTAKE INHIBITORS; IN-VIVO; SIGNAL-TRANSDUCTION; EXTRACELLULAR SEROTONIN; DOCOSAHEXAENOIC ACID; 5-HT1B AUTORECEPTORS; PREFRONTAL CORTEX; CHRONIC LITHIUM AB Serotonergic 5-HT2A/2c receptors can be coupled to phospholipase A(2) (PLA(2)) activation to release the second messenger, arachidonic acid (AA), from membrane phosphotipids. We wished to see if this signaling process in rat brain would be altered by chronic administration followed by 3days of washout of the selective serotonin reuptake inhibitor, fluoxetine. We injected [H-3]AA intravenously in unanesthetized rats and used quantitative autoradiography to determine the incorporation coefficient k(*) for AA (regional brain radioactivity/integrated plasma radioactivity), a marker of PLA(2) activation, in each of 86 brain regions. k* was measured following acute i.p. saline or (+/-)-2,5-dimethoxy-4-iodophenyt-2aminopropane (DOI, 1.0mg/kg i.p.), a 5-HT2A/2c receptor agonist, in rats injected for 21 days with 10mg/kg i.p. ftuoxetine or saline daily, followed by 3days without injection. Acute DOI produced statistically significant increments in k* in brain regions with high densities of 5-HT2A/2C receptors, but the increments did not differ significantly between the chronic ftuoxetine- and saline-treated rats. Additionally, chronic fluoxetine compared with saline widely and significantly increased baseline values of k*. These results suggest that 5-HT2A/2C receptorinitiated AA signaling is unaffected by chronic fluoxetine plus 3days of washout in the rat, but that baseline AA signaling is nevertheless upregulated. This upregulation likely occurs independently of significant active drug in brain, considering the short brain half-lives of it and its norfLuoxetine metabolite. Such upreguLation may contribute to ftuoxetine's efficacy against human depression. Published by Elsevier B.V. and ECNP. C1 NIA, Brain Physiol & Metabol Sect, NIH, Bethesda, MD 20892 USA. NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. RP Rapoport, SI (reprint author), NIA, Brain Physiol & Metabol Sect, NIH, Bldg 9,Room 1S128,9 Mem Dr, Bethesda, MD 20892 USA. EM sir@helix.nih.gov FU Intramural NIH HHS NR 76 TC 16 Z9 16 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD DEC PY 2006 VL 16 IS 8 BP 561 EP 571 DI 10.1016/j.euroneuro.2006.01.008 PG 11 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 114WF UT WOS:000242695600003 PM 16517130 ER PT J AU de Serres, FJ Blanco, I Fernandez-Bustillo, E AF de Serres, F. J. Blanco, I. Fernandez-Bustillo, E. TI Estimated numbers and prevalence of Pl*S and Pl*Z deficiency alleles of alpha(1)-antitrypsin deficiency in Asia SO EUROPEAN RESPIRATORY JOURNAL LA English DT Article DE alpha(1)-antitrypsin deficiency; alpha(1)-protease; alpha(1)-protease inhibitor; genetic epidemiology; protease inhibitor phenotypes ID SERUM-PROTEIN POLYMORPHISMS; RED-CELL ENZYME; ALPHA-1-ANTITRYPSIN PHENOTYPES; PIM SUBTYPES; GENETIC EPIDEMIOLOGY; POPULATION GROUPS; SAUDI-ARABIA; JAPANESE; FREQUENCIES; EUROPE AB The current study focuses on updating estimates of the numbers of individuals carrying the two most common deficiency alleles, protease inhibitor (PI)*S and PI*Z, for a,antitrypsin deficiency (AT-D) in 20 Asian countries. A total of 170 cohorts with 31,177 individuals were selected from 20 Asian countries. The total AT-D populations in the countries selected were: 7,264 ZZ; 36,754 SZ; 6,672,479 MZ; 46,492 SS; and 16,881,108 MS. Marked differences among the Asian countries and regions were also found for the prevalence of the deficiency alleles PI*S and PI*Z. These numbers demonstrate that AT-D is not just a genetic disease that affects smaller numbers than various countries, for example, in Europe. There were marked differences between the prevalence of the PI*S and PI*Z deficiency alleles among these 20 Asian countries as well as among the countries within a given geographic region in Asia. The largest numbers of ZZ phenotypes (3,000-14,000) were in Afghanistan, Pakistan, Saudi Arabia and Thailand; with < 1,700 in each of the remaining countries. C1 Natl Inst Environm Hlth Sci, Ctr Evaluat Risks Human Reprod, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. Hosp Valle Nalon, Div Internal Med, Resp Dis Branch, Sama De Langreo, Spain. Hosp Univ Cent Asturias, Biostat Unit, Oviedo, Principado, Spain. RP de Serres, FJ (reprint author), Natl Inst Environm Hlth Sci, Ctr Evaluat Risks Human Reprod, Natl Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA. EM deserres@bellsouth.net NR 51 TC 15 Z9 15 U1 2 U2 2 PU EUROPEAN RESPIRATORY SOC JOURNALS LTD PI SHEFFIELD PA 146 WEST ST, STE 2.4, HUTTONS BLDG, SHEFFIELD S1 4ES, ENGLAND SN 0903-1936 J9 EUR RESPIR J JI Eur. Resp. J. PD DEC PY 2006 VL 28 IS 6 BP 1091 EP 1099 DI 10.1183/09031936.00029806 PG 9 WC Respiratory System SC Respiratory System GA 115HJ UT WOS:000242725100007 PM 17005586 ER PT J AU Nadif, R Mintz, M Marzec, J Jedlicka, A Kauffmann, F Kleeberger, SR AF Nadif, R. Mintz, M. Marzec, J. Jedlicka, A. Kauffmann, F. Kleeberger, S. R. TI IL18 and IL18R1 polymorphisms, lung CT and fibrosis: a longitudinal study in coal miners SO EUROPEAN RESPIRATORY JOURNAL LA English DT Article DE computed tomography; epidemiology; genetics; IL18; IL18R1 ID WORKERS PNEUMOCONIOSIS; GENE POLYMORPHISMS; INTERLEUKIN-18; ASSOCIATION; EXPRESSION; ASTHMA; IL-18; SARCOIDOSIS; ARTHRITIS; DISEASE AB It has been suggested that interleukin (IL)-18 plays a role in the development of inflammatory and fibrosing lung diseases. Associations of polymorphisms in the genes coding for IL-18 (108 /G-656T, C-607A, G-137C, T113G, C127T) and its receptor (IL8R1/C-69T) with coal workers' pneumoconiosis (CWP) were studied in 200 miners who were examined in 1990, 1994 and 1999. Coal-dust exposure was assessed according to job history and ambient measures. The main health outcome was lung computed tomography (CT) score in 1990. Internal coherence was assessed by studying CT score in 1994, 4-yr change in CT score and CWP incidence and prevalence. CT score in 1990 was a good predictor of radiographic grade in 1999 and, therefore, an appropriate subclinical quantitative trait. The IL18 -137C allele was associated with lower CT score in 1990 and 1994 (11.24 versus 1.69 and 1.57 versus 2.46, respectively), slower progression of CT score between 1990 and 1994 and lower pneumoconiosis prevalence in 1999 relative to the G allele (0.33 versus 0.77 and 8.2 versus 19.6%, respectively). Smoking- or dust-adjustment, and stratification on IL18R1 genotype and adjustment for haplotype effects did not change the conclusions. In conclusion, the results of the present study suggest a role for IL18 in reducing the development of this fibrosing lung disease. C1 INSERM, U780, F-94807 Villejuif, France. Univ Paris Sud, Fac Med, IFR69, Villejuif, France. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. NIEHS, Lab Resp Biol, Res Triangle Pk, NC 27709 USA. RP Nadif, R (reprint author), INSERM, U780, 16 Ave Paul Vaillant Couturier, F-94807 Villejuif, France. EM nadif@vjf.inserm.fr RI Nadif, Rachel/R-2876-2016 OI Nadif, Rachel/0000-0003-4938-9339 FU NIEHS NIH HHS [ES-09606] NR 25 TC 11 Z9 13 U1 0 U2 2 PU EUROPEAN RESPIRATORY SOC JOURNALS LTD PI SHEFFIELD PA 146 WEST ST, STE 2.4, HUTTONS BLDG, SHEFFIELD S1 4ES, ENGLAND SN 0903-1936 J9 EUR RESPIR J JI Eur. Resp. J. PD DEC PY 2006 VL 28 IS 6 BP 1100 EP 1105 DI 10.1183/09031936.00031506 PG 6 WC Respiratory System SC Respiratory System GA 115HJ UT WOS:000242725100008 PM 16971411 ER PT J AU Bellino, FL AF Bellino, Francis L. TI Advances in endocrinology of aging research, 2005-2006 SO EXPERIMENTAL GERONTOLOGY LA English DT Review DE endocrinology of aging; steroidal signaling; cholestanoic acid; sirtuins; insulin secretion; insulin signaling; klotho; gonadotropins; FSH; bone cells; bone density; model organisms ID PANCREATIC BETA-CELLS; LUTEINIZING-HORMONE; DAUER FORMATION; MENOPAUSAL TRANSITION; INSULIN-SECRETION; KLOTHO; LONGEVITY; ELEGANS; SIRT1; MICE AB The purpose of this brief review is to highlight some of the more important advances in endocrinology of aging research over the past year. Four advances were chosen and briefly described. First, exploration of the early steps in the generation of the internal steroidal hormonal signal involved in lifespan extension via the insulin/IGF-like signaling pathway in the nematode by two research groups revealed that the product of cholestanoic acid derivatives metabolized by a cytochrome P-450-like protein activates a protein with homology to the mammalian nuclear receptor superfamily, a process strikingly similar to the steroid hormone signaling pathway documented in mammalian systems. Second is the discovery that sirtuins, proteins that regulate lifespan in model organisms, enhance pancreatic insulin secretion in mice following a glucose challenge, suggesting the potential to regulate mammalian lifespan through regulation of the insulin signaling pathway. Third, the newly discovered hormone klotho, which also plays a role in regulating lifespan, in this case in mice, is reported to not only negatively affect insulin sensitivity but, perhaps more importantly, significantly affects calcium and phosphate metabolism as a required cofactor of Fgf-23 signaling. Finally the gonadotropin FSH is shown to directly affect bone density in mice separate from any direct effect of estrogen, suggesting that reproductive hormones other than estrogen can directly impact menopause-associated pathophysiology in non-reproductive tissues. (c) 2006 Elsevier Inc. All rights reserved. C1 NIA, Biol Aging Program, Bethesda, MD 20891 USA. RP Bellino, FL (reprint author), 4899 Elmer Derr Rd, Frederick, MD 21703 USA. EM bellinof@mail.nih.gov FU Intramural NIH HHS [NIH0010113396]; PHS HHS [NIH0010113396] NR 25 TC 9 Z9 9 U1 0 U2 5 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 DEC PY 2006 VL 41 IS 12 BP 1228 EP 1233 DI 10.1016/j.exger.2006.09.007 PG 6 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 122IQ UT WOS:000243219800007 PM 17110071 ER PT J AU Boger, HA Middaugh, LD Huang, P Zaman, V Smith, AC Hoffer, BJ Tomac, AC Granholm, AC AF Boger, H. A. Middaugh, L. D. Huang, P. Zaman, V. Smith, A. C. Hoffer, B. J. Tomac, A. C. Granholm, A. -Ch. TI A partial GDNF depletion leads to earlier age-related deterioration of motor function and tyrosine hydroxylase expression in the substantia nigra SO EXPERIMENTAL NEUROLOGY LA English DT Article DE dopamine; substantia nigra; Parkinson's disease; animal models; movement disorders; neurodegeneration ID MICE LACKING GDNF; MIDBRAIN DOPAMINERGIC-NEURONS; NEUROTROPHIC FACTOR GDNF; PARKINSONS-DISEASE; STRIATAL DOPAMINE; HETEROZYGOUS MICE; GROWTH-FACTOR; ALZHEIMERS-DISEASE; KIDNEY DEVELOPMENT; BETA SUPERFAMILY AB Glial cell line-derived neurotrophic factor (GDNF) is a trophic factor for peripheral organs, spinal cord, and midbrain dopamine (DA) neurons. Levels of GDNF deteriorate in the substantia nigra in Parkinson's disease (PD). A heterozygous mouse model was created to assess whether chronic reductions in this neurotrophic factor impact motor function and the nigrostriatal dopamine system during the aging process. Due to the important role GDNF plays in kidney development, kidney function and histology were assessed and were found to be normal in both wild-type (WT) and GDNF(+/-) mice up to 22 months of age. Further, the animals of both genotypes had similar weights throughout the experiment. Locomotor activity was assessed for male WT and GDNF(+/-) mice at 4-month intervals from 4 to 20 months of age. Both GDNF(+/-) and WT mice exhibited an age-related decline in horizontal activity, although this was found 4 months earlier in GDNF(+/-) mice, at 12 months of age. Comparison of young (8 month old) and aged (20 month old) GDNF(+/-) and WT mice on an accelerating rotarod apparatus established a deficiency for aged but not young GDNF(+/-) mice, while aged WT mice performed as well as young WT mice on this task. Finally, both WT and GDNF(+/-) mice exhibited an age-related decrease in substantia nigra TH immunostaining, which was accelerated in the GDNF(+/-) mice. These behavioral and histological alterations suggest that GDNF may be an important factor for maintenance of rnotor coordination and spontaneous activity as well as DA neuronal function during aging, and further suggest that GDNF(+/-) mice may serve as a model for neuroprotective or rescue studies. (c) 2006 Elsevier Inc. All rights reserved. C1 Med Univ S Carolina, Ctr Aging, Dept Neurosci, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biometry & Epidemiol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Comparat Med, Charleston, SC 29425 USA. NIDA, Intramural Res Program, Baltimore, MD 21224 USA. RP Granholm, AC (reprint author), Med Univ S Carolina, Ctr Aging, Dept Neurosci, 26 Bee St, Charleston, SC 29425 USA. EM granholm@musc.edu FU NIA NIH HHS [AG023630, P01 AG023630] NR 88 TC 64 Z9 67 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 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD DEC PY 2006 VL 202 IS 2 BP 336 EP 347 DI 10.1016/j.expneurol.2006.06.006 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 106NJ UT WOS:000242107300009 PM 16889771 ER PT J AU Yakovich, AJ Ragone, FL Alfonzo, JD Sackett, DL Werbovetz, KA AF Yakovich, Adam J. Ragone, Frank L. Alfonzo, Juan D. Sackett, Dan L. Werbovetz, Karl A. TI Leishmania tarentolae: Purification and characterization of tubulin and its suitability for antileishmanial drug screening SO EXPERIMENTAL PARASITOLOGY LA English DT Article DE Leishmania; tubulin; dinitroaniline; drug discovery ID AMINO-ACID-SEQUENCE; ALPHA-TUBULIN; PARASITIC PROTOZOAN; BETA-TUBULIN; PHOSPHOROTHIOAMIDATE HERBICIDES; DIFFERENTIAL EXPRESSION; PLASMODIUM-FALCIPARUM; TRYPANOSOMA-CRUZI; PORCINE BRAIN; MEXICANA AB Previously, tubulin has been purified from Leishmania amazonensis and used to identify novel molecules with selective antimitotic activity. However, L. amazonensis is pathogenic and requires a relatively expensive medium for large-scale cultivation. Herein, the purification and characterization of tubulin from the non-pathogenic Leishmania tarentolae is reported, together with the sequence of alpha- and beta-tubulin from this organism. This protein was purified by sonication, diethylaminoethyl-Sepharose chromatography, and one assembly disassembly cycle in 1% overall recovery based on total cellular protein. Leishmania tarentolae tubulin was indistinguishable from the corresponding L. amazonensis protein in terms of binding affinity for dinitroaniline sulfanilamides and sensitivity to assembly inhibition by these compounds. The amino acid sequences derived from the L. tarentolae alpha- and beta-tubulin genes were 99.6 and 99.4% identical to the corresponding amino acid sequences from the Leishmania major Friedlin strain. These results indicate that tubulin from L. tarentolae is suitable for use in drug screening. (c) 2006 Elsevier Inc. All rights reserved. C1 Ohio State Univ, Coll Pharm, Div Med Chem & Pharmacognosy, Columbus, OH 43210 USA. Ohio State Univ, Coll Biol Sci, Columbus, OH 43210 USA. NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. RP Werbovetz, KA (reprint author), Ohio State Univ, Coll Pharm, Div Med Chem & Pharmacognosy, Columbus, OH 43210 USA. EM werbovetz.l@osu.edu RI Werbovetz, Karl/E-4290-2011 FU Intramural NIH HHS; NIAID NIH HHS [R01 AI061021-03, R01 AI061021, R01 AI 061021] NR 34 TC 11 Z9 12 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 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD DEC PY 2006 VL 114 IS 4 BP 289 EP 296 DI 10.1016/j.exppara.2006.04.008 PG 8 WC Parasitology SC Parasitology GA 115HY UT WOS:000242726600007 PM 16753146 ER PT J AU Zhou, M Veenstra, TD AF Zhou, Ming Veenstra, Timothy D. TI Multiplexed immunofluoreseence microscopy for the interrogation of cellular protein complexes SO EXPERT REVIEW OF PROTEOMICS LA English DT Review DE antibody; multidimensional fluorescence microscopy; protein interactions; protein topology; proteome AB Knowing that a specific protein is present within a cell provides little insight into its function. In a study by Schubert and colleagues, the investigators present a multidimensional method that utilizes fluorescence microscopy and automated antibody introduction and detection, which is potentially capable of localizing hundreds of proteins within individual cells. The method, referred to as multiepitope-ligand cartography, is validated in the analysis of cell-surface receptors in peripheral mononuclear blood cells, and then used to map protein complexes in a series of disease models, including psoriasis and chronic constriction injury. Within each experiment, the locales of each protein are presented in a binary format and the data are interpreted to recognize specific proteins that control the topology of the protein network. The hope is that by identifying partnerships between proteins and those proteins that are most responsible for these interactions, novel diagnostic features and therapeutic targets can be established. C1 SAIC Frederick Inc, Natl Canc Inst Frederick, Lab Proteom & Analyt Technol, Frederick, MD 21702 USA. RP Veenstra, TD (reprint author), SAIC Frederick Inc, Natl Canc Inst Frederick, Lab Proteom & Analyt Technol, Frederick, MD 21702 USA. EM veenstra@ncifcrf.org NR 5 TC 4 Z9 4 U1 1 U2 2 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1478-9450 J9 EXPERT REV PROTEOMIC JI Expert Rev. Proteomics PD DEC PY 2006 VL 3 IS 6 BP 581 EP 583 DI 10.1586/14789450.3.6.581 PG 3 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 136PE UT WOS:000244235800011 PM 17181472 ER PT J AU Zhang, W Shin, EJ Wang, TG Lee, PH Pang, H Wie, MB Kim, WK Kim, SJ Huang, WH Wang, YJ Zhang, WQ Hong, JS Kim, HC AF Zhang, Wei Shin, Eun-Joo Wang, Tongguang Lee, Phil Ho Pang, Hao Wie, Myung-Bok Kim, Won-Ki Kim, Seong-Jin Huang, Wen-Hsin Wang, Yongjun Zhang, Wanqin Hong, Jau-Shyong Kim, Hyoung-Chun TI 3-hydroxymorphinan, a metabolite of dextromethorphan, protects nigrostriatal pathway against MPTP-elicited damage both in vivo and in vitro SO FASEB JOURNAL LA English DT Article DE PD; substantia nigra pars compacta (SNpc); striatum; astroglia; neurotrophic factors; microglia; ROS ID NIGRAL DOPAMINERGIC-NEURONS; PARKINSONS-DISEASE; NEUROTROPHIC FACTOR; MICROGLIAL ACTIVATION; NADPH OXIDASE; HISTONE DEACETYLASE; SUBSTANTIA-NIGRA; VALPROIC ACID; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE MODEL; MESENCEPHALIC NEURONS AB We investigated the neuroprotective property of analogs of dextromethorphan (DM) in lipopolysaccharide (LPS) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) models to identify neuroprotective drugs for Parkinson's disease (PD). In vivo studies showed that daily injections with DM analogs protected dopamine (DA) neurons in substantia nigra pars compacta and restored DA levels in striatum using two different models for PD. Of the five analogs studied, 3-hydroxymorphinan (3-HM), a metabolite of DM, was the most potent, and restored DA neuronal loss and DA depletion up to 90% of the controls. Behavioral studies showed an excellent correlation between potency for preventing toxin-induced decrease in motor activities and neuroprotective effects among the DM analogs studied, of which 3-HM was the most potent in attenuating behavioral damage. In vitro studies revealed two glia-dependent mechanisms for the neuroprotection by 3-HM. First, astroglia mediated the 3-HM-induced neurotrophic effect by increasing the gene expression of neurotrophic factors, which was associated with the increased acetylation of histone H3. Second, microglia participated in 3-HM-mediated neuroprotection by reducing MPTP-elicited reactive microgliosis as evidenced by the decreased production of reactive oxygen species. In summary, we show the potent neuroprotection by 3-HM in LPS and MPTP PD models investigated. With its high efficacy and low toxicity, 3-HM may be a novel therapy for PD.-Zhang, W., Shin, E-J., Wang, T., Lee, P. H., Pang, H., Wie, M-B., Kim, W-K., Kim, S-J., Huang, W-H., Wang, Y., Zhang, W., Hong, J-S., Kim, H-C. 3-Hydroxymorphinan, a metabolite of dextromethorphan, protects nigrostriatal pathway against MPTP-elicited damage both in vivo and in vitro. C1 NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. Capital Univ Med Sci, Beijing Tiantan Hosp, Dept Neurol, Beijing, Peoples R China. Kangweon Natl Univ, Coll Pharm, Neuropsychopharmacol & Toxicol Program, Chunchon, South Korea. Kangweon Natl Univ, Dept Chem, Chunchon 200701, South Korea. Kangweon Natl Univ, Dept Vet Med, Chunchon 200701, South Korea. NCI, Lab Cell Regulat & Carcinogensis, NIH, Bethesda, MD 20892 USA. Dalian Med Univ, Dept Physiol, Dalian, Peoples R China. RP Kim, HC (reprint author), Kangweon Natl Univ, Coll Pharm, Neuropsychopharmacol & Toxicol Program, Chunchon 200701, South Korea. EM kimhc@kangwon.ac.kr FU Intramural NIH HHS NR 65 TC 47 Z9 49 U1 1 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD DEC PY 2006 VL 20 IS 14 BP 2496 EP 2511 DI 10.1096/fj.06-6006com PG 16 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 111YB UT WOS:000242490700010 PM 17142799 ER PT J AU Bloom, MS Whitcomb, BW AF Bloom, Michael S. Whitcomb, Brian W. TI Matching and the assumptions of standard frequentist statistics SO FERTILITY AND STERILITY LA English DT Letter ID COHORT C1 NICHHD, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA. RP Bloom, MS (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA. OI Bloom, Michael/0000-0002-0028-5494 NR 4 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD DEC PY 2006 VL 86 IS 6 BP 1805 EP 1805 DI 10.1016/j.fertnstert.2006.08.076 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 117HH UT WOS:000242863400048 PM 17055496 ER PT J AU Espey, MG AF Espey, Michael Graham TI Tumor macrophage redox and effector mechanisms associated with hypoxia SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Review DE tumor-associated macrophage; innate; iNOS; hypoxia; nitric oxide; oxygen; NOX-2; antimicrobial peptide; M2 ID NITRIC-OXIDE SYNTHASE; IMMATURE MYELOID CELLS; RESPIRATORY BURST; ARGINASE-I; ANTIBACTERIAL PEPTIDE; ANTICANCER THERAPIES; ISCHEMIC TISSUES; GENE-EXPRESSION; INNATE IMMUNITY; OXYGEN-TENSION AB Monocytes are recruited from the circulation into solid tumors where they differentiate into macrophages with unique phenotypes. While macrophages utilize oxygen in a broad range of immune effector functions, the generation of reactive oxygen and nitrogen oxide species is less clear in the setting of hypoxia, which can be a prominent feature of solid tumors. The relationships among innate immunity, redox systems, and the plasticity of phenotypic changes tumor-associated macrophages undergo in conjunction with tumor hypoxia will be examined. C1 NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. RP Espey, MG (reprint author), NCI, Radiat Biol Branch, NIH, 10-B3-B69,9000 Rockville Pike, Bethesda, MD 20892 USA. EM SP@nih.gov FU Intramural NIH HHS [Z99 DK999999] NR 94 TC 13 Z9 14 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD DEC 1 PY 2006 VL 41 IS 11 BP 1621 EP 1628 DI 10.1016/j.freeradbiomed.2006.08.026 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 103EU UT WOS:000241869300001 PM 17145549 ER PT J AU Stadtman, ER AF Stadtman, Earl R. TI Protein oxidation and aging SO FREE RADICAL RESEARCH LA English DT Review ID METHIONINE SULFOXIDE REDUCTASE; METAL-CATALYZED OXIDATION; AMINO-ACID-RESIDUES; LIPID-PEROXIDATION PRODUCT; BOVINE SERUM-ALBUMIN; GLUTAMINE-SYNTHETASE; OXIDIZED PROTEINS; AQUEOUS-SOLUTION; ESCHERICHIA-COLI; TYROSYL RESIDUES AB Organisms are constantly exposed to various forms of reactive oxygen species (ROS) that lead to oxidation of proteins, nucleic acids, and lipids. Protein oxidation can involve cleavage of the polypeptide chain, modification of amino acid side chains, and conversion of the protein to derivatives that are highly sensitive to proteolytic degradation. Unlike other types of modification (except cysteine oxidation), oxidation of methionine residues to methionine sulfoxide is reversible; thus, cyclic oxidation and reduction of methionine residues leads to consumption of ROS and thereby increases the resistance of proteins to oxidation. The importance of protein oxidation in aging is supported by the observation that levels of oxidized proteins increase with animal age. The age-related accumulation of oxidized proteins may reflect age-related increases in rates of ROS generation, decreases in antioxidant activities, or losses in the capacity to degrade oxidized proteins. C1 NHLBI, NIH, Biochem & Biophys Ctr, Bethesda, MD 20892 USA. RP Stadtman, ER (reprint author), NHLBI, NIH, Biochem & Biophys Ctr, Bldg 50,Room 2140,50 S Dr,MSC-8012, Bethesda, MD 20892 USA. EM erstadtman@nih.gov NR 112 TC 424 Z9 447 U1 8 U2 73 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1071-5762 J9 FREE RADICAL RES JI Free Radic. Res. PD DEC PY 2006 VL 40 IS 12 BP 1250 EP 1258 DI 10.1080/10715760600918142 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 102XY UT WOS:000241848100005 PM 17090414 ER PT J AU Nekhai, S Jeang, KT AF Nekhai, Sergei Jeang, Kuan-Teh TI Transcriptional and post-transcriptional regulation of HIV-1 gene expression: role of cellular factors for Tat and Rev SO FUTURE MICROBIOLOGY LA English DT Review DE Cdk2; Cdk9; CRM1; DDX3; HIV-1; protein phosphatase-1; Rev; RNA helicase; Tat ID IMMUNODEFICIENCY-VIRUS TYPE-1; RNA-POLYMERASE-II; LONG-TERMINAL REPEAT; NF-KAPPA-B; CONSTITUTIVE TRANSPORT ELEMENT; CHROMATIN-REMODELING COMPLEX; PROTEIN PHOSPHATASE 2A; NUCLEAR EXPORT SIGNAL; VIRAL MESSENGER-RNA; HNRNP A/B PROTEINS AB The emergence of drug-resistant HIV-1 strains presents a challenge for the design of new therapy. Targeting host cell factors that regulate HIV-1 replication might be one way to overcome the propensity for HIV-1 to mutate in order to develop resistance to antivirals. This article reviews the interplay between viral proteins Tat and Rev and their cellular cofactors in the transcriptional and post-transcriptional regulation of HIV-1 gene expression. HIV-1 Tat regulates viral transcription by recruiting cellular factors to the HIV promoter. Tat interacts with protein kinase complexes Cdk9/cyclin T1 and Cdk2/cyclin E; acetyltransferases p300/CBP p300/CBP-associated factor and hGCN5; protein phosphatases and other factors. HIV-1 Rev regulates post-transcriptional processing of viral mRNAs. Rev primarily functions to export unspliced and partially spliced viral RNAs from the nucleus into the cytoplasm. For this activity, Rev cooperates with cellular transport protein CRM1 and RNA helicases DDX1 and DDX3, amongst others. C1 Howard Univ, Dept Biochem, Ctr Sickle Cell Dis, Washington, DC 20059 USA. NIAID, NIH, Mol Microbiol Lab, Mol Virol Sect, Bethesda, MD 20892 USA. RP Nekhai, S (reprint author), Howard Univ, Dept Biochem, Ctr Sickle Cell Dis, 520 W St, Washington, DC 20059 USA. EM snekhai@boward.edu; kjeang@niaid.nih.gov RI Jeang, Kuan-Teh/A-2424-2008 FU Intramural NIH HHS; NIAID NIH HHS [R21 AI056973, R21 AI056973-02] NR 115 TC 53 Z9 56 U1 3 U2 6 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1746-0913 J9 FUTURE MICROBIOL JI Future Microbiol. PD DEC PY 2006 VL 1 IS 4 BP 417 EP 426 DI 10.2217/17460913.1.4.417 PG 10 WC Microbiology SC Microbiology GA 205LY UT WOS:000249116600014 PM 17661632 ER PT J AU Schoen, RE Weissfeld, JL Pinsky, PF Riley, T AF Schoen, Robert E. Weissfeld, Joel L. Pinsky, Paul F. Riley, Thomas TI Yield of advanced adenoma and cancer based on polyp size detected at screening flexible sigmoidoscopy SO GASTROENTEROLOGY LA English DT Article ID COMPUTED TOMOGRAPHIC COLONOGRAPHY; COLORECTAL-CANCER; ASYMPTOMATIC ADULTS; VIRTUAL COLONOSCOPY; RANDOMIZED-TRIAL; CT COLONOGRAPHY; LINE FINDINGS; AVERAGE-RISK; NEOPLASIA; SURVEILLANCE AB Background & Alms: Observational screening of the colon with subsequent referral for colonoscopy raises questions about the threshold of polyp size that necessitates referral. To examine the yield at colonoscopy when a given size lesion is observed, we assessed the yield of advanced adenoma and cancer at colonoscopy based on the size of the abnormality detected at flexible sigmoidoscopy (FSG). Methods: We used data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, a randomized, controlled, community-based study of FSG. Results: Subsequent colonoscopy was performed on 10,850 subjects (60.4% male; mean age, 62.9 years) with a polyp visualized on screening FSG. For women with a polyp 0.5-0.9 cm on FSG (n=1426), the yield in the distal colon on colonoscopy was 0.6% for cancer (number needed to screen [NNS] = 166) and 14.5% for advanced adenoma (NNS = 7). In men (n = 2183), the yield was 0.7% (NNS = 142) for cancer and 15.9% (NNS = 6) for advanced adenoma. Among persons with polyps 0.5-0.9 cm identified on FSG, 5.5% (198/3609) had distal advanced adenomas that measured < 1.0 cm but had villous histology or high-grade dysplasia, and 9.9% (357/3609) had adenomas >= 1 cm. Conclusions: The yield for a distal advanced adenomatous lesion when a polyp 0.5-0.9 cm is observed at FSG is substantial and is due to the presence of advanced histology in polyps < 1 cm and to detection of polyps that measure >= 1.0 cm on colonoscopy. Establishing thresholds for observation versus evaluation will require careful assessment of the overall yield. C1 Univ Pittsburgh, Dept Med, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15261 USA. NCI, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. Informat Management Serv Inc, Rockville, MD USA. RP Schoen, RE (reprint author), Div Gastroenterol Hepatol & Nutr, Mazzanine Level,C Wing,PUH,200 Lothrop St, Pittsburgh, PA 15213 USA. EM rschoen@pitt.edu FU NCI NIH HHS [N01-CN2551] NR 27 TC 16 Z9 17 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD DEC PY 2006 VL 131 IS 6 BP 1683 EP 1689 DI 10.1053/j.gastro.2006.08.025 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 119RP UT WOS:000243031100011 PM 17188959 ER PT J AU Boirivant, M Pallone, F Di Giacinto, C Fina, D Monteleone, I Marinaro, M Caruso, R Colantoni, A Palmieri, G Sanchez, M Strober, W MacDonald, TT Monteleone, G AF Boirivant, Monica Pallone, Francesco Di Giacinto, Claudia Fina, Daniele Monteleone, Ivan Marinaro, Mariarosaria Caruso, Roberta Colantoni, Alfredo Palmieri, Giampiero Sanchez, Massimo Strober, Warren MacDonald, Thomas T. Monteleone, Giovanni TI Inhibition of Smad7 with a specific antisense oligonucleotide facilitates TGF-beta 1-mediated suppression of colitis SO GASTROENTEROLOGY LA English DT Article ID GROWTH-FACTOR-BETA; INFLAMMATORY-BOWEL-DISEASE; TGF-BETA; TRANSCRIPTION FACTOR; MURINE MODEL; T-CELLS; MICE; INTERLEUKIN-4; MECHANISM; FIBROSIS AB Background & Aims: Defective transforming growth factor (TGF)-beta 1 signaling due to high levels of Smad7 is a feature of inflammatory bowel disease (IBD). In this study, we analyzed the effect of reducing Smad7 levels with antisense oligonucleotide on mouse models of colitis. Methods: Mucosal samples taken from colitic tissue of mice with colitis due to either haptenating reagents (trinitrobenzene sulfonic acid [TNBS] or oxazolone) or to transfer of T cells (SCID transfer colitis) were analyzed for Smad3 and/or Smad7 expression by Western blotting and, in some cases, content of TGF-beta 1 by enzyme-linked immunosorbent assay. The effect of oral Smad7 antisense oligonucleotide on mucosal inflammation was assessed. Results: TGF-beta 1 levels were increased in the inflamed tissues of mice with colitis induced by either TNBS or oxazolone. Nevertheless, TGF-beta 1 did not exert a regulatory effect, probably because TGF-beta 1 signaling was blocked, as indicated by the presence of reduced Smad3 phosphorylation and high levels of Smad7. Oral administration of Smad7 antisense oligonucleotide to colitic mice restored TGF-beta 1 signaling via Smad3 and ameliorated inflammation in hapten-induced colitis. In addition, Smad7 antisense oligonucleotide had a therapeutic effect on relapsing TNBS-induced colitis but not on cell-transfer colitis. Conclusions: These data suggest that colitis models associated with high endogenous TGF-beta 1 levels and defective TGF-beta 1 signaling due to high levels of Smad7 can be ameliorated by down-regulation of Smad7 and by oral administration of Smad7 antisense oligonucleotide. This may represent a new approach to the control of IBD, particularly during active phases when its Smad7 profile resembles that of hapten-induced colitis. C1 Univ Roma Tor Vergata, Dipartimento Med Interna, Cattedra Gastroenterol, I-00133 Rome, Italy. Univ Roma Tor Vergata, Anat Pathol Unit, I-00133 Rome, Italy. Ist Super Sanita, Dept Infect Parasit & Immunemediated Dis, I-00161 Rome, Italy. Ist Super Sanita, Dept Cell Biol & Neurosci, I-00161 Rome, Italy. NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA. Barts & London Sch Med & Dent, Inst Cell & Mol Sci, London, England. RP Monteleone, G (reprint author), Univ Roma Tor Vergata, Dipartimento Med Interna, Cattedra Gastroenterol, Via Montpellier 1, I-00133 Rome, Italy. EM gi.monteleone@med.uniroma2.it RI BOIRIVANT, MONICA/B-9977-2016 NR 25 TC 78 Z9 80 U1 0 U2 9 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD DEC PY 2006 VL 131 IS 6 BP 1786 EP 1798 DI 10.1053/j.gastro.2006.09.016 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 119RP UT WOS:000243031100023 PM 17087939 ER PT J AU Nieters, A Kallinowski, B Brennan, P Ott, M Maynadie, M Benavente, Y Foretova, L Cocco, PL Staines, A Vornanen, M Whitby, D Boffetta, P Becker, N De Sanjose, S AF Nieters, Alexandra Kallinowski, Birgit Brennan, Paul Ott, Melanie Maynadie, Marc Benavente, Yolanda Foretova, Lenka Cocco, Pier Luigi Staines, Anthony Vornanen, Martine Whitby, Denise Boffetta, Paolo Becker, Nikolaus De Sanjose, Silvia TI Hepatitis C and risk of lymphoma: Results of the European Multicenter Case-Control Study EPILYMPH SO GASTROENTEROLOGY LA English DT Article ID NON-HODGKINS-LYMPHOMA; B-CELL LYMPHOMA; VIRUS-INFECTION; LYMPHOPROLIFERATIVE DISORDERS; HEPATOCELLULAR-CARCINOMA; MIXED CRYOGLOBULINEMIA; HCV INFECTION; POLYMORPHISMS; PREVALENCE; METAANALYSIS AB Background & Aims: Increasing evidence points toward a role of hepatitis C virus (HCV) infection in the etiology of malignant lymphomas. However, previous epidemiologic studies were limited in size to establish an association between HCV infection and specific lymphoma subtypes. We performed a large, multicenter, case-control study to address this question. Methods: The study comprised 5 European countries and included newly diagnosed cases of any lymphoid malignancy recruited between 1998 and 2004. Controls were matched to cases by 5-year age group, sex, and study center. In-person interviews were conducted to collect data on demographic, medical, and family history as well as environmental exposures. Serum samples of 1807 cases and 1788 controls (excluding human immunodeficiency virus-positive and organ-transplantation subjects) were screened for HCV infection using an enzyme immunoassay. Positive as well as randomly selected negative samples were subjected to HCV RNA detection and HCV genotyping. Results: HCV infection was detected in 53 (2.9%) lymphoma cases and in 41 (2.3%) control subjects (odds ratio [OR], 1.42; 95% confidence interval [CI]: 0.93-2.15). Restricted to individuals who tested positive for HCV-RNA (indicating persistent infection and active viral replication), the OR was 1.82 (95% CI: 1.13-2.91). In subtype-specific analyses, HCV prevalence was associated with diffuse large B-cell lymphoma (OR, 2.19; 95% CI: 1.23-3.91) but not with chronic lymphocytic leukemia or follicular, Hodgkin's, or T-cell lymphoma. The sample size was not sufficient to derive any conclusions for rare lymphoma entities such as splenic marginal zone lymphoma. Conclusions: These results support a model that chronic HCV replication contributes to lymphomagenesis and establish a specific role of HCV infection in the pathogenesis of diffuse large B-cell lymphoma. C1 German Canc Res Ctr, D-69120 Heidelberg, Germany. Int Agcy Res Canc, F-69372 Lyon, France. Univ Calif San Francisco, Gladstone Inst Virol & Immunol, San Francisco, CA 94143 USA. Dijon Univ Hosp, Dijon, France. Catalan Inst Oncol, Barcelona, Spain. Masaryk Mem Canc Inst, Brno, Czech Republic. Univ Cagliari, Dept Publ Hlth, Occupat Hlth Sect, Cagliari, Italy. Publ Hlth Univ Coll Dublin, Dublin, Ireland. Tampere Univ Hosp, Tampere, Finland. NCI, Viral Epidemiol Sect, AVP, SAIC, Frederick, MD 21701 USA. RP Nieters, A (reprint author), German Canc Res Ctr, D-69120 Heidelberg, Germany. EM a.nieters@dkfz.de RI de Sanjose Llongueras, Silvia/H-6339-2014; Benavente, Yolanda/H-9810-2014 FU NCI NIH HHS [N01-CO-12400] NR 46 TC 77 Z9 79 U1 2 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD DEC PY 2006 VL 131 IS 6 BP 1879 EP 1886 DI 10.1053/gastro.2006.09.019 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 119RP UT WOS:000243031100031 PM 17087949 ER PT J AU Sanyal, AJ Fontana, RJ Di Bisceglie, AM Everhart, JE Doherty, MC Everson, GT Donovan, JA Mallet, PF Mehta, S Sheikh, MY Reid, AE Ghany, MG Gretch, DR AF Sanyal, Arun J. Fontana, Robert J. Di Bisceglie, Adrian M. Everhart, James E. Doherty, Michael C. Everson, Gregory T. Donovan, John A. Mallet, Peter F. Mehta, Savant Sheikh, Muhammad Y. Reid, Andrea E. Ghany, Marc G. Gretch, David R. CA HALT-C Trial Grp TI The prevalence and risk factors associated with esophageal varices in subjects with hepatitis C and advanced fibrosis SO GASTROINTESTINAL ENDOSCOPY LA English DT Article; Proceedings Paper CT 54th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 24-28, 2003 CL BOSTON, MA SP Amer Assoc Study Liver Dis ID CIRRHOTIC-PATIENTS; NATURAL-HISTORY; PORTAL-HYPERTENSION; LIVER-CIRRHOSIS; GASTROINTESTINAL-TRACT; PROGNOSTIC INDICATORS; RANDOMIZED-TRIAL; VIRUS-INFECTION; PREVENTION; HEMORRHAGE AB Background: The factors predictive of the presence or the absence of esophageal varices in hepatitis C virus (HCV) and advanced fibrosis have not been defined. Objectives: To define the prevalence of esophageal varices and the factors that are positively and negatively with such varices in hepatitis C and advanced fibrosis. Design: A prospective study of esophageal varices and associated risk factors in subjects with hepatitis C and advanced fibrosis. Setting: Prerandomization data from the HALT-C (hepatitis C long-term antiviral treatment against cirrhosis) clinical trial. Patients and Intervention: Subjects with bridging fibrosis or cirrhosis, who were virologic nonresponders to treatment with pegylated interferon alpha 2a and ribavirin, underwent encloscopy Results: Sixteen percent of subjects with bridging fibrosis (95/598) and 39% of subjects with cirrhosis (164/418) had varices (P < .0001); 2% of subjects with bridging fibrosis (13/598) and 11% of those with cirrhosis (48/418) had medium or large varices. Subjects with bridging fibrosis and varices had a significantly lower platelet count and higher bilirubin and international normalized ratio (INR) compared with those without varices, suggesting that the biopsy may have underestimated the severity of fibrosis. A platelet count > 150,000/mm(3) was associated with a negative predictive value of 99% for esophageal varices. By logistic regression modeling, African American race and female sex were protective, whereas a lower platelet count and higher bilirubin and INR predicted varices (c statistic, 0.758). Conclusions: The risk of having varices increases with decreasing platelet counts, increasing bilirubin, and INR. The probability of having medium or large varices at platelet counts > 150,000/mm(3) is negligible in this population. C1 Virginia Commonwealth Univ, Med Ctr, Dept Internal Med, Div Gastroenterol,Hlth Syst, Richmond, VA 23298 USA. Univ Michigan, Med Ctr, Div Gastroenterol, Ann Arbor, MI 48109 USA. St Louis Univ, Sch Med, Div Gastroenterol & Hepatol, St Louis, MO 63103 USA. NIDDK, Div Digest Dis & Nutr, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. New England Res Inst, Watertown, MA 02172 USA. Univ Colorado, Sch Med, Sect Hepatol, Div Gastroenterol & Hepatol, Denver, CO 80202 USA. Univ So Calif, Keck Sch Med, Div Gastrointestinal & Liver Dis, Los Angeles, CA 90089 USA. Univ Texas, SW Med Ctr, Div Digest & Liver Dis, Dallas, TX 75230 USA. Univ Massachusetts, Med Ctr, Div Gastroenterol, Worcester, MA 01605 USA. Univ Calif Irvine, Div Gastroenterol, Irvine, CA 92717 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. NIDDK, Liver Dis Branch, Div Digest Dis & Nutr, NIH,Dept Hlth & Human Serv, Bethesda, MD USA. Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. RP Sanyal, AJ (reprint author), Virginia Commonwealth Univ, Med Ctr, Dept Internal Med, Div Gastroenterol,Hlth Syst, Box 980341, Richmond, VA 23298 USA. FU NCRR NIH HHS [M01RR-00633, M01RR-01066, M01RR-00827, M01RR-00051, M01RR-06192, M01RR-00043, M01RR-00042, M01RR-00065]; NIDDK NIH HHS [N01-DK-9-2326, N01-DK-9-2323, N01-DK-9-2327, N01-DK-9-2322, N01-DK-9-2324, N01-DK-9-2320, N01-DK-9-2325, N01-DK-9-2328, N01-DK-9-2319, N01-DK-9-2321, N01-DK-9-2318] NR 33 TC 55 Z9 57 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD DEC PY 2006 VL 64 IS 6 BP 855 EP 864 DI 10.1016/j.gie.2006.03.007 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 116AM UT WOS:000242774900002 PM 17140886 ER PT J AU Podskalny, J AF Podskalny, Judith TI NIH Career Development Awards: which grant is right for you? SO GASTROINTESTINAL ENDOSCOPY LA English DT Article; Proceedings Paper CT ASGE 2nd Workshop on Achieving Academic Success CY JUL 22-23, 2006 CL Washington, DC SP Amer Soc Gastrointestinal Endoscopy C1 NIDDK, Bethesda, MD 20892 USA. RP Podskalny, J (reprint author), NIDDK, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD DEC PY 2006 VL 64 IS 6 SU S BP S14 EP S14 DI 10.1016/j.gie.2006.10.039 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 117GP UT WOS:000242861400006 PM 17113845 ER PT J AU Sakamoto, A Liu, J Greene, A Chen, M Weinstein, L AF Sakamoto, Akio Liu, Jie Greene, Andrew Chen, Min Weinstein, Lee TI Tissue-specific imprinting of the G protein G(s)alpha is associated with tissue-specific differences in histone methylation SO GENES & GENETIC SYSTEMS LA English DT Meeting Abstract C1 Kyushu Univ, Dept Orthopaed Surg, Fukuoka 812, Japan. NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GENETICS SOC JAPAN PI SHIZUOKA-KEN PA NATIONAL INST GENETICS YATA 1111, MISHIMA, SHIZUOKA-KEN, 411-8540, JAPAN SN 1341-7568 EI 1880-5779 J9 GENES GENET SYST JI Genes Genet. Syst. PD DEC PY 2006 VL 81 IS 6 BP 440 EP 440 PG 1 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 149HQ UT WOS:000245138300133 ER PT J AU Leaf, I Tennessen, J Mukhopadhyay, M Westphal, H Shawlot, W AF Leaf, Irina Tennessen, Jason Mukhopadhyay, Mahua Westphal, Heiner Shawlot, William TI Sfrp5 is not essential for axis formation in the mouse SO GENESIS LA English DT Article DE Sfrp5; axis formation; foregut; visceral endoderm ID ANTERIOR VISCERAL ENDODERM; POSTIMPLANTATION DEVELOPMENT; SPEMANN ORGANIZER; EXPRESSION; ANTAGONISTS; INDUCTION; GENES; DICKKOPF-1; EMBRYO; BINDS AB Secreted frizzled related protein (Sfrp) genes encode extracellular factors that can modulate Wnt signaling. During early post-implantation mouse development Sfrp5 is expressed in the anterior visceral endoderm (AVE) and the ventral foregut endoderm. The AVE is important in anterior-posterior axis formation and the ventral foregut endoderm contributes to multiple gut tissues. Here to determine the essential role of Sfrp5 in early mouse development we generated Sfrp5-deficient mice by gene targeting. We report that Sfrp5-deficient mice are viable and fertile. To determine whether the absence of an axis phenotype might be due to genetic redundancy with Dkk1 in the AVE we generated Sfrp5;Dkk1 double mutant mice. AVE development and primitive streak formation appeared normal in Sfrp5(-/-);Dkk1(-/-) embryos. These results indicate that Sfrp5 is not essential for axis formation or foregut morphogenesis in the mouse and also imply that Sfrp5 and Dkk1 together are not essential for AVE development. C1 Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN USA. NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. RP Shawlot, W (reprint author), Texas Inst Genom Med, 2121 W Holcombe Blvd, Houston, TX 77030 USA. EM wshawlot@tigm.org OI Tennessen, Jason/0000-0002-3527-5683 NR 22 TC 17 Z9 18 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1526-954X J9 GENESIS JI Genesis PD DEC PY 2006 VL 44 IS 12 BP 573 EP 578 DI 10.1002/dvg.20248 PG 6 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 119RL UT WOS:000243030700001 PM 17133501 ER PT J AU Soares, TN Telles, MPC Resende, LV Silveira, L Jacomo, ATA Morato, RG Diniz, JAF Eizirik, E Brondani, RPV Brondani, C AF Soares, Thannya Nascimento Telles, Mariana P. C. Resende, Lucileide V. Silveira, Leandro Jacomo, Anah Tereza A. Morato, Ronaldo G. Diniz-Filho, Jose Alexandre F. Eizirik, Eduardo Brondani, Rosana P. V. Brondani, Claudio TI Paternity testing and behavioral ecology: A case study of jaguars (Panthera onca) in Emas National Park, Central Brazil SO GENETICS AND MOLECULAR BIOLOGY LA English DT Article DE ecological stress; infanticide; Jaguar; microsatellites; paternity ID RANGE SIZE; INFANTICIDE; POPULATION; MAMMALS; STRATEGIES; MACROECOLOGY; COSTS AB We used microsatellite loci to test the paternity of two male jaguars involved in an infanticide event recorded during a long-term monitoring program of this species. Seven microsatellite primers originally developed for domestic cats and previously selected for Panthera onca were used. In order to deal with uncertainty in the mother's genotypes for some of the loci, 10000 values of Wwere derived by simulation procedures. The male that killed the two cubs was assigned as the true sire. Although the reasons for this behavior remain obscure, it shows, in principle, a low recognition of paternity and kinship in the species. Since the two cubs were not very young, one possibility is that the adult male did not recognize the cubs and killed them for simple territorial reasons. Thus, ecological stress in this local population becomes a very plausible explanation for this infanticide, without further sociobiological implications. C1 Univ Catolica Goias, Inst Trop Subumido, Lab Genet & Melhoramento, BR-74605010 Goiania, Go, Brazil. Assoc Pro Carnivoros, Atibaia, SP, Brazil. Jaguar Conservat Fund, Mineiros, Go, Brazil. IBAMA, CENAP, Atibaia, SP, Brazil. Univ Fed Goias, Inst Ciencias Biol, Dept Biol Geral, Goiania, Go, Brazil. NCI, Lab Genom Divers, NIH, Frederick, MD 21701 USA. EMBRAPA, CNPAF, Biotechnol Lab, BR-74001 Goiania, Go, Brazil. RP Telles, MPC (reprint author), Univ Catolica Goias, Inst Trop Subumido, Lab Genet & Melhoramento, Caixa Postal 86,Av Univ 1440, BR-74605010 Goiania, Go, Brazil. EM tellesmpc@uol.com.br RI Eizirik, Eduardo/K-8034-2012; Soares, Thannya/J-5208-2014; Telles, Mariana/I-2670-2012; Diniz-Filho, Jose Alexandre/D-9405-2013 OI Eizirik, Eduardo/0000-0002-9658-0999; Diniz-Filho, Jose Alexandre/0000-0002-0967-9684 NR 28 TC 10 Z9 10 U1 5 U2 24 PU SOC BRASIL GENETICA PI RIBEIRAO PRET PA RUA CAP ADELMIO NORBET DA SILVA, 736, ALTO DA BOA VISTA, 14025-670 RIBEIRAO PRET, BRAZIL SN 1415-4757 J9 GENET MOL BIOL JI Genet. Mol. Biol. PD DEC PY 2006 VL 29 IS 4 BP 735 EP 740 DI 10.1590/S1415-47572006000400025 PG 6 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 114JP UT WOS:000242662800025 ER PT J AU Peters, JA Vadaparampil, ST Kramer, J Moser, RP Court, LJP Loud, J Greene, MH AF Peters, June A. Vadaparampil, Susan T. Kramer, Joan Moser, Richard P. Court, Lori Jo Peterson Loud, Jennifer Greene, Mark H. TI Familial testicular cancer: Interest in genetic testing among high-risk family members SO GENETICS IN MEDICINE LA English DT Article DE genetic testing; familial; testicular cancer; social support; psychosocial ID BREAST-OVARIAN CANCER; AFRICAN-AMERICAN WOMEN; GERM-CELL TUMORS; NONPOLYPOSIS COLORECTAL-CANCER; PROSTATE-CANCER; SUSCEPTIBILITY GENES; HEREDITARY BREAST; PSYCHOLOGICAL DISTRESS; CANDIDATE REGIONS; RANDOMIZED TRIAL AB Purpose: This study is part of an ongoing National Cancer Institute multidisciplinary, etiologically-focused, cross-sectional study of Familial Testicular Cancer (FTC). The current report targets interest in clinical genetic testing for susceptibility to FTC. Methods: Demographics, knowledge, health beliefs, and psychological and social factors were evaluated as covariates related to interest in genetic testing. Results: The majority (66%) of 229 participants (64 affected men, 66 unaffected men, and 99 women) from 47 multiple-case FTC families expressed interest in having a genetic test within 6 months, should such a test become available. Interest was similar among the three subgroups mentioned above. Worries about insurance discrimination based on genetic test results were associated with a significantly lower interest in testing. Alternatively, participants were more likely to be interested in genetic testing if they were younger and had higher levels of family support, a physician's recommendation supporting testing, cancer distress, and a need for information to inform the health care of their children. Conclusions: This study reveals social and relationship factors that FTC survivors and their relatives considered important when contemplating the use of new genetic technologies. This is the first study describing hypothetical interest in genetic testing for familial testicular cancer. C1 NCI, CGB, DCEG, NIH,HHS,DHHS, Rockville, MD 20852 USA. Univ S Florida, Coll Med, Dept Interdisciplinary Oncol, Tampa, FL USA. NCI, NIH, DCCPS, DHHS, Rockville, MD USA. RP Peters, JA (reprint author), NCI, CGB, DCEG, NIH,HHS,DHHS, 6120 Execut Blvd,EPS 7026, Rockville, MD 20852 USA. EM petersju@mail.nih.gov FU Intramural NIH HHS NR 94 TC 9 Z9 10 U1 5 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD DEC PY 2006 VL 8 IS 12 BP 760 EP 770 DI 10.1097/01.gim.0000250506.15979.0c PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 121MX UT WOS:000243162800005 PM 17172939 ER PT J AU Burton, SK Withrow, K Arnos, KS Kalfoglou, AL Pandya, A AF Burton, Sarah K. Withrow, Kara Arnos, Kathleen S. Kalfoglou, Andrea L. Pandya, Arti TI A focus group study of consumer attitudes toward genetic testing and newborn screening for deafness SO GENETICS IN MEDICINE LA English DT Article DE hearing loss; deafness; molecular testing; genetic testing; focus groups; consumer attitudes; newborn screening ID EARLY HEARING DETECTION; INTERVENTION PROGRAMS; PARENTAL ATTITUDES; WOMENS ATTITUDES; GUIDELINES; DIAGNOSIS AB Purpose: Progress in identifying genes for deafness together with implementation of universal audiologic screening of newborns has provided the opportunity for more widespread use of molecular tests to detect genetic forms of hearing loss. Efforts to assess consumer attitudes toward these advances have lagged behind. Methods: Consumer focus groups were held to explore attitudes toward genetic advances and technologies for hearing loss, views about newborn hearing screening, and reactions to the idea of adding molecular screening for hearing loss at birth. Focus group discussions were recorded, transcribed and analyzed. Results: Five focus groups with 44 participants including hearing parents of deaf children, deaf parents and young deaf adults were held. Focus group participants supported the use of genetic tests to identify the etiology of hearing loss but were concerned that genetic information might influence reproductive decisions. Molecular newborn screening was advocated by some; however, others expressed concern about its effectiveness. Conclusion: Documenting the attitudes of parents and other consumers toward genetic technologies establishes the framework for discussions on the appropriateness of molecular newborn screening for hearing loss and informs specialists about potential areas of public education necessary prior to the implementation of such screening. C1 Virginia Commonwealth Univ, Dept Human Genet, Richmond, VA 23298 USA. Gallaudet Univ, Dept Biol, Genet Program, Washington, DC 20002 USA. NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA. RP Burton, SK (reprint author), Virginia Commonwealth Univ, Coll Med, Dept Human Genet & Pediat, POB 980033, Richmond, VA 23298 USA. FU NIDCD NIH HHS [R01 DC006707, R01 DC005831] NR 25 TC 21 Z9 24 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD DEC PY 2006 VL 8 IS 12 BP 779 EP 783 DI 10.1097/01.gim.0000250501.59830.ff PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 121MX UT WOS:000243162800007 PM 17172941 ER PT J AU Elnitski, L Jin, VX Farnham, PJ Jones, SJM AF Elnitski, Laura Jin, Victor X. Farnham, Peggy J. Jones, Steven J. M. TI Locating mammalian transcription factor binding sites: A survey of computational and experimental techniques SO GENOME RESEARCH LA English DT Review ID CHIP-CHIP DATA; CHROMATIN-IMMUNOPRECIPITATION MICROARRAY; EUKARYOTIC DNA-REPLICATION; CIS-REGULATORY ELEMENTS; GENOME-WIDE PREDICTION; GENE-EXPRESSION DATA; IN-VIVO; HYPERSENSITIVE SITES; SEQUENCE COMPARISONS; GEL-ELECTROPHORESIS AB Fields such as genomics and systems biology are built on the synergism between computational and experimental techniques. This type of synergism is especially important in accomplishing goals like identifying all functional transcription factor binding sites in vertebrate genomes. Precise detection of these elements is a prerequisite to deciphering the complex regulatory networks that direct tissue specific and lineage specific patterns of gene expression. This review summarizes approaches for in silico, in vitro, and in vivo identification of transcription factor binding sites. A variety of techniques useful for localized- and high-throughput analyses are discussed here, with emphasis on aspects of data generation and verification. C1 NHGRI, Genom Funct Anal Sect, NIH, Gaithersburg, MD 20878 USA. Univ Calif Davis, Genome & Biomed Sci Facil, Davis, CA 95616 USA. British Columbia Canc Res Ctr, Genome Sci Ctr, Vancouver, BC V5Z 4E6, Canada. RP Elnitski, L (reprint author), NHGRI, Genom Funct Anal Sect, NIH, Gaithersburg, MD 20878 USA. EM elnitski@mail.nih.gov RI Tang, Macy/B-9798-2014; Jones, Steven/C-3621-2009; OI Farnham, Peggy/0000-0003-4469-7914 FU Intramural NIH HHS; NCI NIH HHS [CA45240]; NHGRI NIH HHS [HG003129]; NIDDK NIH HHS [DK167889] NR 156 TC 126 Z9 134 U1 1 U2 11 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 DEC PY 2006 VL 16 IS 12 BP 1455 EP 1464 DI 10.1101/gr.4140006 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 111VF UT WOS:000242482600003 PM 17053094 ER PT J AU Shakhnovich, BE Koonin, EV AF Shakhnovich, Boris E. Koonin, Eugene V. TI Origins and impact of constraints in evolution of gene families SO GENOME RESEARCH LA English DT Article ID CAENORHABDITIS-ELEGANS GENOME; PROTEIN EVOLUTION; SACCHAROMYCES-CEREVISIAE; FUNCTIONAL DIVERGENCE; DUPLICATE GENES; RATES; SELECTION; SUBFUNCTIONALIZATION; PRESERVATION; NETWORKS AB Recent investigations of high-throughput genomic and phenomic data have uncovered a variety of significant but relatively weak correlations between a gene's functional and evolutionary characteristics. In particular, essential genes and genes with paralogs have a slight propensity to evolve more slowly than nonessential genes and singletons, respectively. However, given the weakness and multiplicity of these associations, their biological relevance remains uncertain. Here, we show that existence of an essential paralog can be used as a specific and strong gauge of selection. We partition gene families in several genomes into two classes: those that include at least one essential gene (E-families) and those without essential genes (N-families). We find that weaker purifying selection causes N-families to evolve in a more dynamic regime with higher rates both of duplicate fixation and pseudogenization. Because genes in E-families are subject to significantly stronger purifying selection than those in N-families, they survive longer and exhibit greater sequence divergence. Longer average survival time also allows for divergence of upstream regulatory regions, resulting in change of transcriptional context among paralogs in E-families. These findings are compatible with differential division of ancestral functions (subfunctionalization) or emergence of novel functions (neofunctionalization) being the prevalent modes of evolution of paralogs in E-families as opposed to pseudogenization (nonfunctionalization), which is the typical fate of paralogs in N-families. Unlike other characteristics of genes, such as essentiality, existence of paralogs, or expression level, membership in an E-family or an N-family strongly correlates with the level of selection and appears to be a major determinant of a gene's evolutionary fate. C1 Boston Univ, Bioinformat Program, Boston, MA 02215 USA. NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Shakhnovich, BE (reprint author), Boston Univ, Bioinformat Program, Boston, MA 02215 USA. EM Borya@acs.bu.edu NR 52 TC 33 Z9 36 U1 0 U2 4 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 DEC PY 2006 VL 16 IS 12 BP 1529 EP 1536 DI 10.1101/gr.5346206 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 111VF UT WOS:000242482600009 PM 17053091 ER PT J AU Ishida, Y David, VA Eizirik, E Schaffer, AA Neelam, BA Roelke, ME Hannah, SS O'Brien, SJ Menotti-Raymond, M AF Ishida, Yasuko David, Victor A. Eizirik, Eduardo Schaffer, Alejandro A. Neelam, Beena A. Roelke, Melody E. Hannah, Steven S. O'Brien, Stephen J. Menotti-Raymond, Marilyn TI A homozygous single-base deletion in MLPH causes the dilute coat color phenotype in the domestic cat SO GENOMICS LA English DT Article DE dilute; linkage mapping; microsatellite; melanophilin (MLPH); domestic cat; coat color; pigmentation; eumelanin; phaeomelanin ID MOLECULAR-GENETIC DISSECTION; UNCONVENTIONAL MYOSIN-VA; GRISCELLI-SYNDROME; MELANOSOME TRANSPORT; FELIS-CATUS; REGION MUTATIONS; LINKS RAB27A; MELANOPHILIN; SLAC2-A/MELANOPHILIN; DEFECTS AB Three proteins have been described in humans and mice as being essential for even distribution, transport, and translocation of pigment granules, with defects in these molecules giving rise to lighter skin/coat color. The dilute phenotype in domestic cats affects both eumelanin and phaeomelanin pigment pathways; for example, black pigmentation combined with dilute appears gray and orange pigments appear cream. The dilute pigmentation segregates as a fully penetrant, autosomal recessive trait. We conducted classical linkage mapping with microsatellites in a large multigeneration pedigree of domestic cats and detected tight linkage for dilute on cat chromosome C1 (theta = 0.08, LOD = 10.8 1). Fine-mapping identified a genomic region exhibiting conserved synteny to human chromosome 2, which included one of the three dilute candidate genes, melanophilin (MLPH). Sequence analysis in dilute cats identified a single base pair deletion in exon 2 of MLPH transcripts that introduces a stop codon 11 amino acids downstream, resulting in the truncation of the bulk of the MLPH protein. The occurrence of this homozygous variant in 97 unrelated dilute cats representing 26 cat breeds and random-bred cats, along with 89 unrelated wild-type cats representing 29 breeds and random-bred cats, supports the finding that dilute is caused by this single mutation in HLPH (p < 0.00001). Single-nucleotide polymorphism analyses in dilute individuals identified a single haplotype in dilute cats, suggesting that a single mutation event in MLPH gave rise to dilute in domestic cats. (c) 2006 Elsevier Inc. All rights reserved. C1 NCI, Lab Genom Divers, Frederick, MD 21702 USA. PUCRS, Ctr Biol Genom & Mol, BR-90619900 Porto Alegre, RS, Brazil. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Dept Hlth & Human Serv, Bethesda, MD 20894 USA. NCI, Adv Biomed Comp Ctr, SAIC Frederick, Frederick, MD 21702 USA. NCI, Lab Genom Divers, SAIC Frederick, Frederick, MD 21702 USA. Nestle Purina PetCare, St Louis, MO 63134 USA. RP Ishida, Y (reprint author), NCI, Lab Genom Divers, Bldg 560,Room 11-38, Frederick, MD 21702 USA. EM ishiday@ncifcrf.gov; raymond@ncifcrf.gov RI Schaffer, Alejandro/F-2902-2012; Eizirik, Eduardo/K-8034-2012 OI Eizirik, Eduardo/0000-0002-9658-0999 FU Intramural NIH HHS NR 43 TC 50 Z9 51 U1 2 U2 16 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD DEC PY 2006 VL 88 IS 6 BP 698 EP 705 DI 10.1016/j.ygeno.2006.06.006 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 113KT UT WOS:000242597500004 PM 16860533 ER PT J AU Alberts, DS Markman, M Muggia, F Ozols, RF Eldermire, E Bookman, MA Chen, T Curtin, J Hess, LM Liebes, L Young, RC Trimble, E AF Alberts, D. S. Markman, M. Muggia, F. Ozols, R. F. Eldermire, E. Bookman, M. A. Chen, T. Curtin, J. Hess, L. M. Liebes, L. Young, R. C. Trimble, E. TI Proceedings of a GOG workshop on intraperitoneal therapy for ovarian cancer SO GYNECOLOGIC ONCOLOGY LA English DT Review DE ovarian cancer; intraperitoneal chemotherapy; oncology ID GYNECOLOGIC-ONCOLOGY-GROUP; STAGE-III OVARIAN; PHASE-III; INTRAVENOUS CISPLATIN; PERITONEAL-CAVITY; FOLLOW-UP; CHEMOTHERAPY; CARBOPLATIN; TRIAL; PACLITAXEL AB Ovarian cancer is the leading cause of gynecologic cancer deaths in the U.S. The concept of intraperitoneal ding delivery for therapy of intraperitoneal cancers, such as ovarian cancer, arose in the 1960s. The field of intraperitoneal cisplatin therapy for ovarian cancer was initiated in the late 1970s and early 1980s. The markedly improved survival data resulting from a phase III trial of intraperitoneal cisplatin for ovarian cancer in early 2006 led to an NCl Clinical Announcement and a Gynecologic Oncology Group-sponsored workshop on intraperitoneal therapy in January, 2006, in San Diego, California. The proceedings of this workshop summarize both research trial results and practical implementation issues associated with intraperitoneal therapy discussed at this workshop. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Arizona, Arizona Canc Ctr, Tucson, AZ 85724 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NYU, Inst Canc, New York, NY USA. NYU, Sch Med, New York, NY USA. Case Western Reserve Univ Hosp, Cleveland, OH 44106 USA. NCI, Bethesda, MD 20892 USA. RP Alberts, DS (reprint author), Univ Arizona, Arizona Canc Ctr, 1515 N Campbell Ave,POB 245024, Tucson, AZ 85724 USA. EM dalberts@azcc.arizona.edu OI Curtin, John/0000-0002-9370-5119; Muggia, Franco/0000-0003-0703-9146 FU NCI NIH HHS [U10 CA027469] NR 43 TC 22 Z9 23 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD DEC PY 2006 VL 103 IS 3 BP 783 EP 792 DI 10.1016/j.ygyno.2006.09.012 PG 10 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 116NL UT WOS:000242809500002 PM 17070570 ER PT J AU Weiss, JM Weiss, NS Ulrich, CM Doherty, JA Chen, C AF Weiss, Jocelyn M. Weiss, Noel S. Ulrich, Cornelia M. Doherty, Jennifer A. Chen, Chu TI Nucleotide excision repair genotype and the incidence of endometrial cancer: Effect of other risk factors on the association SO GYNECOLOGIC ONCOLOGY LA English DT Article DE polymorphism; NER; DNA repair; endometrial; effect modification ID POST-MENOPAUSAL WOMEN; CIGARETTE-SMOKING; POSTMENOPAUSAL WOMEN; PLASMA ANDROSTENEDIONE; CONVERSION; ESTRADIOL; ESTRONE; OBESITY AB Objectives. Certain nucleotide excision repair (NER) genotypes appear to be associated with an altered risk of endometrial cancer. These associations could be modified by characteristics and exposures that themselves influence risk of disease. Methods. We conducted a population-based case-control study in western Washington State to address the role of specific NER genotypes in conjunction with relevant exposures, such as postmenopausal hormone therapy, obesity, parity, oral contraceptive use, and cigarette smoking on risk of endometrial cancer. Case women (n = 371), ages 50-69 years, were diagnosed with invasive endometrial cancer between 1994 and 1999. Control women (n = 420), matched to cases on age and county of residence, were selected using random-digit dialing (ages 50-65) and random selection from HCFA data files (ages 66-69). Results. Risk of endometrial cancer was not associated with ERCCI, ERCC2 (XPD), ERCC4 (XPF), or ERCC5 (XPG) genotype. A reduced risk of endometrial cancer was observed with presence of the XPA g23a variant allele, but only among women with a history of oral contraceptive use (OR 0.47, 95% Cl 0.32-0.69). A decreased risk associated with carriage of at least one variant allele for both XPC A499V and XPC K939Q was restricted to women with BMI < 30 kg/m(2) (OR 0.45, 95% Cl 0.25-0.82). The size of the association between these genotypes and risk of endometrial cancer did not differ by postmenopausal hormone use, parity, or smoking. Conclusions. Our study provides limited evidence for interactions between NER genotypes and DNA damage-causing exposures in the etiology of endometrial cancer. Subsequent studies are needed to confirm the observed associations. Published by Elsevier Inc. C1 NCI, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, Seattle, WA 98104 USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA. RP Weiss, JM (reprint author), NCI, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, 6120 Execut Blvd,EPS 8123,MSC 7240, Bethesda, MD 20892 USA. EM weissjoc@mail.nih.gov FU NCI NIH HHS [R35-CA39779, R01-CA75977, R03-CA80636, R01-CA 105212, K05-CA92002]; NICHD NIH HHS [N01-HD23166] NR 24 TC 21 Z9 23 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD DEC PY 2006 VL 103 IS 3 BP 891 EP 896 DI 10.1016/j.ygyno.2006.05.020 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 116NL UT WOS:000242809500019 PM 16806437 ER PT J AU Landgren, O Rapkin, JS Mellemkjaer, L Gridley, G Goldin, LR Engels, EA AF Landgren, Ola Rapkin, Joshua S. Mellemkjaer, Lene Gridley, Gloria Goldin, Lynn R. Engels, Eric A. TI Respiratory tract infections in the pathway to multiple myeloma: a popugation-based study in Scandinavia SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Article DE multiple myeloma; etiology; pneumonia; infectious agents; MGUS ID UNDETERMINED SIGNIFICANCE; MONOCLONAL GAMMOPATHY; RISK AB Encounter with infectious antigens has been proposed to initiate the cascade of events associated with progression from premalignancy (monoclonal gammopathy of undetermined significance, MGUS) to multiple myeloma (MM). We conducted a population-based case-control study to evaluate risk of developing MM associated with a personal history of various respiratory tracts infections occurring > 1 year prior to MM. Inpatient (1977-1997) and outpatient (1994-1997) diagnoses were obtained for all MM patients (n=4,476) diagnosed in Denmark (1977-1997) and 16,727 matched controls. A personal history of pneumonia was associated with a 1.6-fold (95%CI 1.3-2.0) increased risk of MM; the elevated risk was restricted to 1-4.99 years prior to the diagnosis of MM (OR=1.7,95%CI 1.3-2.2). Individuals with two and three or more previous episodes of pneumonia had a 1.7-fold (95%CI 1.0-3.0; p=0.05) and a 1.5-fold (95%CI 0.6-3.9) elevated MM risk, respectively. Pneumonia could be a trigger to the development of MM or a manifestation of immune disturbances in late-stage MGUS. C1 NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark. RP Landgren, O (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,Bldg EPS Room 7110, Bethesda, MD 20892 USA. EM landgreo@mail.nih.gov FU Intramural NIH HHS NR 18 TC 28 Z9 28 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD DEC PY 2006 VL 91 IS 12 BP 1697 EP 1700 PG 4 WC Hematology SC Hematology GA 116NJ UT WOS:000242809300017 PM 17145609 ER PT J AU Masse, LC Wilson, M Baranowski, T Nebeling, L AF Masse, Louise C. Wilson, Mark Baranowski, Tom Nebeling, Linda TI Improving psychometric methods in health education and health behavior research SO HEALTH EDUCATION RESEARCH LA English DT Editorial Material C1 Univ British Columbia, Ctr Community Child Hlth Res, Dept Pediat, Vancouver, BC V6H 3V4, Canada. Univ Calif Berkeley, Grad Sch Educ, Berkeley, CA 94720 USA. Baylor Coll Med, Dept Pediat, Childrens Nutr Res Ctr, Houston, TX 77030 USA. NCI, Div Canc Control & Populat Sci, Behav Res Program, Hlth Promot Res Branch, Bethesda, MD 20892 USA. RP Masse, LC (reprint author), Univ British Columbia, Ctr Community Child Hlth Res, Dept Pediat, L408,4480 Oak St, Vancouver, BC V6H 3V4, Canada. EM lmasse@cw.bc.ca OI Baranowski, Tom/0000-0002-0653-2222 NR 11 TC 7 Z9 7 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1153 J9 HEALTH EDUC RES JI Health Educ. Res. PD DEC PY 2006 VL 21 SU 1 BP 1 EP 3 DI 10.1093/her/cyl147 PG 3 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA 119IP UT WOS:000243006300001 ER PT J AU Heesch, KC Masse, LC Dunn, AL AF Heesch, K. C. Masse, L. C. Dunn, A. L. TI Using Rasch modeling to re-evaluate three scales related to physical activity: enjoyment, perceived benefits and perceived barriers SO HEALTH EDUCATION RESEARCH LA English DT Article ID INTERVENTION; DETERMINANTS; MEDIATORS; EXERCISE; ADULTS; WOMEN AB Studies suggest that enjoyment, perceived benefits and perceived barriers may be important mediators of physical activity. However, the psychometric properties of these scales have not been assessed using Rasch modeling. The purpose of this study was to use Rasch modeling to evaluate the properties of three scales commonly used in physical activity studies: the Physical Activity Enjoyment Scale, the Benefits of Physical Activity Scale and the Barriers to Physical Activity Scale. The scales were administered to 378 healthy adults, aged 25-75 years (50% women, 62% Whites), at the baseline assessment for a lifestyle physical activity intervention trial. The ConQuest software was used to assess model fit, item difficulty, item functioning and standard error of measurement. For all scales, the partial credit model fit the data. Item content of one scale did not adequately cover all respondents. Response options of each scale were not targeting respondents appropriately, and standard error of measurement varied across the total score continuum of each scale. These findings indicate that each scale's effectiveness at detecting differences among individuals may be limited unless changes in scale content and response format are made. C1 Univ Queensland, Sch Human Movement Studies, Brisbane, Qld 4072, Australia. Univ Oklahoma, Dept Hlth & Exercise Sci, Norman, OK 73019 USA. NCI, Hlth Promot Res Branch, Bethesda, MD 20892 USA. Cooper Inst, Dallas, TX 75230 USA. RP Heesch, KC (reprint author), Univ Queensland, Sch Human Movement Studies, Brisbane, Qld 4072, Australia. EM kheesch@hms.uq.edu.au RI Heesch, Kristi/B-7863-2009; Heesch, Kristiann/J-1288-2012 OI Heesch, Kristiann/0000-0003-1931-3683 NR 32 TC 24 Z9 24 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1153 J9 HEALTH EDUC RES JI Health Educ. Res. PD DEC PY 2006 VL 21 SU 1 BP 58 EP 72 DI 10.1093/her/cyl054 PG 15 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA 119IP UT WOS:000243006300006 ER PT J AU Jeong, WI Park, O Radaeva, S Gao, B AF Jeong, Won-Il Park, Ogyi Radaeva, Svetlana Gao, Bin TI STAT1 inhibits liver fibrosis in mice by inhibiting stellate cell proliferation and stimulating NK cell cytotoxicity SO HEPATOLOGY LA English DT Article ID CHRONIC HEPATITIS-C; COLLAGEN GENE-EXPRESSION; GROWTH-FACTOR RECEPTOR; FAT-STORING CELLS; INTERFERON-GAMMA; VIRUS-INFECTION; LIPOCYTE ACTIVATION; FACTOR-BETA; IN-VIVO; ALPHA AB Liver fibrosis, a common scarring response to chronic liver injury, is a precursor to cirrhosis and liver cancer. Here, we identified signal transducer and activator of transcription I (STAT1) as an important negative regulator in liver fibrosis. Our findings show that disruption of the STAT1. gene accelerated liver fibrosis and hepatic stellate cell (HSC) proliferation in an in vivo model of carbon tetrachloride (CCl4)-induced liver fibrosis. In vitro treatment with IFN-gamma inhibited proliferation and activation of wild-type HSCs, but not STAT1(-/-)HSCs. Moreover, compared to wild-type cells, cellular proliferation stimulated by serum or platelet-derived growth factor (PDGF) was enhanced and accelerated in STATI(-/-) HSCs, which was partially mediated via elevated PDGF receptor 13 expression on such cells. Polyinosinic-polycytidylic acid (poly I:C) or IFN-gamma treatment inhibited liver fibrosis in wild-type mice but not in STAT1-/- mice. Induction of NK cell killing of activated HSCs by poly I:C was attenuated in STAT1(-/-) mice compared to wild-type mice, which was likely due to reduced NKG2D and TRAIL expression on STATI(-/-) NK cells. Finally, activation of TGF-beta/Smad3 signaling pathway was accelerated, whereas induction of Smad7 was diminished in the liver of STAT1(-/-) mice after CCl4 administration compared to wild-type mice. In conclusion, activation of STAT1 attenuates liver fibrosis through inhibition of HSC proliferation, attenuation of TGF-beta signaling, and stimulation of NK cell killing of activated HSCs. STAT1 could be a new therapeutic target for treating liver fibrosis. C1 NIAAA, Sect Liver Biol, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. RP Gao, B (reprint author), NIAAA, Sect Liver Biol, Lab Physiol Studies, NIH, 5625 Fishers Lane,Room 2S-33, Bethesda, MD 20892 USA. EM bgao@mail.nih.gov RI JEONG, WON IL/B-6615-2011 NR 50 TC 115 Z9 127 U1 1 U2 11 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD DEC PY 2006 VL 44 IS 6 BP 1441 EP 1451 DI 10.1002/hep.21419 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 112QC UT WOS:000242540700014 PM 17133483 ER PT J AU Heo, J Factor, VM Uren, T Takahama, Y Lee, JS Major, M Feinstone, SM Thorgeirsson, SS AF Heo, Jeonghoon Factor, Valentina M. Uren, Tania Takahama, Yasushi Lee, Ju-Seog Major, Marian Feinstone, Stephen M. Thorgeirsson, Snorri S. TI Hepatic precursors derived from murine embryonic stem cells contribute to regeneration of injured liver SO HEPATOLOGY LA English DT Article ID IN-VITRO DIFFERENTIATION; HEPATOCYTE DIFFERENTIATION; GENE-EXPRESSION; MOUSE-LIVER; BODY CELLS; GENERATION; EFFICIENT; FUSION; MICE; DEFICIENCY AB We established an efficient system for differentiation, expansion and isolation of hepatic progenitor cells from mouse embryonic stem (ES) cells and evaluated their capacity to repopulate injured liver. Using mouse ES cells transfected with the green fluorescent protein (GFP) reporter gene regulated by albumin (ALB) enhancer/promoter, we found that a serum-free chemically defined medium supports formation of embryoid bodies (EBs) and differentiation of hepatic lineage cells in the absence of exogenous growth factors or feeder cell layers. The first GFP(+) cells expressing ALB were detected in dose proximity to "beating" myocytes after 7 days of EB cultures. GFP+ cells increased in number, acquired hepatocyte-like morphology and hepatocyte-specific markers (i.e., ALB, AAT, TO, and G6P), and by 28 days represented more than 30% of cells isolated from EB outgrowths. The FACS-purified GFP(+) cells developed into functional hepatocytes without evidence of cell ftision and participated in the repairing of diseased liver when transplanted into MUP-uPA/SCID mice. The ES cell-derived hepatocytes were responsive to normal growth regulation and proliferated at the same rate as the host hepatocytes after an additional growth stimulus from CCl4-induced liver injury. The transplanted GFP+ cells also differentiated into biliary epithelial cells. In conclusion, a highly enriched population of committed hepatocyte precursors can be generated from ES cells in vitro for effective cell replacement therapy. C1 NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. US FDA, Lab Hepatitis Viruses, Div Viral Prod, CBER, Bethesda, MD 20014 USA. RP Thorgeirsson, SS (reprint author), NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, 37 Convent Dr,Bldg 37,Room 4146, Bethesda, MD 20892 USA. EM snorri_s_thorgeirsson@nih.gov FU Intramural NIH HHS NR 37 TC 98 Z9 110 U1 3 U2 10 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD DEC PY 2006 VL 44 IS 6 BP 1478 EP 1486 DI 10.1002/hep.21441 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 112QC UT WOS:000242540700017 PM 17133486 ER PT J AU Everson, GT Hoefs, JC Seeff, LB Bonkovsky, HL Naishadham, D Shiffinan, ML Kahn, JA Lok, ASF Di Bisceglie, AM Lee, WM Dienstag, JL Ghany, MG Morishima, C AF Everson, Gregory T. Hoefs, John C. Seeff, Leonard B. Bonkovsky, Herbert L. Naishadham, Deepa Shiffinan, Mitchell L. Kahn, Jeffrey A. Lok, Anna S. F. Di Bisceglie, Adrian M. Lee, William M. Dienstag, Jules L. Ghany, Marc G. Morishima, Chihiro CA HALT-C Trial Grp TI Impact of disease severity on outcome of antiviral therapy for chronic hepatitis C: Lessons from the HALT-C trial SO HEPATOLOGY LA English DT Article ID VIRUS-INFECTION; UNITED-STATES; PEGINTERFERON ALPHA-2A; LIVER-TRANSPLANTATION; COMBINATION THERAPY; PLUS RIBAVIRIN; CIRRHOSIS; PREVALENCE; MANAGEMENT; MORBIDITY AB In patients with chronic hepatitis C, advanced fibrosis and cirrhosis are associated with lower rates of sustained virologic response (SVR) to interferon (IFN)-based therapy. In this study, we assessed virologic response to retreatment with peginterferon alfa-2a and ribavirin (RBV), as a function of the baseline fibrosis score (Ishak staging) and platelet count, in 1,046 patients enrolled in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial. All patients had failed prior treatment with IFN or peginterferon +/- RBV and had Ishak fibrosis scores >= 3. Four groups of patients with increasingly severe liver disease were compared: (A) bridging fibrosis (Ishak 3 and 4) with platelet counts > 125,000/mm(3) (n = 559); (B) bridging fibrosis with platelet counts <= 125,000/mm(3) (n = 96); (C) cirrhosis (Ishak 5 and 6) with platelet counts > 125,000/mm3 (n = 198); and (D) cirrhosis with platelet counts 5125,000/mm3 (n = 193). SVR rates were 23%, 17%, 10%, and 9% in groups A, B, C, and D, respectively (P < .0001 for trend). Reduction in SVR as a function of increasingly severe disease was independent of age, percent African American, HCV genotype, HCV level, and type of prior therapy. Dose reduction lowered SVR frequencies, but to a lesser extent than disease severity. By logistic regression, cirrhosis (P < .0001) was the major determinant that impaired virologic response, independent of dose reduction or platelet count. In conclusion, disease severity is a major independent determinant of rate of SVR in patients with advanced chronic hepatitis C. New strategies are needed to optimize antiviral therapy in these "difficult-to-cure" patients. C1 Univ Colorado, Sch Med, Hlth Sci Ctr, Div Gastroenterol & Hepatol,Sect Hepatol, Denver, CO 80262 USA. Univ Calif Irvine, Div Gastroenterol, Irvine, CA 92717 USA. NIDDK, Div Digest Dis & Nutr, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT USA. Univ Connecticut, Ctr Hlth, Dept Biol Mol & Struct, Farmington, CT USA. Univ Connecticut, Ctr Hlth, Liver Biliary Pancret Ctr, Farmington, CT USA. New England Res Inst, Watertown, MA 02172 USA. Virginia Commonwealth Univ, Med Ctr, Hepatol Sect, Richmond, VA 23284 USA. Univ So Calif, Keck Sch Med, Div Gastrointestinal & Liver Dis, Los Angeles, CA 90089 USA. Univ Michigan, Div Gastroenterol, Ann Arbor, MI 48109 USA. St Louis Univ, Sch Med, St Louis, MO 63103 USA. Univ Texas, SW Med Ctr, Dallas, TX 75230 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. NIDDK, Liver Dis Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. RP Everson, GT (reprint author), Univ Colorado, Sch Med, Hlth Sci Ctr, Div Gastroenterol & Hepatol,Sect Hepatol, 4200 E 9th Ave,B-154, Denver, CO 80262 USA. EM greg.everson@uchsc.edu RI Lok, Anna /B-8292-2009; OI Yang, Shuman/0000-0002-9638-0890 FU NCRR NIH HHS [M01RR-00042, M01RR-00043, M01RR-00051, M01RR-00065, M01RR-00633, M01RR-00827, M01RR-01066, M01RR-06192]; NIDDK NIH HHS [N01-DK-9-2326, N01-DK-9-2318, N01-DK-9-2319, N01-DK-9-2320, N01-DK-9-2321, N01-DK-9-2322, N01-DK-9-2323, N01-DK-9-2324, N01-DK-9-2325, N01-DK-9-2327, N01-DK-9-2328] NR 27 TC 109 Z9 111 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD DEC PY 2006 VL 44 IS 6 BP 1675 EP 1684 DI 10.1002/hep.21440 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 112QC UT WOS:000242540700038 PM 17133499 ER PT J AU Balan, V Aravind, L Grill, DE Therneau, TM Sulkowski, MS Nelson, DR Praestgaard, J Rosati, M Birse, CE Moore, PA Subramanian, GM AF Balan, Vijayan Aravind, L. Grill, Diane E. Therneau, Terry M. Sulkowski, Mark S. Nelson, David R. Praestgaard, Jens Rosati, Marianne Birse, Charles E. Moore, Paul A. Subramanian, G. Mani TI Global transcriptional effects of PEG-IFN-alpha and ribavirin on peripheral blood cells obtained from patients with chronic hepatitis C SO HEPATOLOGY RESEARCH LA English DT Article DE PEG-IFN-alpha; cDNA array; TaqMan PCR; gene expression ID MULTIPLE SEQUENCE ALIGNMENT; GENE-EXPRESSION; INTERFERON-ALPHA; VIRUS-INFECTION; PLUS RIBAVIRIN; PROTEIN; ARRAYS; MECHANISMS; RESPONSES; ACCURACY AB The global transcriptional profile during the first 4 weeks of treatment with pegylated interferon alfa (PEG-IFN-alpha) therapy for chronic hepatitis C (CHC) was evaluated. cDNA array technology was used to assess expression of 10,918 human genes in peripheral blood cells obtained from 17 CHC patients at days 0, 7, and 28 following treatment with PEG-IFN-alpha and ribavirin. Hierarchical average linkage clustering identified seven temporal profiles of differential expression comprising 148 genes. Gene expression profiles were comparable between the PEG-IFN-alpha-2a and PEG-IFN-alpha-2b therapy. Genes representing a broad range of molecular functions were differentially regulated with distinct temporal patterns of expression. The initial global response to interferon treatment appears to be a net up-regulation of genes, consistent with gene responses identified previously in vitro, though by 4 weeks an overall down-regulation of genes was observed. Novel transcription factors potentially involved in secondary gene regulation cascades, a potential dsRNA receptor and members of the ubiquitin signaling, including a novel predicted deubiquitinating peptidase were all identified as being up-regulated upon treatment with IFN. The overall findings provide new light on possible physiological effects of IFN-alpha and open new lines of investigations on the mode of action of PEG-IFN-alpha combination therapy. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Mayo Clin, Phoenix, AZ 85054 USA. NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. Mayo Clin, Rochester, MS USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Univ Florida, Gainesville, FL USA. Human Genome Sci Inc, Rockville, MD 20850 USA. RP Balan, V (reprint author), Mayo Clin, 5777 E Mayo Blvd, Phoenix, AZ 85054 USA. EM balan.vijayan@mayo.edu; mani_subramanian@hgsi.com NR 48 TC 0 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1386-6346 J9 HEPATOL RES JI Hepatol. Res. PD DEC PY 2006 VL 36 IS 4 BP 277 EP 287 DI 10.1016/j.hepres.2006.08.007 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 198HI UT WOS:000248617200007 PM 17030011 ER PT J AU Chan, SSL Longley, MJ Copeland, WC AF Chan, Sherine S. L. Longley, Matthew J. Copeland, William C. TI Modulation of the W748S mutation in DNA polymerase gamma by the E1143G polymorphismin mitochondrial disorders SO HUMAN MOLECULAR GENETICS LA English DT Article ID PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA; P55 ACCESSORY SUBUNIT; ALPERS-SYNDROME; POLG MUTATIONS; DELETIONS; IDENTIFICATION; TOXICITY; SPECTRUM; DISEASE; BINDING AB DNA polymerase gamma (pol gamma) is required for replication and repair of mitochondrial DNA. Over 80 mutations in POLG, the gene encoding the catalytic subunit of pol gamma, have been linked with disease. The W748S mutation in POLG is the most common mutation in ataxia-neuropathy spectrum disorders and is generally found in cis with the common E1143G polymorphism. It has been unclear whether E1143G participates in the disease process. We investigated the biochemical consequences of pol gamma proteins containing W748S or E1143G, or both. W748S pol gamma exhibited low DNA polymerase activity, low processivity and a severe DNA-binding defect. However, interactions between the catalytic and accessory subunits were normal. Despite the benefits derived from binding with the accessory subunit, catalytic activities did not reach wild-type (WT) levels. Also, nucleotide selectivity decreased 2.1-fold compared with WT. Surprisingly, pol gamma containing only E1143G was 1.4-fold more active than WT, and this increased polymerase activity could be due to higher thermal stability for E1143G pol gamma. The E1143G substitution partially rescued the deleterious effects of the W748S mutation, as DNA binding, catalytic activity and fidelity values were intermediate for W748S-E1143G. However, W748S-E1143G had a notably lower change in enthalpy for protein folding than W748S alone. We suggest that when E1143G is in cis with other pathogenic mutations, it can modulate the effects of these mutations. For W748S-E1143G pol gamma, the benefits bestowed by E1143G include increased DNA binding and polymerase activity; however, E1143G was somewhat detrimental to protein stability. C1 NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Copeland, WC (reprint author), NIEHS, Mol Genet Lab, NIH, POB 12233,111 TW Alexander Dr,Bldg 101,Rm E316, Res Triangle Pk, NC 27709 USA. EM copelan1@niehs.nih.gov FU Intramural NIH HHS; NIEHS NIH HHS [Z01 ES065078-12] NR 38 TC 61 Z9 61 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD DEC PY 2006 VL 15 IS 23 BP 3473 EP 3483 DI 10.1093/hmg/ddl424 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 108XA UT WOS:000242271300010 PM 17088268 ER PT J AU Fedorova, OV Agalakova, NI Morrell, CH Lakatta, EG Bagrov, AY AF Fedorova, Olga V. Agalakova, Natalia I. Morrell, Christopher H. Lakatta, Edward G. Bagrov, Alexei Y. TI ANP differentially modulates marinobufagenin-induced sodium pump inhibition in kidney and aorta SO HYPERTENSION LA English DT Article DE sodium-potassium exchanging adenosinetriphosphatase natriuretic hormones; ANP; ouabain; marinobufagenin; cGMP ID ATRIAL-NATRIURETIC-PEPTIDE; NA+-K+-ATPASE; DEPENDENT PROTEIN-KINASE; CONGESTIVE-HEART-FAILURE; CYCLIC-GMP; NA/K-ATPASE; ENDOGENOUS LIGAND; RAT AORTA; ADENOSINE-TRIPHOSPHATASE; KALIURETIC PEPTIDE AB NaCl loading and plasma volume expansion stimulate 2 natriuretic systems, vasoconstrictor, digitalis-like Na/K-ATPase inhibitors and vasorelaxant ANP peptides. Several hormones, including ANP, regulate activity of the Na/K-ATPase by modulation of its phosphorylation state. We studied effects of ANP on Na/K-ATPase phosphorylation and inhibition by an endogenous sodium pump ligand, marinobufagenin, in the aorta and renal medulla from male Sprague-Dawley rats. Marinobufagenin dose-dependently inhibited the Na/K-ATPase in renal and vascular membranes at the level of higher (nanomolar) and lower affinity ( micromolar) binding sites. Marinobufagenin ( 1 nmol/L) inhibited Na/K-ATPase in aortic sarcolemma (18%) and in renal medulla (19%). prepro-ANP 104 to 123 (ppANP) and alpha-human ANP ([alpha-hANP] both 1 nmol/L) potentiated marinobufagenin-induced Na/K-ATPase inhibition in the kidney, but reversed the effect of marinobufagenin in the aorta. Similarly, ppANP and alpha-hANP modulated the sodium pump (ouabain-sensitive Rb-86 uptake) inhibitory effects of marinobufagenin in the aorta and renal medulla. In renal medulla, ppANP and alpha-hANP induced alpha-1 Na/K-ATPase phosphorylation, whereas in aorta, both peptides dephosphorylated Na/K-ATPase. The effect of ppANP on Na/K-ATPase phosphorylation and inhibition was mimicked by a protein kinase G activator, 8-Br-PET-cGMP (10 mu mol/L), and prevented by a protein kinase G inhibitor, KT5823 ( 60 nmol/L). Our results suggest that alpha-1 Na/K-ATPase inhibition by marinobufagenin in the kidney is enhanced via Na/K-ATPase phosphorylation by ANP, whereas in the aorta, ANP exerts an opposite effect. The concurrent production of a vasorelaxant, ANP, and a vasoconstrictor, marinobufagenin, potentiate each other's natriuretic effects, but ANP peptides may offset the deleterious vasoconstrictor effect of marinobufagenin. C1 NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. Loyola Coll, Baltimore, MD 21210 USA. RP Bagrov, AY (reprint author), NIA, Cardiovasc Sci Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM BagrovA@mail.nih.gov FU Intramural NIH HHS NR 55 TC 23 Z9 23 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD DEC PY 2006 VL 48 IS 6 BP 1160 EP 1168 DI 10.1161/01.HYP.0000248129.20524.d0 PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 127PH UT WOS:000243598300027 PM 17043158 ER PT J AU Liu, F Vishkin, U Milner, S AF Liu, Fang Vishkin, Uzi Milner, Stuart TI Bootstrapping free-space optical networks SO IEEE JOURNAL ON SELECTED AREAS IN COMMUNICATIONS LA English DT Article DE Free-Space Optical Networks; minimum-degree spanning tree AB We introduce a challenging problem in establishing and initially configuring or bootstrapping a Free Space Optical (FSO) network. In such networks, it is assumed that each communication node is a base station, including a router and wireless optical communications hardware, and its number of transceivers is limited. In addition, the FSO networks are characterized by narrow beam, directional links (e.g., operating at 1550 nm) and support up to Gbps data rates. The problem of initially configuring the transceivers to form a connected topology is NP-complete because of the transceiver limitation. What makes this problem even more challenging is the need to configure the transceiver in a "distributed" fashion, because a node can have only direct knowledge of its neighbors. We have developed a fully distributed approximation algorithm, which constructs a spanning tree with, maximal node degree at most one larger than that in the optimal solution. Due to its distributed nature, this algorithm outperforms known serial algorithms. For a graph with 200 nodes generated in some randomized model, speed-ups greater than 6 have been demonstrated. C1 Natl Lib Med, Off High Performance Comp & Commun, Bethesda, MD 20894 USA. Univ Maryland, Dept Elect & Comp Engn, College Pk, MD 20742 USA. Univ Maryland, Inst Adv Comp Studies, College Pk, MD 20742 USA. Univ Maryland, Dept Civil & Environm Engn, College Pk, MD 20742 USA. Univ Maryland, Ctr Networking Infrastruct Sensors, College Pk, MD 20742 USA. RP Liu, F (reprint author), Natl Lib Med, Off High Performance Comp & Commun, Bethesda, MD 20894 USA. EM fliu@mail.nih.gov; vishkin@umiacs.umd.edu; milner@umd.edu NR 11 TC 13 Z9 13 U1 1 U2 4 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0733-8716 J9 IEEE J SEL AREA COMM JI IEEE J. Sel. Areas Commun. PD DEC PY 2006 VL 24 IS 12 SU S BP 13 EP 22 DI 10.1109/TWC.2006.019304 PG 10 WC Engineering, Electrical & Electronic; Telecommunications SC Engineering; Telecommunications GA 113MI UT WOS:000242601600003 ER PT J AU Wang, ZS Maier, A Leopold, DA Liang, HL AF Wang, Zhisong Maier, Alexander Leopold, David A. Liang, Hualou TI Relaxation-based multichannel signal combination (RELAX-MUSIC) for ROC analysis of percept-related neuronal activity SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE Fisher linear discriminant (FLD); middle temporal (MT); multichannel combination; receiver operating characteristic (ROC); single unit activity (SUA); structure from motion (SFM); visual cortex ID AREA; RESPONSES; CHOICE; CURVE AB In this letter, we consider how to combine neuronal signals from multiple electrodes to optimally predict behavioral choices from observed neural activity. The predictability is often quantified by the area under the receiver operating characteristic (ROC) curve, also called choice probability (CP) in neurophysiology. We exploit a distribution-free relaxation based multichannel signal combination (RELAX-MUSIC) approach that requires only simple pairwise combination and recursive implementation for optimizing the area under the ROC curve. A permutation test is employed to assess the statistical significance of the derived CP. We demonstrate that the RELAX-MUSIC approach outperforms the commonly used response pooling and Fisher linear discriminant (FLD) methods. The excellent performances of the RELAX-MUSIC approach for predicting perceptual decisions from neural activity are demonstrated via examples using simulated and experimental data. C1 Univ Texas, Hlth Sci Ctr, Sch Hlth Informat Sci, Houston, TX 77030 USA. NIH, Unit Cognit Neurophysiol & Imaging, Bethesda, MD 20892 USA. RP Liang, HL (reprint author), Univ Texas, Hlth Sci Ctr, Sch Hlth Informat Sci, 7000 Fannin,Suite 600, Houston, TX 77030 USA. EM Hualou.Liang@uth.tmc.edu RI Maier, Alexander/B-7489-2009; OI Maier, Alexander/0000-0002-7250-502X; Leopold, David/0000-0002-1345-6360 FU Intramural NIH HHS [ZIA MH002838-06]; NIMH NIH HHS [R01 MH072034, R03 MH067776]; NINDS NIH HHS [R01 NS054314] NR 14 TC 2 Z9 2 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD DEC PY 2006 VL 53 IS 12 BP 2615 EP 2618 DI 10.1109/TBME.2006.886605 PN 2 PG 4 WC Engineering, Biomedical SC Engineering GA 110FK UT WOS:000242363500007 PM 17152443 ER PT J AU Singh, NJ Schwartz, RH AF Singh, Nevil J. Schwartz, Ronald H. TI The lymphopenic mouse in immunology: From patron to pariah SO IMMUNITY LA English DT Editorial Material ID CD4(+) T-CELLS; HOMEOSTATIC PROLIFERATION; AUTOIMMUNE-DISEASE; ADOPTIVE TRANSFER; MHC COMPLEXES; CUTTING EDGE; IN-VIVO; SURVIVAL; NAIVE; LYMPHOCYTES AB A recent surge of interest in the behavior of T and B cells in lymphopenic model systems has resurrected a certain cynicism about the validity of using such models to answer important immunological questions. Here we discuss this skepticism in a broader historical context. C1 NIAID, Lab Cellular & Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Schwartz, RH (reprint author), NIAID, Lab Cellular & Mol Immunol, NIH, 4-111 Ctr Dr,MSC-0420, Bethesda, MD 20892 USA. EM rs34r@nih.gov FU Intramural NIH HHS NR 33 TC 12 Z9 13 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD DEC PY 2006 VL 25 IS 6 BP 851 EP 855 DI 10.1016/j.immuni.2006.12.002 PG 5 WC Immunology SC Immunology GA 120LY UT WOS:000243087500001 PM 17174925 ER PT J AU Sen, R AF Sen, Ranjan TI Control of B lymphocyte apoptosis by the transcription factor Nk-kappa B SO IMMUNITY LA English DT Review ID BRUTONS TYROSINE KINASE; CELL ANTIGEN RECEPTOR; GERMINAL CENTER REACTIONS; FLICE-INHIBITORY PROTEIN; FAS-MEDIATED APOPTOSIS; FAMILY-MEMBER BIM; CUTTING EDGE; SIGNAL-TRANSDUCTION; NEGATIVE SELECTION; POSITIVE SELECTION AB B cells maintain homeostasis by balancing cell viability and cell death. B lymphocytes are susceptible to mitochondria- and receptor-initiated cell death at various stages of peripheral differentiation and during immune responses. The inducible transcription factor NF-kappa B enhances cell viability by activating genes that counteract both cell-death pathways. This review uses characteristic features of NF-kappa B activation and down-regulation to provide insight into the regulation of B cell apoptosis in the periphery. In particular, the temporal patterns of NF-kappa B induction, differences between Rel family members, and the intersection between canonical and noncanonical signaling pathways in keeping B cells alive are discussed. C1 NIA, Lab Cellular & Mol Biol, Baltimore, MD 21224 USA. RP Sen, R (reprint author), NIA, Lab Cellular & Mol Biol, Baltimore, MD 21224 USA. EM rs465z@nih.gov FU Intramural NIH HHS NR 133 TC 62 Z9 66 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD DEC PY 2006 VL 25 IS 6 BP 871 EP 883 DI 10.1016/j.immuni.2006.12.003 PG 13 WC Immunology SC Immunology GA 120LY UT WOS:000243087500007 PM 17174931 ER PT J AU Bajenoff, M Egen, JG Koo, LY Laugier, JP Brau, F Glaichenhaus, N Germain, RN AF Bajenoff, Marc Egen, Jackson G. Koo, Lily Y. Laugier, Jean Pierre Brau, Frederic Glaichenhaus, Nicolas Germain, Ronald N. TI Stromal cell networks regulate lymphocyte entry, migration, and territoriality in lymph nodes SO IMMUNITY LA English DT Article ID FOLLICULAR DENDRITIC CELLS; B-CELLS; T-CELLS; IN-VIVO; ANTIGEN; CHEMOKINES; IMMUNITY; TRAFFICKING; FOLLICLES; MOTILITY AB After entry into lymph nodes (LNs), B cells migrate to follicles, whereas T cells remain in the paracortex, with each lymphocyte type showing apparently random migration within these distinct areas. Other than chemokines, the factors contributing to this spatial segregation and to the observed patterns of lymphocyte movement are poorly characterized. By combining confocal, electron, and intravital microscopy, we showed that the fibroblastic reticular cell network regulated naive T cell access to the paracortex and also supported and defined the limits of T cell movement within this domain, whereas a distinct follicular dendritic cell network similarly served as the substratum for movement of follicular B cells. These results highlight the central role of stromal microanatomy in orchestrating cell migration within the LN. C1 NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. Univ Nice, INSERM, F-06560 Valbonne, France. Univ Nice, Ctr Commun Microscopie Appl, F-06103 Nice, France. Univ Nice, CNRS, UMR 6097, F-06560 Valbonne, France. RP Germain, RN (reprint author), NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. EM rgermain@niaid.nih.gov OI Egen, Jackson/0000-0003-2053-0837 FU Intramural NIH HHS [Z01 AI000545-19] NR 51 TC 509 Z9 514 U1 0 U2 30 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD DEC PY 2006 VL 25 IS 6 BP 989 EP 1001 DI 10.1016/j.immuni.2006.10.011 PG 13 WC Immunology SC Immunology GA 120LY UT WOS:000243087500017 PM 17112751 ER PT J AU Pratt, BF O'Connor, DH Lafont, BAP Mankowski, JL Fernandez, CS Triastuti, R Brooks, AG Kent, SJ Smith, MZ AF Pratt, Bridget F. O'Connor, David H. Lafont, Bernard A. P. Mankowski, Joseph L. Fernandez, Caroline S. Triastuti, Retno Brooks, Andrew G. Kent, Stephen J. Smith, Miranda Z. TI MHC class I allele frequencies in pigtail macaques of diverse origin SO IMMUNOGENETICS LA English DT Article DE pigtail macaques; MHC class I; reference strand-mediated conformational analysis (RSCA); CD8(+) T cell ID SIMIAN IMMUNODEFICIENCY VIRUS; MEDIATED CONFORMATIONAL-ANALYSIS; T-LYMPHOCYTE RESPONSES; CYNOMOLGUS MACAQUES; ANALYSIS RSCA; DNA; INFECTION; MOLECULE; EPITOPES; VACCINES AB Pigtail macaques (Macaca nemestrina) are an increasingly common primate model for the study of human AIDS. Major Histocompatibility complex (MHC) class I-restricted CD8(+) T cell responses are a critical part of the adaptive immune response to HIV-1 in humans and simian immunodeficiency virus (SIV) in macaques; however, MHC class I alleles have not yet been comprehensively characterized in pigtail macaques. The frequencies of ten previously defined alleles (four Mane-A and six Mane-B) were investigated in detail in 109 pigtail macaques using reference strand-mediated conformational analysis (RSCA). The macaques were derived from three separate breeding colonies in the USA, Indonesia and Australia, and allele frequencies were analysed within and between these groups. Mane-A*10, an allele that restricts the immunodominant SIV Gag epitope KP9, was the most common allele, present in 32.1% of the animals overall, with similar frequencies across the three cohorts. Additionally, RSCA identified a new allele (Mane-A*17) common to three Indonesian pigtail macaques responding to the same Gag CD8(+) T cell epitope. This broad characterization of common MHC class I alleles in more than 100 pigtail macaques further develops this animal model for the study of virus-specific CD8(+) T cell responses. C1 Univ Melbourne, Dept Microbiol & Immunol, Melbourne, Vic 3010, Australia. Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53706 USA. NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Mol & Comparat Pathobiol, Baltimore, MD 21218 USA. Bogor Agr Univ, Primate Res Ctr, Bogor, Indonesia. RP Kent, SJ (reprint author), Univ Melbourne, Dept Microbiol & Immunol, Melbourne, Vic 3010, Australia. EM skent@unimelb.edu.au RI Lafont, Bernard/B-7236-2014; OI Pratt, Bridget/0000-0002-4934-3560; o'connor, david/0000-0003-2139-470X; Kent, Stephen/0000-0002-8539-4891; Smith, Miranda/0000-0002-6404-9204; Brooks, Andrew/0000-0002-4085-9683 NR 19 TC 32 Z9 32 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD DEC PY 2006 VL 58 IS 12 BP 995 EP 1001 DI 10.1007/s00251-006-0164-8 PG 7 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 120GQ UT WOS:000243072900006 PM 17096100 ER PT J AU Weiler, A May, GE Qi, Y Wilson, N Watkins, DI AF Weiler, Andrea May, Gernma E. Qi, Ying Wilson, Nancy Watkins, David I. TI Polymorphisms in eight host genes associated with control of HIV replication do not mediate elite control of viral replication in SIV-infected Indian rhesus macaques SO IMMUNOGENETICS LA English DT Article DE genetic polymorphism; AIDS progression; rhesus macaque ID DISEASE PROGRESSION; CLASS-I; VIRUS; CCR5; AIDS; ALLELES; RESTRICTION; VARIANTS; MUTATION; PATHOGENESIS AB Polymorphisms in several host genes in HIV-infected individuals facilitate slow progression to AIDS. We have identified several SIV-infected Indian rhesus macaques that naturally control viral replication. We investigated whether spontaneous control of SIV in any of these animals could be explained by mutations in host genes. Such variables could confound studies of associations between MHC class I alleles and control of viral replication. We searched for polymorphisms in CCR5, CXCR6, GPR15, RANTES, IL-10, APOBEC3G, TNF-alpha, and TSG101 and looked for associations with decreased viral replication. We did not detect any correlations between plasma viral concentration and polymorphisms in host genes examined in this study. In addition, we did not find the polymorphisms present in humans in any of our macaques. C1 Univ Wisconsin, Wisconsin Natl Primate Res Ctr, Madison, WI 53715 USA. Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53715 USA. SAIC Frederick, Lab Genom Divers, NCI, Ft Detrick, MD 21702 USA. RP Weiler, A (reprint author), Univ Wisconsin, Wisconsin Natl Primate Res Ctr, 1223 Capitol Court, Madison, WI 53715 USA. EM amweiler@wisc.edu FU NCRR NIH HHS [P52 RR000167, R24 RR016038] NR 26 TC 14 Z9 14 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD DEC PY 2006 VL 58 IS 12 BP 1003 EP 1009 DI 10.1007/s00251-006-0166-6 PG 7 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 120GQ UT WOS:000243072900007 PM 17106666 ER PT J AU Pascal, V Stulberg, MJ Anderson, SK AF Pascal, Veronique Stulberg, Michael J. Anderson, Stephen K. TI Regulation of class I major histocompatibility complex receptor expression in natural killer cells: one promoter is not enough! SO IMMUNOLOGICAL REVIEWS LA English DT Review DE human; rodent; natural killer cells; transcription factors; Ly49; KIR ID IL-4/IL-13 GENE-CLUSTER; PERIPHERAL NK CELLS; INTERGENIC TRANSCRIPTION; DNA METHYLATION; TH2 CELLS; PROBABILISTIC REGULATION; CLONAL ACQUISITION; CYTOTOXIC ACTIVITY; LY49 RECEPTORS; MHC MOLECULES AB The class I major histocompatibility complex (MHC) receptors expressed by natural killer (NK) cells play an important role in regulating their function. The number and type of inhibitory receptors expressed by NK cells must be tightly controlled in order to avoid the generation of dominantly inhibited NK cells. The selective stochastic expression of the class I MHC receptors generates a variegated NK cell population capable of discriminating subtle changes in MHC expression on potential target cells. The molecular mechanisms controlling the cell-specific and probabilistic expression of these receptors are without doubt very complex. The traditional approach of considering a core promoter modulated by upstream enhancer elements is likely too simplistic a paradigm to adequately explain the regulation of these genes, as well as other gene clusters that are not expressed in an 'all or none' fashion. Our studies on the regulation of the mouse Ly49 and human killer immunoglobulin-like receptor (KIR) clusters of class I MHC receptor genes have revealed the presence of multiple transcripts in both sense and antisense orientations. In both systems, an antisense promoter overlaps a promoter that produces sense transcripts, creating a bidirectional element. In the Ly49 genes, the competing promoters behave as probabilistic switches, and it is likely that the human bidirectional promoters will have a similar property. The antisense transcripts generated in the Ly49 genes are far removed from the promoter responsible for Ly49 expression in mature NK cells, whereas the antisense KIR transcripts detected are within the adult promoter region. This finding suggests that the mechanism of promoter regulation in the KIR genes may be quite different from that of the Ly49 genes. This review summarizes the current state of knowledge regarding class I MHC receptor gene regulation. The models proposed for the control of the probabilistic expression of the Ly49 and KIR genes are discussed in the context of current knowledge regarding the complex control of other well-studied gene clusters such as the beta-globin and cytokine clusters. C1 NCI, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA. NCI, Expt Immunol Lab, Ctr Canc Res, Frederick, MD USA. RP Anderson, SK (reprint author), NCI, Basic Res Program, SAIC Frederick Inc, Bldg 560,Rm 31-93, Frederick, MD 21702 USA. EM andersonst@mail.nih.gov RI Anderson, Stephen/B-1727-2012 OI Anderson, Stephen/0000-0002-7856-4266 FU Intramural NIH HHS; PHS HHS [N01-C0-12400] NR 98 TC 30 Z9 31 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD DEC PY 2006 VL 214 BP 9 EP 21 DI 10.1111/j.1600-065X.2006.00452.x PG 13 WC Immunology SC Immunology GA 103NF UT WOS:000241892800002 PM 17100872 ER PT J AU Bryceson, YT March, ME Ljunggren, HG Long, EO AF Bryceson, Yenan T. March, Michael E. Ljunggren, Hans-Gustaf Long, Eric O. TI Activation, coactivation, and costimulation of resting human natural killer cells SO IMMUNOLOGICAL REVIEWS LA English DT Review DE innate immunity; natural killer cell; signaling; synergy ID HUMAN NK CELLS; CLASS-I MOLECULES; DEPENDENT CELLULAR CYTOTOXICITY; RICH TYROSINE KINASE-2; VIRUS-INFECTED CELLS; IMMUNOGLOBULIN-LIKE RECEPTOR; MISSING SELF-RECOGNITION; PHOSPHOLIPASE-C-GAMMA; CUTTING EDGE; INHIBITORY RECEPTOR AB Natural killer (NK) cells possess potent perforin- and interferon-gamma-dependent effector functions that are tightly regulated. Inhibitory receptors for major histocompatibility complex class I display variegated expression among NK cells, which confers specificity to individual NK cells. Specificity is also provided by engagement of an array of NK cell activation receptors. Target cells may express ligands for a multitude of activation receptors, many of which signal through different pathways. How inhibitory receptors intersect different signaling cascades is not fully understood. This review focuses on advances in understanding how activation receptors cooperate to induce cytotoxicity in resting NK cells. The role of activating receptors in determining specificity and providing redundancy of target cell recognition is discussed. Using Drosophila insect cells as targets, we have examined the contribution of individual receptors. Interestingly, the strength of activation is not determined simply by additive effects of parallel activation pathways. Combinations of signals from different receptors can have different outcomes: synergy, no enhancement over individual signals, or additive effects. Cytotoxicity requires combined signals for granule polarization and degranulation. The integrin leukocyte function-associated antigen-1 contributes a signal for polarization but not for degranulation. Conversely, CD16 alone or in synergistic combinations, such as NKG2D and 2B4, signals for phospholipase-C-gamma- and phosphatidylinositol-3-kinase-dependent degranulation. C1 NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. Karolinska Univ Hosp, Huddinge Hosp, Ctr Infect Med, Dept Med, Stockholm, Sweden. RP Long, EO (reprint author), NIAID, Immunogenet Lab, NIH, 12441 Parklwan Dr, Rockville, MD 20852 USA. EM eLong@nih.gov RI Long, Eric/G-5475-2011 OI Long, Eric/0000-0002-7793-3728 FU Intramural NIH HHS [ZIA AI000525-22] NR 199 TC 262 Z9 272 U1 1 U2 11 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD DEC PY 2006 VL 214 BP 73 EP 91 DI 10.1111/j.1600-065X.2006.00457.x PG 19 WC Immunology SC Immunology GA 103NF UT WOS:000241892800007 PM 17100877 ER PT J AU Khakoo, SI Carrington, M AF Khakoo, Salim I. Carrington, Mary TI KIR and disease: a model system or system of models? SO IMMUNOLOGICAL REVIEWS LA English DT Review DE KIR-HLA interactions; natural killer cells; haplotypic diversity; genetic association studies ID NATURAL-KILLER-CELLS; IMMUNOGLOBULIN-LIKE RECEPTOR; MAJOR HISTOCOMPATIBILITY COMPLEX; IG-LIKE RECEPTORS; MHC CLASS-I; LARGE GRANULAR LYMPHOCYTES; C-VIRUS-INFECTION; HUMAN NK CELLS; HUMAN-IMMUNODEFICIENCY-VIRUS; CHINESE HAN POPULATION AB The discovery of an unexpected level of diversity among the killer cell immunoglobulin-like receptors has led to a search for their role in human disease. Due to their polymorphism and also that of their human leukocyte antigen class I ligands, these studies are difficult to perform and complex to interpret. Nevertheless, as the number of data sets increase, consistent trends and themes are beginning to emerge in both viral and inflammatory disorders. In this review, we summarize the findings from a number of disease association studies and discuss these in the context of the activating and inhibitory roles of the members of this gene family. C1 NCI, Basic Res Program, SAIC Frederick Inc, Lab Genom Divers, Frederick, MD 21702 USA. Univ Southampton, Canc Sci Div, Southampton, Hants, England. RP Carrington, M (reprint author), NCI, Basic Res Program, SAIC Frederick Inc, Lab Genom Divers, POB B,Bldg 560,Room 21-89, Frederick, MD 21702 USA. EM carringt@ncifcrf.gov OI Khakoo, Salim/0000-0002-4057-9091 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 186 TC 174 Z9 183 U1 0 U2 8 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD DEC PY 2006 VL 214 BP 186 EP 201 DI 10.1111/j.1600-065X.2006.00459.x PG 16 WC Immunology SC Immunology GA 103NF UT WOS:000241892800015 PM 17100885 ER PT J AU Sinha, RK Yang, GB Alexander, C Mage, RG AF Sinha, Rajesh K. Yang, Guibin Alexander, Cornelius Mage, Rose G. TI De novo expression of MECA-79 glycoprotein-determinant on developing B lymphocytes in gut-associated lymphoid tissues SO IMMUNOLOGY LA English DT Article DE MECA-79; sulphated O-linked glycoprotein; B-lymphocyte exit; appendix; rabbit ID NEONATAL RABBIT APPENDIX; L-SELECTIN; LYMPHATIC ENDOTHELIUM; ANTIBODY REPERTOIRE; P-SELECTIN; CELL; DIVERSIFICATION; LIGANDS; BINDING; RECOGNITION AB Rabbit is one of several species that depend on development of B lymphocytes in gut-associated lymphoid tissues for primary immunoglobulin-repertoire diversification. The rabbit appendix is an important site of early B-lymphocyte development. We previously reported that peripheral lymph node addressin detected by monoclonal antibody (mAb) MECA-79 played a role in recruitment of immature blood-borne B cells into neonatal rabbit appendix. Here, we report expression of an similar to 127 000 MW O-linked sulphated proteoglycan on developing B cells in appendix and Peyer's patches recognized by the mAb MECA-79. Binding of the mAb to B lymphocytes was sensitive to enzyme treatment with O-sialoglycoprotease and expression was partially inhibited by sodium chlorate, a metabolic inhibitor of sulphation. The proportions of MECA-79(+) B lymphocytes gradually increased from < 0.5% at 3 days to > 70% at 6 weeks in appendix and Peyer's patches. The proportions of MECA-79(+) B lymphocytes in spleen and peripheral blood were very low (0.5-2%). However, the MECA-79 determinant was detected on B cells in splenic germinal centres after immunization. In situ labelling of appendix cells showed that the MECA-79 determinant was expressed on fluorescein-labelled B lymphocytes that migrated from appendix into mesenteric lymph nodes. B-cell MECA-79 may be involved in interactions with T cells and/or dendritic cells. Alternatively, because we found that lymphatic endothelium in the thymus-dependent area of appendix, a site for lymphocyte exit, expressed P-selectin (CD62P), interaction of the MECA-79 determinant on B cells with CD62P may have a role in the exit of B lymphocytes from rabbit appendix. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Sinha, RK (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Room 11 N311,10 Ctr Dr,MSC 1892, Bethesda, MD 20892 USA. EM rsinha@niaid.nih.gov NR 24 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD DEC PY 2006 VL 119 IS 4 BP 461 EP 469 DI 10.1111/j.1365-2567.2006.02457.x PG 9 WC Immunology SC Immunology GA 103VS UT WOS:000241915600004 PM 17177829 ER PT J AU Nakayama, M Hisatsune, J Yamasaki, E Nishi, Y Wada, A Kurazono, H Sap, J Yahiro, K Moss, J Hirayama, T AF Nakayama, Masaaki Hisatsune, Jyunzo Yamasaki, Eiki Nishi, Yoshito Wada, Akihiro Kurazono, Hisao Sap, Jan Yahiro, Kinnosuke Moss, Joel Hirayama, Toshiya TI Clustering of Helicobacter pylori VacA in lipid rafts, mediated by its receptor, receptor-like protein tyrosine phosphatase beta, is required for intoxication in AZ-521 cells SO INFECTION AND IMMUNITY LA English DT Article ID CYTOCHROME-C RELEASE; MEMBRANE CHANNEL FORMATION; ANION-SELECTIVE CHANNELS; GPI-ANCHORED PROTEINS; VACUOLATING CYTOTOXIN; RPTP-BETA; CELLULAR VACUOLATION; TOXIN VACA; PLASMA-MEMBRANE; BINDING AB Helicobacter pylori vacuolating cytotoxin, VacA, induces multiple effects on epithelial cells through different cellular events: one involves pore formation, leading to vacuolation, mitochondrial damage, and apoptosis, and the second involves cell signaling, resulting in stimulation of proinflammatory responses and cell detachment. Our recent data demonstrated that VacA uses receptor-like protein tyrosine phosphatase beta (RPTP beta) as a receptor, of which five residues (QTTQP) at positions 747 to 751 are involved in binding. In AZ-521 cells, which mainly express RPTP beta, VacA, after binding to RPTP beta in non-lipid raft microdomains on the cell surface, is localized with RPTP beta in lipid rafts in a temperature- and VacA concentration-dependent process. Methyl-beta-cyclodextrin (MCD) did not block binding to RPTP beta but inhibited translocation of VacA with RPTP beta to lipid rafts and all subsequent events. On the other hand, 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB), which disrupts anion channels, did not inhibit translocation of VacA to lipid rafts or VacA-induced activation of p38 mitogen-activated protein (MAP) kinase, but inhibited VacA internalization followed by vacuolation. Thus, p38 MAP kinase activation did not appear to be required for internalization. In contrast, phosphatidylinositol-specific phospholipase C (PI-PLC) inhibited translocation, as well as p38 MAP kinase/ATF-2 activation, internalization, and VacA-induced vacuolation. Neither NPPB nor PI-PLC affected VacA binding to cells and to its receptor, RPTP beta. Thus, receptor-dependent translocation of VacA to lipid rafts is critical for signaling pathways leading to p38 MAP kinase/ATF-2 activation and vacuolation. C1 Nagasaki Univ, Inst Trop Med, Dept Bacteriol, Nagasaki 8528523, Japan. Osaka Prefecture Univ, Grad Sch Life & Environm Sci, Lab Vet Publ Hlth, Sakai, Osaka 5998531, Japan. Univ Copenhagen, Dept Mol Pathol, DK-2100 Copenhagen, Denmark. NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Hirayama, T (reprint author), Nagasaki Univ, Inst Trop Med, Dept Bacteriol, Nagasaki 8528523, Japan. EM hirayama@net.nagasaki-u.ac.jp FU Intramural NIH HHS NR 46 TC 33 Z9 34 U1 0 U2 3 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 DEC PY 2006 VL 74 IS 12 BP 6571 EP 6580 DI 10.1128/IAI.00356-06 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 109KX UT WOS:000242308100007 PM 17030583 ER PT J AU McConchie, BW Norris, HH Bundoc, VG Trivedi, S Boesen, A Urban, JF Keane-Myers, AM AF McConchie, Brittany W. Norris, Hillary H. Bundoc, Virgilio G. Trivedi, Shweta Boesen, Agnieszka Urban, Joseph F., Jr. Keane-Myers, Andrea M. TI Ascaris suum-derived products suppress mucosal allergic inflammation in an interleukin-10-independent manner via interference with dendritic cell function SO INFECTION AND IMMUNITY LA English DT Article ID SCHISTOSOMA-MANSONI INFECTION; HETEROLOGOUS IMMUNE-RESPONSE; GABONESE SCHOOLCHILDREN; HELMINTH INFECTIONS; HYGIENE HYPOTHESIS; NEMATODE ASCARIS; MOLECULAR-WEIGHT; ABA-1 ALLERGEN; T-CELLS; MODULATION AB We have previously demonstrated that protection from allergic inflammation by Ascaris suum infection was characterized by a global increase in interleukin-10 (IL-10) and the development of protective CD4(+)/D25(+) T cells (L. Schopf, S. Luccioli, V. Bundoc, P. Justice, C. C. Chan, B. J. Wetzel, H. H. Norris, J. F. Urban, Jr., and A. Keane-Myers, Investig. Ophthalmol. Vis. Sci. 46:2772-2780, 2005). Here, we used A. suum pseudocoelomic fluid (PCF) in lieu of infection to define molecular mechanisms of allergic protection in a mouse model of allergic inflammation. Mice were sensitized with ragweed (RW) and PCF (RW/PCF), PCF alone, or RW alone and then challenged intratracheally, intranasally, and supraocularly with RW. Histological examination of the eyes and lungs, analysis of the bronchoalveolar lavage fluid (BALF), and characterization of ex vivo cytokine responses were performed to determine allergic inflammatory responses. RW/PCF-treated mice had suppressed allergic immune responses compared to mice given RW alone. To investigate whether IL-10 was involved in PCF-mediated allergic protection, similar experiments were performed using mice genetically deficient for IL-10. Persistent protection from allergic disease was observed in the absence of IL-10, indicating the primary mechanism of PCF protection is IL-10 independent. Ex vivo and in vitro analysis of PCF-treated dendritic cells (DC) demonstrated reduced activation receptor expression and cytokine production in response to either RW or lipopolysaccharide stimulation. These findings extend previous studies that showed infection with A. suum alters expression of allergic disease and suggest that PCF can contribute to this effect by interference with DC function. C1 NIAID, Lab Allerg Dis, NIH, Rockville, MD 20852 USA. USDA ARS, Nutr Requirements & Funct Lab, Beltsville Human Nutr Res Ctr, Beltsville, MD 20705 USA. RP McConchie, BW (reprint author), Twinbrook 2 Room 125,12441 Parklawn Dr, Rockville, MD 20852 USA. EM akeane@niaid.nih.gov OI Urban, Joseph/0000-0002-1590-8869 FU Intramural NIH HHS NR 36 TC 26 Z9 27 U1 0 U2 2 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 DEC PY 2006 VL 74 IS 12 BP 6632 EP 6641 DI 10.1128/IAI.00720-06 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 109KX UT WOS:000242308100013 PM 16966410 ER PT J AU Botkin, DJ Abbott, AN Stewart, PE Rosa, PA Kawabata, H Watanabe, H Norris, SJ AF Botkin, Douglas J. Abbott, April N. Stewart, Philip E. Rosa, Patricia A. Kawabata, Hiroki Watanabe, Haruo Norris, Steven J. TI Identification of potential virulence determinants by Himar1 transposition of infectious Borrelia burgdorferi B31 SO INFECTION AND IMMUNITY LA English DT Article ID LYME-DISEASE SPIROCHETE; RANDOM INSERTIONAL MUTAGENESIS; LINEAR PLASMIDS 1P25; ANTIGENIC VARIATION; MUTANTS; PROTEIN; TRANSFORMATION; CASSETTES; SEQUENCE; GENOME AB Lyme disease Borrelia organisms are highly invasive spirochetes that alternate between vertebrate and arthropod hosts and that establish chronic infections and elicit inflammatory reactions in mammals. Although progress has been made in the targeted mutagenesis of individual genes in infectious Borrelia burgdorferi, the roles of the vast majority of gene products in pathogenesis remain unresolved. In this study, we examined the feasibility of using transposon mutagenesis to identify infectivity-related factors in B. burgdorferi. The transformable, infectious strain 5A18 NP1 was transformed with the spirochete-adapted Himar1 transposon delivery vector pMarGent to create a small library of 33 insertion mutants. Single mouse inoculations followed by culture of four tissue sites and serology were used to screen the mutants for infectivity phenotypes. Mutants that appeared attenuated (culture positive at some sites) or noninfectious (negative at all sites) and contained the virulence-associated plasmids lp25 and lp28-1 were examined in more extensive animal studies. Three of these mutants (including those with insertions in the putative fliG-1-encoded flagellar motor switch protein and the guaB-encoded IMP dehydrogenase) were noninfectious, whereas four clones appeared to exhibit reduced infectivity. Serological reactivity in VlsE enzyme-linked immunosorbent assays correlated with the assignment of mutants to the noninfectious or attenuated-infectivity groups. The results of this study indicate that random transposon mutagenesis of infectious B. burgdorferi is feasible and will be of value in studying the pathogenesis of Lyme disease Borrelia. C1 Univ Texas, Hlth Sci Ctr, Dept Pathol & Lab Med, Houston, TX 77030 USA. Univ Texas, Hlth Sci Ctr, Grad Sch Biomed Sci, Houston, TX 77030 USA. Univ Texas, Hlth Sci Ctr, Program Microbiol & Mol Genet, Houston, TX 77030 USA. NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. Natl Inst Infect Dis, Dept Bacteriol, Shinjuku Ku, Tokyo 1628640, Japan. RP Norris, SJ (reprint author), Univ Texas, Sch Med, Dept Pathol & Lab Med, POB 20708, Houston, TX 77225 USA. EM steven.j.norris@uth.tmc.edu OI Norris, Steven/0000-0002-2501-8034 FU Intramural NIH HHS; NIAID NIH HHS [R01 AI059048, T32 AI055449, T32 AI 055449, R01 AI 59048] NR 32 TC 28 Z9 29 U1 0 U2 2 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 DEC PY 2006 VL 74 IS 12 BP 6690 EP 6699 DI 10.1128/IAI.00993-06 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 109KX UT WOS:000242308100019 PM 17015459 ER PT J AU Bolz, DD Sundsbak, RS Ma, Y Akira, S Weis, JH Schwan, TG Weis, JJ AF Bolz, Devin D. Sundsbak, Rhianna S. Ma, Ying Akira, Shizuo Weis, John H. Schwan, Tom G. Weis, Janis J. TI Dual role of MyD88 in rapid clearance of relapsing fever Borrelia spp. SO INFECTION AND IMMUNITY LA English DT Article ID TOLL-LIKE RECEPTOR-2; OUTER SURFACE LIPOPROTEINS; LYME-DISEASE SPIROCHETE; INNATE IMMUNE-RESPONSE; CUTTING EDGE; ANTIGENIC VARIATION; MOUSE MODEL; HOST-DEFENSE; ARTHRITIS DEVELOPMENT; B1B LYMPHOCYTES AB Relapsing fever Borrelia spp. undergo antigenic variation, achieve high levels in blood, and require rapid production of immunoglobulin M (IgM) for clearance. MyD88-deficient mice display defective clearance of many pathogens; however, the IgM response to persistent infection is essentially normal. Therefore, MyD88(-/-) mice provided a unique opportunity to study the effect of nonantibody, innate host defenses to relapsing fever Borrelia. Infected MyD88(-/-) mice harbored extremely high levels of B. hermsii in the blood compared to wild-type littermates. In the comparison of MyD88(-/-) mice and B- and T-cell-deficient scid mice, two features stood out: (i) bacterial numbers in blood were at least 10-fold greater in MyD88-/- mice than scid mice, even though the production of IgM still occurred in MyD88-/- mice; and (ii) many of the MyD88-/- mice were able to exert partial clearance, although with delayed kinetics relative to wild-type mice, a feature not seen in scid mice. Further analysis revealed a delay in the IgM response to lipoproteins expressed by the original inoculum; however, by 6 days of infection antibodies were produced in MyD88-/- mice that could clear spirochetemia in scid mice. While these results indicated that the production of IgM was delayed in MyD88-/- mice, they also point to a second, antibody-independent role for MYD88 signaling in host defense to relapsing fever Borrelia. This second defect was apparent only when antibody levels were limiting. C1 Univ Utah, Dept Pathol, Salt Lake City, UT 84112 USA. Osaka Univ, Dept Host Def, Res Inst Microbial Dis, Osaka, Japan. Natl Inst Hlth, Natl Inst Allergy & Infect Dis, Rocky Mt Labs, Lab Zoonot Pathogens, Hamilton, MT 59840 USA. RP Weis, JJ (reprint author), Univ Utah, Dept Pathol, 15 N Med Dr E 2100, Salt Lake City, UT 84112 USA. EM janis.weis@path.utah.edu RI Akira, Shizuo/C-3134-2009 FU Intramural NIH HHS; NCI NIH HHS [5P30 CA 42014, P30 CA042014]; NIAID NIH HHS [R01 AI043521, AI 24158, AI 32223, AI 43521, R01 AI024158, R01 AI032223, R29 AI043521, R56 AI032223]; NIGMS NIH HHS [GM 07464, T32 GM007464] NR 78 TC 13 Z9 13 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD DEC PY 2006 VL 74 IS 12 BP 6750 EP 6760 DI 10.1128/IAI.01160-06 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 109KX UT WOS:000242308100025 PM 17030581 ER PT J AU Skaleric, U Gaspirc, B McCartney-Francis, N Masera, A Wahl, SM AF Skaleric, Uros Gaspirc, Boris McCartney-Francis, Nancy Masera, Andrej Wahl, Sharon M. TI Proinflammatory and antimicrobial nitric oxide in gingival fluid of diabetic patients with periodontal disease SO INFECTION AND IMMUNITY LA English DT Article ID PORPHYROMONAS-GINGIVALIS; ALPHA PRODUCTION; TNF-ALPHA; IN-VIVO; SYNTHASE; RETINOPATHY; MELLITUS; MACROPHAGES; TISSUE; NO AB Abnormal nitric oxide (NO) synthesis has been implicated in the pathogenesis of both periodontal disease and diabetes mellitus. In diabetic patients, increased inducible NO synthase in inflamed gingiva correlated with NO in gingival crevicular fluid. Although increased NO reflected more-severe inflammation, it was associated with reductions in CFU of Prevotella intermedia, a major periodontopathogen, highlighting dual roles for NO. C1 Univ Ljubljana, Fac Med, Dept Oral Med & Periodontol, Ljubljana 1000, Slovenia. NIDCR, Oral Infect & Immun Branch, NIH, Bethesda, MD USA. Univ Ljubljana, Fac Med, Inst Pathol, Ljubljana 61000, Slovenia. RP Skaleric, U (reprint author), Univ Ljubljana, Fac Med, Dept Oral Med & Periodontol, Hrvatski 6, Ljubljana 1000, Slovenia. EM uros.skaleric@mf.uni-lj.si RI Gaspirc, Boris/A-6110-2008 FU Intramural NIH HHS NR 33 TC 14 Z9 15 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD DEC PY 2006 VL 74 IS 12 BP 7010 EP 7013 DI 10.1128/IAI.00071-06 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 109KX UT WOS:000242308100054 PM 17015454 ER PT J AU Berra, L Kolobow, T AF Berra, Lorenzo Kolobow, Theodor TI Reply to the comment by Dr. Spronk et al. SO INTENSIVE CARE MEDICINE LA English DT Letter ID ENDOTRACHEAL-TUBE; MECHANICAL VENTILATION; MUCUS SHAVER; DIAMETER C1 Massachusetts Gen Hosp, Boston, MA 02113 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Berra, L (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02113 USA. EM lberra@partners.org NR 13 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD DEC PY 2006 VL 32 IS 12 BP 2082 EP 2083 DI 10.1007/s00134-006-0403-3 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 110EU UT WOS:000242361900032 ER PT J AU Mbulaiteye, SM Engels, EA AF Mbulaiteye, Sam M. Engels, Eric A. TI Kaposi's sarcoma risk among transplant recipients in the United States (1993-2003) SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE human herpesvirus 8; immunosuppression; cancer; chimerism ID HUMAN HERPES VIRUS-8; HUMAN-HERPESVIRUS-8 INFECTION; RENAL-TRANSPLANTATION; ORGAN-TRANSPLANTATION; SAUDI-ARABIA; CANCER RISK; EPIDEMIOLOGY; TRANSMISSION; SEROPREVALENCE; ANTIBODIES AB Kaposi's sarcoma (KS) risk is high in immunosuppressed transplant recipients. KS develops in recipients with pre-existing infection with human herpesvirus 8 (HHV-8), the causative agent for KS, but it can also occur in recipients infected by donors. The relative importance of these sources of infection in recipients in the United States is unknown. We report recipient and donor characteristics associated with KS among transplant recipients in the United States. KS risk, after solid organ transplantation during 1993-2003, was analyzed using data from the Organ Procurement and Tissue Network. Associations were determined using proportional hazards regression. Sixtyfive KS cases were identified among 234,127 transplants (incidence 8.8 per 100,000 person-years). Most cases occurred in the first 2 years after transplantation (incidence 12.5 per 100,000 person-years). KS risk increased steadily with recipient age (p(trend) < 0.001) and was associated with the recipient being male (HR 1.8, 95% CI, 1.0-3.2), Hispanic (2.1, 1.1-3.8) and a non-U.S. citizen (3.9, 1.8-8.6). Mismatch at the HLA-B locus, but not at HLA-A or HLA-DR loci, was associated with heightened risk (HR 3.6, 95%CI 1.1-11 for 1-2 vs. 0 HLA-B mismatches). KS was unrelated to donor, characteristics and was not significantly related to use of specific antirejection medications. Our study found that KS incidence was low among transplant recipients in the United States, but it was associated with recipient age, sex and citizenship, perhaps reflecting pre-existing HHV-8 infection. The high KS risk immediately posttransplant and in persons with HLA-B mismatch highlights the role of immunosuppression and/or immune stimulation in KS pathogenesis. (c) 2006Wiley-Liss,Inc. C1 NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Mbulaiteye, SM (reprint author), 6120 Execut Blvd,Execut Plaza S Rm 7080, Rockville, MD 20852 USA. EM mbulaits@mail.nih.gov FU Intramural NIH HHS; PHS HHS [231-00-0115] NR 34 TC 44 Z9 47 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 DEC 1 PY 2006 VL 119 IS 11 BP 2685 EP 2691 DI 10.1002/ijc.22233 PG 7 WC Oncology SC Oncology GA 104NH UT WOS:000241964600027 PM 16929513 ER PT J AU Noailles, P Graham, D Hartman, J Pfieffer, K Becker, K Cadet, J AF Noailles, P. Graham, D. Hartman, J. Pfieffer, K. Becker, K. Cadet, J. TI The molecular consequences of in utero METH exposure on early development of the rat cortex SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE LA English DT Meeting Abstract CT 16th Biennial Meeting of the International-Society-for-Developmental-Neuroscience CY AUG 24-28, 2006 CL Banff, CANADA SP Int Soc Dev Neurosci DE methamphetamine; in utero; microarray C1 NIA, DHHS, NIH, Bethesda, MD 20892 USA. NR 0 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 0736-5748 J9 INT J DEV NEUROSCI JI Int. J. Dev. Neurosci. PD DEC PY 2006 VL 24 IS 8 BP 503 EP 503 DI 10.1016/j.ijdevneu.2006.09.082 PG 1 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 128NE UT WOS:000243663700079 ER PT J AU Liu, QR Zhu, XG Gong, JP Lu, L Shaham, Y Pletnikova, O Troncoso, JC Uhl, GR AF Liu, Q. R. Zhu, X. G. Gong, J. P. Lu, L. Shaham, Y. Pletnikova, O. Troncoso, J. C. Uhl, G. R. TI Differential regulation of sense and antisense human BDNF/BDNFOS genes and rodent BDNF gene: Possible roles in Alzheimer's disease and addictions SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE LA English DT Meeting Abstract CT 16th Biennial Meeting of the International-Society-for-Developmental-Neuroscience CY AUG 24-28, 2006 CL Banff, CANADA SP Int Soc Dev Neurosci DE neurotrophin; addiction; Alzheimer's disease; gene regulation C1 NIH, NIDA IRP, Baltimore, MD USA. Johns Hopkins Sch Med, Baltimore, MD USA. RI Liu, Qing-Rong/A-3059-2012 OI Liu, Qing-Rong/0000-0001-8477-6452 NR 0 TC 0 Z9 0 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0736-5748 J9 INT J DEV NEUROSCI JI Int. J. Dev. Neurosci. PD DEC PY 2006 VL 24 IS 8 BP 559 EP 559 DI 10.1016/j.ijdevneu.2006.09.208 PG 1 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 128NE UT WOS:000243663700205 ER PT J AU Villegas, R Shu, XO Li, HL Yang, G Matthews, CE Leitzmann, M Li, Q Cai, H Gao, YT Zheng, W AF Villegas, Raquel Shu, Xiao-Ou Li, Honglan Yang, Gong Matthews, Charles E. Leitzmann, Michael Li, Qi Cai, Hui Gao, Yu-Tang Zheng, Wei TI Physical activity and the incidence of type 2 diabetes in the Shanghai women's health study SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE occupational; daily living leisure; commuting physical activity; type 2 diabetes ID CORONARY-HEART-DISEASE; IMPAIRED FASTING GLUCOSE; BODY-MASS INDEX; CHINESE ADULTS; INSULIN LEVELS; LEISURE-TIME; LIFE-STYLE; HIGH-RISK; MELLITUS; POPULATION AB Background Leisure-time physical activity (LPA) has been associated with a reduced risk of type 2 diabetes. However, the potential effect of other types of physical activity on type 2 diabetes is still uncertain. The aim of this study was to examine the effect of occupational, commuting, daily living, and LPA on the incidence of type 2 diabetes in a cohort of middle-aged women. Methods We prospectively followed 70 658 women who had no prior history of diabetes at study recruitment for 4.6 years. Participants completed in-person interviews at baseline that collected information on diabetes risk factors including physical activity habits. Anthropometric measurements were taken by trained interviewers. Multivariate-adjusted hazard ratios were estimated by levels of occupational, commuting, daily living, and LPA. Results We documented 1973 incident cases of diabetes during 326 625 person-years of follow-up. LPA and daily living physical activity (DPA) were associated with a moderately reduced risk of type 2 diabetes. The relative risk for type 2 diabetes associated with LPA and DPA categories were 1.00, 0.89, 1.05, and 0.83, (P trend = 0.12) and 1.00, 0.98, 0.95, and 0.88, (P trend = 0.06) respectively. LPA was associated with lower risk of type 2 diabetes in employed participants (P trend = 0.09) while DPA was mainly associated with a reduction in risk in non-employed participants (P trend < 0.01). While occupational physical activity was not associated with type 2 diabetes risk in this population, commuting to work was associated with a reduction in risk. A combination of DPA and LPA was associated with a reduced risk of type 2 diabetes. Conclusions This study suggests that physical activity, either from leisure-time exercise or daily activity reduces the risk of type 2 diabetes in women, supporting the current health promotion efforts encouraging both exercise and non-exercise activity levels. C1 Vanderbilt Univ, Sch Med, Epidemiol Ctr, Vanderbilt Ingram Canc Ctr,Dept Med, Nashville, TN 37232 USA. Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China. NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Shu, XO (reprint author), Vanderbilt Univ, Ctr Hlth Serv Res, 6009 Med Ctr E, Nashville, TN 37232 USA. EM xiao-ou.shu@vanderbilt.edu RI matthews, Charles/E-8073-2015 OI matthews, Charles/0000-0001-8037-3103 FU NCI NIH HHS [R01 CA 70867] NR 44 TC 27 Z9 29 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD DEC PY 2006 VL 35 IS 6 BP 1553 EP 1562 DI 10.1093/ije/dyl209 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 130NN UT WOS:000243806400027 PM 16984936 ER PT J AU Babin, V Baucom, J Darden, TA Sagui, C AF Babin, Volodymyr Baucom, Jason Darden, Thomas A. Sagui, Celeste TI Molecular dynamics simulations of polarizable DNA in crystal environment SO INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY LA English DT Article; Proceedings Paper CT 46th Annual Sanibel Symposium CY FEB 26-MAR 03, 2006 CL St Simons Isl, GA SP Univ Florida, Quantum Theory Project DE DNA; electrostatics; polarizable; crystal ID PARTICLE-MESH EWALD; T-G-G; B-DNA; FORCE-FIELDS; D(CCAACGTTGG)(2) DECAMER; BIOMOLECULAR SIMULATIONS; AB-INITIO; C-G; WATER; MAGNESIUM AB We have investigated the role of the electrostatic description and cell environment in molecular dynamics (MD) simulations of DNA. Multiple unrestrained MD simulations of the DNA duplex d(CCAACGTTGG)(2) have been carried out using two different force fields: a traditional description based on atomic point charges and a polarizable force field. For the time scales probed, and given the "right" distribution of divalent ions, the latter performs better than the nonpolarizable force field. In particular, by imposing the experimental unit cell environment, an initial configuration with ideal B-DNA duplexes in the unit cell acquires sequence-dependent features that very closely resemble the crystallographic ones. Simultaneously, the all-atom root-mean-square coordinates deviation (RMSD) with respect to the crystallographic structure is seen to decay. At later times, the polarizable force field is able to maintain this lower RMSD, while the nonpolarizable force field starts to drift away. (c) 2006 Wiley Periodicals, Inc. C1 N Carolina State Univ, Dept Phys, Raleigh, NC 27695 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. RP Sagui, C (reprint author), N Carolina State Univ, Dept Phys, Raleigh, NC 27695 USA. EM darden@niehs.nih.gov; sagui@ncsu.edu NR 35 TC 9 Z9 9 U1 2 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7608 J9 INT J QUANTUM CHEM JI Int. J. Quantum Chem. PD DEC PY 2006 VL 106 IS 15 SI SI BP 3260 EP 3269 DI 10.1002/qua.21152 PG 10 WC Chemistry, Physical; Mathematics, Interdisciplinary Applications; Physics, Atomic, Molecular & Chemical SC Chemistry; Mathematics; Physics GA 100BP UT WOS:000241642400026 ER PT J AU Nguyen, RHN Gange, SJ Wabwire-Mangen, F Sewankambo, NK Serwadda, D Wawer, MJ Quinn, TC Gray, RH AF Nguyen, Ruby H. N. Gange, Stephen J. Wabwire-Mangen, Fred Sewankambo, Nelson K. Serwadda, David Wawer, Maria J. Quinn, Thomas C. Gray, Ronald H. TI Reduced fertility among HIV-infected women associated with viral load in Rakai district, Uganda SO INTERNATIONAL JOURNAL OF STD & AIDS LA English DT Article DE fertility; HIV; viral load; Africa; pregnancy ID IMMUNODEFICIENCY-VIRUS-INFECTION; DISEASE PROGRESSION; AIDS-PREVENTION; COMMUNITY TRIAL; PREGNANT-WOMEN; MATERNAL HIV-1; COTE-DIVOIRE; SUBFERTILITY; POPULATION; PREVALENCE AB We assessed whether HIV-1 viral load affects the likelihood of live birth among HIV-positive women in a nested case-control study of HIV-positive women from a community cohort in Rakai District, Uganda. Cases were women who had a live birth (n = 270), and controls were sexually active women who did not use contraception and did not become pregnant during follow-up (n = 263). In women with a live birth and non-pregnant controls, median HIV viral loads were 4.12 logl(10) copies/mL and 4.41 log(10) copies/mL, respectively (P = 0.001). A non-linear association was observed, and a segmented linear regression with spline knot at 4.5 log(10) copies/mL was fit. We observed a decline in the log (adjusted odds ratio [adj. OR]) = -0.08 (95% confidence interval [CI]: -0.36, 0.20) between 3.0 and 4.49 log(10) viral load and -0.92 (95% CI: -1.21, -0.63) between 4.5 and 6.5 log(10) viral load. The two reductions differed significantly from one another (P < 0.001). Each increase in log(10) viral load after 4.5 log(10) resulted in an adj. OR of live birth which was 12% of the previous viral load category. Our data suggest that there may be considerable differences in the ability to produce a live birth among HIV-positive women with high viral loads. C1 Natl Inst Environm Hlth Sci, Epidemiol Branch, Durham, NC USA. Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. Makerere Univ, Kampala, Uganda. Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. Johns Hopkins Univ, Dept Med, Baltimore, MD USA. NIAID, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Populat & Family Hlth Sci, Baltimore, MD USA. RP Nguyen, RHN (reprint author), NIEHS, Epidemiol Branch, NIH, 111 TW Alexander Dr,POB 12233,MD A3-05, Res Triangle Pk, NC 27709 USA. EM nguyen5@niehs.nih.gov OI Sewankambo, Nelson/0000-0001-9362-053X; Gange, Stephen/0000-0001-7842-512X FU FIC NIH HHS [R D43 TW0010-AITRP]; NICHD NIH HHS [R01HD38883] NR 32 TC 12 Z9 12 U1 0 U2 1 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 0956-4624 J9 INT J STD AIDS JI Int. J. STD AIDS PD DEC PY 2006 VL 17 IS 12 BP 842 EP 846 DI 10.1258/095646206779307586 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 122IH UT WOS:000243218900013 PM 17212863 ER PT J AU Li, J Yao, JH Summers, RM Petrick, N Manry, MT Hara, AK AF Li, Jiang Yao, Jianhua Summers, Ronald M. Petrick, Nicholas Manry, Michael T. Hara, Amy K. TI An efficient feature selection algorithm for computer-aided polyp detection SO INTERNATIONAL JOURNAL ON ARTIFICIAL INTELLIGENCE TOOLS LA English DT Article; Proceedings Paper CT 18th International Florida-Artificial-Intelligence-Research-Society Conference CY MAY 15-17, 2005 CL Clearwater, FL SP Florida Artificial Intelligence Res Soc DE feature selection; CAD; piecewise linear network; orthonormal least squares; branch and bound; floating search ID FEATURE SUBSET-SELECTION; SELF-ORGANIZING MAP; GENETIC ALGORITHMS; VARIABLE SELECTION; CT COLONOGRAPHY; IDENTIFICATION; NETWORK AB We present an efficient feature selection algorithm for computer aided detection (CAD) computed tomographic (CT) colonography. The algorithm (1) determines an appropriate piecewise linear network (PLN) model by cross validation, (2) applies the orthonormal least square (OLS) procedure to the PLN model utilizing a Modified Schmidt procedure, and (3) uses a floating search algorithm to select features that minimize the output variance. The undesirable "nesting effect" is prevented by the floating search approach, and the piecewise linear OLS procedure makes this algorithm very computationally efficient because the Modified Schmidt procedure only requires one data pass during the whole searching process. The selected features are compared to those obtained by other methods, through cross validation with support vector machines (SVMS). C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. NIBIB, CDRH, Joint Lab Assessment Med Imaging Syst, FDA, Rockville, MD 20852 USA. Univ Texas, Dept Elect Engn, Arlington, TX 76019 USA. Mayo Clin Scottsdale, Scottsdale, AZ USA. RP Li, J (reprint author), NIH, Ctr Clin, Bethesda, MD 20892 USA. EM lij3@cc.nih.gov; jyao@cc.nih.gov; rms@cc.nih.gov; nicholas.petrick@fda.hhs.gov; manry@uta.edu; hara.amy@mayo.edu NR 31 TC 8 Z9 8 U1 0 U2 1 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA 5 TOH TUCK LINK, SINGAPORE 596224, SINGAPORE SN 0218-2130 J9 INT J ARTIF INTELL T JI Int. J. Artif. Intell. Tools PD DEC PY 2006 VL 15 IS 6 BP 893 EP 915 DI 10.1142/S021821300600303X PG 23 WC Computer Science, Artificial Intelligence; Computer Science, Interdisciplinary Applications SC Computer Science GA 120WW UT WOS:000243118500004 ER PT J AU Campos, M Amaral, J Becerra, SP Fariss, RN AF Campos, Mercedes Amaral, Juan Becerra, S. Patricia Fariss, Robert N. TI A novel imaging technique for experimental choroidal neovascularization SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID SUB-RETINAL NEOVASCULARIZATION; SUBRETINAL NEOVASCULARIZATION; MACULAR DEGENERATION; RAT; MODEL; ANGIOGRAPHY AB PURPOSE. Choroidal neovascularization (CNV) is the end point of several ocular diseases that lead to blindness. The authors developed an imaging technique for visualizing and quantifying morphologic changes associated with experimental laser-induced CNV. METHODS. CNV was induced using laser energy to disrupt Bruch's membrane. Rats were euthanatized immediately after laser injury and at 1, 2, 3, 4, 7, 14, and 60 days. Nonlasered eyes were used as the control. Eyes were enucleated and fixed, and the posterior eye cups were fluorescently labeled with markers for nuclei (DAPI; 4 ',6'-diamino-2-phenylindole), endothelial cells (isolectin IB4), microglia (CD11b), and filamentous actin (phalloidin). FITC-dextran perfusion was compared with our technique. A confocal microscope was used to evaluate flat-mounted specimens. Computer software generated three-dimensional reconstructions for qualitative and quantitative analysis of confocal image stacks. RESULTS. In nonlasered areas, RPE cells were visualized as a uniform hexagonal array. Immediately after laser exposure, a circular area devoid of fluorescent labeling was observed, indicating disruption of the choroid-Bruch's membrane-RPE complex. One day after laser exposure, cellular debris and fragmented nuclei were present, and an autofluorescent ring was visible at the site of Bruch's membrane disruption. The ring correlated with bubble formation and CNV induction. Three days after laser injury, phalloidin-labeled RPE cells and isolectin-labeled endothelial cells increased significantly, reflecting cell proliferation and migration. By day 4, isolectin-positive cells forming vascular tubes were visualized. The volume of CNV vessels increased exponentially during the next 3 days. By 7 days, a well-defined isolectin-labeled CNV network was present, and its volume was preserved for several weeks. CNV volumes calculated on the basis of FITC-dextran perfusion were significantly lower than volumes obtained using lectin-labeled samples. CONCLUSIONS. A novel imaging technique was developed that allows a three-dimensional reconstruction and measurement of laser-induced CNV lesions in rat choroid/RPE flatmounts. This technique provides excellent morphologic detail and facilitates the study of critical early events in CNV, including the rupture of Bruch's membrane and the formation of endothelial clusters before vessel formation. CNV complexes are labeled at an earlier stage and more reproducibly than with FITC-dextran perfusion, providing a more accurate preclinical evaluation of antiangiogenic molecules. C1 NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Fariss, RN (reprint author), NEI, Retinal Cell & Mol Biol Lab, NIH, Bldg 7,Rm 204,7 Mem Dr,MSC 0703, Bethesda, MD 20892 USA. EM farissr@nei.nih.gov FU Intramural NIH HHS NR 26 TC 41 Z9 44 U1 1 U2 5 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 DEC PY 2006 VL 47 IS 12 BP 5163 EP 5170 DI 10.1167/iovs.06-0156 PG 8 WC Ophthalmology SC Ophthalmology GA 110TW UT WOS:000242404900005 PM 17122098 ER PT J AU Rosenthal, JM Kim, J de Monastario, F Thompson, DJS Bone, RA Landrum, JT de Moura, FF Khachik, F Chen, H Schleicher, RL Ferris, FL Chew, EY AF Rosenthal, Julie M. Kim, Jonghyeon de Monastario, Francisco Thompson, Darby J. S. Bone, Richard A. Landrum, John T. de Moura, Fabiana F. Khachik, Frederick Chen, Huiping Schleicher, Rosemary L. Ferris, Frederick L., III Chew, Emily Y. TI Dose-ranging study of lutein supplementation in persons aged 60 years or older SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; SUBFOVEAL CHOROIDAL NEOVASCULARIZATION; RESONANCE RAMAN MEASUREMENT; RANDOMIZED CLINICAL-TRIALS; MACULAR DEGENERATION; PHOTODYNAMIC THERAPY; BIOLOGICAL VARIATION; BEVACIZUMAB AVASTIN; BETA-CAROTENE AB PURPOSE. To examine the dose-response relationship between oral lutein supplementation and serum lutein concentrations in persons aged 60 years and older, with or without age- related macular degeneration (AMD). METHODS. Forty-five participants with no AMD, large drusen, or advanced AMD, were randomized to receive one of three doses (2.5, 5, or 10 mg) of lutein for 6 months and to be observed for 6 additional months after the cessation of lutein supplementation. RESULTS. The mean age of the participants (33 women) was 71 years (range: 60-91). The serum lutein concentrations of each dose group were similar before supplementation, increased at 1 month, and peaked by 3 months. Median serum concentrations of the 2.5- ,5-, and 10-mg groups from baseline to month 6 increased from 18.7 to 35.1 mu g/dL (2-fold increase), from 17.8 to 59.2 mu g/dL (2.9-fold increase), and from 15.1 to 66.8 mu g/dL (4-fold increase), respectively (all P < 0.001). The increases in lutein serum concentrations did not vary with AMD disease severity (P = 0.98). No toxicity was observed with any dose of lutein. No significant changes were detected in visual acuity or visual field tests. CONCLUSIONS. Increasing doses of lutein supplements significantly increased the serum levels of lutein and zeaxanthin, and doses up to 10 mg were safely administered. A long-term large clinical trial is necessary to investigate the safety and efficacy of lutein in reducing the risk of the development of advanced AMD. C1 NEI, Clin Trials Branch, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA. EMMES Corp, Rockville, MD USA. NEI, Off Clin Director, NIH, Bethesda, MD 20892 USA. Florida Int Univ, Dept Chem & Biochem, Miami, FL 33199 USA. Univ Maryland, Joint Inst Food Safety & Appl Nutr, Dept Chem & Biochem, College Pk, MD 20742 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. RP Chew, EY (reprint author), CRC, Room 3-2531,10 Ctr Dr,MSC 1204, Bethesda, MD 20892 USA. EM echew@nei.nih.gov RI Khachik, Frederick/C-5055-2009; OI De Moura, Fabiana F./0000-0001-8176-5352 FU Intramural NIH HHS [Z99 EY999999, ZIA EY000485-01]; NIGMS NIH HHS [S06GM0825] NR 35 TC 32 Z9 39 U1 0 U2 4 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD DEC PY 2006 VL 47 IS 12 BP 5227 EP 5233 DI 10.1167/iovs.05-1513 PG 7 WC Ophthalmology SC Ophthalmology GA 110TW UT WOS:000242404900016 PM 17122107 ER PT J AU Khachik, F de Moura, FF Chew, EY Douglass, LW Ferris, FL Kim, J Thompson, DJS AF Khachik, Frederick de Moura, Fabiana F. Chew, Emily Y. Douglass, Larry W. Ferris, Frederick L., III Kim, Jonghyeon Thompson, Darby J. S. TI The effect of lutein and zeaxanthin supplementation on metabolites of these carotenoids in the serum of persons aged 60 or older SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID MACULAR DEGENERATION; STRUCTURAL ELUCIDATION; HUMAN PLASMA; GEOMETRICAL-ISOMERS; OXIDATION-PRODUCTS; IDENTIFICATION; MACULOPATHY; EXTRACTS; RETINAS; TISSUES AB PURPOSE. To investigate the effect of lutein supplementation at doses of 2.5, 5.0, and 10 mg/d for 6 months on distribution of these carotenoids and their metabolites in the serum of elderly human subjects, with and without age-related macular degeneration. To determine whether supplementation with lutein can interact with the serum levels of other dietary carotenoids, retinol, and alpha-tocopherol. METHODS. Forty-five subjects received daily supplements of lutein (containing 5% zeaxanthin) for 6 months and were followed up for another 6 months after supplementation. Blood was collected at various intervals and lutein, zeaxanthin, and their metabolites in the sera were quantified by normal-phase high-performance liquid chromatography (HPLC)-UV/visible detection. Other dietary carotenoids, retinol, and alpha-to-copherol were identified and quantified on a C-18 reversed phase HPLC column. RESULTS. After 6 months of supplementation with 10 mg of lutein, the increases in the mean serum levels from baseline were: 210 to 1000 nM/L (P < 0.0001) for lutein and 56 to 95 nM/L (P < 0.0001) for zeaxanthin. Similarly, the mean concentrations (nM/L) of carotenoid metabolites increased from 49 to 98 (P < 0.0001) for 3-hydroxy-ss, epsilon-caroten-3'-one (3'-oxolutein); 31 to 80 (P < 0.0001) for 3'- hydroxy-epsilon,epsilon-caroten-3-one; and 19 to 25 (P < 0.0001) for epsilon, epsilon-carotene- 3,3'-dione. The serum levels of these carotenoids gradually decline within 6 months after supplementation. CONCLUSIONS. The increase in the serum levels of lutein/zeaxanthin correlates with increases in the serum levels of their metabolites that have previously been identified in the ocular tissues. Elderly human subjects with and without AMD can safely take supplements of lutein up to 10 mg/d for 6 months with no apparent toxicity or side effects. C1 Univ Maryland, Dept Chem & Biochem, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. Univ Maryland, Dept Avian Sci, College Pk, MD 20742 USA. NEI, Clin Trials Branch, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA. EMMES Corp, Rockville, MD USA. RP Khachik, F (reprint author), Univ Maryland, Dept Chem & Biochem, Joint Inst Food Safety & Appl Nutr, Bldg 091, College Pk, MD 20742 USA. EM khachik@umd.edu RI Khachik, Frederick/C-5055-2009; OI De Moura, Fabiana F./0000-0001-8176-5352 FU Intramural NIH HHS [Z99 EY999999, ZIA EY000485-01] NR 30 TC 32 Z9 39 U1 0 U2 4 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD DEC PY 2006 VL 47 IS 12 BP 5234 EP 5242 DI 10.1167/iovs.06-0504 PG 9 WC Ophthalmology SC Ophthalmology GA 110TW UT WOS:000242404900017 PM 17122108 ER PT J AU Gupta, A Mehta, S Godbole, SV Sahay, S Ralshe, L Reynolds, SJ Ghate, M Gangakhedkar, RR Divekar, AD Risbud, AR Mehendale, SM Bollinger, RC AF Gupta, Amita Mehta, Shruti Godbole, Sheela V. Sahay, Seema Ralshe, Louise Reynolds, Steven J. Ghate, Manisha Gangakhedkar, Raman R. Divekar, Anand D. Risbud, Arun R. Mehendale, Sanjay M. Bollinger, Robert C. TI Same-sex behavior and high rates of HIV among men attending sexually transmitted infection clinics in Pune, India (1993-2002) SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article; Proceedings Paper CT 15th International AIDS Conference CY JUL 11-17, 2004 CL Bangkok, THAILAND DE India; men; MSM; homosexual; same-sex behaviors; male-to-male sex; HIV; sexually transmitted infections; syphilis; gonorrhea; genital ulcer disease; prevalence; risk factors; trends ID IMMUNODEFICIENCY-VIRUS TYPE-1; HOMOSEXUAL MEN; RISK-FACTORS; TRANSMISSION; ACQUISITION; EPIDEMIC; DISEASE AB Objectives: To determine HIV/sexually transmitted infection (STI) prevalence, trends, and risk behaviors of men who have sex with men (MSM) and compare these with those of non-MSM attending STI clinics in Pune, India over a 10-year period. Design: Cross-sectional. Methods: From 1993 through 2002, men attending 3 STI clinics in Pune underwent HIV/STI screening. Demographic, risk behavior, clinical, and laboratory data were collected using standardized questionnaires and laboratory procedures. Results: Of 10,785 men screened, 708 (6.6%) were NISM. Among these 708 MSM, 189 (31.7%) had 10 or more lifetime partners, 253 (35.7%) were married, 163 (23.1%) had sex with a hijra (eunuch), and 87 (13.3%) had exchanged money for sex. A total of 134 (18.9%) were HIV-positive, 149 (21.5%) had genital ulcer disease (GUD), 37 (5.8%) had syphilis, and 29 (4.3%) had gonorrhea (GC). Over the decade, neither HIV nor GC prevalence changed among MSM (P = 0.7), but syphilis and GUD decreased significantly (P < 0.0001). Compared with non-MSM, MSM were more likely to initiate sexual activity at age < 16 years, to have > 10 lifetime partners, to have sex with a hijra, and to use condoms regularly, but they did not differ significantly in HIV prevalence and had a lower prevalence of GC, GUD, and syphilis. Independent factors associated with HIV among MSM were employment (adjusted odds ratio [AOR] = 3.08; P = 0.02), history of GUD (AOR = 1.86; P = 0.003), and syphilis (AOR = 2.09; P = 0.05). Conclusions: Same-sex and high-risk sexual behaviors are prevalent among men attending STI clinics in India. Although syphilis and GUD rates decreased, HIV prevalence remained high during the decade, highlighting the importance of additional targeted efforts to reduce HIV risk among all men, including MSM, in India. C1 Johns Hopkins Sch Med, Div Infect Dis, Baltimore, MD USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Natl AIDS Res Inst, Pune, Maharashtra, India. NIAID, NIH, Bethesda, MD 20892 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA. RP Gupta, A (reprint author), Johns Hopkins Univ, Div Infect Dis, 600 N Wolfe St,Jefferson 2-121B, Baltimore, MD 21287 USA. EM agupta25@jhmi.edu FU FIC NIH HHS [D43 TW 00010]; NIAID NIH HHS [AI 35173, 1R21 AI 33879-01, 1R01 AI 41369] NR 31 TC 34 Z9 35 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD DEC 1 PY 2006 VL 43 IS 4 BP 483 EP 490 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 106VH UT WOS:000242129600016 PM 17019372 ER PT J AU Chesney, MA AF Chesney, Margaret A. TI The elusive gold standard - Future perspectives for HIV adherence assessment and intervention SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Editorial Material DE HIV; adherence; AIDS ID ANTIRETROVIRAL THERAPY ADHERENCE; SELF-REPORT; PROTEASE INHIBITORS; REPORTED ADHERENCE; PHYSICAL-ACTIVITY AB There is no "gold standard" for the assessment of adherence to HIV/AIDS medications. Similarly, there is no single optimal tool that enhances adherence to HIV/AIDS treatment regimens. This article presents a model that provides a heuristic for selecting adherence assessment approaches and intervention strategies based on the purpose for which each is to be used. First, a broad distinction is made between research and clinical settings. Second, with each of these settings, the selection of assessments and interventions is based on the extent to which the focus is on HIV/AIDS in general or on adherence in particular. Examples applying the model are provided. Finally, new dimensions are discussed for expanding the model, with particular attention to applying the model to the resource-limited settings that are so important in efforts to reduce the morbidity and mortality associated with the global threat of HIV/AIDS. C1 NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA. RP Chesney, MA (reprint author), NIH, Natl Ctr Complementary & Alternat Med, 31 Ctr Dr,Room 2B11,MSC 2182, Bethesda, MD 20892 USA. EM chesneym@mail.nih.gov NR 35 TC 85 Z9 87 U1 3 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD DEC 1 PY 2006 VL 43 SU 1 BP S149 EP S155 DI 10.1097/01.qai.0000243112.91293.26 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 110AX UT WOS:000242351800021 PM 17133199 ER PT J AU Gordon, CM AF Gordon, Christopher M. TI Commentary on meta-analysis of randomized controlled trials for HIV treatment adherence interventions - Research directions and implications for practice SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article; Proceedings Paper CT Proceedings of the State of the Science Meeting on Intervention Research to Improve ARV Adherence CY NOV, 2005 CL Yale Univ, New Haven, CT SP Natl Inst Drug Abuse HO Yale Univ DE adherence; antiretroviral therapy; highly active antiretroviral therapy; HIV/AIDS; interventions; meta-analysis ID ACTIVE ANTIRETROVIRAL THERAPY; PREVENTION; OUTCOMES; INFECTION; CARE; MEDICATION; SETTINGS; PROGRAMS; IMPACT; HAITI AB This meta-analysis of randomized controlled trials (RCTs) of interventions for adherence to antiretroviral therapy for HIV indicates that participants who received an adherence intervention were 1.5 times as likely to report 95% adherence and 1.25 times as likely to achieve an undetectable viral load than participants in comparison conditions. The magnitude of the aggregated intervention effect is an encouraging message for HIV treatment providers, but more work is needed. For the next generation of international adherence research, there are multiple challenges that require the collaboration of providers, patients, government funders, donor agencies, and policy-makers. This commentary examines the strengths and limitations of the evidence base, identifies critical research directions, and calls for the development of a formal process to guide the rapid implementation of efficacious adherence interventions into community and clinical practice. C1 NIMH, Secondary HIV Prevent Treatment Adherence & Trans, Ctr Mental Hlth Res AIDS, Bethesda, MD 20892 USA. RP Gordon, CM (reprint author), NIMH, Secondary HIV Prevent Treatment Adherence & Trans, Ctr Mental Hlth Res AIDS, 6001 Execut Blvd,Room 6204, Bethesda, MD 20892 USA. EM cgordon1@mail.nih.gov NR 33 TC 14 Z9 14 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD DEC 1 PY 2006 VL 43 SU 1 BP S36 EP S40 DI 10.1097/01.qai.0000248347.87512.ba PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 110AX UT WOS:000242351800006 PM 17133203 ER PT J AU Parrino, J Graham, BS AF Parrino, Janie Graham, Barney S. TI Smallpox vaccines: Past, present, and future SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE poxvirus; vaccination; immunization; variola; monkeypox ID RANDOMIZED CONTROLLED-TRIAL; VIRUS ANKARA; CLINICAL-RESPONSES; LETHAL MONKEYPOX; CELL-CULTURE; VACCINATION; IMMUNOGENICITY; CHALLENGE; PROTECTS; STRAIN AB The global eradication of smallpox was a tremendous achievement made possible by the development of an effective vaccine. Routine vaccination of the general population is no longer recommended. However, stocks of variola virus, the causative agent of smallpox, still exist in 2 secure laboratories, and permanent disposal has been controversial. In addition, there is speculation that variola virus may exist outside of these 2 facilities, and there is a concern that the threat of smallpox will be used as a bioterrorist weapon. In 2002, this concern led to a vaccination campaign in US military and civilian healthcare workers and first responders. Although the historical live virus vaccine has proven efficacy, it also is associated with serious adverse events and rare fatal reactions, particularly in the setting of immunodeficiency and atopic eczema. In addition, this vaccine was historically produced using animal intermediaries in a process that was prone to contamination and not acceptable for current manufacturing standards. Development of alternative poxvirus vaccines is focused on replication-defective viruses, gene-based vectors, and subunit approaches to improve safety and immunogenicity. The conundrum is that in the absence of an intentional release of variola, efficacy evaluation of new candidate vaccines will be limited to animal model testing, which creates new challenges for the vaccine licensure process. Although motivated by the threat of bioterrorism, the hope is for new poxvirus vaccines to have their greatest utility against other pathogenic orthopoxviruses such as monkeypox and for the development of recombinant poxvirus-based vectors to treat and prevent other diseases. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Graham, BS (reprint author), NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr,MSC-3017,Bldg 40,Room 2502, Bethesda, MD 20892 USA. EM bgraham@nih.gov FU Intramural NIH HHS NR 40 TC 51 Z9 53 U1 1 U2 8 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD DEC PY 2006 VL 118 IS 6 BP 1320 EP 1326 DI 10.1016/j.jaci.2006.09.037 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 117NP UT WOS:000242880300018 PM 17157663 ER PT J AU O'Shaughnessy, EM Meletiadis, J Stergiopoulou, T Demchok, JP Walsh, TJ AF O'Shaughnessy, Elizabeth M. Meletiadis, Joseph Stergiopoulou, Theodouli Demchok, Joanne P. Walsh, Thomas J. TI Antifungal interactions within the triple combination of amphotericin B, caspofungin and voriconazole against Aspergillus species SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article DE azoles; polyenes; echinocandins; synergy; antagonism; fractional inhibitory concentration index ID IN-VITRO; INVASIVE ASPERGILLOSIS; PULMONARY ASPERGILLOSIS; ITRACONAZOLE; THERAPY; SYNERGY; FUMIGATUS; PHARMACOKINETICS; ANTAGONISM; EFFICACY AB Objectives: The in vitro effects of caspofungin combined with voriconazole and amphotericin B were tested in triplicate experiments against nine clinical isolates of Aspergillus fumigatus, Aspergillus flavus and Aspergillus terreus. Methods: The isolates were tested against a range of concentrations of voriconazole (0.015-1.0 mg/L), caspofungin (0.125-256 mg/L) and five concentrations of amphotericin B (0.1-0.5 mg/L) with a microdilution chequerboard method based on the CLSI M38-A reference method and the results were analysed with the fractional inhibitory concentration (FIC) index. The effect of individual drugs on the FIC index of each of the double combinations was also evaluated. Results: The triple combination of voriconazole, caspofungin and amphotericin B against all Aspergillus spp. was synergistic (FIC index 0.49-0.57) at low median concentrations of amphotericin B (0.10-0.22 mg/L) and voriconazole (0.07-0.15 mg/L) over a wide range of caspofungin concentrations (4.32-17.28 mg/L). Antagonistic interactions (FIC index 1.65-2.15) were found at higher median concentrations of amphotericin B (0.3-0.5 mg/L) and voriconazole (0.23-0.68 mg/L) over a similarly wide range of caspofungin concentrations (1.47-32 mg/L). Conclusions: These concentration-dependent interactions may have important clinical implications, which require further evaluation in animal models of invasive aspergillosis. C1 NCI, Pediat Oncol Branch, Immunocompromised Host Sect, NIH, Bethesda, MD 20892 USA. RP Walsh, TJ (reprint author), NCI, Pediat Oncol Branch, Immunocompromised Host Sect, NIH, 10 Ctr Dr,Bldg 10,Room 1-5888, Bethesda, MD 20892 USA. EM walsht@mail.nih.gov FU Intramural NIH HHS NR 40 TC 31 Z9 33 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD DEC PY 2006 VL 58 IS 6 BP 1168 EP 1176 DI 10.1093/jac/dkl392 PG 9 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 115EC UT WOS:000242716600010 PM 17071635 ER PT J AU Humbert, IA Poletto, CJ Saxon, KG Kearney, PR Crujido, L Wright-Harp, W Payne, J Jeffries, N Sonies, BC Ludlow, CL AF Humbert, Ianessa A. Poletto, Christopher J. Saxon, Keith G. Kearney, Pamela R. Crujido, Lisa Wright-Harp, Wilhelmina Payne, Joan Jeffries, Neal Sonies, Barbara C. Ludlow, Christy L. TI The effect of surface electrical stimulation on hyolaryngeal movement in normal individuals at rest and during swallowing SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE dysphagia; videofluoroscopy; neuromuscular stimulation; neck muscles ID ASPIRATION; PNEUMONIA; DYSPHAGIA AB The effect of surface electrical stimulation on hyolaryngeal movement in normal individuals at rest and during swallowing. JAppl Phvsiol 101: 1657-1663, 2006. First published July 27, 2006; doi: 10.1152/japplphysiol.00348.2006.-Surface electrical stimulation is currently used in therapy for swallowing problems, although little is known about its physiological effects on neck muscles or swallowing. Previously, when one surface electrode placement was used in dysphagic patients at rest, it lowered the hyolaryngeal complex. Here we examined the effects of nine other placements in normal volunteers to determine 1) whether movements induced by surface stimulation using other placements differ, and 2) whether lowering the hyolaryngeal complex by surface electrical stimulation interfered with swallowing in healthy adults. Ten bipolar surface electrode placements overlying the submental and laryngeal regions were tested. Maximum tolerated stimulation levels were applied at rest while participants held their mouths closed. Videofluoroscopic recordings were used to measure hyoid bone and subglottic air column (laryngeal) movements from resting position and while swallowing 5 ml of liquid barium, with and without stimulation. Videofluoroscopic recordings of swallows were rated blind to condition using the National Institutes of Health-Swallowing Safety Scale. Significant (P < 0.0001) laryngeal and hyoid descent occurred with stimulation at rest. During swallowing. significant (P <= 0.01) reductions in both the larynx and hyoid bone peak elevation occurred during stimulated swallows. The stimulated swallows were also judged less safe than nonstimulated swallows using the National Institutes of Health-Swallowing Safety Scale (P = 0.0275). Because surface electrical stimulation reduced hyolaryngeal elevation during swallowing in normal volunteers, our findings suggest that surface electrical stimulation will reduce elevation during swallowing therapy for dysphagia. C1 NINDS, Laryngeal & Speech Sect, Bethesda, MD 20892 USA. Howard Univ, Dept Commun Sci & Disorders, Washington, DC 20059 USA. NINDS, Off Clin Director, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Rehabil, Bethesda, MD 20892 USA. RP Ludlow, CL (reprint author), NINDS, Laryngeal & Speech Sect, 10 Ctr Dr,MSC 1416,Bldg 10,Rm 5D38, Bethesda, MD 20892 USA. EM ludlowc@ninds.nih.gov OI Ludlow, Christy/0000-0002-2015-6171 FU Intramural NIH HHS NR 20 TC 51 Z9 59 U1 1 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD DEC PY 2006 VL 101 IS 6 BP 1657 EP 1663 DI 10.1152/japplphysiol.00348.2006 PG 7 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 112PF UT WOS:000242537900017 PM 16873602 ER PT J AU Wasserman, DH Fueger, PT AF Wasserman, David H. Fueger, Patrick T. TI Point: Glucose phosphorylation is a significant barrier to muscle glucose uptake by the working muscle SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Editorial Material ID HUMAN SKELETAL-MUSCLE; UPTAKE IN-VIVO; INSULIN-RESISTANCE; DYNAMIC EXERCISE; CONSCIOUS MOUSE; TRANSGENIC MICE; TRANSPORT; OVEREXPRESSION; GLUT4; RAT C1 Vanderbilt Univ, Dept Mol Physiol & Biophys, Sch Med, Nashville, TN 37232 USA. Vanderbilt Univ, Mouse Metab Phenotyping Ctr, Sch Med, Nashville, TN 37232 USA. Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Sarah W Stedman Nutr & Metab Ctr, Durham, NC USA. RP Wasserman, DH (reprint author), Vanderbilt Univ, Dept Mol Physiol & Biophys, Sch Med, Nashville, TN 37232 USA. EM david.wasserman@vanderbilt.edu RI Fueger, Patrick/G-8956-2013 NR 30 TC 2 Z9 2 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD DEC PY 2006 VL 101 IS 6 BP 1803 EP 1805 DI 10.1152/japplphysiol.00817.2006 PG 3 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 112PF UT WOS:000242537900035 PM 17106068 ER PT J AU Wasserman, DH Fueger, PT AF Wasserman, David H. Fueger, Patrick T. TI Last Word: Point : Counterpoint author responds to commentaries on "Glucose phosphorylation is/is not a significant barrier to muscle glucose uptake by the working muscle" SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Letter ID EXERCISE C1 Vanderbilt Univ, Sch Med, Mouse Metab Phenotyping Ctr, Nashville, TN USA. Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN USA. Duke Univ, Med Ctr, Sarah W Stedman Nutr & Metab Ctr, Durham, NC 27706 USA. Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27706 USA. RP Wasserman, DH (reprint author), Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN USA. RI Fueger, Patrick/G-8956-2013 NR 5 TC 0 Z9 0 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD DEC PY 2006 VL 101 IS 6 BP 1810 EP 1810 DI 10.1152/japplphysiol.01080.2006 PG 1 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 112PF UT WOS:000242537900041 ER PT J AU Allina, J Hu, B Sullivan, DM Fiel, MI Thung, SN Bronk, SF Huebert, RC van de Water, J LaRusso, NF Gershwin, ME Gores, GJ Odin, JA AF Allina, Jorge Hu, Bin Sullivan, Daniel M. Fiel, Maria Isabel Thung, Swan N. Bronk, Steven F. Huebert, Robert C. van de Water, Judy LaRusso, Nicholas F. Gershwin, M. E. Gores, Gregory J. Odin, Joseph A. TI T cell targeting and phagocytosis of apoptotic biliary epithelial cells in primary biliary cirrhosis SO JOURNAL OF AUTOIMMUNITY LA English DT Article DE pyruvate dehydrogenase; autoantigen; apoptosis; protein S-glutathionylation; primary biliary cirrhosis ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; PYRUVATE-DEHYDROGENASE COMPLEX-E2; OXIDANT-SENSITIVE PROTEINS; MITOCHONDRIAL AUTOANTIGENS; MOLECULAR MIMICRY; IMMUNE-RESPONSE; EXPRESSION; IDENTIFICATION; ACTIVATION; DISEASES AB Primary biliary cirrhosis (PBC) is characterized by loss of tolerance against ubiquitously expressed mitochondrial autoantigens followed by biliary and salivary gland epithelial cell (BEC and SGEC) destruction by autoreactive T cells. It is unclear why BECs and SGECs are targeted. Previous work demonstrated that the reduced form of the major PBC autoantigen predominated in apoptotic BECs and SGECs as opposed to an oxidized form in other apoptotic cells. This led to the hypothesis that presentation of novel self-peptides from phagocytosed apoptotic BECs might contribute to BEC targeting by autoreactive T cells. The effect of autoantigen redox status on self-peptide formation was examined along with the phagocytic ability of BECs. Oxidation of PBC autoantigens first was shown to be due to protein S-glutathionylation of lipoyllysine residues. Absence of protein S-glutathionylation generated novel self-peptides and affected T cell recognition of a lipoyllysine containing peptide. Liver biopsy staining revealed BEC phagocytosis of apoptotic BECs (3.74 +/- 2.90% of BEC) was present in PBC (7 of 7 cases) but not in normal livers (0 of 3). BECs have the ability to present novel mitochondrial self-peptides derived from pha,gocytosed apoptotic BECs. Apoptotic cell phagocytosis by non-professional phagocytes may influence the tissue specificity of autoimmune diseases. (c) 2006 Elsevier Ltd. All rights reserved. C1 Mt Sinai Sch Med, Dept Med, New York, NY USA. Mt Sinai Sch Med, Dept Pathol, New York, NY USA. NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. Mayo Clin, Coll Med, Dept Med, Rochester, MN USA. Univ Calif Davis, Sch Med, Dept Internal Med, Davis, CA 95616 USA. RP Odin, JA (reprint author), 1 Gustave L Levy Pl,Box 1123, New York, NY 10029 USA. EM joseph.odin@msnyuhealth.org OI Huebert, Robert/0000-0002-9812-7573 FU NCI NIH HHS [1 R24 CA095823-01]; NIDDK NIH HHS [K08 DK059653, DK59653, DK 39588] NR 44 TC 62 Z9 64 U1 2 U2 3 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD DEC PY 2006 VL 27 IS 4 BP 232 EP 241 DI 10.1016/j.jaut.2006.11.004 PG 10 WC Immunology SC Immunology GA 142KX UT WOS:000244649600003 PM 17222534 ER PT J AU Liu, XM Gutacker, MM Musser, JM Fu, YX AF Liu, Xiaoming Gutacker, Michaela M. Musser, James M. Fu, Yun-Xin TI Evidence for recombination in Mycobacterium tuberculosis SO JOURNAL OF BACTERIOLOGY LA English DT Article ID LENGTH-POLYMORPHISM ANALYSIS; POPULATION GENETIC-ANALYSIS; SIMULTANEOUS INFECTION; DNA-SEQUENCES; DETECTING RECOMBINATION; STATISTICAL PROPERTIES; PATHOGENIC BACTERIA; STRAINS; EVOLUTION; BOOTSTRAP AB Due to its mostly isolated living environment, Mycobacterium tuberculosis is generally believed to be highly clonal, and thus recombination between different strains must be rare and is not critical for the survival of the species. To investigate the roles recombination could have possibly played in the evolution of M. tuberculosis, an analysis was conducted on previously determined genotypes of 36 synonymous single nucleotide polymorphisms (SNPs) in 3,320 M. tuberculosis isolates. The results confirmed the predominant clonal structure of the M. tuberculosis population. However, recombination between different strains was also suggested. To further resolve the issue, 175 intergenic SNPs and 234 synonymous SNPs were genotyped in 37 selected representative strains. A clear mosaic polyrnorphic pattern ahead of the MT0105 locus encoding a PPE (Pro-Pro-Glu) protein was obtained, which is most likely a result of recombination hot spot. Given that PPE proteins are thought to be critical in host-pathogen interactions, we hypothesize that recombination has been influential in the history of M. tuberculosis and possibly a major contributor to the diversity observed ahead of the MT0105 locus. C1 Univ Texas, Ctr Human Genet, Houston, TX 77225 USA. NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. RP Fu, YX (reprint author), Univ Texas, Ctr Human Genet, POB 20186, Houston, TX 77225 USA. EM Yunxin.Fu@uth.tmc.edu RI Liu, Xiaoming/C-2743-2008 OI Liu, Xiaoming/0000-0001-8285-5528 FU NIGMS NIH HHS [R01 GM060777, R01 GM6077] NR 58 TC 38 Z9 39 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD DEC PY 2006 VL 188 IS 23 BP 8169 EP 8177 DI 10.1128/JB.01062-06 PG 9 WC Microbiology SC Microbiology GA 108YR UT WOS:000242275600022 PM 16997954 ER PT J AU Wang, XD Mukhopadhyay, P Wood, MJ Outten, FW Opdyke, JA Storz, G AF Wang, Xunde Mukhopadhyay, Partha Wood, Matthew J. Outten, F. Wayne Opdyke, Jason A. Storz, Gisela TI Mutational analysis to define an activating region on the redox-sensitive transcriptional regulator OxyR SO JOURNAL OF BACTERIOLOGY LA English DT Article ID POLYMERASE ALPHA-SUBUNIT; DISULFIDE BOND FORMATION; C-TERMINAL REGION; ESCHERICHIA-COLI; RNA-POLYMERASE; DNA-BINDING; SALMONELLA-TYPHIMURIUM; HYDROGEN-PEROXIDE; CONTACT SITE; PROTEIN AB The OxyR transcription factor is a key regulator of the Escherichia coli response to oxidative stress. Previous studies showed that OxyR binding to a target promoter enhances RNA polymerase binding and vice versa, suggesting a direct interaction between OxyR and RNA polymerase. To identify the region of OxyR that might contact RNA polymerase, we carried out alanine scanning and random mutagenesis of oxyR. The combination of these approaches led to the identification of several mutants defective in the activation of an OxyR target gene. A subset of the mutations map to the DNA-binding domain, other mutations appear to affect dimerization of the regulatory domain, while another group is suggested to affect disulfide bond formation. The two mutations, D142A and R273H, giving the most dramatic phenotype are located in a patch on the surface of the oxidized OxyR protein and possibly define an activating region on OxyR. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Storz, G (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bldg 18T,Room 101,18 Lib Dr,MSC 5430, Bethesda, MD 20892 USA. EM storz@helix.nih.gov RI MUKHOPADHYAY, PARTHA/G-3890-2010; OI MUKHOPADHYAY, PARTHA/0000-0002-1178-1274; Outten, Franklin/0000-0002-9095-0194; Storz, Gisela/0000-0001-6698-1241 FU Intramural NIH HHS NR 26 TC 17 Z9 18 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD DEC PY 2006 VL 188 IS 24 BP 8335 EP 8342 DI 10.1128/JB.01318-06 PG 8 WC Microbiology SC Microbiology GA 116JH UT WOS:000242798100002 PM 17012382 ER PT J AU Hook-Barnard, I Johnson, XB Hinton, DM AF Hook-Barnard, India Johnson, Xanthia B. Hinton, Deborah M. TI Escherichia coli RNA polymerase recognition of a sigma(70)-dependent promoter requiring a-35 DNA element and an extended-10 TGn motif SO JOURNAL OF BACTERIOLOGY LA English DT Article ID AROMATIC-AMINO-ACIDS; SINGLE-STRANDED-DNA; SIGMA(70) SUBUNIT; TRANSCRIPTION INITIATION; ACTIVATOR MOTA; REITERATIVE TRANSCRIPTION; COACTIVATOR ASIA; STRUCTURAL BASIS; OPEN COMPLEX; START SITE AB Escherichia coli sigma(70)-dependent promoters have typically been characterized as either -10/-35 promoters, which have good matches to both the canonical -10 and the -35 sequences or as extended -10 promoters (TGn/-10 promoters), which have the TGn motif and an excellent match to the -10 consensus sequence. We report here an investigation of a promoter, P-minor, that has a nearly perfect match to the -35 sequence and has the TGn motif. However, P-minor contains an extremely poor sigma(70) -10 element. We demonstrate that P-minor. is active both in vivo and in vitro and that mutations in either the -35 or the TGn motif eliminate its activity. Mutation of the TGn motif can be compensated for by mutations that make the -10 element more canonical, thus converting the -35/TGn promoter to a -35/-10 promoter. Potassium permanganate footprinting on the nontemplate and template strands indicates that when polymerase is in a stable (open) complex with P-minor the DNA is single stranded from positions -11 to +4. We also demonstrate that transcription from P-minor incorporates nontemplated ribonucleoside triphosphates at the 5' end of the P-minor transcript, which results in an anomalous assignment for the start site when primer extension analysis is used. P-minor represents one of the few -35/TGn promoters that have been characterized and serves as a model for investigating functional differences between these promoters and the better-characterized -10/-35 and extended -10 promoters used by E. coli RNA polymerase. C1 NIDDKD, Gene Express & Regulat Sect, Lab Mol & Cell Biol, NIH, Bethesda, MD 20892 USA. RP Hinton, DM (reprint author), NIDDKD, Gene Express & Regulat Sect, Lab Mol & Cell Biol, NIH, Bldg 8,Room 2A-13, Bethesda, MD 20892 USA. EM dhinton@helix.nih.gov FU Intramural NIH HHS NR 54 TC 19 Z9 19 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD DEC PY 2006 VL 188 IS 24 BP 8352 EP 8359 DI 10.1128/JB.00853-06 PG 8 WC Microbiology SC Microbiology GA 116JH UT WOS:000242798100004 PM 17012380 ER PT J AU Correia, FF D'Onofrio, A Rejtar, T Li, LY Karger, BL Makarova, K Koonin, EV Lewis, K AF Correia, Frederick F. D'Onofrio, Anthony Rejtar, Tomas Li, Lingyun Karger, Barry L. Makarova, Kira Koonin, Eugene V. Lewis, Kim TI Kinase activity of overexpressed HipA is required for growth arrest and multidrug tolerance in Escherichia coli SO JOURNAL OF BACTERIOLOGY LA English DT Article ID PERSISTER CELLS; PSEUDOMONAS-AERUGINOSA; CONTROLLED EXPRESSION; AFFECTS LETHALITY; AFFECTS FREQUENCY; MUREIN SYNTHESIS; DNA-SYNTHESIS; INHIBITION; RESISTANCE; PROTEINS AB Overexpression of the HipA protein of the HipBA toxin/antitoxin module leads to multidrug tolerance in Escherichia coli. HipA is a "toxin" that causes reversible dormancy, whereas HipB is an antitoxin that binds HipA and acts as a transcriptional repressor of the hipBA operon. Comparative sequence analysis shows that HipA is a member of the phosphatidylinositol 3/4-kinase superfamily. The kinase activity of HipA was examined. HipA was autophosphorylated in the presence of ATP in vitro, and the purified protein appeared to carry a single phosphate group on serine 150. Thus, HipA is a serine kinase that is at least partially phosphorylated in vivo. Overexpression of HipA caused inhibition of cell growth and increase in persister formation. Replacing conserved aspartate 309 in the conserved kinase active site or aspartate 332 in the Mg2+-binding site with glutamine produced mutant proteins that lost the ability to stop cellular growth upon overexpression. Replacing serine 150 with alanine yielded a similarly inactive protein. The mutant proteins were then examined for their ability to increase antibiotic tolerance. Cells overexpressing wild-type HipA were highly tolerant to cefotaxime, a cell wall synthesis inhibitor, to ofloxacin, a fluoroquinolone inhibitor of DNA gyrase, and to topoisomerase IV and were almost completely resistant to killing by mitomycin C, which forms DNA adducts. The mutant proteins did not protect cells from cefotaxime or ofloxacin and had an impaired ability to protect from mitomycin C. Taken together, these results suggest that the protein kinase activity of HipA is essential for persister formation. C1 Northeastern Univ, Dept Biol, Boston, MA 02115 USA. Northeastern Univ, Antimicrobial Discovery Ctr, Boston, MA 02115 USA. Northeastern Univ, Barnett Inst, Boston, MA 02115 USA. Northeastern Univ, Dept Chem, Boston, MA 02115 USA. NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Lewis, K (reprint author), Northeastern Univ, Dept Biol, Boston, MA 02115 USA. EM k.lewis@neu.edu FU NHGRI NIH HHS [R01 HG002033, R01-HG-02033-04A1]; NIGMS NIH HHS [GM061162-05A1, R01 GM061162] NR 36 TC 93 Z9 96 U1 0 U2 11 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD DEC PY 2006 VL 188 IS 24 BP 8360 EP 8367 DI 10.1128/JB.01237-06 PG 8 WC Microbiology SC Microbiology GA 116JH UT WOS:000242798100005 PM 17041039 ER PT J AU Huff, LM Lee, JS Robey, RW Fojo, T AF Huff, Lyn M. Lee, Jong-Seok Robey, Robert W. Fojo, Tito TI Characterization of gene rearrangements leading to activation of MDR-1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DOUBLE-STRAND BREAKS; DISTANT UPSTREAM PROMOTER; MULTIDRUG-RESISTANCE; CELL-LINE; THERAPEUTIC STRATEGIES; TOPOISOMERASE-II; P-GLYCOPROTEIN; DNA BREAKS; REPAIR; TRANSCRIPTION AB Expression of the MDR-1/P-glycoprotein gene confers drug resistance both in vitro and in vivo. We previously reported that gene rearrangements resulting in a hybrid MDR-1 transcript represent a common mechanism for acquired activation of MDR-1/P-glycoprotein. We have identified hybrid MDR-1 transcripts in nine MDR-1- overexpressing cell lines and two patients with relapsed ALL. We characterize these rearrangements as follows. 1) Non-MDR-1 sequences in the hybrid MDR-1 transcripts are expressed in unselected cell lines, showing that these sequences are constitutively expressed. 2) The rearrangements occur randomly and involve partner genes (sequences) on chromosome 7 and on chromosomes other than 7. Breakpoints have been characterized in six cell lines. In one, the rearrangement occurred within intron 2 of MDR-1; in the other five, the rearrangement occurred 24 to > 96 kb 5' of the normal start of transcription of MDR-1. In one cell line, homologous recombination involving an Alu repeat was observed. However, in the remaining five cell lines, nonhomologous recombination was observed. 3) The rearrangements arise during drug selection. The acquired rearrangements are not detected in parental cells. 4) Five of the six active promoters that captured MDR-1 controlled MDR-1 from a distance of 29 to more than 110 kb 5' to MDR-1. Transcription was initiated in an antegrade or retrograde direction. We conclude that drug selection with natural products targeting DNA or microtubules leads to DNA damage, nonhomologous recombination, and acquired drug resistance, wherein MDR-1 expression is driven by a random but constitutively active promoter. C1 NCI, NIH, Canc Res Ctr, Med Oncol Branch, Bethesda, MD 20892 USA. Seoul Natl Univ, Bandung Hosp, Seoul 151742, South Korea. RP Fojo, T (reprint author), NCI, NIH, Canc Res Ctr, Med Oncol Branch, Bldg 10,Rm 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. EM tfojo@helix.nih.gov FU Intramural NIH HHS NR 57 TC 35 Z9 35 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 1 PY 2006 VL 281 IS 48 BP 36501 EP 36509 DI 10.1074/jbc.M602998200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 108DP UT WOS:000242220800005 PM 16956878 ER PT J AU Kanneganti, TD Body-Malapel, M Amer, A Park, JH Whitfield, J Franchi, L Taraporewala, ZF Miller, D Patton, JT Inohara, N Nunez, G AF Kanneganti, Thirumala-Devi Body-Malapel, Mathilde Amer, Amal Park, Jong-Hwan Whitfield, Joel Franchi, Luigi Taraporewala, Zenobia F. Miller, David Patton, John T. Inohara, Naohiro Nunez, Gabriel TI Critical role for Cryopyrin/Nalp3 in activation of caspase-1 in response to viral infection and double-stranded RNA SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INTERLEUKIN-1-BETA CONVERTING-ENZYME; VACCINIA VIRUS-INFECTION; NF-KAPPA-B; ANTIVIRAL RESPONSE; HUMAN MACROPHAGES; GENE-EXPRESSION; RIG-I; IMMUNITY; INFLAMMASOME; INNATE AB Viralinfection induces the production of interleukin (IL)-1 ss and IL-18 in macrophages through the activation of caspase-1, but the mechanism by which host cells sense viruses to induce caspase-1 activation is unknown. In this report, we have identified a signaling pathway leading to caspase-1 activation that is induced by double-stranded RNA (dsRNA) and viral infection that is mediated by Cryopyrin/Nalp3. Stimulation of macrophages with dsRNA, viral RNA, or its analog poly(I:C) induced the secretion of IL-1 ss and IL-18 in a cryopyrin-dependent manner. Consistently, caspase-1 activation triggered by poly(I:C), dsRNA, and viral RNA was abrogated in macrophages lacking cryopyrin or the adaptor ASC (apoptosis-associated speck-like protein containing a caspase-activating and recruitment domain) but proceeded normally in macrophages deficient in Toll-like receptor 3 or 7. We have also shown that infection with Sendai and influenza viruses activates the cryopyrin inflammasome. Finally, cryopyrin was required for IL-1 ss production in response to poly(I:C) in vivo. These results identify a mechanism mediated by cryopyrin and ASC that links dsRNA and viral infection to caspase-1 activation resulting in IL-1 ss and IL-18 production. C1 Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA. RP Nunez, G (reprint author), Univ Michigan, Sch Med, Dept Pathol, 4215 CCGC,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM bclx@umich.edu RI Patton, John/P-1390-2014; Amer, Amal/E-2643-2011; OI Kanneganti, Thirumala-Devi/0000-0002-6395-6443 FU Intramural NIH HHS; NIAID NIH HHS [AI064748, AI063331] NR 58 TC 348 Z9 360 U1 1 U2 15 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 DEC 1 PY 2006 VL 281 IS 48 BP 36560 EP 36568 DI 10.1074/jbc.M607594200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 108DP UT WOS:000242220800012 PM 17008311 ER PT J AU Lindtner, S Zolotukhin, AS Uranishi, H Bear, J Kulkarni, V Smulevitch, S Samiotaki, M Panayotou, G Felber, BK Pavlakis, GN AF Lindtner, Susan Zolotukhin, Andrei S. Uranishi, Hiroaki Bear, Jenifer Kulkarni, Viraj Smulevitch, Sergey Samiotaki, Martina Panayotou, George Felber, Barbara K. Pavlakis, George N. TI RNA-binding motif protein 15 binds to the RNA transport element RTE and provides a direct link to the NXF1 export pathway SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MEDIATED POSTTRANSCRIPTIONAL REGULATION; SIMIAN RETROVIRUS TYPE-1; EXON JUNCTION COMPLEX; INTRON-CONTAINING RNA; VIRAL MESSENGER-RNA; NUCLEAR EXPORT; MAMMALIAN-CELLS; MEGAKARYOBLASTIC LEUKEMIA; NUCLEOCYTOPLASMIC EXPORT AB Retroviruses/retroelements provide tools enabling the identification and dissection of basic steps for post-transcriptional regulation of cellular mRNAs. The RNA transport element (RTE) identified in mouse retrotransposons is functionally equivalent to constitutive transport element of Type D retroviruses, yet does not bind directly to the mRNA export receptor NXF1. Here, we report that the RNA-binding motif protein 15 (RBM15) recognizes RTE directly and specifically in vitro and stimulates export and expression of RTE-containing reporter mRNAs in vivo. Tethering of RBM15 to a reporter mRNA showed that RBM15 acts by promoting mRNA export from the nucleus. We also found that RBM15 binds to NXF1 and the two proteins cooperate in stimulating RTE-mediated mRNA export and expression. Thus, RBM15 is a novel mRNA export factor and is part of the NXF1 pathway. We propose that RTE evolved as a high affinity RBM15 ligand to provide a splicing-independent link to NXF1, thereby ensuring efficient nuclear export and expression of retrotransposon transcripts. C1 NCI, Human Retrovirus Pathogenesis Sect, Vaccine Branch, Canc Res Ctr,NIH, Ft Detrick, MD 21702 USA. NCI, Human Retrovirus Sect, Vaccine Branch, Canc Res Ctr,NIH, Ft Detrick, MD 21702 USA. Alexander Fleming Biomed Sci Res Ctr, Vari 16672, Greece. RP Felber, BK (reprint author), NCI, Human Retrovirus Pathogenesis Sect, Vaccine Branch, Canc Res Ctr,NIH, Bldg 535,Rm 209, Ft Detrick, MD 21702 USA. EM felber@ncifcrf.gov NR 78 TC 34 Z9 35 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 1 PY 2006 VL 281 IS 48 BP 36915 EP 36928 DI 10.1074/jbc.M608745200 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 108DP UT WOS:000242220800051 PM 17001072 ER PT J AU Taylor, RM Baniulis, D Burritt, JB Gripentrog, JM Lord, CI Riesselman, MH Maaty, WS Bothner, BP Angel, TE Dratz, EA Linton, GF Malech, HL Jesaitis, AJ AF Taylor, Ross M. Baniulis, Danas Burritt, James B. Gripentrog, Jeannie M. Lord, Connie I. Riesselman, Marcia H. Maaty, Walid S. Bothner, Brian P. Angel, Thomas E. Dratz, Edward A. Linton, Gilda F. Malech, Harry L. Jesaitis, Algirdas J. TI Analysis of human phagocyte flavocytochrome b(558) by mass spectrometry SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CHRONIC GRANULOMATOUS-DISEASE; LASER-DESORPTION/IONIZATION-TIME; NEUTROPHIL CYTOCHROME-B; NADPH OXIDASE; MEMBRANE-PROTEINS; ANTIPEPTIDE ANTIBODIES; CHROMOSOMAL LOCATION; GLYCOSYLATION SITES; P22(PHOX) SUBUNIT; CELL-LINE AB The catalytic core of the phagocyte NADPH oxidase is a heterodimeric integral membrane protein (flavocytochrome b (Cyt b)) that generates superoxide and initiates a cascade of reactive oxygen species critical for the host inflammatory response. In order to facilitate structural characterization, the present study reports the first direct analysis of human phagocyte Cyt b by matrix-assisted laser desorption/ionization and nanoelectrospray mass spectrometry. Mass analysis of in-gel tryptic digest samples provided 73% total sequence coverage of the gp91(phox) subunit, including three of the six proposed transmembrane domains. Similar analysis of the p22(phox) subunit provided 72% total sequence coverage, including assignment of the hydrophobic N-terminal region and residues that are polymorphic in the human population. To initiate mass analysis of Cyt b post-translational modifications, the isolated gp91phox subunit was subject to sequential in-gel digestion with Flavobacterium meningosepticum peptide N-glycosidase F and trypsin, with matrix-assisted laser desorption/ionization and liquid chromatography-mass spectrometry/mass spectrometry used to demonstrate that Asn-132, -149, and -240 are genuinely modified by N-linked glycans in human neutrophils. Since the PLB-985 cell line represents an important model system for analysis of the NADPH oxidase, methods were developed for the purification of Cyt b from PLB-985 membrane fractions in order to confirm the appropriate modification of N-linked glycosylation sites on the recombinant gp91phox subunit. This study reports extensive sequence coverage of the integral membrane protein Cyt b by mass spectrometry and provides analytical methods that will be useful for evaluating post-translational modifications involved in the regulation of superoxide production. C1 Montana State Univ, Dept Microbiol, Bozeman, MT 59717 USA. Montana State Univ, Dept Chem & Biochem, Bozeman, MT 59717 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Taylor, RM (reprint author), Montana State Univ, Dept Microbiol, 109 Lewis Hall, Bozeman, MT 59717 USA. EM rosst@montana.edu OI Malech, Harry/0000-0001-5874-5775 FU NIAID NIH HHS [R01 AI 64107]; NIGMS NIH HHS [R01 GM 62547] NR 62 TC 19 Z9 19 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 DEC 1 PY 2006 VL 281 IS 48 BP 37045 EP 37056 DI 10.1074/jbc.M607354200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 108DP UT WOS:000242220800066 PM 17015440 ER PT J AU Ghorbel, S Sinha-Datta, U Dundr, M Brown, M Franchini, G Nicot, C AF Ghorbel, Sofiane Sinha-Datta, Uma Dundr, Miroslav Brown, Megan Franchini, Genoveffa Nicot, Christophe TI Human T-cell leukemia virus type I p30 nuclear/nucleolar retention is mediated through interactions with RNA and a constituent of the 60 S ribosomal subunit SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NUCLEOLAR TARGETING SIGNAL; CAULIFLOWER-MOSAIC-VIRUS; KAPPA-B PATHWAY; HTLV-I; ARABIDOPSIS-THALIANA; HUMAN ANGIOGENIN; ENTRY SITE; HIV-1 REV; PROTEIN; TRANSCRIPTION AB Human T-cell leukemia virus type I is the etiological agent of adult T-cell leukemia/lymphoma, an aggressive and fatal lymphoproliferative malignancy. The virus has evolved strategies to escape immune clearance by remaining latent in most infected cells in vivo. We demonstrated previously that virally encoded p30 protein is a potent post-transcriptional inhibitor of virus replication (Nicot, C., Dundr, M., Johnson, J. M., Fullen, J. R., Alonzo, N., Fukumoto, R., Princler, G. L., Derse, D., Misteli, T., and Franchini, G. (2004) Nat. Med. 10, 197-201). p30 is unable to shuttle out of the nucleus in heterokaryon assays, suggesting the existence of specific retention signals. Because suppression of virus replication relies on nuclear retention of the tax/rex mRNA by p30, determining the retention features of p30 will offer hints to break latency in infected cells and insights into new therapeutic approaches. In this study, we used live cell imaging technologies to study the kinetics of p30 and to delineate its retention signals and their function in virus replication. Notably, this is the first study to identify p30 nucleolar retention domains. Using mutants of p30 that localized in different cellular compartments, we show that post-transcriptional control of virus replication by p30 occurs in the nucleoplasm. We further demonstrate that p30 nuclear/nucleolar retention is dependent upon de novo RNA transcripts and interactions with components of the ribosomal machinery. C1 Univ Kansas, Med Ctr, Dept Microbiol Immunol & Mol Genet, Kansas City, KS 66160 USA. NCI, Anim Models & Retroviral Vaccines Sect, NIH, Bethesda, MD 20892 USA. Rosalind Franklin Univ Med & Sci, Dept Cell Biol & Anat, N Chicago, IL 60064 USA. RP Nicot, C (reprint author), Univ Kansas, Med Ctr, Dept Microbiol Immunol & Mol Genet, 3901 Rainbow Blvd,3025 Wahl Hall W, Kansas City, KS 66160 USA. EM cnicot@kumc.edu FU NCRR NIH HHS [P20 RR016443]; NIAID NIH HHS [R01 AI058944, AI058944] NR 34 TC 24 Z9 24 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 1 PY 2006 VL 281 IS 48 BP 37150 EP 37158 DI 10.1074/jbc.M603981200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 108DP UT WOS:000242220800076 PM 17008317 ER PT J AU Davis, CW Mattei, LM Nguyen, HY Ansarah-Sobrinho, C Doms, RW Pierson, TC AF Davis, Carl W. Mattei, Lisa M. Nguyen, Hai-Yen Ansarah-Sobrinho, Camilo Doms, Robert W. Pierson, Theodore C. TI The location of asparagine-linked glycans on West Nile virions controls their interactions with CD209 (dendritic cell-specific ICAM-3 grabbing nonintegrin) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID VIRUS ENVELOPE PROTEINS; RECEPTORS DC-SIGN; N-GLYCOSIDASE-F; C-TYPE LECTIN; DENGUE VIRUS; IN-VITRO; EXTRACELLULAR GLYCOSIDASES; CARBOHYDRATE-RECOGNITION; DIPLOCOCCUS PNEUMONIAE; STRUCTURAL BASIS AB Mammalian cell-derived West Nile virus preferentially infects cells expressing the C-type lectin CD209L (dendritic cell-specific ICAM-3 grabbing nonintegrin-related protein; liver- and lymph node-specific ICAM-3 grabbing nonintegrin) but not cells expressing CD209 (dendritic cell-specific ICAM-3 grabbing nonintegrin). In contrast, Dengue virus infection is enhanced in cells expressing either attachment factor. The West Nile virus envelope (E) protein contains a single N-linked glycosylation site at residue 154, whereas Dengue virus E contains sites at residues 153 and 67. We introduced a glycosylation site at position 67 into West Nile virus E. Reporter virus particles pseudotyped with this E protein infected cells using either CD209 or CD209L. We also introduced glycosylation sites at several novel positions. All sites allowed CD209L-mediated infection, but only a subset promoted CD209 use. As seen for other viruses, mannose-rich glycans on West Nile virus were required for its interactions with CD209. Surprisingly, however, mannose-rich glycans were not required for CD209L-mediated infection. Complex glycans, particularly N-acetylglucosamine-terminated structures, were able to mediate reporter virus particle interactions with CD209L. We propose that CD209L recognizes glycosylated flaviviruses with broad specificity, whereas CD209 is selective for flaviviruses bearing mannose-rich glycans. The location of the N-linked glycosylation sites on a virion determines the types of glycans incorporated, thus controlling viral tropism for CD209-expressing cells. C1 NIH, Viral Dis Lab, Viral Pathogenesis Sect, Bethesda, MD 20892 USA. Univ Penn, Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA. RP Pierson, TC (reprint author), NIH, Viral Dis Lab, Viral Pathogenesis Sect, 4 Ctr Dr,Bldg 4,Room 216, Bethesda, MD 20892 USA. EM piersontc@mail.nih.gov FU Intramural NIH HHS; NIAID NIH HHS [U54 AI57168, T32 AI07632, AI50469] NR 63 TC 44 Z9 47 U1 0 U2 4 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 DEC 1 PY 2006 VL 281 IS 48 BP 37183 EP 37194 DI 10.1074/jbc.M605429200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 108DP UT WOS:000242220800079 PM 17001080 ER PT J AU Iwahara, J Clore, GM AF Iwahara, Junji Clore, G. Marius TI Sensitivity improvement for correlations involving arginine side-chain N epsilon/H epsilon resonances in multi-dimensional NMR experiments using broadband N-15 180 degrees pulses SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE arginine guanidino group; broadband N-15 180 pulse; off-resonance; pulse imperfection; sensitivity improvement ID ADIABATIC PULSES; SPECTROSCOPY; PROTEINS; ASSIGNMENT; EXCITATION; INVERSION; SEQUENCE; SCHEMES; HSQC; H2O AB Due to practical limitations in available N-15 rf field strength, imperfections in N-15 180 pulses arising from off-resonance effects can result in significant sensitivity loss, even if the chemical shift offset is relatively small. Indeed, in multi-dimensional NMR experiments optimized for protein backbone amide groups, cross-peaks arising from the Arg guanidino N-15 epsilon (similar to 85 ppm) are highly attenuated by the presence of multiple INEPT transfer steps. To improve the sensitivity for correlations involving Arg N epsilon-H epsilon groups, we have incorporated N-15 broadband 180 degrees pulses into 3D N-15-separated NOE-HSQC and HNCACB experiments. Two N-15-WURST pulses incorporated at the INEPT transfer steps of the 3D N-15-separated NOE-HSQC pulse sequence resulted in a similar to 1.5-fold increase in sensitivity for the Arg N epsilon-H epsilon signals at 800 MHz. For the 3D HNCACB experiment, five N-15 Abramovich-Vega pulses were incorporated for broadband inversion and refocusing, and the sensitivity of Arg(1)H epsilon-N-15 epsilon-C-13 gamma/C-13 delta correlation peaks was enhanced by a factor of similar to 1.7 at 500 MHz. These experiments eliminate the necessity for additional experiments to assign Arg H-1 epsilon and N-15 epsilon resonances. In addition, the increased sensitivity afforded for the detection of NOE cross-peaks involving correlations with the N-15.epsilon/H-1 epsilon of Arg in 3D N-15-separated NOE experiments should prove to be very useful for structural analysis of interactions involving Arg side-chains. C1 NIDDKD, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Clore, GM (reprint author), NIDDKD, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. EM mariusc@intra.niddk.nih.gov RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 FU Intramural NIH HHS NR 21 TC 6 Z9 6 U1 0 U2 8 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD DEC PY 2006 VL 36 IS 4 BP 251 EP 257 DI 10.1007/s10858-006-9089-7 PG 7 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 124JS UT WOS:000243364700005 PM 17036160 ER PT J AU Hu, KF Vogeli, B Clore, GM AF Hu, Kaifeng Vogeli, Beat Clore, G. Marius TI C-13-detected HN(CA)C and HMCMC experiments using a single methyl-reprotonated sample for unambiguous methyl resonance assignment SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE C-13-detected NMR spectroscopy; methyl resonance assignment; IIBMannose ID HETERONUCLEAR CROSS POLARIZATION; MANNITOL TRANSPORTER IIMANNITOL; COLI PHOSPHOTRANSFERASE SYSTEM; NMR-SPECTROSCOPY; LARGE PROTEINS; DEUTERATED PROTEINS; PROTONATED PROTEINS; C-13; MAGNETIZATION; COUPLINGS AB Methyl groups provide an important source of structural and dynamic information in NMR studies of proteins and their complexes. For this purpose sequence-specific assignments of methyl H-1 and C-13 resonances are required. In this paper we propose the use of C-13-detected 3D HN(CA)C and HMCMC experiments for assignment of methyl H-1 and C-13 resonances using a single selectively methyl protonated, perdeuterated and C-13/N-15-labeled sample. The high resolution afforded in the C-13 directly-detected dimension allows one to rapidly and unambiguously establish correlations between backbone HN strips from the 3D HN(CA)C spectrum and methyl group HmCm strips from the HMCMC spectrum by aligning all possible side-chain carbon chemical shifts and their multiplet splitting patterns. The applicability of these experiments for the assignment of methyl H-1 and C-13 resonances is demonstrated using the 18.6 kDa B domain of the Escherichia coli mannose transporter (IIBMannose). C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Clore, GM (reprint author), NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM mariusc@intra.niddk.nih.gov RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 FU Intramural NIH HHS NR 35 TC 4 Z9 4 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD DEC PY 2006 VL 36 IS 4 BP 259 EP 266 DI 10.1007/s10858-006-9090-1 PG 8 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 124JS UT WOS:000243364700006 PM 17036159 ER PT J AU Corsi, A De Maio, F Ippolito, E Cherman, N Robey, PG Riminucci, M Bianco, P AF Corsi, Alessandro De Maio, Fernando Ippolito, Ernesto Cherman, Natasha Robey, Pamela Gehron Riminucci, Mara Bianco, Paolo TI Monostotic fibrous dysplasia of the proximal femur and liposclerosing myxofibrous tumor: Which one is which? SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE fibrous dysplasia; monostotic; guanine nucleotide-binding protein; alpha stimulating activity polypeptide; mutation; liposclerosing myxofibrous tumor ID ARG(201) CODON; GNAS1 GENE; BONE; MUTATIONS; LESIONS AB Clinical, histological, and genetic studies of two cases of isolated fibro-osseous lesions of the femur in adults show the overlap between monostotic fibrous dysplasia (MFD) of the proximal femur and the so-called liposclerosing myxofibrous tumor. The two cases highlight how the incomplete understanding of the natural history of MFD may result in diagnostic pitfalls or incorrect classification of individual lesions. C1 Univ Roma La Sapienza, Dipartimento Med Sperimentale & Patol, I-00161 Rome, Italy. Univ Roma Tor Vergata, Dipartimento Chirurgia Ortoped, Rome, Italy. Natl Inst Dental & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. Univ Aquila, Dipartimento Med Sperimentale, I-67100 Laquila, Italy. Parco Sci Biomed San Raffaele, Rome, Italy. RP Bianco, P (reprint author), Univ Roma La Sapienza, Dipartimento Med Sperimentale & Patol, Viale Regina Elena 324, I-00161 Rome, Italy. EM p.bianco@flashnet.it RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 16 TC 7 Z9 8 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD DEC PY 2006 VL 21 IS 12 BP 1955 EP 1958 DI 10.1359/JBMR.060818 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 108ZY UT WOS:000242278900017 PM 17002568 ER PT J AU Collins, MT AF Collins, Michael T. TI Spectrum and natural history of fibrous dysplasia of bone SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article; Proceedings Paper CT Conference on Pagets Disease of Bone/Fibrous Dysplasia - Advances and Challenges CY JAN 12-14, 2006 CL Ft Landerdale, FL ID MCCUNE-ALBRIGHT-SYNDROME; GROWTH-HORMONE EXCESS; PHOSPHATE; HYPOPHOSPHATEMIA C1 NIDCR, Skeletal Clin Studies Unit, CSDB,Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Collins, MT (reprint author), NIDCR, Skeletal Clin Studies Unit, CSDB,Dept Hlth & Human Serv, NIH, Bldg 30,Room 228,MSC 4320, Bethesda, MD 20892 USA. EM mc247k@nih.gov FU Intramural NIH HHS NR 19 TC 19 Z9 19 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD DEC PY 2006 VL 21 SU 2 BP P99 EP P104 DI 10.1359/JBMR.06S219 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 129ME UT WOS:000243732800020 PM 17229019 ER PT J AU Riminucci, M Saggio, I Robey, PG Bianco, P AF Riminucci, Mara Saggio, Isabella Robey, Pamela Gehron Bianco, Paolo TI Fibrous dysplasia as a stem cell disease SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article; Proceedings Paper CT Conference on Pagets Disease of Bone/Fibrous Dysplasia - Advances and Challenges CY JAN 12-14, 2006 CL Ft Landerdale, FL DE fibrous dysplasia; GNAS; skeletal stem cells; embryonic stem cells ID MCCUNE-ALBRIGHT-SYNDROME; STIMULATORY G-PROTEIN; OSTEOGENESIS IMPERFECTA; ACTIVATING MUTATIONS; MESENCHYMAL CELLS; BONE; GENE; GS; IDENTIFICATION; METHYLATION AB At a time when significant attention is devoted worldwide to stem cells as a potential toot for curing incurable diseases, fibrous dysplasia of bone (FD) provides a paradigm for stein cell diseases. Consideration of the time and mechanism of the causative mutations and of nature of the pluripotent cells that mutate in early embryonic development indicates that, as a disease of the entire organism, FD can be seen as a disease of pluripotent embryonic cells. As a disease of bone as an organ, in turn, FD can be seen as a disease of postnatal skeletal stem cells, which give rise to dysfunctional osteoblasts. Recognizing FD as a stem cell disease provides a novel conceptual angle and a way to generate appropriate models of the disease, which will continue to provide further insight into its natural history and pathogenesis. In addition, skeletal stem cells may represent a tool for innovative treatments. These can be conceived as directed to alter the in vivo behavior of mutated stem cells, to replace mutated cells through local transplantation, or to correct the genetic defect in the stem cells themselves. In vitro and in vivo models are currently being generated that will permit exploration of these avenues in depth. C1 Univ Roma La Sapienza, Dipartimento Med Sperimentale & Patol, I-00161 Rome, Italy. Univ Aquila, Dept Expt Med, I-67100 Laquila, Italy. Univ Roma La Sapienza, Dept Genet & Mol Biol, Rome, Italy. NIDCR, Craniofacial & Skeletal Dis Branch, DHHS, NIH, Bethesda, MD USA. RP Bianco, P (reprint author), Univ Roma La Sapienza, Dipartimento Med Sperimentale & Patol, Viale Regina Elena 324, I-00161 Rome, Italy. EM p.bianco@flashnet.it RI Robey, Pamela/H-1429-2011; OI Robey, Pamela/0000-0002-5316-5576; saggio, isabella/0000-0002-9497-7415 FU Intramural NIH HHS NR 55 TC 25 Z9 25 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD DEC PY 2006 VL 21 SU 2 BP P125 EP P131 DI 10.1359/JBMR.06S224 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 129ME UT WOS:000243732800025 PM 17229001 ER PT J AU Weinstein, LS AF Weinstein, Lee S. TI Gs alpha mutations in fibrous dysplasia and McCune-Albright syndrome SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article; Proceedings Paper CT Conference on Pagets Disease of Bone/Fibrous Dysplasia - Advances and Challenges CY JAN 12-14, 2006 CL Ft Landerdale, FL DE G protein; fibrous dysplasia; bone marrow stromal cell; cAMP; McCune-Albright syndrome ID STIMULATORY G-PROTEIN; NONFUNCTIONING PITUITARY-TUMORS; ACTIVATING G(S)ALPHA MUTATION; HUMAN ENDOCRINE TUMORS; C-FOS PROTOONCOGENE; GNAS1 GENE; PREMATURE THELARCHE; ADENYLYL-CYCLASE; KINASE CASCADE; BONE AB Fibrous dysplasia (FD) is a focal bone lesion composed of immature mesenchymal osteoblastic precursor cells. Some FD patients also have hyperpigmented skin lesions (cafe-au-lait spots), gonadotropin-independent sexual precocity, and/or other endocrine and nonendocrine manifestations (McCune-Albright syndrome [MAS]). MAS results from somatic mutations occurring during early development, resulting in a widespread mosaic of normal and mutant-bearing cells, which predicts that the clinical presentation of each patient is determined by the extent and distribution of abnormal cells. These mutations encode constitutively active forms of G(s)alpha the ubiquitously expressed G protein alpha-subunit that couples hormone receptors to intracellular cAMP generation. These mutations lead to substitution of amino acid residues that are critical for the intrinsic GTPase activity that is normally required to deactivate the G protein. This leads to prolonged activation of G(s)alpha and its downstream effectors even with minimal receptor activation. This explains why MAS patients have stimulation of multiple peripheral endocrine glands in the absence of circulating stimulatory pituitary hormones and increased skin pigment, which is normally induced by melanocyte-stimulating hormone through G(s)alpha/cAMP. Similar mutations are also present in 40% of pituitary tumors in acromegaly patients and less commonly in other endocrine tumors. FD results from increased cAMP in bone marrow stromal cells, leading to increased proliferation and abnormal differentiation. Parental origin of the mutated allele may also affect the clinical presentation, because G(s)alpha is imprinted and expressed only from the maternal allele in some tissues (e.g., pituitary somatotrophs). C1 NIDDK, Signal Transduct Sect, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Weinstein, LS (reprint author), NIDDK, Signal Transduct Sect, Metab Dis Branch, NIH, Bldg 10,Room 8C101, Bethesda, MD 20892 USA. OI Weinstein, Lee/0000-0002-1899-5152 FU Intramural NIH HHS NR 66 TC 26 Z9 26 U1 1 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD DEC PY 2006 VL 21 SU 2 BP P120 EP P124 DI 10.1359/JBMR.06S223 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 129ME UT WOS:000243732800024 PM 17229000 ER PT J AU Nunes, FD Lopez, LN Lin, HW Davies, C Azevedo, RB Gow, A Kachar, B AF Nunes, Fabio D. Lopez, Lanier N. Lin, Harrison W. Davies, Caroline Azevedo, Ricardo B. Gow, Alexander Kachar, Bechara TI Distinct subdomain organization and molecular composition of a tight junction with adherens junction features SO JOURNAL OF CELL SCIENCE LA English DT Article DE apical junctional complex; outer hair cell; reticular lamina; organ of Corti; tight-adherens junction; cochlea ID RECESSIVE DEAFNESS DFNB29; OUTER HAIR-CELLS; C-ELEGANS; ADHESION; STRANDS; P120-CATENIN; ARCHITECTURE; COMPLEXES; CADHERINS; OCCLUDIN AB Most polarized epithelia constrain solute diffusion between luminal and interstitial compartments using tight junctions and generate mechanical strength using adherens junctions. These intercellular junctions are typically portrayed as incongruent macromolecular complexes with distinct protein components. Herein, we delineate the molecular composition and subdomain architecture of an intercellular junction between sensory and non-sensory cells of the inner ear. In this junction, claudins partition into claudin-14 and claudin-9/6 subdomains that are distinguishable by strand morphology, which contrasts with in vitro data that most claudins co-assemble into heteromeric strands. Surprisingly, canonical adherens junction proteins (p120ctn, alpha- and beta-catenins) colocalize with the claudin-9/6 subdomain and recruit a dense cytoskeletal network. We also find that catenins colocalize with claudin-9 and claudin-6, but not claudin-14, in a heterologous system. Together, our data demonstrate that canonical tight junction and adherens junction proteins can be recruited to a single junction in which claudins partition into subdomains and form a novel hybrid tight junction with adherens junction organization. C1 Wayne State Univ, Sch Med, Dept Neurol, Carman & Ann Adams Dept Pediat,Ctr Mol Med & Gene, Detroit, MI 48201 USA. Natl Inst Deafness & Commun Disorders, Lab Cellular Biol, NIH, Bethesda, MD 20892 USA. RP Gow, A (reprint author), Wayne State Univ, Sch Med, Dept Neurol, Carman & Ann Adams Dept Pediat,Ctr Mol Med & Gene, Detroit, MI 48201 USA. EM agow@med.wayne.edu; kacharb@nidcd.nih.gov RI Nunes, Fabio/B-4543-2011; Azevedo, Ricardo/D-6273-2012 OI Nunes, Fabio/0000-0002-7785-6785; FU NIDCD NIH HHS [R01 DC006262, R01-DC006262] NR 31 TC 54 Z9 54 U1 0 U2 3 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD DEC 1 PY 2006 VL 119 IS 23 BP 4819 EP 4827 DI 10.1242/jcs.03233 PG 9 WC Cell Biology SC Cell Biology GA 119ES UT WOS:000242995800005 PM 17130295 ER PT J AU Daniotti, JL Crespo, PM Yamashita, T AF Daniotti, Jose L. Crespo, Pilar M. Yamashita, Tadashi TI In vivo modulation of epidermal growth factor receptor phosphorylation in mice expressing different Gangliosides SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE gangliosides; EGF receptor; ganglioside glycosyltransferase; skin; mice; glycolipid ID CELL-GROWTH; GM3; SYNTHASE; MOUSE; GD3; PROLIFERATION; GLYCOLIPIDS; SENSITIVITY; MEMBRANE; BRAIN AB We studied in this work the in vivo phosphorylation of the epidermal growth factor receptor (EGFr) in skin from knockout mice lacking different ganglioside glycosyltransferases. Results show an enhancement of EGFr phosphorylation, after EGF stimulation, in skin from Sial-T2 knockout and Sial-T2/GaINAc-T double knockout mice as compared with wild-type and Sial-Ti knockout mice. Qualitative analysis of ganglioside composition in mice skin suggest that the increase of EGFr phosphorylation observed in skin from Sial-T2 knockout and Sial-T2/Gal NA&T double knockout mice in response to EGF might not be primary attributed to the expression of GD3 or a-series gangliosides in mice skin. These studies provide, for the first time, an approach for studying the molecular mechanisms involved in the in vivo regulation of EGFr function by gangliosides. J. Cell. Biochem. 99: 1442-1451, 2006. (c) 2006 Wiley-Liss, Inc. C1 Univ Nacl Cordoba, Fac Ciencias Quim, CONICET, Ctr Invest Quim Biol Cordoba,CIQUIBIC,Dept Quim B, RA-5000 Cordoba, Argentina. NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. RP Daniotti, JL (reprint author), Univ Nacl Cordoba, Fac Ciencias Quim, CONICET, Ctr Invest Quim Biol Cordoba,CIQUIBIC,Dept Quim B, Ciudad Univ, RA-5000 Cordoba, Argentina. EM daniotti@dqb.fcq.unc.edu.ar NR 31 TC 6 Z9 6 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD DEC 1 PY 2006 VL 99 IS 5 BP 1442 EP 1451 DI 10.1002/jcb.21034 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 104RI UT WOS:000241976100020 PM 16817235 ER PT J AU Samuel, W Kutty, RK Nagineni, S Vijayasarathy, C Chandraratna, RAS Wiggert, B AF Samuel, William Kutty, R. Krishnan Nagineni, Sahrudaya Vijayasarathy, Camasamudram Chandraratna, Roshantha A. S. Wiggert, Barbara TI N-(4-hydroxyphenyl)retinamide induces apoptosis in human retinal pigment epithelial cells: Retinoic acid receptors regulate apoptosis, reactive oxygen species generation, and the expression of heme oxygenase-1 and Gadd153 SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID FENRETINIDE-INDUCED APOPTOSIS; OVARIAN-CARCINOMA CELLS; CANCER-CELLS; HUMAN HEAD; PYRROLIDINE DITHIOCARBAMATE; GROWTH-INHIBITION; BREAST-CANCER; UP-REGULATION; DEATH; LINES AB N-(4-hydroxyphenyl)retinamide (4HPR, fenretinide), a retinoic acid (RA) derivative and a potential cancer preventive agent, is known to exert its chemotherapeutic effects in cancer cells through induction of apoptosis. Earlier work from our laboratory has shown that relatively low concentrations of 4HPR induce neuronal differentiation of cultured human retinal pigment epithelial (ARPE-19) cells (Chen et al, 2003, J. Neurochem 84:972-981). However, at higher concentrations of 4HPR, these cells showed morphological changes including cell shrinkage and cell death. Here we demonstrate that ARPE-19 cells treated with 4HPR exhibit a dose- and time-dependent induction of apoptosis as evidenced by morphological changes, mono- and oligonucleosome generation, and increased activity of caspases 2 and 3. The 4HPR-induced apoptosis as well as the activation of caspases 2 and 3 were blocked by both retinoic acid receptors (RAR) pan-antagonists, AGN193109 and AGN194310, and by an RAR alpha-specific antagonist AGN194301. 4HPR treatment also increased reactive oxygen species (ROS) generation in ARPE-19 cells in a time-dependent manner as determined from the oxidation of 2',7'-dichlorofluorescin. In addition, the increase in the expression of heme oxygenase-1 (HO-1), a stress response protein, and the growth arrest and DNA damage-inducible transcription factor 153 (Gadd153) in response to the ROS generation were also blocked by these receptor antagonists. Pyrrolidine dithiocarbamate (PDTC), a free-radical scavenger, inhibited 4HPR-induced ROS generation, the expression of its downstream mediator, Gadd153, and apoptosis in the pretreated cells. Therefore, our results, clearly demonstrate that 4HPR induces apoptosis in ARPE-1 9 cells and that RARs mediate this process by regulating ROS generation as well as the expression of Gadd153 and HO-1. C1 NEI, NIH, Biochem Sect, LRCMB, Bethesda, MD 20892 USA. Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA. Allergan Pharmaceut Inc, Dept Biol & Chem, Irvine, CA 92715 USA. Allergan Pharmaceut Inc, Dept Retinoid Res, Irvine, CA 92715 USA. RP Samuel, W (reprint author), NEI, NIH, Biochem Sect, LRCMB, Bldg 7,Room 329,7 Mem Dr, Bethesda, MD 20892 USA. EM samuelw@nei.nih.gov FU Intramural NIH HHS NR 63 TC 19 Z9 20 U1 0 U2 1 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 DEC PY 2006 VL 209 IS 3 BP 854 EP 865 DI 10.1002/jcp.20774 PG 12 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 101QD UT WOS:000241754600036 PM 16972258 ER PT J AU Ralston, E Lu, Z Biscocho, N Soumaka, E Mavroidis, M Prats, C Lomo, T Capetanaki, Y Ploug, T AF Ralston, E. Lu, Z. Biscocho, N. Soumaka, E. Mavroidis, M. Prats, C. Lomo, T. Capetanaki, Y. Ploug, T. TI Blood vessels and desmin control the positioning of nuclei in skeletal muscle fibers SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID SODIUM-CHANNELS; LACKING DESMIN; GOLGI-COMPLEX; ORGANIZATION; MOUSE; MICE; ANGIOGENESIS; MICROTUBULES; PROTEINS; CULTURE AB Skeletal muscle fibers contain hundreds to thousands of nuclei which lie immediately under the plasmalemma and are spaced out along the fiber, except for a small cluster of specialized nuclei at the neuromuscular junction. How the nuclei attain their positions along the fiber is not understood. Here we show that the nuclei are preferentially localized near blood vessels (BV), particularly in slow-twitch, oxidative fibers. Thus, in rat soleus muscle fibers, 81% of the nuclei appear next to BV. Lack of desmin markedly perturbs the distribution of nuclei along the fibers but does not prevent their close association with BV. Consistent with a role for desmin in the spacing of nuclei, we show that denervation affects the organization of desmin filaments as well as the distribution of nuclei. During chronic stimulation of denervated muscles, new BV form, along which muscle nuclei align themselves. We conclude that the positioning of nuclei along muscle fibers is plastic and that BV and desmin intermediate filaments each play a distinct role in the control of this positioning. C1 NIAMS, LIS, OST, NIH, Bethesda, MD 20892 USA. Univ Copenhagen, Panum Inst, Dept Med Physiol, Muscle Res Ctr, DK-2200 Copenhagen N, Denmark. Univ Oslo, Dept Physiol, Oslo, Norway. Acad Athens, Div Cell Biol, Ctr Basic Res, Fdn Biomed Res, Athens, Greece. RP Ralston, E (reprint author), NIAMS, LIS, OST, NIH, Bldg 50,Rm 1535, Bethesda, MD 20892 USA. EM ralstone@mail.nih.gov RI Prats, Clara/F-5993-2014; OI Soumaka, Elisavet/0000-0001-8705-6741 FU Intramural NIH HHS; NIAMS NIH HHS [AR 39617] NR 39 TC 36 Z9 38 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 DEC PY 2006 VL 209 IS 3 BP 874 EP 882 DI 10.1002/jcp.20780 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 101QD UT WOS:000241754600038 PM 16972267 ER PT J AU Illoh, K Campbell, C Illoh, O Diehl, J Cherry, J Elkhaloun, A Chen, Y Hallenbeck, J AF Illoh, Kachi Campbell, Catherine Illoh, Orieji Diehl, John Cherry, James Elkhaloun, Abdel Chen, Yong Hallenbeck, John TI Mucosal tolerance to E-selectin and response to systemic inflammation SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE E-selectin; gene expression; immune tolerance; inflammation ID FOCAL CEREBRAL-ISCHEMIA; GROWTH-FACTOR-I; IFN-GAMMA; RAT-BRAIN; STROKE; PROTEIN; EXPRESSION; LIPOPOLYSACCHARIDE; INDUCTION; INJURY AB Mucosal tolerance to E-selectin has been shown to prevent stroke and reduce brain infarcts in experimental stroke models. However, the effective E-selectin dose range required to achieve mucosal tolerance and the precise mechanisms of neuroprotection remain unclear. We sought to examine the mechanisms of cytoprotection using gene expression profiling of tissues in the setting of mucosal tolerance and inflammatory challenge. Using spontaneously hypertensive rats (SHRs), we achieved immune tolerance with 0.1 to 5 mu g E-selectin per nasal instillation and observed a dose-related anti-E-selectin immunoglobulin G antibody production. We also show the distinct patterns of gene expression changes in the brain and spleen with the different tolerizing doses and lipopolysaccharide (LPS) exposure. Prominent differences were seen with such genes as insulin-like growth factors in the brain and downregulation of those encoding the major histocompatibility complex class I molecules in the spleen. In all, mucosal tolerance to E-selectin and subsequent exposure to LPS resulted in significant tissue changes. These changes, while giving an insight to the underlying mechanisms, serve as possible targets for future studies to facilitate translation to human clinical trials. C1 Univ Texas, Hlth Sci Ctr, Dept Neurol, Houston, TX 77030 USA. NINDS, SRA Int, NIH, Bethesda, MD USA. Univ Texas, Hlth Sci Ctr, Dept Pathol & Lab Med, Houston, TX 77030 USA. SAIC Frederick Inc, NCI, NIH, Frederick, MD USA. NHGRI, NIH, Bethesda, MD 20892 USA. NINDS, Stroke Branch, NIH, Bethesda, MD USA. RP Illoh, K (reprint author), Univ Texas, Hlth Sci Ctr, Dept Neurol, 6431 Fannin St,MSB 7-044, Houston, TX 77030 USA. EM kachikwu.illoh@uth.tmc.edu FU Intramural NIH HHS [Z99 NS999999] NR 39 TC 5 Z9 7 U1 0 U2 0 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 DEC PY 2006 VL 26 IS 12 BP 1538 EP 1550 DI 10.1038/sj.jcbfm.9600308 PG 13 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 111HJ UT WOS:000242441700008 PM 16596122 ER PT J AU Wiener, L Battles, H Ryder, C Pao, M AF Wiener, Lori Battles, Haven Ryder, Celia Pao, Maryland TI Psychotropic medication use in human immunodeficiency virus-infected youth receiving treatment at a single institution SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID SCHOOL-AGE-CHILDREN; PSYCHIATRIC MORBIDITY; HIV; ADOLESCENTS; PREVALENCE; DISORDERS; ADJUSTMENT; HIV/AIDS; RATES AB A cross-sectional study designed to document the use of psychotropic medication in a population of human immunodeficiency virus (HIV)-infected children and adolescents (n = 64) found 45% of the sample had been prescribed at least one psychotropic medication over a 4-year period. The most common medication category prescribed was antidepressants (30%), followed by stimulant-type medications (25%). This study suggests that psychotropic medications are commonly prescribed to HIV-infected children and adolescents. Close partnership with mental health professionals to develop treatment approaches for psychiatric disorders in youth living with HIV is recommended. C1 NCI, HIV AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. NIH, Clin Ctr Nursing Dept, Bethesda, MD 20892 USA. NIMH, NIH, Bethesda, MD 20892 USA. RP Wiener, L (reprint author), NCI, Coordinator Pediat HIV Psychosocial Support & Res, 10-10S255,9000 Rockville Pike, Bethesda, MD 20892 USA. EM wienerl@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 27 TC 4 Z9 4 U1 2 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD DEC PY 2006 VL 16 IS 6 BP 747 EP 753 DI 10.1089/cap.2006.16.747 PG 7 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 127RZ UT WOS:000243605300037 PM 17201618 ER PT J AU Shaw, DS Schonberg, M Sherrill, J Huffman, D Lukon, J Obrosky, D Kovacs, M AF Shaw, Daniel S. Schonberg, Michael Sherrill, Joel Huffman, Drew Lukon, Joella Obrosky, David Kovacs, Maria TI Responsivity to offspring's expression of emotion among childhood-onset depressed mothers SO JOURNAL OF CLINICAL CHILD AND ADOLESCENT PSYCHOLOGY LA English DT Article ID PROBLEM BEHAVIOR; MENTAL-HEALTH; DEVELOPMENTAL PSYCHOPATHOLOGY; PARENTAL SOCIALIZATION; POSITIVE EMOTIONS; NEGATIVE EMOTIONS; MAJOR DEPRESSION; CHILDREN; FAMILY; RISK AB This study examined responsivity of mothers with childhood-onset depression (COD) in relation to children's overt expression of positive and negative emotion. It was hypothesized that COD and control mothers would differ in contingent responsivity to their children's expression of both. positivity and different types of negative emotionality. Using observations and maternal reports of their own emotional reactions, COD mothers were found to be less responsive to children's expression of distress. A Gender x Group interaction was also found with respect to observed maternal responsiveness to child positivity, such that COD mothers were more responsive to girls' than boys' expression of positivity. The results are discussed in reference to transactional models of early child psychopathology. C1 Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. NIMH, Pittsburgh, PA USA. RP Shaw, DS (reprint author), Univ Pittsburgh, Dept Psychol, 210 S Bouquet St,4101 Sennott Sq, Pittsburgh, PA 15260 USA. EM casey@pitt.edu NR 80 TC 31 Z9 31 U1 1 U2 4 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 1537-4416 J9 J CLIN CHILD ADOLESC JI J. Clin. Child Adolesc. Psychol. PD DEC PY 2006 VL 35 IS 4 BP 490 EP 503 DI 10.1207/s15374424jccp3504_1 PG 14 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA 096ZW UT WOS:000241416800001 PM 17007595 ER PT J AU Kanaya, AM Fyr, CW Vittinghoff, E Havel, PJ Cesari, M Nicklas, B Harris, T Newman, AB Satterfield, S Cummings, SR AF Kanaya, Alka M. Fyr, Christina Wassel Vittinghoff, Eric Havel, Peter J. Cesari, Matteo Nicklas, Barbara Harris, Tamara Newman, Anne B. Satterfield, Suzanne Cummings, Steve R. CA Health ABC Study TI Serum adiponectin and coronary heart disease risk in older Black and White Americans SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ADIPOSE-SPECIFIC PROTEIN; INSULIN-RESISTANCE; PLASMA ADIPONECTIN; MYOCARDIAL-INFARCTION; LIPOPROTEIN-LIPASE; ETHNIC-DIFFERENCES; DIABETES-MELLITUS; MEN; HYPOADIPONECTINEMIA; ASSOCIATION AB Context: Adiponectin may influence the risk of coronary heart disease (CHD) independently of traditional cardiovascular risk factors. Objective: Because body composition and adiponectin levels vary by race, we examined the relationship of adiponectin with prevalent and incident CHD in a cohort of older Black and White adults. Design and Setting: We conducted a cross-sectional and prospective cohort study at two U. S. clinical centers. Participants: Participants included 3075 well-functioning adults between ages 70 and 79 yr enrolled in the Health, Aging, and Body Composition study. Main Outcome Measures: Prevalent CHD was defined as history of myocardial infarction, coronary artery bypass graft, percutaneous coronary transluminal angioplasty, angina, or major electrocardiogram abnormalities. After excluding those with prevalent CHD, incident CHD was defined as hospitalized myocardial infarction or CHD death. Results: At baseline, 602 participants (19.6%) had CHD. During 6 yr of follow-up, 262 (10.6%) incident CHD events occurred. Whites had higher median adiponectin than Blacks (12 vs. 8 mu g/ml, P < 0.001). Race modified the effect of adiponectin (P for interaction was 0.002 for prevalent CHD, and P = 0.02 for incident CHD). Among Whites, an inverse association of adiponectin with CHD was explained by high-density lipoprotein and glucose. Among Blacks, a doubling of adiponectin was associated with a 40% higher risk of both prevalent CHD (odds ratio, 1.41; 95% confidence interval, 1.11-1.78) and incident CHD (hazards ratio, 1.37; 95% confidence interval, 1.01-1.87) after adjusting for explanatory variables. Conclusion: High circulating concentrations of adiponectin were associated with higher risk of CHD in older Blacks, even accounting for traditional CHD risk factors. C1 Univ Calif San Francisco, San Francisco, CA 94115 USA. Univ Calif Davis, Davis, CA 95616 USA. Univ Florida, Dept Aging & Geriatr Res, Gainesville, FL 32611 USA. Wake Forest Univ, Med Ctr, Winston Salem, NC 27157 USA. Intramural Res Program, NIH, Bethesda, MD 20892 USA. Univ Tennessee, Knoxville, TN 37996 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Calif Pacific Med Ctr, San Francisco, CA 94118 USA. RP Kanaya, AM (reprint author), Univ Calif San Francisco, 1635 Divisadero St,Suite 600, San Francisco, CA 94115 USA. EM Alka.Kanaya@ucsf.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 FU NIA NIH HHS [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, P30-AG15272]; NIAMS NIH HHS [K12 AR047659, K12 AR47659] NR 34 TC 53 Z9 58 U1 0 U2 2 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 DEC PY 2006 VL 91 IS 12 BP 5044 EP 5050 DI 10.1210/jc.2006-0107 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 113EN UT WOS:000242581300052 PM 16984981 ER PT J AU Choi, YH Park, S Hockman, S Zmuda-Trzebiatowska, E Svennelid, F Haluzik, M Gavrilova, O Ahmad, F Pepin, L Napolitano, M Taira, M Sundler, F Holst, LS Degerman, E Manganiello, VC AF Choi, Young Hun Park, Sunhee Hockman, Steven Zmuda-Trzebiatowska, Emilia Svennelid, Fredrik Haluzik, Martin Gavrilova, Oksana Ahmad, Faiyaz Pepin, Laurent Napolitano, Maria Taira, Masato Sundler, Frank Holst, Lena Stenson Degerman, Eva Manganiello, Vincent C. TI Alterations in regulation of energy homeostasis in cyclic nucleotide phosphodiesterase 3B-null mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID 3B GENE-EXPRESSION; INSULIN-SECRETION; ADIPOSE-TISSUE; GLUCOSE-PRODUCTION; PROTEIN-KINASE; KNOCKOUT MICE; FATTY-ACIDS; RESISTANCE; LIVER; ADIPOCYTE AB Cyclic nucleotide phosphodiesterase 3B (PDE3B) has been suggested to be critical for mediating insulin/IGF-1 inhibition of cAMP signaling in adipocytes, liver, and pancreatic beta cells. In Pde3b-KO adipocytes we found decreased adipocyte size, unchanged insulin-stimulated phosphorylation of protein kinase B and activation of glucose uptake, enhanced catecholamine-stimulated lipolysis and insulin-stimulated hpogenesis, and blocked insulin inhibition of catecholamine-stimulated lipolysis. Glucose, alone or in combination with glucagon-like peptide-1, increased insulin secretion more in isolated pancreatic KO islets, although islet size and morphology and immunoreactive insulin and glucagon levels were unchanged. The beta(3)-adrenergic agonist CL 316,243 (CL) increased lipolysis and serum insulin more in KO mice, but blood glucose reduction was less in CL-treated KO mice. Insulin resistance was observed in KO mice, with liver an important site of alterations in insulin-sensitive glucose production. In KO mice, liver triglyceride and cAMP contents were increased, and the liver content and phosphorylation states of several insulin signaling, gluconeogenic, and inflammation- and stress-related components were altered. Thus, PDE3B may be important in regulating certain cAMP signaling pathways, including lipolysis, insulin-induced antilipolysis, and cAMP-mediated insulin secretion. Altered expression and/or regulation of PDE3B may contribute to metabolic dysregulation, including systemic insulin resistance. C1 NIH, PCCMB, NHLBI, Bethesda, MD 20892 USA. Lund Univ, Dept Expt Med Sci, Lund, Sweden. NIDDK, Diabet Branch, NIH, Bethesda, MD USA. RP Choi, YH (reprint author), NIH, PCCMB, NHLBI, 9000 Rockville Pike,Bldg 10,Room 5N307, Bethesda, MD 20892 USA. EM Choiy@nhlbi.nih.gov NR 45 TC 77 Z9 81 U1 1 U2 5 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 2006 VL 116 IS 12 BP 3240 EP 3251 DI 10.1172/JCI24867 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 113OJ UT WOS:000242606900023 PM 17143332 ER PT J AU Ghannoum, MA Arthington-Skaggs, B Chaturvedi, V Espinel-Ingroff, A Pfaller, MA Rennie, R Rinaldi, MG Walsh, TJ AF Ghannoum, M. A. Arthington-Skaggs, B. Chaturvedi, V. Espinel-Ingroff, A. Pfaller, M. A. Rennie, R. Rinaldi, M. G. Walsh, T. J. TI Interlaboratory study of quality control isolates for a broth microdilution method (modified CLSI M38-A) for testing susceptibilities of dermatophytes to antifungals SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article AB The Clinical and Laboratory Standards Institute (CLSI; formerly National Committee for Clinical Laboratory Standards, or NCCLS) M38-A standard for the susceptibility testing of filamentous fungi does not specifically address the testing of dermatophytes. In 2003, a multicenter study investigated the reproducibility of the microdilution method developed at the Center for Medical Mycology, Cleveland, Ohio, for testing the susceptibility of dermatophytes. Data from that study supported the introduction of this method for testing dermatophytes in the future version of the CLSI M38-A standard. In order for the method to be accepted by CLSI, appropriate quality control isolates needed to be identified. To that end, an interlaboratory study, involving the original six laboratories plus two additional sites, was conducted to evaluate potential candidates for quality control isolates. These candidate strains included five Trichophyton rubrum strains known to have elevated MICs to terbinafine and five Trichophyton mentagrophytes strains. Antifungal agents tested included ciclopirox, fluconazole, griseofulvin, itraconazole, posaconazole, terbinafine, and voriconazole. Based on the data generated, two quality control isolates, one T. rubrum isolate and one T. mentagrophytes isolate, were identified and submitted to the American Type Culture Collection (ATCC) for inclusion as reference strains. Ranges encompassing 95.2 to 97.9% of all data points for all seven drugs were established. C1 Case Western Reserve Univ Hosp, Ctr Med Mycol, EMBA, Cleveland, OH 44106 USA. Ctr Dis Control & Prevent, Mycot Dis Branch, Atlanta, GA USA. Dept Hlth, Albany, NY USA. VCU Med Ctr, Richmond, VA USA. Univ Iowa, Coll Med, Dept Pathol, Iowa City, IA 52242 USA. Univ Alberta Hosp, Natl Ctr Mycol, Edmonton, AB T6G 2B7, Canada. Univ Texas, Hlth Sci Ctr, Audie L Murphy Mem Vet Hosp, Lab Serv, San Antonio, TX USA. NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Ghannoum, MA (reprint author), Case Western Reserve Univ Hosp, Ctr Med Mycol, EMBA, 11100 Euclid Ave, Cleveland, OH 44106 USA. EM mag3@case.edu NR 6 TC 22 Z9 22 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD DEC PY 2006 VL 44 IS 12 BP 4353 EP 4356 DI 10.1128/JCM.00688-06 PG 4 WC Microbiology SC Microbiology GA 117MC UT WOS:000242876300009 PM 17050812 ER PT J AU Yang, J AF Yang, James TI Does CTLA4 influence the suppressive effect of CD25+CD4+ regulatory T cells? Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID LYMPHOCYTE-ASSOCIATED ANTIGEN-4; BLOCKADE; CANCER C1 NCI, Surg Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Yang, J (reprint author), NCI, Surg Branch, Ctr Canc Res, Bldg 10, Bethesda, MD 20892 USA. NR 9 TC 0 Z9 0 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 DEC 1 PY 2006 VL 24 IS 34 BP 5470 EP 5471 DI 10.1200/JCO.2006.08.5969 PG 2 WC Oncology SC Oncology GA 112OJ UT WOS:000242535400026 ER PT J AU Freeman, MP Hibbeln, JR Wisner, KL Davis, JM Mischoulon, D Peet, M Keck, PE Mayangell, LB Richardson, AJ Lake, J Stoll, AL AF Freeman, Marlene P. Hibbeln, Joseph R. Wisner, Katherine L. Davis, John M. Mischoulon, David Peet, Malcolm Keck, Paul E., Jr. Mayangell, Lauren B. Richardson, Alexandra J. Lake, James Stoll, Andrew L. TI Omega-3 fatty acids: Evidence basis for treatment and future research in psychiatry SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Review ID POLYUNSATURATED FATTY-ACIDS; PLACEBO-CONTROLLED TRIAL; ETHYL-EICOSAPENTAENOIC ACID; RANDOMIZED DOUBLE-BLIND; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; DEPENDENT DIABETES-MELLITUS; BLOOD-CELL MEMBRANES; DOSE FISH-OIL; DOCOSAHEXAENOIC ACID AB Objective: To determine if the available data support the use of omega-3 essential fatty acids (EFA) for clinical use in the prevention and/or treatment of psychiatric disorders. Participants: The authors of this article were invited participants in the Omega-3 Fatty Acids Subcommittee, assembled by the Committee on Research on Psychiatric Treatments of the American Psychiatric Association (APA). Evidence: Published literature and data presented at scientific meetings were reviewed. Specific disorders reviewed included major depressive disorder, bipolar disorder, schizophrenia, dementia, borderline personality disorder and impulsivity, and attention-deficit/hyperactivity disorder. Meta-analyses were conducted in major depressive and bipolar disorders and schizophrenia, as sufficient data were available to conduct such analyses in these areas of interest. Consensus Process: The subcommittee prepared the manuscript, which was reviewed and approved by the following APA committees: the Committee on Research on Psychiatric Treatments, the Council on Research, and the Joint Reference Committee. Conclusions: The preponderance of epidemiologic and tissue compositional studies supports a protective effect of omega-3 EFA intake, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in mood disorders. Meta-analyses of randomized controlled trials demonstrate a statistically significant benefit in unipolar and bipolar depression (p = .02). The results were highly heterogeneous, indicating that it is important to examine the characteristics of each individual study to note the differences in design and execution. There is less evidence of benefit in schizophrenia. EPA and DHA appear to have negligible risks and some potential benefit in major depressive disorder and bipolar disorder, but results remain inconclusive in most areas of interest in psychiatry. Treatment recommendations and directions for future research are described. Health benefits of omega-3 EFA may be especially important in patients with psychiatric disorders, due to high prevalence rates of smoking and obesity and the metabolic side effects of some psychotropic medications. C1 Univ Arizona, Coll Med, Womens Mental Hlth Program, Dept Psychiat, Tucson, AZ 85724 USA. Univ Arizona, Coll Med, Womens Mental Hlth Program, Dept Obstet & Gynecol, Tucson, AZ 85724 USA. Univ Arizona, Coll Med, Womens Mental Hlth Program, Dept Nutr Sci, Tucson, AZ 85724 USA. NIAAA, Bethesda, MD USA. Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Pittsburgh, PA USA. Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA. Maryland Psychiat Res Ctr, Baltimore, MD 21228 USA. Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. Univ Sheffield, Sch Hlth & Related Res, Sheffield, S Yorkshire, England. Univ Cincinnati, Coll Med, Psychopharmacol Res Program, Dept Psychiat, Cincinnati, OH USA. Baylor Coll Med, Dept Psychiat, Houston, TX 77030 USA. Dept Vet Affairs, VISN Mental Illness Res Educ & Clin Core 16, Houston, TX USA. Univ Oxford, Dept Physiol Human Anat & Genet, Oxford, England. Stanford Univ, Dept Psychiat, Palo Alto, CA 94304 USA. Stanford Univ, Ctr Integrative Med, Palo Alto, CA 94304 USA. Harvard Univ, Sch Med, Dept Psychiat, McLean Hosp, Boston, MA USA. RP Freeman, MP (reprint author), Univ Arizona, Coll Med, Womens Mental Hlth Program, Dept Psychiat, 1501 N Campbell Ave,POB 245002, Tucson, AZ 85724 USA. EM marlenef@email.arizona.edu FU NCCIH NIH HHS [5 K23 AT001129-05]; NIMH NIH HHS [5K23MH066265] NR 133 TC 383 Z9 396 U1 5 U2 95 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 DEC PY 2006 VL 67 IS 12 BP 1954 EP 1967 PG 16 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 120LI UT WOS:000243085800016 PM 17194275 ER PT J AU Hanna, EZ AF Hanna, Eleanor Z. TI Comments on guest editorial, "Chronic fatigue syndrome, mast cells, and tricyclic antidepressants" SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Letter C1 NIH, Off Res Womens Hlth, Bethesda, MD 20892 USA. NIH, Trans Working Grp Res Chron Farigue Syndrome, Bethesda, MD 20892 USA. RP Hanna, EZ (reprint author), NIH, Off Res Womens Hlth, Bldg 10, Bethesda, MD 20892 USA. EM hannae@od.nih.gov NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD DEC PY 2006 VL 26 IS 6 BP 690 EP 690 DI 10.1097/01.jcp.0000253315.66210.22 PG 1 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 108RI UT WOS:000242256500035 PM 17110844 ER PT J AU Ahlqist, J Fotheringham, J Akhyani, N Yao, K Fogdell-Hahn, A Jacobson, S AF Ahlqist, J. Fotheringham, J. Akhyani, N. Yao, K. Fogdell-Hahn, A. Jacobson, S. TI Differential tropism of human herpesvirus 6 (HHV-6) variants and induction of latency by HHV-6A in oligodendrocytes SO JOURNAL OF CLINICAL VIROLOGY LA English DT Meeting Abstract CT 5th International Conference on Human Herpesvirus 6 and 7 (HHV-6&7) CY MAY 01-03, 2006 CL Barcelona, SPAIN SP HHV-6 Fdn C1 NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. EM jenny.ahlquist@ki.se NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1386-6532 J9 J CLIN VIROL JI J. Clin. Virol. PD DEC PY 2006 VL 37 SU 1 MA 7 BP S99 EP S99 DI 10.1016/S1386-6532(06)70026-9 PG 1 WC Virology SC Virology GA 131CG UT WOS:000243845000027 ER PT J AU Ahlqvist, J Hammarstedt, M Jacobson, S Garoff, H Fogdell-Hahn, A AF Ahlqvist, J. Hammarstedt, M. Jacobson, S. Garoff, H. Fogdell-Hahn, A. TI Viable HHV-6A viral particles purified with iodixanol gradients SO JOURNAL OF CLINICAL VIROLOGY LA English DT Meeting Abstract CT 5th International Conference on Human Herpesvirus 6 and 7 (HHV-6&7) CY MAY 01-03, 2006 CL Barcelona, SPAIN SP HHV-6 Fdn C1 NINDS, NIH, Bethesda, MD 20892 USA. Karolinska Inst, Div Neurol, Dept Clin Neurosci, Huddinge, Sweden. EM jenny.ahlquist@ki.se NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1386-6532 J9 J CLIN VIROL JI J. Clin. Virol. PD DEC PY 2006 VL 37 SU 1 MA 6 BP S98 EP S98 PG 1 WC Virology SC Virology GA 131CG UT WOS:000243845000026 ER PT J AU Ahlqvist, J Donati, D Martinelli, E Akhyani, N Hou, J Major, EO Jacobson, S Fogdell-Hahn, A AF Ahlqvist, J. Donati, D. Martinelli, E. Akhyani, N. Hou, J. Major, E. O. Jacobson, S. Fogdell-Hahn, A. TI Complete replication cycle and acquisition of tegument in nucleus of human herpesvirus 6A (HHV-6A) in astrocytes and in T-cells SO JOURNAL OF CLINICAL VIROLOGY LA English DT Meeting Abstract CT 5th International Conference on Human Herpesvirus 6 and 7 (HHV-6&7) CY MAY 01-03, 2006 CL Barcelona, SPAIN SP HHV-6 Fdn C1 NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. Karolinska Univ Hosp, Div Neurol, Dept Clin Neurosci, Karolinska Inst, SE-14186 Stockholm, Sweden. EM jenny.ahlqvist@ki.se NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1386-6532 J9 J CLIN VIROL JI J. Clin. Virol. PD DEC PY 2006 VL 37 SU 1 MA 4 BP S98 EP S98 PG 1 WC Virology SC Virology GA 131CG UT WOS:000243845000024 ER PT J AU Donati, D Fotheringham, J Akhyani, N Fogdell-Hahn, A Vortmeyer, A Heiss, JD Williams, EL Weinstein, S Bruce, DA Bonwetsch, R Gaillard, WD Sato, S Theodore, WH Jacobson, S AF Donati, D. Fotheringham, J. Akhyani, N. Fogdell-Hahn, A. Vortmeyer, A. Heiss, J. D. Williams, E. L. Weinstein, S. Bruce, D. A. Bonwetsch, R. Gaillard, W. D. Sato, S. Theodore, W. H. Jacobson, S. TI HHV-6 and mesial temporal lobe epilepsy: detection of viral DNA and antigen in brain tissue primary cultured astrocytes and implication for a viral role in pathogenesis SO JOURNAL OF CLINICAL VIROLOGY LA English DT Meeting Abstract CT 5th International Conference on Human Herpesvirus 6 and 7 (HHV-6&7) CY MAY 01-03, 2006 CL Barcelona, SPAIN SP HHV-6 Fdn C1 NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Clin Epilepsy Sect, NIH, Bethesda, MD 20892 USA. Siena Univ Hosp, Siena, Italy. Karolinska Inst, Stockholm, Sweden. Childrens Natl Med Ctr, Washington, DC 20010 USA. EM donatid@unisi.it NR 0 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1386-6532 J9 J CLIN VIROL JI J. Clin. Virol. PD DEC PY 2006 VL 37 SU 1 MA 68 BP S115 EP S116 DI 10.1016/S1386-6532(06)70087-7 PG 2 WC Virology SC Virology GA 131CG UT WOS:000243845000088 ER PT J AU Fotheringham, J Akhyani, N Rashti, F Yao, K Williams, EL Jacobson, S AF Fotheringham, J. Akhyani, N. Rashti, F. Yao, K. Williams, E. L. Jacobson, S. TI Efficacy of anti-viral compounds in HHV-6 infected glial cells SO JOURNAL OF CLINICAL VIROLOGY LA English DT Meeting Abstract CT 5th International Conference on Human Herpesvirus 6 and 7 (HHV-6&7) CY MAY 01-03, 2006 CL Barcelona, SPAIN SP HHV-6 Fdn C1 NINDS, Viral Immunol Sect, NIH, Bethesda, MD 20892 USA. EM fotherij@ninds.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1386-6532 J9 J CLIN VIROL JI J. Clin. Virol. PD DEC PY 2006 VL 37 SU 1 MA 58 BP S113 EP S113 DI 10.1016/S1386-6532(06)70077-4 PG 1 WC Virology SC Virology GA 131CG UT WOS:000243845000078 ER PT J AU Glaser, C Honarmand, S Yao, K Gagnon, S Akhyani, N Espinosa, A Forghani, B Jacobson, S AF Glaser, C. Honarmand, S. Yao, K. Gagnon, S. Akhyani, N. Espinosa, A. Forghani, B. Jacobson, S. TI Human herpesvirus 6 - an underappreciated pathogen in encephalitis SO JOURNAL OF CLINICAL VIROLOGY LA English DT Meeting Abstract CT 5th International Conference on Human Herpesvirus 6 and 7 (HHV-6&7) CY MAY 01-03, 2006 CL Barcelona, SPAIN SP HHV-6 Fdn C1 Viral & Rickettsial Dis Branch, Richmond, CA USA. NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. EM cglaser@dhs.ca.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1386-6532 J9 J CLIN VIROL JI J. Clin. Virol. PD DEC PY 2006 VL 37 SU 1 MA 65 BP S115 EP S115 DI 10.1016/S1386-6532(06)70084-1 PG 1 WC Virology SC Virology GA 131CG UT WOS:000243845000085 ER PT J AU Grivel, JC AF Grivel, J. -C. TI HHV-6 and HIV-1 co-infection ex vivo SO JOURNAL OF CLINICAL VIROLOGY LA English DT Meeting Abstract CT 5th International Conference on Human Herpesvirus 6 and 7 (HHV-6&7) CY MAY 01-03, 2006 CL Barcelona, SPAIN SP HHV-6 Fdn C1 NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. EM grivelj@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1386-6532 J9 J CLIN VIROL JI J. Clin. Virol. PD DEC PY 2006 VL 37 SU 1 MA 50 BP S110 EP S110 DI 10.1016/S1386-6532(06)70069-5 PG 1 WC Virology SC Virology GA 131CG UT WOS:000243845000070 ER PT J AU Jacobson, S Yamanishi, K AF Jacobson, Steve Yamanishi, Koichi TI Welcome from the Co-Chairs of the 5th International Conference on HHV-6 & 7 SO JOURNAL OF CLINICAL VIROLOGY LA English DT Editorial Material C1 NINDS, Viral Immunol Sect, NIH, Bethesda, MD USA. Natl Inst Biomed Innovat, Osaka, Japan. RP Jacobson, S (reprint author), NINDS, Viral Immunol Sect, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1386-6532 J9 J CLIN VIROL JI J. Clin. Virol. PD DEC PY 2006 VL 37 SU 1 BP S1 EP S1 PG 1 WC Virology SC Virology GA 131CG UT WOS:000243845000001 ER PT J AU Margolis, L AF Margolis, L. TI Interactions of herpesviruses 6 and 7 with HIV-1 in human lymphoid tissue SO JOURNAL OF CLINICAL VIROLOGY LA English DT Meeting Abstract CT 5th International Conference on Human Herpesvirus 6 and 7 (HHV-6&7) CY MAY 01-03, 2006 CL Barcelona, SPAIN SP HHV-6 Fdn C1 NICHHD, Bethesda, MD 20892 USA. EM margolil@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1386-6532 J9 J CLIN VIROL JI J. Clin. Virol. PD DEC PY 2006 VL 37 SU 1 MA 12 BP S100 EP S100 DI 10.1016/S1386-6532(06)70031-2 PG 1 WC Virology SC Virology GA 131CG UT WOS:000243845000032 ER PT J AU Williams, EL Fotheringham, J Akhyani, N Jacobson, S AF Williams, E. L. Fotheringham, J. Akhyani, N. Jacobson, S. TI Astrocytic HHV-6 infection dysregulates glutamate uptake and expression of glutamate transporters SO JOURNAL OF CLINICAL VIROLOGY LA English DT Meeting Abstract CT 5th International Conference on Human Herpesvirus 6 and 7 (HHV-6&7) CY MAY 01-03, 2006 CL Barcelona, SPAIN SP HHV-6 Fdn C1 NINDS, Viral Immunol Sect, NIH, Bethesda, MD 20892 USA. EM williamse@ninds.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1386-6532 J9 J CLIN VIROL JI J. Clin. Virol. PD DEC PY 2006 VL 37 SU 1 MA 3 BP S97 EP S98 DI 10.1016/S1386-6532(06)70022-1 PG 2 WC Virology SC Virology GA 131CG UT WOS:000243845000023 ER PT J AU Yao, K Akhyani, N Donati, D Sengamalay, N Fotheringham, J Ghedin, E Bishop, M Barrett, J Kashanchi, F Jacobson, S AF Yao, Karen Akhyani, Nahid Donati, Donatella Sengamalay, Naomi Fotheringham, Julie Ghedin, Elodie Bishop, Michael Barrett, John Kashanchi, Fatah Jacobson, Steven TI Detection of HHV-6B in post-mortem central nervous system tissue of a post-bone marrow transplant recipient: a multi-virus array analysis SO JOURNAL OF CLINICAL VIROLOGY LA English DT Article; Proceedings Paper CT 5th International Conference on Human Herpesvirus 6 and 7 (HHV-6&7) CY MAY 01-03, 2006 CL Barcelona, SPAIN SP HHV-6 Fdn DE HHV-6; multi-virus array; central nervous system; post-bone marrow transplant ID HUMAN HERPESVIRUS-6; HUMAN ASTROCYTES; VIRAL-DNA; HUMAN-HERPESVIRUS-6; SCLEROSIS; TROPISM; PLASMA; BLOOD; CELL AB Background: HHV-6 has been implicated in a number of neurological disorders. Recent evidence has suggested high incidence of HHV-6 infection in patients (46%) undergoing allogeneic bone marrow transplant (BMT). Objective: To investigate whether HHV-6 plays a role in the development of fatal encephalopathy in an allogeneic post-BMT patient using an unbiased approach. Results: Detection of HHV-6 viral DNA sequence and RNA expression were demonstrated in fresh frozen post-mortem autopsy material derived from the insular cortex using a multi-virus array platform. In addition, PCR analysis by real-time quantitative TaqMan demonstrated high viral burden in multiple brain regions tested. Sequencing analysis of PCR product confirmed the virus to be HHV-6 variant B. Conclusions: Active infection as demonstrated by expression of viral RNA and high viral load in the CNS suggest a possible pathogenic role of HHV-6 in development neurologic complications post-BMT. (c) 2006 Elsevier B.V. All rights reserved. C1 NINDS, Viral Immunol Sect, NIH, Bethesda, MD 20892 USA. Inst Gen Res, Rockville, MD 20850 USA. NCI, NIH, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. George Washington Univ, Sch Med, Washington, DC 20037 USA. Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. RP Jacobson, S (reprint author), NINDS, Viral Immunol Sect, NIH, Bethesda, MD 20892 USA. EM jacobsons@ninds.nih.gov NR 20 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1386-6532 J9 J CLIN VIROL JI J. Clin. Virol. PD DEC PY 2006 VL 37 SU 1 BP S57 EP S62 DI 10.1016/S1386-6532(06)70013-0 PG 6 WC Virology SC Virology GA 131CG UT WOS:000243845000013 PM 17276371 ER PT J AU Zahn, R Garrard, P Talazko, J Gondan, M Bubrowski, P Juengling, F Slawik, H Dykierek, P Koester, B Hull, M AF Zahn, Roland Garrard, Peter Talazko, Jochen Gondan, Matthias Bubrowski, Philine Juengling, Freimut Slawik, Helen Dykierek, Petra Koester, Bernd Hull, Michael TI Patterns of regional brain hypometabolism associated with knowledge of semantic features and categories in Alzheimer's disease SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; CONCEPTUAL KNOWLEDGE; NAMING IMPAIRMENT; MEMORY IMPAIRMENT; PREMOTOR CORTEX; DEMENTIA; DEFICITS; SYSTEMS; PET; DISORDERS AB The study of semantic memory in patients with Alzheimer's disease (AD) has raised important questions about the representation of conceptual knowledge in the human brain. It is still unknown whether semantic memory impairments are caused by localized damage to specialized regions or by diffuse damage to distributed representations within nonspecialized brain areas. To our knowledge, there have been no direct correlations of neuroimaging of in vivo brain function in AD with performance on tasks differentially addressing visual and functional knowledge of living and nonliving concepts. We used a semantic verification task and resting 18-fluorodeoxyglucose positron emission tomography in a group of mild to moderate AD patients to investigate this issue. The four task conditions required semantic knowledge of (1) visual, (2) functional properties of living objects, and (3) visual or (4) functional properties of nonliving objects. Visual property verification of living objects was significantly correlated with left posterior fusiform gyrus metabolism (Brodmann's area [BA] 37/19). Effects of visual and functional property verification for nonliving objects largely overlapped in the left anterior temporal (BA 38/20) and bilateral premotor areas (BA 6), with the visual condition extending more into left lateral precentral areas. There were no associations with functional property verification for living concepts. Our results provide strong support for anatomically separable representations of living and nonliving concepts, as well as visual feature knowledge of living objects, and against distributed accounts of semantic memory that view visual and functional features of living and nonliving objects as distributed across a common set of brain areas. C1 Natl Inst Neurol Disorders & Stroke, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. Univ Freiburg, D-7800 Freiburg, Germany. UCL, London WC1E 6BT, England. Royal Free Hosp, London, England. Univ Regensburg, D-8400 Regensburg, Germany. Hosp & Univ Bern, Bern, Switzerland. RP Zahn, R (reprint author), Natl Inst Neurol Disorders & Stroke, Cognit Neurosci Sect, NIH, 5C205,Bldg 10,MSC 1440,10 Ctr Dr, Bethesda, MD 20892 USA. EM zahnr@ninds.nih.gov RI Zahn, Roland/C-4665-2008; Hull, Michael/F-2618-2012; Juengling, Freimut/L-8071-2016 OI Zahn, Roland/0000-0002-8447-1453; Juengling, Freimut/0000-0002-2538-3074 NR 57 TC 15 Z9 15 U1 1 U2 3 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD DEC PY 2006 VL 18 IS 12 BP 2138 EP 2151 DI 10.1162/jocn.2006.18.12.2138 PG 14 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 114FC UT WOS:000242651100013 PM 17129196 ER PT J AU Kim, NK Xie, J AF Kim, Nak-Kyeong Xie, Jun TI Protein multiple alignment incorporating primary and secondary structure information SO JOURNAL OF COMPUTATIONAL BIOLOGY LA English DT Article DE Gibbs sampling; likelihood function; protein sequence motifs; secondary structures; segment overlap ID SEQUENCE ALIGNMENT; BAYESIAN MODELS; EM ALGORITHM; PREDICTION; PROGRAMS; DATABASE; IDENTIFICATION; ACCURACY; MATRICES; MOTIFS AB Identifying common local segments, also called motifs, in multiple protein sequences plays an important role for establishing homology between proteins. Homology is easy to establish when sequences are similar (sharing an identity > 25%). However, for distant proteins, it is much more difficult to align motifs that are not similar in sequences but still share common structures or functions. This paper is a first attempt to align multiple protein sequences using both primary and secondary structure information. A new sequence model is proposed so that the model assigns high probabilities not only to motifs that contain conserved amino acids but also to motifs that present common secondary structures. The proposed method is tested in a structural alignment database BAliBASE. We show that information brought by the predicted secondary structures greatly improves motif identification. A website of this program is available at www.stat.purdue.edu/similar to junxie/2ndmodel/sov.html. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Purdue Univ, Dept Stat, W Lafayette, IN 47907 USA. RP Xie, J (reprint author), 150 N Univ St, W Lafayette, IN 47907 USA. EM junxie@stat.purdue.edu NR 27 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1066-5277 J9 J COMPUT BIOL JI J. Comput. Biol. PD DEC PY 2006 VL 13 IS 10 BP 1735 EP 1748 DI 10.1089/cmb.2006.13.1735 PG 14 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 131CV UT WOS:000243846600006 PM 17238842 ER PT J AU Tabak, J O'Donovan, MJ Rinzel, J AF Tabak, Joel O'Donovan, Michael J. Rinzel, John TI Differential control of active and silent phases in relaxation models of neuronal rhythms SO JOURNAL OF COMPUTATIONAL NEUROSCIENCE LA English DT Article DE excitatory network; synaptic depression; cellular adaptation; episodic activity; mean field model ID DEVELOPING SPINAL-CORD; NETWORK ACTIVITY; RETINAL WAVES; GENERATION; INHIBITION; MECHANISMS; EXPRESSION; FREQUENCY; BURSTS; ADAPTATION AB Rhythmic bursting activity, found in many biological systems, serves a variety of important functions. Such activity is composed of episodes, or bursts (the active phase, AP) that are separated by quiescent periods (the silent phase, SP). Here, we use mean field, firing rate models of excitatory neural network activity to study how AP and SP durations depend on two critical network parameters that control network connectivity and cellular excitability. In these models, the AP and SP correspond to the network's underlying bistability on a fast time scale due to rapid recurrent excitatory connectivity. Activity switches between the AP and SP because of two types of slow negative feedback: synaptic depression-which has a divisive effect on the network input/output function, or cellular adaptation-a subtractive effect on the input/output function. We show that if a model incorporates the divisive process (regardless of the presence of the subtractive process), then increasing cellular excitability will speed up the activity, mostly by decreasing the silent phase. Reciprocally, if the subtractive process is present, increasing the excitatory connectivity will slow down the activity, mostly by lengthening the active phase. We also show that the model incorporating both slow processes is less sensitive to parameter variations than the models with only one process. Finally, we note that these network models are formally analogous to a type of cellular pacemaker and thus similar results apply to these cellular pacemakers. C1 Florida State Univ, Dept Biol Sci, Tallahassee, FL 32306 USA. NYU, Courant Inst Math Sci, New York, NY 10003 USA. NYU, Ctr Neural Sci, New York, NY 10003 USA. NINDS, Lab Neural Control, NIH, Bethesda, MD 20892 USA. RP Tabak, J (reprint author), Florida State Univ, Dept Biol Sci, B-157, Tallahassee, FL 32306 USA. EM joel@neuro.fsu.edu RI tabak, joel/K-1549-2013; o'donovan, michael/A-2357-2015; OI o'donovan, michael/0000-0003-2487-7547; Tabak, Joel/0000-0002-0588-957X NR 41 TC 21 Z9 21 U1 1 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5313 EI 1573-6873 J9 J COMPUT NEUROSCI JI J. Comput. Neurosci. PD DEC PY 2006 VL 21 IS 3 BP 307 EP 328 DI 10.1007/s10827-006-8862-7 PG 22 WC Mathematical & Computational Biology; Neurosciences SC Mathematical & Computational Biology; Neurosciences & Neurology GA 093KB UT WOS:000241166100006 PM 16896520 ER PT J AU Kerner, JF AF Kerner, JF TI Knowledge translation versus knowledge integration: A "funder's" perspective SO JOURNAL OF CONTINUING EDUCATION IN THE HEALTH PROFESSIONS LA English DT Article DE knowledge translation; knowledge integration; funding-agency perspective; continuing education; evidence; dissemination; diffusion ID CANCER CONTROL; DISSEMINATION; DIFFUSION; GAP AB Each year, billions of US tax dollars are spent on basic discovery intervention development, and efficacy research, while hundreds of billions of US tax dollars are also spent on health service delivery programs. However, little is spent on or known about how best to ensure that the lessons learned from science inform and improve the quality of health services and the availability of evidence-based approaches. To close this discovery-delivery gap, researchers and their funding agencies not only must recognize the gap between basic discovery and intervention development, addressed in part through translational research investments, but they must also work together with practitioners and their funding agencies to recognize the growing gap between innovative interventions developed through research and what is actually delivered to reduce the burden of chronic disease within the United States. From a funding-agency perspective, the complexity of the challenges of translating lessons learned from science to public health, primary care, or disease specialty service settings requires a multifaceted partnership approach to accelerate the translation of research into practice. This essay reviews the background and challenges of closing the development-to-delivery gap and some exemplar strategies that have been used by funding agencies to address these challenges to date. C1 NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Kerner, JF (reprint author), NCI, Div Canc Control & Populat Sci, 6130 Execut Blvd,EPN 6144, Bethesda, MD 20892 USA. OI Kerner, Jon/0000-0002-8792-3830 NR 28 TC 53 Z9 55 U1 0 U2 7 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 WIN PY 2006 VL 26 IS 1 BP 72 EP 80 DI 10.1002/chp.53 PG 9 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 033NL UT WOS:000236855300009 PM 16557513 ER PT J AU Lindsay, JR Shanmugam, VK Oldfield, EH Remaley, AT Nieman, LK AF Lindsay, J. R. Shanmugam, V. K. Oldfield, E. H. Remaley, A. T. Nieman, L. K. TI A comparison of immunometric and radioimmunoassay measurement of ACTH for the differential diagnosis of Cushing's syndrome SO JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION LA English DT Article DE Cushing's syndrome; ACTH; radioimmunoassay; immunometric ID CORTICOTROPIN-RELEASING HORMONE; IMMUNORADIOMETRIC ASSAY; WHITE WOMEN; PLASMA; ANTIBODIES AB Objective: Measurement of plasma ACTH levels by radioimmunoassay (RIA) is used to identify adrenal causes (AA) of Cushing's syndrome (CS) and to distinguish ectopic CS (EAS) from Cushing's disease (CD) using CRH stimulation testing and inferior petrosal sinus sampling (IPSS). We wished to determine whether diagnostic criteria developed with RIA would also be applicable for immunoradiometric (IRMA) or immunochemiluminescent (ICMA) assays. Subjects and methods: ACTH was measured by RIA, immunoradiometric and/or immunochemiluminescent assay on samples obtained during three types of diagnostic testing in a tertiary referral setting: a) basally (63 CD, 5 AA, 2 EAS and 37 non-CS patients); b) in 44 CD patients following CRH; c) in 6 ectopic CS and 17 CD patients during IPSS. The primary outcome was comparison of diagnostic utility. Results: a) IRMA results, while lower, correlated highly with RIA (r=0.9, p < 0.0001) and had similar sensitivity (100 vs 80%) and specificity (89 vs 94%) for the diagnosis of AA (p=0.3); b) the sensitivity for CID of CRH testing using IRMA was similar to that of RIA (85 vs 83%, p=11.0); c) during IPSS, IRMA had similar sensitivity (100%) and specificity (100 vs 83%) compared with ICMA or RIA (p=1.0). Conclusions: ACTH immunometric assays correlate closely to RIA and offer similar diagnostic utility. C1 NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. NINDS, Surg Neurol Branch, Bethesda, MD 20892 USA. Warren Grant Magnuson Clin Ctr, Clin Chem Serv, Dept Lab Med, Bethesda, MD 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 24 TC 11 Z9 11 U1 0 U2 4 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 0391-4097 J9 J ENDOCRINOL INVEST JI J. Endocrinol. Invest. PD DEC PY 2006 VL 29 IS 11 BP 983 EP 988 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 137XO UT WOS:000244326500008 PM 17259795 ER PT J AU Chatterton, RT Zujewski, J Mateo, ET Eng-Wong, J Jordan, VC AF Chatterton, Robert T., Jr. Zujewski, JoAnne Mateo, Esnar T. Eng-Wong, Jennifer Jordan, V. Craig TI Effect of raloxifene on salivary sex steroid concentrations in premenopausal women SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID ESTROGEN-RECEPTOR MODULATION; DEVELOPING BREAST-CANCER; BONE-MINERAL DENSITY; LONG-TERM TAMOXIFEN; POSTMENOPAUSAL WOMEN; ADJUVANT CHEMOTHERAPY; ANTI-ESTROGENS; HIGH-RISK; PROGESTERONE; ENDOCRINE AB Raloxifene is a selective oestrogen receptor modulator used clinically for the treatment and the prevention of osteoporosis in postmenopausal women. The drug has been evaluated in the Study of Tamoxifen and Raloxifene as an agent to reduce breast cancer incidence in postmenopausal women at high risk. However, about 30% of women who develop breast cancer do so in their premenopausal years. In this pilot study, salivary oestradiol and progesterone were determined throughout the menstrual cycle for a total of 22 subjects, 14 of whom completed pre- and postraloxifene (60 mg daily) salivary collections. The mean concentration of oestradiol during the menstrual cycle when subjects were taking raloxifene was significantly greater (P < 0.001) than during baseline cycles. Neither salivary progesterone and cortisol nor menstrual cycle length were affected by raloxifene treatment. These data demonstrate that raloxifene administered to premenopausal women increases the concentration of oestradiol that diffuses into the salivary glands, and which presumably represents the concentration available to other organs as well. The results reflect increases in serum oestradiol reported earlier. C1 Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. NCI, Canc Res Ctr, Bethesda, MD 20892 USA. Northwestern Univ, Feinberg Sch Med, Dept Obstet & Gynecol, Chicago, IL 60611 USA. Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Fox Chase Canc Ctr, Chicago, IL 60611 USA. RP Jordan, VC (reprint author), Fox Chase Canc Ctr, 333 Cottman Ave, Philadelphia, PA 19111 USA. EM V.Craig.Jordan@fccc.edu RI Jordan, V. Craig/H-4491-2011 FU NCI NIH HHS [5 P50 CA89018, R21 CA87319] NR 42 TC 4 Z9 4 U1 0 U2 1 PU SOC ENDOCRINOLOGY PI BRISTOL PA 22 APEX COURT, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD DEC PY 2006 VL 191 IS 3 BP 599 EP 604 DI 10.1677/joe.1.06791 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 127BW UT WOS:000243561300008 PM 17170217 ER PT J AU Spotts, EL Prescott, C Kendler, K AF Spotts, Erica L. Prescott, Carol Kendler, Kenneth TI Examining the origins of gender differences in marital quality: A behavior genetic analysis SO JOURNAL OF FAMILY PSYCHOLOGY LA English DT Article DE marital quality; gender differences; genetics; nonshared environment ID EQUAL-ENVIRONMENT ASSUMPTION; POPULATION-BASED TWIN; MAJOR DEPRESSION; SOCIAL SUPPORT; INTERPERSONAL RELATIONSHIPS; PSYCHIATRIC-ILLNESS; MARRIAGE; SATISFACTION; WOMEN; HEALTH AB Numerous researchers have examined gender differences in marital quality, with mixed results. In this study, the authors further this investigation by looking for genetic and environmental sources of variation in marital quality. The 1st aim of the study was to replicate previous findings of genetic and nonshared environmental influences on marital quality. The 2nd was to explore the etiology of gender differences in marital quality. The Virginia Adult Twin Study of Psychiatric and Substance Use Disorders sample of twin men and twin women was used. Genetic and nonshared environmental factors were again found to influence marital quality. Findings also suggest small differences between men and women in the levels of genetic and environmental influence on variance in marital quality. The men's reports of marital warmth and conflict were influenced by the same genetic factors, but women's reports of marital warmth and conflict were influenced by different genetic factors. Results are discussed in the context of previous research on social support and implications for future studies of the etiology of marital quality. C1 George Washington Univ, Ctr Family Res, Washington, DC 20052 USA. Univ So Calif, Dept Psychol, Los Angeles, CA 90089 USA. Virginia Commonwealth Univ, Dept Psychiat, Med Coll Virginia, Richmond, VA 23284 USA. Virginia Commonwealth Univ, Dept Human Genet, Med Coll Virginia, Richmond, VA 23284 USA. RP Spotts, EL (reprint author), NIA, Behav & Social Res Program, NIH, 7201 Wisconsin Ave, Bethesda, MD 20892 USA. EM spottse@mail.nih.gov NR 40 TC 15 Z9 15 U1 1 U2 5 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0893-3200 J9 J FAM PSYCHOL JI J. Fam. Psychol. PD DEC PY 2006 VL 20 IS 4 BP 605 EP 613 DI 10.1037/0893-3200.20.4.605 PG 9 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA 116DD UT WOS:000242781800009 PM 17176195 ER PT J AU Otsu, M Nakajima, S Kida, M Maeyama, Y Toita, N Hatano, N Kawamura, N Kobayashi, R Tatsuzawa, O Onodera, M Kobayashi, E Sagawa, H Kato, I Candotti, F Bali, P Hershfield, MS Sakiyama, Y Ariga, T AF Otsu, Makoto Nakajima, Satoru Kida, Miyuki Maeyama, Yoshihiro Toita, Nariaki Hatano, Norikazu Kawamura, Nobuaki Kobayashi, Ryouji Tatsuzawa, Osamu Onodera, Masafumi Kobayashi, Eiji Sagawa, Hiroaki Kato, Ikunoshin Candotti, Fabio Bali, Pawan Hershfield, Michael S. Sakiyama, Yukio Ariga, Tadashi TI Steady ongoing hematological and immunological reconstitution achieved in ADA-deficiency patients treated by stem cell gene therapy with no myelopreparative conditioning SO JOURNAL OF GENE MEDICINE LA English DT Meeting Abstract CT 12th Annual Meeting of the Japan-Society-of-Gene-Therapy CY AUG 24-26, 2006 CL Nippon Med Sch, Tokyo, JAPAN SP Japan Soc Gene Therapy HO Nippon Med Sch C1 Hokkaido Univ, Grad Sch Med, Dpt Pediat, Sapporo, Hokkaido 060, Japan. Univ Tokyo, Inst Med Sci, Ctr Med Expt, Tokyo, Japan. Univ Tsukuba, Grad Sch Comprehens Human Sci, Tsukuba, Ibaraki 305, Japan. Duke Univ, Med Ctr, Genet & Mol Biol Branch, NIH, Durham, NC 27706 USA. RI Ariga, Tadashi/A-4252-2012 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 1099-498X J9 J GENE MED JI J. Gene. Med. PD DEC PY 2006 VL 8 IS 12 BP 1442 EP 1442 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 118ZF UT WOS:000242981300024 ER PT J AU Maibach, EW Weber, D Massett, H Hancock, GR Price, S AF Maibach, Edward W. Weber, Deanne Massett, Holly Hancock, Gregory R. Price, Simani TI Understanding consumers' health information preferences: Development and validation of a brief screening instrument SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID PATIENT COMMUNICATION; SEEKING BEHAVIOR; CARE; SATISFACTION; INTERNET; POPULATION; DECISIONS; ATTITUDES; QUALITY; LIFE AB The impact of health communication is generally enhanced when it is targeted or tailored to the needs of a specific population or individual. In a segmentation analysis of the U.S adult population - using data from 2,636 respondents to a mail panel survey - we identified four segments of the adult population that vary significantly with regard to health information preferences based on their degree of engagement in health enhancement, and their degree of independence in health decision making. We also created a brief (10 item), easy-to-administer screening instrument that indicates into which segment people fall. The purpose of this article is to describe the segments, and the screening instrument, and to present initial tests of its validity. We believe this instrument offers a practical tool for differentiating motivationally coherent subgroups of the adult population with regard to their health information preferences, and therefore may have practical value in improving health communication and health services provision efforts. Additional research is needed to further validate the tool and test its utility in guiding the creation of targeted health messages and programs. C1 George Washington Univ, Publ Hlth Commun & Mkt Program, Dept Prevent & Community Hlth, Sch Publ Hlth & Hlth Serv, Washington, DC 20037 USA. Porter Novelli, Washington, DC USA. Natl Canc Inst, Rockville, MD USA. Univ Maryland, College Pk, MD 20742 USA. WESTAT Corp, Rockville, MD 20850 USA. RP Maibach, EW (reprint author), George Washington Univ, Publ Hlth Commun & Mkt Program, Dept Prevent & Community Hlth, Sch Publ Hlth & Hlth Serv, 2175 K St,Suite 700, Washington, DC 20037 USA. EM emaibach@gwu.edu OI Maibach, Edward/0000-0003-3409-9187 NR 48 TC 31 Z9 31 U1 1 U2 7 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PD DEC PY 2006 VL 11 IS 8 BP 717 EP 736 DI 10.1080/10810730600934633 PG 20 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 120KD UT WOS:000243082700002 PM 17190779 ER PT J AU Wu, YF Chalmers, J Li, LM Yao, CH Huxley, R Li, X Gao, RL Kong, LZ Yang, XG AF Wu, Yangfeng Chalmers, John Li, Liming Yao, Chonghua Huxley, Rachel Li, Xian Gao, Runlin Kong, Lingzhi Yang, Xiaoguang TI Hypertension in China: Data from the 4th national hypertension survey in China SO JOURNAL OF HYPERTENSION LA English DT Meeting Abstract CT 21sth Scientific Meeting of the International-Society-of-Hypertension/5th Asian-Pacific Congress of Hypertension/29th Annual Scientific Meeting of the Japanese-Society-of-Hypertension CY OCT 15-19, 2006 CL Fukuoka, JAPAN SP Int Soc Hypertens, Japanese Soc Hypertens C1 George Inst Int Hlth, Sydney, NSW, Australia. Chinese Acad Med Sci, Peking Union Med Coll, Beijing 100037, Peoples R China. Beijing Anzhen Hosp, Beijing, Peoples R China. NHLBI, Beijing, Peoples R China. Chinese Ctr Dis Control & Prevent, Natl Inst Nutr & Food Safety, Beijing, Peoples R China. EM yangfengwu@263.net RI Huxley, Rachel/J-4638-2013; Huxley, Rachel/C-7032-2013 OI Huxley, Rachel/0000-0002-2705-6616; Huxley, Rachel/0000-0002-2705-6616 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD DEC PY 2006 VL 24 SU 6 BP 41 EP 41 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 116AD UT WOS:000242774000107 ER PT J AU Barzilay, J Davis, B Cutler, J Alderman, MH Pressel, S Whelton, P Basil, J Margolis, K Ong, S Sadler, L Summerson, J AF Barzilay, J. Davis, Barry Cutler, Jeffrey Alderman, Michael H. Pressel, Sara Whelton, Paul Basil, J. Margolis, K. Ong, S. Sadler, L. Summerson, J. TI Fasting glucose levels and incident diabetes mellitus in older non-diabetic adults randomdized to three different classes of antihypertensive treatment SO JOURNAL OF HYPERTENSION LA English DT Meeting Abstract CT 21sth Scientific Meeting of the International-Society-of-Hypertension/5th Asian-Pacific Congress of Hypertension/29th Annual Scientific Meeting of the Japanese-Society-of-Hypertension CY OCT 15-19, 2006 CL Fukuoka, JAPAN SP Int Soc Hypertens, Japanese Soc Hypertens C1 Emory Univ, Sch Med, Atlanta, GA 30322 USA. Univ Texas, Sch Publ Hlth, Austin, TX 78712 USA. NHLBI, Bethesda, MD USA. Albert Einstein Coll Med, Bronx, NY USA. Tulane Univ, New Orleans, LA 70118 USA. Med Univ S Carolina, Charleston, SC USA. St Vincent Hosp, NW Lipid Res Ctr, Worcester, MA 01604 USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. EM alderman@aecom.yu.edu 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 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD DEC PY 2006 VL 24 SU 6 BP 52 EP 52 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 116AD UT WOS:000242774000149 ER PT J AU Adachi, M Nicol, CJ Gonzalez, FJ Takayanagi, R AF Adachi, Masahiro Nicol, Christopher J. Gonzalez, Frank J. Takayanagi, Ryoichi TI The influence of PPARgamma in endothelial cells against high fat diet-induced hypertension SO JOURNAL OF HYPERTENSION LA English DT Meeting Abstract CT 21sth Scientific Meeting of the International-Society-of-Hypertension/5th Asian-Pacific Congress of Hypertension/29th Annual Scientific Meeting of the Japanese-Society-of-Hypertension CY OCT 15-19, 2006 CL Fukuoka, JAPAN SP Int Soc Hypertens, Japanese Soc Hypertens C1 Kyushu Univ, Grad Sch Med Sci, Dept Geriatr Med, Fukuoka 812, Japan. Natl Inst Hlth, Natl Canc Inst, Bethesda, MD USA. Kyushu Univ, Grad Sch Med Sci, Dept Med & Bioregulat Sci, Fukuoka 812, Japan. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD DEC PY 2006 VL 24 SU 6 BP 92 EP 92 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 116AD UT WOS:000242774000302 ER PT J AU Cook, NR Cutler, JA Obarzanek, E Buring, JE Rexrode, KM Kumanyika, SK Appel, L Whelton, PK AF Cook, Nancy R. Cutler, Jeffrey A. Obarzanek, Eva Buring, Julie E. Rexrode, Kathryn M. Kumanyika, Shiriki K. Appel, Lawrence Whelton, Paul K. TI The effects of dietary sodium reduction on cardiovascular disease: Long-term follow-up of the trials of hypertension prevention SO JOURNAL OF HYPERTENSION LA English DT Meeting Abstract CT 21sth Scientific Meeting of the International-Society-of-Hypertension/5th Asian-Pacific Congress of Hypertension/29th Annual Scientific Meeting of the Japanese-Society-of-Hypertension CY OCT 15-19, 2006 CL Fukuoka, JAPAN SP Int Soc Hypertens, Japanese Soc Hypertens C1 Brigham & Womens Hosp, Boston, MA 02115 USA. NHLBI, Bethesda, MD 20892 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Johns Hopkins Univ, Baltimore, MD USA. Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70118 USA. EM ncook@rics.bwh.harvard.edu 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 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD DEC PY 2006 VL 24 SU 6 BP 141 EP 142 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 116AD UT WOS:000242774001004 ER PT J AU Appel, LJ Sacks, FM Carey, VJ Conlin, PR Erlinger, TP Miller, ER AF Appel, Lawrence J. Sacks, Frank M. Carey, Vincent J. Conlin, Paul R. Erlinger, Thomas P. Miller, Edgar R., III TI The effects of macronutrient intake on blood pressure: Subgroup analyses from the OmniHeart randomized feeding study SO JOURNAL OF HYPERTENSION LA English DT Meeting Abstract CT 21sth Scientific Meeting of the International-Society-of-Hypertension/5th Asian-Pacific Congress of Hypertension/29th Annual Scientific Meeting of the Japanese-Society-of-Hypertension CY OCT 15-19, 2006 CL Fukuoka, JAPAN SP Int Soc Hypertens, Japanese Soc Hypertens C1 Johns Hopkins Med Inst, Baltimore, MD 21205 USA. Harvard Sch Publ Hlth, Boston, MA USA. Channing Labs, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Texas, Med Branch, Austin, TX 78712 USA. NIA, Baltimore, MD 21224 USA. EM lappel@jhmi.edu 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 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD DEC PY 2006 VL 24 SU 6 BP 177 EP 177 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 116AD UT WOS:000242774001147 ER PT J AU Elsenhofer, G AF Elsenhofer, Graeme TI Pheochromocytoma: recent advances and speed bumps in the road to further progress SO JOURNAL OF HYPERTENSION LA English DT Editorial Material ID PARAGANGLIOMA; MUTATIONS; DIAGNOSIS C1 NINDS, NIH, Bethesda, MD 20892 USA. RP Elsenhofer, G (reprint author), NINDS, NIH, Bldg 10,Room 6N252, Bethesda, MD 20892 USA. EM eisenhoferg@ninds.nih.gov NR 8 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0263-6352 EI 1473-5598 J9 J HYPERTENS JI J. Hypertens. PD DEC PY 2006 VL 24 IS 12 BP 2341 EP 2343 PG 3 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 111WS UT WOS:000242487200002 ER PT J AU Sugaya, M Fang, L Cardones, AR Kakinuma, T Jaber, SH Blauvelt, A Hwang, ST AF Sugaya, Makoto Fang, Lei Cardones, Adela R. Kakinuma, Takashi Jaber, Samer H. Blauvelt, Andrew Hwang, Sam T. TI Oncostatin M enhances CCL21 expression by microvascular endothelial cells and increases the efficiency of dendritic cell trafficking to lymph nodes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SARCOMA-ASSOCIATED HERPESVIRUS; LEUKEMIA INHIBITORY FACTOR; KAPOSIS-SARCOMA; T-CELLS; LANGERHANS CELLS; GROWTH-FACTOR; CUTTING EDGE; IN-VIVO; CHEMOKINE; RECEPTOR AB CCL21, a lymphatic endothelial cell (LEC)-derived chemokine, and its receptor CCR7 regulate dendritic cell (DC) trafficking to lymph nodes (LN), but it is unclear how CCL21 expression is regulated. Oncostatin M (OSM) is an IL-6-like cytokine synthesized by activated DC and other leukocytes. In vitro, OSM (but not TNF-alpha) stimulated CCL21 mRNA and protein expression by human dermal microvascular EC (DMEC) in an ERK1/2-dependent fashion. Conditioned medium from OSM-treated DMEC stimulated CCL21-dependent chemotaxis of mouse bone marrow-derived DC (BMDC). Cultured BMDC expressed OSM, which was increased with the addition of LPS. Topical application of the contact-sensitizing hapten, trinitrochlorobenzene, resulted in enhanced OSM expression in the skin, whereas cutaneous injection of TNF-a did not. Injection of OSM into the footpad increased CCL21 mRNA expression in the draining LN by similar to 10-fold and in mouse skin by similar to 4-fold without increasing CCR7 mRNA. In vitro, OSM increased the permeability of DMEC and lung microvascular EC monolayers to FITC-dextran beads, and, in vivo, it enhanced accumulation of Evans blue dye in draining LN by similar to 3-fold (p = 0.0291). Of note, OSM increased trafficking of BMDC injected in footpads to draining LN by 2-fold (p = 0.016). In summary, OSM up-regulates CCL21 expression in skin and draining regional LN. We propose that OSM is a regulator of CCL21 expression and endothelial permeability in skin, contributing to efficient migration of DC to regional LN. The Journal of Immunology, 2006, 177: 7665-7672. C1 NCI, Dermatol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Hwang, ST (reprint author), 10 Ctr Dr,Room 12N258, Rockville, MD 20852 USA. EM hwangs@mail.nih.gov FU Intramural NIH HHS NR 45 TC 27 Z9 28 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 2006 VL 177 IS 11 BP 7665 EP 7672 PG 8 WC Immunology SC Immunology GA 108TJ UT WOS:000242261800023 PM 17114436 ER PT J AU Chiu, WK Fann, M Weng, NP AF Chiu, Wai Kan Fann, Monchou Weng, Nan-ping TI Generation and growth of CD28(null)CD8(+) memory T cells mediated by IL-15 and its induced cytokines SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CD28 EXPRESSION; GENE-EXPRESSION; IN-VIVO; HUMAN CD8(+)CD28(+); DOWN-REGULATION; PROLIFERATION; CENTENARIANS; LYMPHOCYTES; ACTIVATION; EXPANSION AB Accumulation of CD28(null)CD8(+) T cells and the defects of these cells in response to antigenic stimulation are the hallmarks of age-associated decline of T cell function. However, the mechanism of these age-associated changes is not fully understood. In this study, we report an analysis of the growth of human CD28(null) and CD28(+)CD8(+) memory T cells in response to homeostatic cytokine IL-15 in vitro. We showed that 1) there was no proliferative defect of CD28(null)CD8(+) memory T cells in response to IL-15 compared with their CD28(+) counterparts; 2) stable loss of CD28 expression occurred in those actively dividing CD28+CD8+ memory T cells responding to IL-15; 3) the loss of CD28 was in part mediated by TNF-alpha that was induced by IL-15; and 4) CCL4 (MIP-1 beta), also induced by IL-15, had a significant inhibitory effect on the growth of CD28(null) cells, which in turn down-regulated their expression of CCL4 receptor CCR5. Together, these findings, demonstrate that CD28(null)CD8(+) memory T cells proliferate normally in response to IL-15 and that IL-15 and its induced cytokines regulate the generation and growth of CD28(null)CD8(+) T cells, suggesting a possible role of IL-15 in the increase in CD28(null)CD8(+) T cells that occurs with aging. C1 NIA, NIH, Immunol Lab, Baltimore, MD 21224 USA. RP Weng, NP (reprint author), NIA, NIH, Immunol Lab, 5600 Nathan Shock Dr,Box 21, Baltimore, MD 21224 USA. EM wengn@mail.nih.gov FU Intramural NIH HHS [Z01 AG000757-10] NR 33 TC 43 Z9 44 U1 1 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 2006 VL 177 IS 11 BP 7802 EP 7810 PG 9 WC Immunology SC Immunology GA 108TJ UT WOS:000242261800038 PM 17114451 ER PT J AU Orr, N Bekker, V Chanock, S AF Orr, Nick Bekker, Vincent Chanock, Stephen TI Genetic association studies: Marking them well SO JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material ID SINGLE-NUCLEOTIDE POLYMORPHISMS; LINKAGE DISEQUILIBRIUM; HUMAN GENOME; HAPLOTYPE BLOCKS; DISEASE; POPULATIONS C1 NCI, Sect Genom Variat, Pediat Oncol Branch, NIH, Gaithersburg, MD 20877 USA. NCI, Sect Genom Variat, Pediat Oncol Branch, Ctr Canc Res,NIH, Gaithersburg, MD 20877 USA. NCI, Div Canc Epidemiol & Genet, NIH, Gaithersburg, MD 20877 USA. RP Chanock, S (reprint author), NCI, Sect Genom Variat, Pediat Oncol Branch, NIH, 8717 Grovement Circle, Gaithersburg, MD 20877 USA. EM chanocks@mail.nih.gov NR 19 TC 4 Z9 4 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 DEC 1 PY 2006 VL 194 IS 11 BP 1475 EP 1477 DI 10.1086/508552 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 102OD UT WOS:000241820800002 PM 17083030 ER PT J AU Watts, DH Mofenson, LM AF Watts, D. Heather Mofenson, Lynne M. TI Cotrimoxazole prophylaxis in HIV-infected pregnant women: Only a first step SO JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material ID TO-CHILD TRANSMISSION; TRIMETHOPRIM-SULFAMETHOXAZOLE PROPHYLAXIS; MOTHER; MORTALITY; EFFICACY; RISK; PREVENTION; NEVIRAPINE; MORBIDITY; SETTINGS C1 NICHD, Pediat Adolescent & Maternal AIDS Branch, CRMC, NIH, Bethesda, MD 20892 USA. RP Watts, DH (reprint author), NICHD, Pediat Adolescent & Maternal AIDS Branch, CRMC, NIH, Rm 4B11,6100 Execut Blvd,MSC 7510, Bethesda, MD 20892 USA. EM hw59i@nih.gov OI Mofenson, Lynne/0000-0002-2818-9808 NR 27 TC 0 Z9 1 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 DEC 1 PY 2006 VL 194 IS 11 BP 1478 EP 1480 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 102OD UT WOS:000241820800003 ER PT J AU Viani, RM Peralta, L Aldrovandi, G Kapogiannis, BG Mitchell, R Spector, SA Lie, YS Weidler, JM Bates, MP Liu, N Wilson, CM AF Viani, Rolando M. Peralta, Ligia Aldrovandi, Grace Kapogiannis, Bill G. Mitchell, Rick Spector, Stephen A. Lie, Yolanda S. Weidler, Jodi M. Bates, Michael P. Liu, Nancy Wilson, Craig M. CA Adolescent Med Trials Network HIV TI Prevalence of primary HIV-1 drug resistance among recently infected adolescents: A multicenter adolescent medicine trials network for HIV/AIDS interventions study SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 13th Conference on Retroviruses and Opportunistic Infections CY FEB 05-09, 2006 CL Denver, CO ID IMMUNODEFICIENCY-VIRUS TYPE-1; INDIVIDUALS; ADULTS AB This study examined the prevalence of primary human immunodeficiency type 1 (HIV-1) drug resistance among recently infected youth in the United States. Of the 55 subjects studied, major mutations conferring HIV drug resistance were present in 10 (18%). Eight (15%) had nonnucleoside reverse-transcriptase inhibitor (NNRTI) mutations, with the majority (6) having the K103N mutation; 2 (4%) had nucleoside reverse-transcriptase inhibitor (NRTI) mutations; and 2 (4%) had protease inhibitor (PI) mutations. Phenotypic drug resistance was present in 12 (22%) subjects: 10 (18%) for NNRTIs, 2 (4%) for NRTIs, and 3 (5.5%) for PIs. The prevalence of primary HIV-1 drug resistance, particularly to NNRTIs, in this group of recently infected youth was high. C1 Univ Calif San Diego, Sch Med, La Jolla, CA 92093 USA. Univ So Calif, Los Angeles, CA USA. Univ Maryland, Baltimore, MD 21201 USA. NICHHD, NIH, Birmingham, AL USA. WESTAT Corp, Birmingham, AL USA. Monogram Biosci Inc, Birmingham, AL USA. Univ Alabama, Birmingham, AL USA. RP Viani, RM (reprint author), Univ Calif San Diego, Sch Med, 9500 Gilman Dr,MC 0672, La Jolla, CA 92093 USA. EM rviani@ucsd.edu RI Viani, Rolando/C-3501-2013 FU NICHD NIH HHS [U01 HD040474, U01 HD040533] NR 15 TC 34 Z9 37 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 DEC 1 PY 2006 VL 194 IS 11 BP 1505 EP 1509 DI 10.1086/508749 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 102OD UT WOS:000241820800006 PM 17083034 ER PT J AU Brown, EE Brown, BJ Yeager, M Welch, R Cranston, B Hanchard, B Hisada, M AF Brown, Elizabeth E. Brown, Brandon J. Yeager, Meredith Welch, Robert Cranston, Beverly Hanchard, Barrie Hisada, Michie TI Haplotypes of IL6 and IL10 and susceptibility to human T lymphotropic virus type I infection among children SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 12th International Conference on Human Retrovirology - HTLV and Related Viruses CY JUN 22-25, 2005 CL Montego Bay, JAMAICA SP Int Retrovirol Assoc, Natl Inst Hlth, Univ W Indies, Natl Inst Allergy & Infect Dis, Natl Canc Inst, Natl Inst Neurol Dis & Stroke, BD Biosci, Bristol-Myers Squibb, Ohio State Univ, Ctr Retrovirus Res, Dept Vet Biosci, Genome Sci Lab Ltd, Horai Chem Co Ltd, Natl Inst Drug Abuse, Sci Supplies & Technol, Jamaica Med Fdn, J Wray & Nephew Ltd, Red Stripe, UCSF AIDS & Canc Specimen Resource ID CELL LEUKEMIA; INTERLEUKIN-6 IL-6; GENE; POLYMORPHISMS; ASSOCIATION; MYELOPATHY AB To characterize a host polygenic profile associated with susceptibility to human T lymphotropic virus type I (HTLV-I) infection, we examined common variants in 11 immunerelated genes among Jamaican children born to HTLV-I seropositive mothers. Compared with HTLV-I seronegatives, haplotypes of IL6 (-660G/-635C/-236G) and IL10 (-6653C/-1116G) were significantly associated with HTLV-I infection in children independent of maternal provirus load and duration of breast-feeding (odds ratio [OR], 4.5 [95% confidence interval {CI}, 1.2-17.6], and OR, 3.5 [95% CI, 1.4-9.0], respectively). Our findings are the first, to our knowledge, to suggest that host variation in both proinflammatory and anti-inflammatory genes could influence susceptibility to HTLV-I infection. C1 NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA. NCI, Sci Applicat Int Corp Frederick Inc, Core Genotyping Facil, Ctr Adv Technol, Gaithersburg, MD USA. Univ Calif Los Angeles, Dept Epidemiol, Los Angeles, CA USA. Univ W Indies, Dept Pathol, Kingston 7, Jamaica. RP Brown, EE (reprint author), NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,EPS 8005 MSC 7248, Rockville, MD 20852 USA. EM brownbe@mail.nih.gov FU Intramural NIH HHS; NCI NIH HHS [N01-CP-21121, N01-CO-12400] NR 15 TC 2 Z9 2 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 DEC 1 PY 2006 VL 194 IS 11 BP 1565 EP 1569 DI 10.1086/508783 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 102OD UT WOS:000241820800013 PM 17083041 ER PT J AU Schmeisser, H Kontsek, P Esposito, D Gillette, W Schreiber, G Zoon, KC AF Schmeisser, Hana Kontsek, Peter Esposito, Dominic Gillette, William Schreiber, Gideon Zoon, Kathryn C. TI Binding characteristics of IFN-alpha subvariants to IFNAR2-EC and influence of the 6-histidine tag SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Article ID LYMPHOBLASTOID INTERFERON-ALPHA; HUMAN-LEUKOCYTE INTERFERON; RECEPTOR-BINDING; ANTIGENIC PROPERTIES; IMMUNODOMINANT STRUCTURES; AFFINITY PRECIPITATION; LACTATE-DEHYDROGENASE; MUTATIONAL ANALYSIS; ESCHERICHIA-COLI; PURIFICATION AB The expression, purification, detection, and assay of recombinant proteins have been made more convenient and rapid by the use of small affinity tags. To facilitate the purification of interferon-alpha 2c ( IFN-alpha 2c) by metal chelate affinity chromatography, N-terminal 6-histidine tag was introduced via genetic manipulation. Two preparations of IFN material were purified; one contained IFN-alpha 2c with the 6-histidine tag, and the other contained IFN-alpha 2c without the 6-histidine tag. The antigenic properties of the human IFN-alpha 2c subvariant with and without the 6-histidine tag, as well as the effects of the N-terminal 6-histidine tag on IFN-alpha 2c interaction with the extracellular domain of human IFN-alpha receptor chain 2 ( IFNAR2-EC) were examined. For the purposes of this study, IFNs were characterized by Western blots with anti-IFN monoclonal antibodies ( mAb) and bioassays. Immunoblot analyses showed differences between IFN-alpha 2c-6-histidine tag and IFN-alpha 2a, b, c in their interaction with IFNAR2-EC. We also observed differences between IFN-alpha 2c-6-histidine tag and IFN-alpha 2a, b, c in bioactivities. This study is the first report that shows that an N-terminal 6-histidine tag on IFN-alpha 2c can affect its interaction with receptor and cause a different bioactivity. C1 NIAID, NIH, Bethesda, MD 20892 USA. Inst Neuroimmunol, SAS, Bratislava, Slovakia. NCI, SAIC, Frederick, MD 21702 USA. Weizmann Inst Sci, IL-76100 Rehovot, Israel. RP Schmeisser, H (reprint author), NIAID, NIH, 50 Ctr Dr, Bethesda, MD 20892 USA. EM hschmeisser@niaid.nih.gov RI Schreiber, Gideon/C-7332-2008 FU Intramural NIH HHS NR 44 TC 14 Z9 14 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD DEC PY 2006 VL 26 IS 12 BP 866 EP 876 DI 10.1089/jir.2006.26.866 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 120HX UT WOS:000243076600003 PM 17238829 ER PT J AU Samarasinghe, R Tailor, P Tamura, T Kaisho, T Akira, S Ozato, K AF Samarasinghe, Ranmal Tailor, Prafullakumar Tamura, Tomohiko Kaisho, Tsuneyasu Akira, Shizuo Ozato, Keiko TI Induction of an anti-inflammatory cytokine, IL-10, in dendritic cells after toll-like receptor signaling SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Article ID GENE-EXPRESSION; IN-VIVO; TH1 RESPONSE; KAPPA-B; INTERLEUKIN-10; STAT3; MACROPHAGES; DIFFERENTIATION; ACTIVATION; SUBSETS AB Interleukin-10 ( IL-10) is an anti-inflammatory cytokine that modulates innate and adaptive immunity. IL-10 transcripts and the protein were induced in murine bone marrow-derived dendritic cells ( BMDCs) after toll-like receptor ( TLR) stimulation. IL-10 induction was TLR ligand selective, in that CpG DNA, imidazoquinolin, peptidoglycan, and zymosan but not lipopolysaccharide ( LPS) and poly I: C led to IL-10 production. IL-10 induction was, however, completely absent in MyD88(-/-) DCs that lacked a TLR adaptor showing that IL-10 induction depends on TLR signaling. Kinetic analysis of IL-10 induction by CpG and imidazoquinolin revealed a prolonged lag phase prior to a measurable rise in transcript levels, which peaked at 12-24 h after stimulation. Stat3, implicated in IL-10 gene transcription, was also induced after TLR stimulation with the kinetics similar to those of IL-10 induction. Further, Stat3 was phosphorylated and bound to the IL-10 promoter in TLR-stimulated DCs. Supporting a link with IL-10 induction, STAT3 induction was absent in MyD88(-/-) DCs. These data suggest a two- step model where the initial TLR signaling induced proinflammatory cytokines, which then activated Stat3, leading to the induction of IL-10. TLR- stimulated IL-10 production may regulate DC maturation steps, thereby influencing the ensuing immune responses. C1 NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. RIKEN, Res Ctr Allergy & Immunol, Lab Host Def, Yokohama, Kanagawa 2300045, Japan. Osaka Univ, Res Inst Microbial Dis, Dept Host Def, Osaka 5650871, Japan. RP Ozato, K (reprint author), NICHHD, Lab Mol Growth Regulat, NIH, Room 2A01,Bldg 6,6 Ctr Dr, Bethesda, MD 20892 USA. EM ozatok@nih.gov RI Akira, Shizuo/C-3134-2009; Kaisho, Tsuneyasu/B-4130-2012 NR 48 TC 52 Z9 59 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD DEC PY 2006 VL 26 IS 12 BP 893 EP 900 DI 10.1089/jir.2006.26.893 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 120HX UT WOS:000243076600006 PM 17238832 ER PT J AU Takahashi, K Hoashi, T Yamaguchi, Y Mutsuga, N Suzuki, I Vieira, WD Hearing, VJ AF Takahashi, Kaoruko Hoashi, Toshihiko Yamaguchi, Yuji Mutsuga, Noriko Suzuki, Itaru Vieira, Wilfred D. Hearing, Vincent J. TI UV increases the nuclear localization of apurinic/apyrimidinic endonuclease/redox effector factor-1 in human skin SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Letter ID ULTRAVIOLET-RADIATION; REDOX REGULATION; EXPRESSION; CELLS; APOPTOSIS; TRANSLOCATION; PROGRESSION; APE1/REF-1; RESISTANCE; CANCER C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. Galderma, Sophia Antipolis, France. RP Takahashi, K (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA. EM hearingv@nih.gov RI Yamaguchi, Yuji/B-9312-2008 FU Intramural NIH HHS NR 23 TC 3 Z9 3 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 DEC PY 2006 VL 126 IS 12 BP 2723 EP 2727 DI 10.1038/sj.jid.5700466 PG 5 WC Dermatology SC Dermatology GA 108JV UT WOS:000242237000024 PM 16810294 ER PT J AU Budhu, A Wang, XW AF Budhu, Anuradha Wang, Xin Wei TI The role of cytokines in hepatocellular carcinoma SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Review DE liver; inflammation; immune; metastasis; hepatitis ID HEPATITIS-C VIRUS; NECROSIS-FACTOR-ALPHA; GROWTH-FACTOR-BETA; METASTATIC LIVER-TUMORS; MIGRATION INHIBITORY FACTOR; CHRONIC ACTIVE HEPATITIS; TRANSGENIC MOUSE MODEL; MAST-CELLS CORRELATE; NATURAL-KILLER-CELLS; CORE PROTEIN LEADS AB Hepatocellular carcinoma (HCC) is a frequent malignancy worldwide with a high rate of metastasis. The hepatitis B and C viruses are considered major etiological factors associated with the development of HCC, particularly as a result of their induction of chronic inflammation. There is increasing evidence that the inflammatory process is inherently associated with many different cancer types, including HCC. Specifically, this review aims to cover evidence for the potential roles of cytokines, an important component of the, immune system, in promoting HCC carcmogenesis and progression. A global summary of cytokine levels, functions, polymorphisms, and therapies with regard to HCC is presented. In particular, the role of proinflammatory Th1 and anti-inflammatory Th2 cytokine imbalances in the microenvironment of HCC patients with metastasis and the possible clinical significance of these findings are addressed. Overall, multiple studies, spanning many decades, have begun to elucidate the important role of cytokines in HCC. C1 NCI, Liver Carcinogenesis Sect, Lab Human Carcinogenesis, Ctr Canc Res, Bethesda, MD 20892 USA. RP Wang, XW (reprint author), NCI, Liver Carcinogenesis Sect, Lab Human Carcinogenesis, Ctr Canc Res, 37 Convent Dr,Bldg 37,Rm 3044A, Bethesda, MD 20892 USA. EM xw3u@nih.gov RI Wang, Xin/B-6162-2009 NR 174 TC 123 Z9 141 U1 1 U2 5 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD DEC PY 2006 VL 80 IS 6 BP 1197 EP 1213 DI 10.1189/jlb.0506297 PG 17 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 111VT UT WOS:000242484100002 PM 16946019 ER PT J AU Rosenberg, HF Allen, LA AF Rosenberg, Helene F. Allen, Dr Lee-Ann TI Francisella tularensis LVS evades killing by human neutrophils via inhibition of the respiratory burst and phagosome escape SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Editorial Material C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Rosenberg, HF (reprint author), NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. EM hrosenberg@niaid.nih.gov NR 3 TC 4 Z9 4 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD DEC PY 2006 VL 80 IS 6 BP 1222 EP 1223 DI 10.1189/jlb.1306287 PG 2 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 111VT UT WOS:000242484100004 ER PT J AU Rosenberg, HF Sanchez-Madrid, DF AF Rosenberg, Helene F. Sanchez-Madrid, Dr Francisco TI Interview with Dr. Francisco Sanchez-Madrid regarding pivotal advance: CD69 targeting differentially affects the course of collagen-induced arthritis SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Editorial Material ID IMMUNE INTERACTIONS; CYTOSKELETON; MOLECULE; LFA-1 C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Rosenberg, HF (reprint author), NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. EM hrosenberg@niaid.nih.gov NR 9 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD DEC PY 2006 VL 80 IS 6 BP 1231 EP 1232 DI 10.1189/jlb.1305749 PG 2 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 111VT UT WOS:000242484100006 ER PT J AU Anzulovich, A Mir, A Brewer, M Ferreyra, G Vinson, C Baler, R AF Anzulovich, Ana Mir, Alain Brewer, Michelle Ferreyra, Gabriela Vinson, Charles Baler, Ruben TI Elovl3: a model gene to dissect homeostatic links between the circadian clock and nutritional status SO JOURNAL OF LIPID RESEARCH LA English DT Article DE fatty acid; elongase; sterol-regulatory element binding protein target genes; restricted feeding; daily rhythm; phase shift ID STEROL REGULATORY ELEMENT; BROWN ADIPOSE-TISSUE; REV-ERB-ALPHA; LEUCINE ZIPPER PROTEIN; ACID SYNTHASE PROMOTER; SUPRACHIASMATIC NUCLEUS; BINDING PROTEINS; GROWTH-HORMONE; SACCHAROMYCES-CEREVISIAE; TRANSCRIPTION FACTOR AB The ELOVL3 protein is a very long-chain fatty acid elongase found in liver, skin, and brown adipose tissues. Circadian expression of the Elovl3 gene in the liver is perturbed in mutant CLOCK mice but persists in mice with severe hepatic dysfunction. A reliance on an intact clock, combined with the refractoriness to liver decompensation and the finding of a robust sexually dimorphic pattern of expression, evince a particularly complex mode of transcriptional control. The Elovl3 gene upstream region was repressed by RevErb alpha and activated by sterol-regulatory element binding protein-1 (SREBP1) transcription factors. We propose that the temporal coordination of RevErba and SREBP1 activities integrates clock and nutrition signals to drive a subset of oscillatory transcripts in the liver. Proteolytic activation of SREBP1 is circadian in the liver, and because the cycle of SREBP1 activation was reversed after restricting meals to the inactive phase of the day, this factor could serve as an acute sensor of nutritional state. SREBP1 regulates many known lipogenic and cholesterogenic circadian genes; hence, our results could explain how feeding can override brain-derived entraining signals in the liver. This mechanism would permit a rapid adjustment in the sequence of key aspects of the absorptive and postabsorptive phases in the liver. C1 NIDA, Sci Policy Branch, NIH, Bethesda, MD 20892 USA. NIMH, Unit Temporal Gene Express, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Baler, R (reprint author), NIDA, Sci Policy Branch, NIH, Bethesda, MD 20892 USA. EM balerr@mail.nih.gov FU Intramural NIH HHS NR 65 TC 20 Z9 21 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD DEC PY 2006 VL 47 IS 12 BP 2690 EP 2700 DI 10.1194/jlr.M600230-JLR200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 106LA UT WOS:000242100800009 PM 17003504 ER PT J AU Zhan, W Yang, YH AF Zhan, Wang Yang, Yihong TI How accurately can the diffusion profiles indicate multiple fiber orientations? A study on general fiber crossings in diffusion MRI SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE diffusion tensor imaging; fiber crossing; high angular resolution diffusion imaging; Q-space imaging; diffusion spectrum imaging ID HUMAN BRAIN; CIRCULAR SPECTRUM; WEIGHTED MRI; TENSOR MRI; SPIN-ECHO; RESOLUTION; NMR; COEFFICIENTS; ANISOTROPY; SYSTEM AB The q-space imaging techniques and high angular resolution diffusion (HARD) imaging have shown promise to identify intravoxel multiple fibers. The measured orientation distribution function (ODF) and apparent diffusion coefficient (ADC) profiles can be used to identify the orientations of the actual intravoxel fibers. The present study aims to examine the accuracy of these profile-based orientation methods by comparing the angular deviations between the estimated local maxima of the profiles and the real fiber orientation for a fiber crossing simulated with various intersection angles under different b values in diffusion-weighted MRI experiments. Both noisy and noise-free environments were investigated. The diffusion spectrum imaging (DSI), q-ball imaging (QBI), and HARD techniques were used to generate ODF and ADC profiles. To provide a better comparison between ODF and ADC techniques, the phase-corrected angular deviations were also presented for the ADC method based on a circular spectrum mapping method. The results indicate that systematic angular deviations exist between the actual fiber orientations and the corresponding local maxima of either the ADC or ODF profiles. All methods are apt to underestimation of acute intersection and overestimation of obtuse intersection angle. For a typical slow-exchange fiber crossing, the ODF methods have a non-deviation zone around the 90 degrees intersection. Before the phase-correction, the deviation of ADC profiles approaches a peak at the 90 degrees intersection, while after the correction the ADC deviations are significantly reduced. When the b factor is larger than 2 1000 S/mm. the ODF methods have smaller angular deviations than the ADC methods for the intersections close to 90 degrees. QBI method demonstrates a slight yet consistent advantage over the DSI method under the same conditions. In the noisy environment, the mean value of the deviation angles shows a high consistency with the corresponding deviation in the nose-free condition. Published by Elsevier Inc. C1 NIDA, Neuroimaging Res Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Yang, YH (reprint author), NIDA, Neuroimaging Res Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. EM yihongyang@intra.nida.nih.gov FU Intramural NIH HHS NR 30 TC 31 Z9 31 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD DEC PY 2006 VL 183 IS 2 BP 193 EP 202 DI 10.1016/j.jmr.2006.08.005 PG 10 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 111CH UT WOS:000242428100004 PM 16963296 ER PT J AU Ozarslan, E Basser, PJ Shepherd, TM Thelwall, PE Vemuri, BC Blackband, SJ AF Ozarslan, Evren Basser, Peter J. Shepherd, Timothy M. Thelwall, Peter E. Vemuri, Baba C. Blackband, Stephen J. TI Observation of anomalous diffusion in excised tissue by characterizing the diffusion-time dependence of the MR signal SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE diffusion time; power-law; disordered media; fractal; scaling; walk dimension; spectral dimension; fracton ID FIELD-GRADIENT SPECTROSCOPY; PERCOLATION MODEL OBJECTS; RESTRICTED DIFFUSION; MAGNETIC-RESONANCE; FRACTAL NETWORKS; WATER DIFFUSION; POROUS-MEDIA; NMR; PROBE; MICROSTRUCTURE AB This report introduces a novel method to characterize the diffusion-time dependence of the diffusion-weighted magnetic resonance (MR) signal in biological tissues. The approach utilizes the theory of diffusion in disordered media where two parameters, the random walk dimension and the spectral dimension, describe the evolution of the average propagators obtained from q-space MR experiments. These parameters were estimated, using several schemes, on diffusion MR spectroscopy data obtained from human red blood cell ghosts and nervous tissue autopsy samples. The experiments demonstrated that water diffusion in human tissue is anomalous, where the mean-square displacements vary slower than linearly with diffusion time. These observations are consistent with a fractal microstructure for human tissues. Differences observed between healthy human nervous tissue and glioblastoma samples suggest that the proposed methodology may provide a novel, clinically useful form of diffusion MR contrast. (c) 2006 Elsevier Inc. All rights reserved. C1 NICHD, LIMB, STBB, NIH, Bethesda, MD 20892 USA. Univ Florida, Dept Neurosci, Gainesville, FL 32610 USA. Univ Newcastle, Newcastle Magnet Resonance Ctr, Newcastle Upon Tyne, Tyne & Wear, England. Univ Florida, Dept Comp & Informat Sci & Engn, Gainesville, FL 32611 USA. Natl High Magnet Field Lab, Tallahassee, FL 32310 USA. RP Ozarslan, E (reprint author), NICHD, LIMB, STBB, NIH, Bethesda, MD 20892 USA. EM evren@helix.nih.gov RI Ozarslan, Evren/B-4858-2013; Basser, Peter/H-5477-2011 OI Ozarslan, Evren/0000-0003-0859-1311; FU Intramural NIH HHS; NCRR NIH HHS [P41-RR16105]; NINDS NIH HHS [R01-NS36992, R01-NS42075] NR 43 TC 51 Z9 51 U1 2 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 EI 1096-0856 J9 J MAGN RESON JI J. Magn. Reson. PD DEC PY 2006 VL 183 IS 2 BP 315 EP 323 DI 10.1016/j.jmr.2006.08.009 PG 9 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 111CH UT WOS:000242428100017 PM 16962801 ER PT J AU Shanawani, H Dame, L Schwartz, DA Cook-Deegan, R AF Shanawani, H. Dame, L. Schwartz, D. A. Cook-Deegan, R. TI Non-reporting and inconsistent reporting of race and ethnicity in articles that claim associations among genotype, outcome, and race or ethnicity SO JOURNAL OF MEDICAL ETHICS LA English DT Article ID SUSCEPTIBILITY GENE; HEALTH DISPARITIES; AFRICAN-AMERICANS; MEDICAL-RESEARCH; POPULATION; POLYMORPHISM; DISEASE; RISK; RACE/ETHNICITY; COMMUNITIES AB Background: The use of race as a category in medical research is the focus of an intense debate, complicated by the inconsistency of presumed independent variables, race and ethnicity, on which analysis depends. Interpretation is made difficult by inconsistent methods for determining the race or ethnicity of a participant. The failure to specify how race or ethnicity was determined is common in the published literature. Hypothesis: Criteria by which they assign a research participant to racial or ethnic categories are not reported by published articles. Methods: Methods were reviewed for assigning race and ethnicity of research participants in 268 published reports reporting associations among race (or ethnicity), health outcome and genotype. Results: Of the 268 published reports reviewed, it was found that 192 (72%) did not explain their methods for assigning race or ethnicity as an independent variable. This was despite the fact that 180 (67%) of those reports reached conclusions about associations among genetics, health outcome and race or ethnicity. Conclusions: More attention needs to be given to the definition of race and ethnicity in genetic studies, especially in those diseases where health disparities are known to exist. C1 Henry Ford Hosp, Dept Biostat & Res Epidemiol, Detroit, MI 48202 USA. Duke Univ, Ctr Genome Eth Law & Policy, Durham, NC 27706 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Shanawani, H (reprint author), Henry Ford Hosp, Dept Biostat & Res Epidemiol, 1 Ford Pl 5C-69, Detroit, MI 48202 USA. EM hshanawani@yahoo.com OI Cook-Deegan, Robert/0000-0002-8251-4237 NR 49 TC 20 Z9 20 U1 0 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0306-6800 J9 J MED ETHICS JI J. Med. Ethics PD DEC 1 PY 2006 VL 32 IS 12 BP 724 EP 728 DI 10.1136/jme.2005.014456 PG 5 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 112GL UT WOS:000242513700011 PM 17145914 ER PT J AU Buchanan, DR Miller, FG AF Buchanan, D. R. Miller, F. G. TI A public health perspective on research ethics SO JOURNAL OF MEDICAL ETHICS LA English DT Article ID CLINICAL-RESEARCH; DEVELOPING-COUNTRIES; TRIALS; BENEFIT; WOMEN; RISK AB Ethical guidelines for conducting clinical trials have historically been based on a perceived therapeutic obligation to treat and benefit the patient-participants. The origins of this ethical framework can be traced to the Hippocratic oath originally written to guide doctors in caring for their patients, where the overriding moral obligation of doctors is strictly to do what is best for the individual patient, irrespective of other social considerations. In contrast, although medicine focuses on the health of the person, public health is concerned with the health of the entire population, and thus, public health ethics is founded on the societal responsibility to protect and promote the health of the population as a whole. From a public health perspective, research ethics should be guided by giving due consideration to the risks and benefits to society in addition to the individual research participants. On the basis of a duty to protect the population as a whole, a fiduciary obligation to realise the social value of the research and the moral responsibility to distribute the benefits and burdens of research fairly across society, how a public health perspective on research ethics results in fundamental re-assessments of the proper course of action for two salient topical issues in research ethics is shown: stopping trials early for reasons of efficacy and the conduct of research on less expensive yet less effective interventions. C1 Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Amherst, MA 01003 USA. NIH, Bethesda, MD 20892 USA. RP Buchanan, DR (reprint author), Univ Massachusetts, Sch Publ Hlth & Hlth Sci, 306 Arnold House, Amherst, MA 01003 USA. EM Buchanan@schoolph.umass.edu NR 31 TC 17 Z9 17 U1 2 U2 5 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0306-6800 J9 J MED ETHICS JI J. Med. Ethics PD DEC 1 PY 2006 VL 32 IS 12 BP 729 EP 733 DI 10.1136/jme.2006.015891 PG 5 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 112GL UT WOS:000242513700012 PM 17145915 ER PT J AU Chretien, JP Coresh, J Berthier-Schaad, Y Kao, WHL Fink, NE Klag, MJ Marcovina, SM Giaculli, F Smith, MW AF Chretien, J-P Coresh, J. Berthier-Schaad, Y. Kao, W. H. L. Fink, N. E. Klag, M. J. Marcovina, S. M. Giaculli, F. Smith, M. W. TI Three single-nucleotide polymorphisms in LPA account for most of the increase in lipoprotein(a) level elevation in African Americans compared with European Americans SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID STAGE RENAL-DISEASE; APOLIPOPROTEIN(A) GENE; SEQUENCE POLYMORPHISMS; LINKAGE-DISEQUILIBRIUM; PLASMA-CONCENTRATIONS; C/T POLYMORPHISM; APO(A) GENE; LP(A); ASSOCIATION; CAUCASIANS AB Background: The extent which universally common or population-specific alleles can explain between-population variations in phenotypes is unknown. The heritable coronary heart disease risk factor lipoprotein(a) (Lp(a)) level provides a useful case study of between-population variation, as the aetiology of twofold higher Lp(a) levels in African populations compared with non-African populations is unknown. Objective: To evaluate the association between LPA sequence variations and Lp(a) in European Americans and African Americans and to determine the extent to which LPA sequence variations can account for between-population variations in Lp(a). Methods: Serum Lp(a) and isoform measurements were examined in 534 European Americans and 249 African Americans from the Choices for Healthy Outcomes in Caring for End-Stage Renal Disease Study. In addition, 12 LPA variants were genotyped, including 8 previously reported LPA variants with a frequency of > 2% in European Americans or African Americans, and four new variants. Results: Isoform-adjusted Lp(a) level was 2.23-fold higher among African Americans. Three single-nucleotide polymorphisms (SNPs) were independently associated with Lp(a) level (p < 0.02 in both populations). The Lp(a)-increasing SNP (G-21A, which increases promoter activity) was more common in African Americans, whereas the Lp(a)-lowering SNPs (T3888P and G+1/inKIV-8A, which inhibit Lp(a) assembly) were more common in European Americans, but all had a frequency of < 20% in one or both populations. Together, they reduced the isoform-adjusted African American Lp(a) increase from 2.23 to 1.37-fold(a 60% reduction) and the between-population Lp(a) variance from 5.5% to 0.5%. Conclusions: Multiple low-prevalence alleles in LPA can account for the large between-population difference in serum Lp(a) levels between European Americans and African Americans. C1 Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Univ Washington, Dept Med, NW Lipid Res Labs, Seattle, WA 98195 USA. NCI, Lab Gen Divers, Frederick, MD 21701 USA. NCI, Basic Res Program, Sci Applicat Int Corp, Frederick, MD 21701 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]; NCI NIH HHS [N01-CO-12400]; NCRR NIH HHS [M01-RR00052]; NHLBI NIH HHS [R01-HL-62985]; NIDDK NIH HHS [K24-DK-02856, R01-DK-07024, K01-DK067207] NR 38 TC 22 Z9 22 U1 1 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD DEC PY 2006 VL 43 IS 12 BP 917 EP 923 DI 10.1136/jmg.2006.042119 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 111VR UT WOS:000242483900004 PM 16840570 ER PT J AU Siljander, T Toropainen, M Muotiala, A Hoe, NP Musser, JM Vuopio-Varkila, J AF Siljander, Tuula Toropainen, Maija Muotiala, Anna Hoe, Nancy P. Musser, James M. Vuopio-Varkila, Jaana TI emm typing of invasive T28 group A streptococci, 1995-2004, Finland SO JOURNAL OF MEDICAL MICROBIOLOGY LA English DT Article; Proceedings Paper CT 15th European Congress of Clinical Microbiology and Infectious Diseases CY APR 02-05, 2005 CL Copenhagen, DENMARK ID M-PROTEIN; OPACITY-FACTOR; NONINVASIVE INFECTIONS; PUERPERAL SEPSIS; PYOGENES; PHARYNGITIS; SEQUENCE; SEROTYPES; DISEASE; EPIDEMIOLOGY AB A total of 985 group A streptococcus (GAS) bacteraemia isolates collected in Finland during 1995-2004 were T-serotyped, and of these, 336 isolates of serotype T28 were subjected to further emm typing. The total number of isolates referred per year showed an increase within the study period, from 43 in 1995 to 130 in 2004. The annual incidence of invasive GAS (iGAS) bacteraemia showed a general increase during the study period, from 1.1 to 2.5 per 100 000 population. Serotype T28 remained among the most common serotypes, in addition to serotypes TB3264 and T1. The serotype T28 isolates were found to be distributed across six distinct emm types: emm28, emm77, emm53 (including subtypes 53.2 and 53.4), emm87, emm2 and emm4. The serotype distribution and the emm type distribution of serotype T28 fluctuated over time. Within the study period, the proportion of T28/emm28 isolates became the most prominent. During periods of low emm28 incidence, emm types 77 and 53 seemed to show a resurgence. emm typing revealed T28 isolates to be a genetically heterogeneous group harbouring a variety of distinct M proteins. This study confirms that T serotyping alone is not a sufficient method for epidemiological surveillance of iGAS. C1 Natl Publ Hlth Inst, Dept Bacterial & Inflammatory Dis, Hosp Bacteria Lab, FIN-00300 Helsinki, Finland. NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. Methodist Hosp, Res Inst, Ctr Mol & Translat Human Infect Dis Res, Houston, TX 77030 USA. RP Siljander, T (reprint author), Natl Publ Hlth Inst, Dept Bacterial & Inflammatory Dis, Hosp Bacteria Lab, Mannerheimintie 166, FIN-00300 Helsinki, Finland. EM tuula.siljander@ktl.fi NR 40 TC 16 Z9 16 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-2615 J9 J MED MICROBIOL JI J. Med. Microbiol. PD DEC PY 2006 VL 55 IS 12 BP 1701 EP 1706 DI 10.1099/jmm.0.46690-0 PG 6 WC Microbiology SC Microbiology GA 114OL UT WOS:000242675400013 PM 17108274 ER PT J AU Ahlqvist, J Donati, D Martinelli, E Akhyani, N Hou, J Major, EO Jacobson, S Fogdell-Hahn, A AF Ahlqvist, Jenny Donati, Donatella Martinelli, Elena Akhyani, Nahid Hou, Jean Major, Eugene O. Jacobson, Steven Fogdell-Hahn, Anna TI Complete replication cycle and acquisition of tegument in nucleus of human herpesvirus 6A in astrocytes and in T-cells SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE viral egress; electron microscopy; tegusome ID CENTRAL-NERVOUS-SYSTEM; MULTIPLE-SCLEROSIS; SIMPLEX VIRUS-1; HUMAN-HERPESVIRUS-6; HHV-6; INFECTION; VARIANT; PATHWAY; TRANSPORT; RECEPTOR AB The ultrastructural replication cycle of human herpesvirus 6A and 6B, both T-lymphotropic viruses, with tropism for the central nervous system, was compared by electron microscopy in the same cells, that is, in the T-lymphoblastoid cell line SupT-1 and in human astrocytes. Both HHV-6A and HHV-6B replicated efficiently in SupT-1 and formed viral particles. The tegument is the least characterized structure of the herpes-viral particle and both variants were able to form intranuclear membrane compartments called tegusomes in SupT-1 where tegumentation occurred. Also, tegumentation occurred in HHV-6A infected cells in the nucleoplasm without the presence of a tegusome. This suggests that there is more than one possible route of tegumentation. Differences in the replication cycles between HHV-6A and HHV-6B were also observed in the cytoplasm. One such difference was that prominent annulate lamellae were only found in the cytoplasm of HHV-6A infected cells. In astrocytes a successful formation of viral particles was only seen with the HHV-6A variant. The HHV-6A virus life cycle in astrocytes resembled the life cycle in the T-cell line SupT-1, except that no annulate lamellae were found. Complete viral particles were found extracellularly around the astrocytes and the supernatant of infected astrocytes were able to re-infect SupT-1 cells. This suggests that HHV-6A infection in astrocytes can generate complete, viable, and infectious viral particles. The HHV-6 variants behave differently in the same type of cells and have different tropisms for astrocytes, supporting the notion that the variants might induce different diseases. C1 Karolinska Univ Hosp Huddinge, Dept Clin Neurosci, Div Neurol, Karolinska Inst, SE-14186 Stockholm, Sweden. Natl Inst Neurol Disorders & Stroke, Neuroimmunol Branch, NIH, Bethesda, MD USA. Natl Inst Neurol Disorders & Stroke, Lab Mol Med & Neurosci, NIH, Bethesda, MD USA. RP Fogdell-Hahn, A (reprint author), Karolinska Univ Hosp Huddinge, Dept Clin Neurosci, Div Neurol, Karolinska Inst, SE-14186 Stockholm, Sweden. EM Anna.Fogdell-Hahn@ki.se FU Intramural NIH HHS NR 54 TC 4 Z9 4 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD DEC PY 2006 VL 78 IS 12 BP 1542 EP 1553 DI 10.1002/jmv.20737 PG 12 WC Virology SC Virology GA 102OP UT WOS:000241822000006 PM 17063514 ER PT J AU Murphy, E Sun, JH Steenbergen, C AF Murphy, Elizabeth Sun, Junhui Steenbergen, Charles TI Signaling pathways in cardioprotection SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Meeting Abstract CT 23rd Annual Meeting of the Japanese Section of the Internal-Society-for-Heart-Research CY DEC 01-02, 2006 CL Chiba, JAPAN SP Internal Soc Heart Res DE preconditioning; nitric oxide; GSK C1 NIH, NIEHS, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD DEC PY 2006 VL 41 IS 6 BP 1042 EP 1042 DI 10.1016/j.yjmcc.2006.08.028 PG 1 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 120MT UT WOS:000243089700024 ER PT J AU Gustchina, E Louis, JM Bewley, CA Clore, GM AF Gustchina, Elena Louis, John M. Bewley, Carole A. Clore, G. Marius TI Synergistic inhibition of HIV-1 envelope-mediated membrane fusion by inhibitors targeting the N and C-terminal heptad repeats of gp41 SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE HIV-1; Env-mediated cell fusion; HIV-1 fusion inhibitors; synergism; gp41 ID TRIMERIC COILED-COIL; CELL-FUSION; ACTIVE CONFORMATION; POTENT INHIBITORS; ATOMIC-STRUCTURE; VIRUS-INFECTION; TYPE-1 GP41; ENTRY; GLYCOPROTEINS; ECTODOMAIN AB The human immunodeficiency virus type-1 (HIV-1) envelope (Env) proteins that mediate membrane fusion represent a major target for the development of new AIDS therapies. Three classes of Env-mediated membrane fusion inhibitors have been described that specifically target the pre-hairpin intermediate conformation of gp41. Class 2 inhibitors bind to the C-terminal heptad repeat (C-HR) of gp41. The single example of a class 3 inhibitor targets the trimeric N-terminal heptad repeat (N-HR) of gp41 and has been postulated to sequestrate the N-HR of the pre-hairpin intermediate through the formation of fusion incompetent heterotrimers. Here, we show that N-CCG-gp41, a class 2 inhibitor, and N36(Mut(e,g)), a class 3 inhibitor, synergistically inhibit Env-mediated membrane fusion for several representative HIV-1 strains (X4 and R5) in both a cell fusion assay (with membrane-bound CD4) and an Env-pseudo-typed virus neutralization assay. The mechanistic, as well as potential therapeutic, implications of these observations for HIV-Env-mediated membrane fusion are discussed. Published by Elsevier Ltd. C1 NIDDK, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Bewley, CA (reprint author), NIDDK, Phys Chem Lab, NIH, Bldg 5, Bethesda, MD 20892 USA. EM caroleb@mail.nih.gov; mariusc@mail.nih.gov RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 FU Intramural NIH HHS; NIDDK NIH HHS [Z01 DK029023-15] NR 34 TC 15 Z9 16 U1 1 U2 3 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 DEC 1 PY 2006 VL 364 IS 3 BP 283 EP 289 DI 10.1016/j.jmb.2006.09.017 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 111FG UT WOS:000242436200006 PM 17010381 ER PT J AU Mirambeau, G Lyonnais, S Coulaud, D Hameau, L Lafosse, S Jeusset, J Justome, A Delain, E Gorelick, RJ Le Cam, E AF Mirambeau, Gilles Lyonnais, Sebastien Coulaud, Dominique Hameau, Laurence Lafosse, Sophie Jeusset, Josette Justome, Anthony Delain, Etienne Gorelick, Robert J. Le Cam, Eric TI Transmission electron microscopy reveals an optimal HIV-1 nucleocapsid aggregation with single-stranded nucleic acids and the mature HIV-1 nucleocapsid protein SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE TEM; HIVNCp; nucleic acids; nucleoprotein complex; microsedimentation ID IMMUNODEFICIENCY-VIRUS TYPE-1; REVERSE TRANSCRIPTION COMPLEXES; PROVIRAL DNA-SYNTHESIS; MURINE LEUKEMIA-VIRUS; INTEGRATION IN-VITRO; ZINC-FINGER; GENOMIC RNA; RECOGNITION ELEMENT; ORDERED AGGREGATION; CHAPERONE ACTIVITY AB HIV-1 nucleocapsid protein (NCp7) condenses the viral RNA within the mature capsid. In a capsid-free system, NCp7 promotes an efficient mechanism of aggregation with both RNA and DNA. Here, we show an analysis of these macromolecular complexes by dark-field imaging using transmission electron microscopy. Thousands of mature NCp7 proteins co-aggregate with hundreds of single-stranded circular DNA molecules (ssDNA) within minutes, as observed with poly(rA). These co-aggregates are highly stable but dynamic structures, as they dissociate under harsh conditions, and after addition of potent ssDNA or NCp7 competitive ligands. The N-terminal domain and zinc fingers of NCp7 are both required for efficient association. Addition of magnesium slightly. increases the avidity of NCp7 for ssDNA, while it strongly inhibits coaggregation with relaxed circular double-stranded DNA (dsDNA). This DNA selectivity is restricted to mature NCp7, compared to its precursors NCp15 and NCp9. Moreover, for NCp15, the linkage of NCp7 with the Gag C-terminal p6-peptide provokes a deficiency in ssDNA aggregation, but results in DNA spreading similar to prototypical SSB proteins. Finally, this co-aggregation is discussed in a dynamic architectural context with regard to the mature HIV-1 nucleocapsid. On the basis of the present data, we propose that condensation of encapsidated RNA requires the C-terminal processing of NCp. Subsequently, disassembly of the nucleocapsid should be favoured once dsDNA is produced by HIV-1 reverse transcriptase. Published by Elsevier Ltd. C1 Inst Gustave Roussy, Lab Microscopie Mol & Cellulaire, CNRS, UMR 8126, F-94805 Villejuif, France. Univ Paris 06, Div Biochim, UFR Sci Vie, F-75005 Paris, France. NCI, AIDS Vaccine Program, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Mirambeau, G (reprint author), Inst Gustave Roussy, Lab Microscopie Mol & Cellulaire, CNRS, UMR 8126, Rue Camille Desmoulins, F-94805 Villejuif, France. EM gilles.mirambeau@free.fr; elecam@igr.fr OI Lyonnais, Sebastien/0000-0002-3154-8568 FU NCI NIH HHS [N01-CO-12400] NR 80 TC 37 Z9 38 U1 0 U2 3 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 DEC 1 PY 2006 VL 364 IS 3 BP 496 EP 511 DI 10.1016/j.jmb.2006.08.065 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 111FG UT WOS:000242436200024 PM 17020765 ER PT J AU Ross, PD Conway, JF Cheng, NQ Dierkes, L Firek, BA Hendrix, RW Steven, AC Duda, RL AF Ross, Philip D. Conway, James F. Cheng, Naiqian Dierkes, Lindsay Firek, Brian A. Hendrix, Roger W. Steven, Alasdair C. Duda, Robert L. TI A free energy cascade with locks drives assembly and maturation of bacteriophage HK97 capsid SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE differential scanning calorimetry; cryo-electron microscopy; virus capsid structure; context-dependent protein folding; conformational changes ID CONFORMATIONAL-CHANGES; VIRUS MATURATION; COMMON ANCESTRY; SURFACE LATTICE; CROSS-LINKING; PROTEIN; DYNAMICS; STABILITY; STATES; HEAD AB We investigated the thermodynamic basis of HK97 assembly by scanning calorimetry and cryo-electron microscopy. This pathway involves self-assembly of hexamers and pentamers of the precursor capsid protein gp5 into procapsids; proteolysis of their N-terminal A-domains; expansion, a major conformational change; and covalent crosslinking. The thermal denaturation parameters convey the changes in stability at successive steps in assembly, and afford estimates of the corresponding changes in free energy. The procapsid represents a kinetically accessible local minimum of free energy. In maturation, it progresses to lower minima in a cascade punctuated by irreversible processes ("locks"), i.e. proteolysis and crosslinking, that lower kinetic barriers and prevent regression. We infer that Delta-domains not only guide assembly but also restrain the procapsid from premature expansion; their removal by proteolysis is conducive to initiating expansion and to its proceeding to completion. We also analyzed the mutant E219K, whose capsomers reassemble in vitro into procapsids with vacant vertices called "whiffleballs". E219K assemblies all have markedly reduced stability compared to wild-type gp5 (Delta T-p similar to -7 degrees C to -10 degrees C) where T-p is the denaturation temperature). As the mutated residue is buried in the core of gp5, we attribute the observed reduction in stability to steric and electrostatic perturbations of the packing of side-chains in the subunit interior. To explain the whiffleball phenotype, we suggest that these effects propagate to the capsomer periphery in such a way as to differentially affect the stability or solubility of dissociated pentamers, leaving only hexamers to reassemble. Published by Elsevier Ltd. C1 NIAMSD, Struct Biol Res Lab, Bethesda, MD 20892 USA. NIDDKD, Mol Biol Lab, Bethesda, MD 20892 USA. Univ Pittsburgh, Sch Med, Dept Biol Struct, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Dept Biol Sci, Pittsburgh, PA 15260 USA. RP Steven, AC (reprint author), NIAMSD, Struct Biol Res Lab, Bethesda, MD 20892 USA. EM Alasdair_Steven@nih.gov RI Conway, James/A-2296-2010 OI Conway, James/0000-0002-6581-4748 FU Intramural NIH HHS; NIGMS NIH HHS [R01 GM047795, R01 GM47795] NR 46 TC 32 Z9 32 U1 0 U2 2 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD DEC 1 PY 2006 VL 364 IS 3 BP 512 EP 525 DI 10.1016/j.jmb.2006.08.048 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 111FG UT WOS:000242436200025 PM 17007875 ER PT J AU Jiang, YH Stojilkovic, SS AF Jiang, Yonghua Stojilkovic, Stanko S. TI Molecular cloning and characterization of alpha 1-soluble guanylyl cyclase gene promoter in rat pituitary cells SO JOURNAL OF MOLECULAR ENDOCRINOLOGY LA English DT Article ID NITRIC-OXIDE SYNTHASE; BETA(1) SUBUNIT GENES; TRANSCRIPTION INITIATION; GENOMIC ORGANIZATION; HYPERTENSIVE-RATS; DOWN-REGULATION; MESSENGER-RNA; NF-Y; EXPRESSION; PROTEIN AB Soluble guanylyl cyclase is a cytosolic enzyme which catalyzes conversion of GTP to the second messenger cyclic GMP. The transcriptional regulation at the promoter levels of four soluble guanylyl cyclase subunits, termed alpha 1, alpha 2, beta 1, and beta 2, is largely unknown. In this study, we identified the transcription start site of alpha 1-soluble guanylyl cyclase gene in rat pituitary cells and cloned the 3.5 kb 5'-promoter. Sequence analysis of this TATA-less promoter revealed the presence of several putative-binding sites for transcriptional factors, including CCAAT site at -41 to -32 and Sp1 site at -34 to -24. Transfection of pituitary cells with constructs of variable lengths confirmed the relevance of different promoter regions in the control of transcriptional activity. Among them, the -49 to + 156 region was critical for basal transcriptional activity. Electrophoretic mobility shift assay using nuclear proteins extracted from normal and immortalized pituitary cells indicated that the CCAAT/Sp1 site within the -49 to + 156 region was able to specifically interact with CCAAT-binding factor and Sp1. These two sites were partly overlapped and both of them conferred stimulatory effects. The in vivo recruitment of CCAAT-binding factor and Sp1 was confirmed by chromatin immunoprecipitation. These results indicate that the composite CCAAT/Sp1 cis-element contributes to the expression of alpha 1-sGC subunit in resting pituitary cells. C1 NICHD, Sect Cellular Signaling, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Stojilkovic, SS (reprint author), NICHD, Sect Cellular Signaling, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. EM stojilks@mail.nih.gov FU Intramural NIH HHS NR 43 TC 5 Z9 5 U1 0 U2 0 PU SOC ENDOCRINOLOGY PI BRISTOL PA 22 APEX COURT, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0952-5041 J9 J MOL ENDOCRINOL JI J. Mol. Endocrinol. PD DEC PY 2006 VL 37 IS 3 BP 503 EP 515 DI 10.1677/jme.1.02180 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 124GF UT WOS:000243355600012 PM 17170090 ER PT J AU Shapiro, BA Kasprzak, W Grunewald, C Aman, J AF Shapiro, Bruce A. Kasprzak, Wojciech Grunewald, Calvin Aman, Javed TI Graphical exploratory data analysis of RNA secondary structure dynamics predicted by the massively parallel genetic algorithm SO JOURNAL OF MOLECULAR GRAPHICS & MODELLING LA English DT Article DE RNA secondary structure; HIV-1 structural metastability; folding pathway; visual datamining; massively parallel genetic algorithm (MPGAfold); StructureLab analysis workbench ID CONTEXT-FREE GRAMMARS; INCLUDING PSEUDOKNOTS; NUCLEIC-ACID; WEB SERVER; PROGRAMMING ALGORITHM; ABSTRACT SHAPES; RIBOSOMAL-RNA; HIV-1 GENOME; IMPROVES; LEADER AB Studies indicate that RNA may enter intermediate and multiple conformational states, which may impact gene expression and molecular function. It is known that the biologically functional states of RNA molecules may not correspond to their minimum energy conformations, that kinetic barriers may trap the molecule in a local minimum, that folding often occurs during transcription, and that cases exist in which a molecule will transition between one or more functional conformations. Thus, methods for simulating the folding pathway and dynamic behavior of an RNA molecule are important for the prediction of RNA structure and its associated functions. We have developed several data mining techniques guided by interactive visualization tools associated with our massively parallel genetic algorithm for RNA/DNA secondary structure prediction, MPGAfold, and StructureLab analysis workbench. Most of the methods and tools are also applicable to dynamic programming algorithm (DPA) folding data analysis. When applied to MPGAfold results these methodologies are used to determine the significant intermediate and final structures associated with co-transcriptional and full length RNA folding. Since the genetic algorithm is essentially stochastic, multiple runs are required to develop a consensus understanding of an RNA structure. The interactive visualizations facilitate interpretation of results from sequential or full length individual MPGAfold runs, final results of multiple folding runs, including multiple population sizes, and the results from multiple RNA sequences of one family. This paper describes several of these techniques and shows how they are used to help solve this highly combinatoric problem. (c) 2006 Elsevier Inc. All rights reserved. C1 NCI, Canc Res Ctr, Nanobiol Program, Frederick, MD 21702 USA. NCI, Basic Res Program, SAIC Frederick, Frederick, MD 21702 USA. RP Shapiro, BA (reprint author), NCI, Canc Res Ctr, Nanobiol Program, Bldg 469,Room 150, Frederick, MD 21702 USA. EM bshapiro@ncifcrf.gov FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 66 TC 20 Z9 21 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1093-3263 EI 1873-4243 J9 J MOL GRAPH MODEL JI J. Mol. Graph. PD DEC PY 2006 VL 25 IS 4 BP 514 EP 531 DI 10.1016/j.jmgm.2006.04.004 PG 18 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Computer Science, Interdisciplinary Applications; Crystallography; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Computer Science; Crystallography; Mathematical & Computational Biology GA 116JB UT WOS:000242797400014 PM 16725358 ER PT J AU Kim, SK Jacobson, KA AF Kim, Soo-Kyung Jacobson, Kenneth A. TI Computational prediction of homodimerization of the A(3) adenosine receptor SO JOURNAL OF MOLECULAR GRAPHICS & MODELLING LA English DT Article DE GPCRs; purine receptors; rhodopsin; homology modeling; protein-protein docking ID PROTEIN-COUPLED RECEPTOR; 3-DIMENSIONAL STRUCTURE; MOLECULAR-DYNAMICS; OPIOID RECEPTORS; FUNCTIONAL-ROLE; DRUG DISCOVERY; SF9 CELLS; DIMERIZATION; RHODOPSIN; HETERODIMERIZATION AB Increasing evidence suggests that G protein-coupled receptors form functional dimers or larger oligomeric complexes through homo- or heterodimerization, and that various transmembrane (TM) domains contribute dimerization interfaces. In this study, monomeric receptor structures - either the monomeric crystallographic structure of bovine rhodopsin or an A(3) adenosine receptor (AR) homology model - were dimerized by computational methods assuming various TM contact regions, optimized, and compared. The semi-empirical oligomeric structure of mouse rhodopsin studied in a native disc membrane with atomic force microscopy was used to establish the distance between monomers in the initial dimeric models. Among eight variations of symmetrical homodimers of bovine rhodopsin, the favored dimeric assembly closely resembled the semi-empirical model, in which TM domains 4 and 5 were the contact site, thus validating this approach. We used similar methods to generate eight homodimers of the A(3)AR and found the favored dimeric interface similarly to be TM4-5. By this method, dimeric variations - TM1-2, TM2-3, TM2-4, TM3-4, TM4-5, TM5-6, TM6-7, and TM7-1- were constructed with the SYBYL 7.0 program by using a novel "fit-centroids-normal" method. Fitting atoms considered one of eight TM-TM centroids or seven-TM centroids, two centroids of each monomer, and a normal atom passing through the plane containing all centroids. Following molecular dynamics, the most energetically favorable contact modes were identified. In addition to TN4-5, which was favored in both rhodopsin and A(3)AR dimeric models, TM 1-2 dimers in which helices 8 also contacted each other were judged favorable. The largest contact surface area between the monomers among the various homodimers, determined by van der Waals calculation with the MOLCAD surface program, was for the TM4-5 dimer. This contact surface also showed a high degree of shape complementarity. In addition, the TM4-5 dimers made by this theoretical method were more stable than the semi-empirically determined dimer. (c) 2006 Elsevier Inc. All rights reserved. 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, Bldg 8A,Rm B1A-19, 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 NR 67 TC 18 Z9 18 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1093-3263 J9 J MOL GRAPH MODEL JI J. Mol. Graph. PD DEC PY 2006 VL 25 IS 4 BP 549 EP 561 DI 10.1016/j.jmgm.2006.03.003 PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Computer Science, Interdisciplinary Applications; Crystallography; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Computer Science; Crystallography; Mathematical & Computational Biology GA 116JB UT WOS:000242797400017 PM 16781879 ER PT J AU Kim, SK Gao, ZG Jeong, LS Jacobson, KA AF Kim, Soo-Kyung Gao, Zhan-Guo Jeong, Lak Shin Jacobson, Kenneth A. TI Docking studies of agonists and antagonists suggest an activation pathway of the A(3) adenosine receptor SO JOURNAL OF MOLECULAR GRAPHICS & MODELLING LA English DT Article DE Purines; G-protein-coupled receptor; homology modeling; 7TM receptor; binding site; nucleoside ID MUSCARINIC ACETYLCHOLINE-RECEPTOR; PROTEIN-COUPLED RECEPTORS; CROSS-LINKING STRATEGY; CONFORMATIONAL-CHANGES; STRUCTURAL DETERMINANTS; ADENINE NUCLEOSIDES; INTRINSIC EFFICACY; HIGHLY POTENT; DERIVATIVES; RHODOPSIN AB Structural determinants of ligand efficacy in the human A(3) adenosine receptor (AR) were studied using pharmacophore and docking analyses of various categories of A(3) selective ligands: inverse agonist, neutral antagonist (nonnucleoside and nucleoside), and agonist (partial and full). The homology modeling of GPCRs was adapted to provide two templates: the rhodopsin-based resting state for antagonist binding and a putative Meta I state, conformationally altered at a key residue (W6.48), for agonist binding. The preferential binding domains and/or local conformational changes associated with docking of three high affinity A(3)AR ligands were compared: inverse agonist PSB-11 1 ((R)-8-ethyl-4-methyl-2-phenylimidazo [2, 1 -i]purin-5-one); neutral antagonist MRE-3008F20 7 (5-[[(4-methoxyphenyl)amino]carbonyl]amino-8-methyl-2-(2-furyl)pyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidine), and full agonist Cl-IB-MECA 21 (2-chloro-N-6-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine) to define a distinct recognition mode for each. Ribose-containing agonists were more hydrophilic than nonnucleoside antagonists, and H-bonding ability at the fibose 3'- and 5'-positions was required for agonism. From the receptor perspective, common requirements for activation included the destabilization of H-bond networks at W6.48 and H7.43, the specific interactions of the ribose moiety in its putative hydrophilic pocket at T3.36, S7.42, and H7.43, the stabilization of the complex by inward movement of F5.43, and the characteristic rotation of W6.48. By analogy, outward rotation of the W6.48 side-chain upon activation of an internally-crosslinking mutant M-3 muscarinic receptor was indicated by constrained molecular dynamics (MD). Our results are consistent with an anti-clockwise rotation (from the extracellular view) of transmembrane domains 3, 5, 6, and 7, as proposed for other Family A GPCRs. Thus, the putative conformational changes associated with A3AR activation indicate a shared mechanism of GPCR activation similar to rhodopsin. (c) 2006 Elsevier Inc. All rights reserved. C1 NIDDK, Mol Recognit Sect, NIH, LBC, Bethesda, MD 20892 USA. Ewha Womans Univ, Coll Pharm, Med Chem Lab, Seoul 120750, South Korea. RP Jacobson, KA (reprint author), NIDDK, Mol Recognit Sect, NIH, LBC, Bldg 8A,Rm B1A-19, 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 NR 53 TC 37 Z9 37 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1093-3263 J9 J MOL GRAPH MODEL JI J. Mol. Graph. PD DEC PY 2006 VL 25 IS 4 BP 562 EP 577 DI 10.1016/j.jmgm.2006.05.004 PG 16 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Computer Science, Interdisciplinary Applications; Crystallography; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Computer Science; Crystallography; Mathematical & Computational Biology GA 116JB UT WOS:000242797400018 PM 16793299 ER PT J AU Wang, Y Mackes, J Chan, S Haughey, NJ Guo, ZH Xin, OY Furukawa, K Ingram, DK Mattson, MP AF Wang, Yue Mackes, Jennifer Chan, Stephen Haughey, Norman J. Guo, Zhihong Xin Ouyang Furukawa, Katsutoshi Ingram, Donald K. Mattson, Mark P. TI Impaired long-term depression in P2X3 deficient mice is not associated with a spatial learning deficit SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE long-term depression; long-term potentiation; P2X3KO mice; paired-pulse facilitation; water maze ID HIPPOCAMPAL SYNAPTIC PLASTICITY; PROTEIN PHOSPHATASE-1; WORKING-MEMORY; DENTATE GYRUS; CA1 NEURONS; GUINEA-PIG; POTENTIATION; ATP; INVOLVEMENT; RECEPTORS AB The hippocampus is a brain region critical for learning and memory processes believed to result from long-lasting changes in the function and structure of synapses. Recent findings suggest that ATP functions as a neurotransmitter or neuromodulator in the mammalian brain, where it activates several different types of ionotropic and G protein-coupled ATP receptors that transduce calcium signals. However, the roles of specific ATP receptors in synaptic plasticity have not been established. Here we show that mice lacking the P2X3 ATP receptor (P2X3KO mice) exhibit abnormalities in hippocampal synaptic plasticity that can be restored by pharmacological modification of calcium-sensitive kinase and phosphatase activities. Calcium imaging studies revealed an attenuated calcium response to ATP in hippocampal neurons from P2X3KO mice. Basal synaptic transmission, paired-pulse facilitation and long-term potentiation are normal at synapses in hippocampal slices from P2X3KO. However, long-term depression is severely impaired at CA1, CA3 and dentate gyrus synapses. Long-term depression can be partially rescued in slices treated with a protein phosphatase 1-2 A activator or by postsynaptic inhibition of calcium/calmodulin-dependent protein kinase II. Despite the deficit in hippocampal long-term depression, P2X3KO mice performed normally in water maze tests of spatial learning, suggesting that long-term depression is not critical for this type of hippocampus-dependent learning and memory. C1 NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. NIA, Lab Expt Gerontol, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21218 USA. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21218 USA. RP Wang, Y (reprint author), NIA, Neurosci Lab, Intramural Res Program, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM wangyu@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 FU Intramural NIH HHS NR 39 TC 10 Z9 10 U1 0 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 DEC PY 2006 VL 99 IS 5 BP 1425 EP 1434 DI 10.1111/j.1471-4159.2006.04198.x PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 104IE UT WOS:000241951300010 PM 17074061 ER PT J AU Chang, JH Vuppalanchi, D van Niekerk, E Trepel, JB Schanen, NC Twiss, JL AF Chang, Jay H. Vuppalanchi, Deepika van Niekerk, Erna Trepel, Jane B. Schanen, N. Carolyn Twiss, Jeffery L. TI PC12 cells regulate inducible cyclic AMP (cAMP) element repressor expression to differentially control cAMP response element-dependent transcription in response to nerve growth factor and cAMP SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE cyclic AMP response element-binding protein; epigenetics; gene expression; histone deacetylase; inducible cyclic AMP element repressor; neurotrophin ID CREB-BINDING PROTEIN; HISTONE ACETYLTRANSFERASE; DEACETYLASE ACTIVITY; PHOSPHORYLATED CREB; SIGNAL-TRANSDUCTION; NUCLEAR RESPONSE; CBP; INDUCTION; ACTIVATION; CHROMATIN AB Both cyclic AMP (cAMP) and nerve growth factor (NGF) have been shown to cause rapid activation of cAMP response element-binding protein (CREB) by phosphorylation of serine 133, but additional regulatory events contribute to CREB-targeted gene expression. Here, we have used stable transfection with a simple cAMP response element (CRE)-driven reporter to address the kinetics of CRE-dependent transcription during neuronal differentiation of PC12 cells. In naive cells, dibutyryl cAMP (dbcAMP) generated a rapid increase in CRE-driven luciferase activity by 5 h that returned to naive levels by 24 h. Luciferase induction after NGF treatment was delayed until 48 h when CRE-driven luciferase expression became TrkA dependent. Blocking histone deacetylase (HDAC) activity accelerated NGF-dependent CRE-driven luciferase expression by at least 24 h and resulted in a sustained cAMP-dependent expression of CRE-driven luciferase beyond 24 h. Inhibition of protein synthesis before stimulation with NGF or dbcAMP indicated that both stimuli induce expression of a transcriptional repressor that delays NGF-dependent and attenuates cAMP-dependent CRE-driven transcription. NGF caused a rapid but transient HDAC-dependent increase in inducible cAMP element repressor (ICER) expression, but ICER expression was sustained with increased cAMP. Depletion of ICER from PC12 cells indicated that HDAC-dependent ICER induction is responsible for the delay in CRE-dependent transcription after NGF treatment. C1 Alfred I duPont Hosp Children, Nemours Biomed Res, Wilmington, DE 19803 USA. Univ Calif Los Angeles, David Geffen Sch Med, Cellular & Mol Pathol Grad Program, Los Angeles, CA 90024 USA. Univ Delaware, Dept Biol Sci, Newark, DE 19716 USA. NCI, Med Oncol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Twiss, JL (reprint author), Alfred I duPont Hosp Children, Nemours Biomed Res, 1600 Rockland Rd, Wilmington, DE 19803 USA. EM twiss@medsci.udel.edu FU NCRR NIH HHS [P20-RR020173]; NICHD NIH HHS [R01-HD37874]; NIDDK NIH HHS [R21-DK059752]; NINDS NIH HHS [NS007449, R01-NS041596] NR 47 TC 11 Z9 11 U1 0 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 DEC PY 2006 VL 99 IS 6 BP 1517 EP 1530 DI 10.1111/j.1471-4159.2006.04196.x PG 14 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 116XA UT WOS:000242835900007 PM 17059558 ER PT J AU Summy-Long, JY Hu, S Pruss, A Chen, X Phillips, TM AF Summy-Long, J. Y. Hu, S. Pruss, A. Chen, X. Phillips, T. M. TI Response of interleukin-1 beta in the magnocellular system to salt-loading SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Article DE cytokine; oxytocin; vasopressin; neurohypophysis; salt loading ID CORTICOTROPIN-RELEASING-FACTOR; PITUITARY-ADRENAL AXIS; NITRIC-OXIDE SYNTHASE; IMMUNOAFFINITY CAPILLARY-ELECTROPHORESIS; INDUCED FLUORESCENCE DETECTION; MESSENGER-RNA EXPRESSION; ARGININE VASOPRESSIN; OSMOTIC STIMULATION; RAT HYPOTHALAMUS; GENE-EXPRESSION AB Drinking 2% NaCl decreases interleukin (IL)-1 beta in the neural lobe and enhances IL-1 Type 1 receptor expression in magnocellular neurones and pituicytes. To quantify cytokine depletion from the neural lobe during progressive salt loading and determine whether the changes are reversible and correspond with stores of vasopressin (VP) or oxytocin (OT), rats were given water on day 0 and then 2% NaCl to drink for 2, 5, 8 or 5 days followed by 5 days of water (rehydration). Control rats drinking only water were pair-fed amounts eaten by 5-day salt-loaded animals. Animals were decapitated on day 8, the neural lobe frozen and plasma hormones analysed by radioimmunoassay (OT, VP) or enzyme-linked immunosorbent assay (IL-1 beta). IL-1 beta, VP and OT in homogenates of the neural lobe were quantified by immunocapillary electrophoresis with laser-induced fluorescence detection. Differences were determined by ANOVA, Tukey's t-test, Dunnett's procedure, Fisher's least significant difference and linear regression analysis. In response to salt-loading, rats lost body weight similar to pair-fed controls, drank progressively more 2% NaCl and excreted greater urine volumes. Plasma VP increased at days 2 and 8 of salt-loading, whereas osmolality, OT and cytokine were enhanced after 8 days with IL-1 beta remaining elevated after rehydration. In the neural lobe, all three peptides decreased progressively with increasing duration of salt-loading (IL-1 beta, r(2) = 0.98; OT, r(2) = 0.94; VP, r(2) = 0.93), beginning on day 2 (IL-1 beta; VP) or 5 (OT), with only VP replenished by rehydration. IL-1 beta declined more closely (P < 0.0001; ANOVA interaction analysis) with OT (r(2) = 0.96) than VP (r(2) = 0.86), indicative of corelease from the neural lobe during chronic dehydration. Local effects of IL-1 beta on magnocellular terminals, pituicytes and microglia in the neural lobe with activation of forebrain osmoregulatory structures by circulating cytokine may sustain neurosecretion of OT and VP during prolonged salt-loading. C1 Penn State Coll Med, Dept Pharmacol, Hershey, PA 17033 USA. Natl Inst Hlth, UAIR, Bethesda, MD USA. RP Summy-Long, JY (reprint author), Penn State Coll Med, Dept Pharmacol, POB 850, Hershey, PA 17033 USA. EM jsl2@psu.edu FU NIMH NIH HHS [R01-MH65271] NR 88 TC 7 Z9 7 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD DEC PY 2006 VL 18 IS 12 BP 926 EP 937 DI 10.1111/j.1365-2826.2006.01490.x PG 12 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 101GW UT WOS:000241730300005 PM 17076768 ER PT J AU Berman, JW Carson, MJ Chang, L Cox, BM Fox, HS Gonzalez, RG Hanson, GR Hauser, KF Ho, WZ Hong, JS Major, EO Maragos, WF Masliah, E McArthur, JC Miller, DB Nath, A O'Callaghan, JP Persidsky, Y Power, C Rogers, TJ Royal, W AF Berman, Joan W. Carson, Monica J. Chang, Linda Cox, Brian M. Fox, Howard S. Gonzalez, R. Gilberto Hanson, Glen R. Hauser, Kurt F. Ho, Wen-Zhe Hong, Jau-Shyong Major, Eugene O. Maragos, William F. Masliah, Eliezer McArthur, Justin C. Miller, Diane B. Nath, Avindra O'Callaghan, James P. Persidsky, Yuri Power, Christopher Rogers, Thomas J. Royal, Walter, III TI NeuroAIDS, Drug Abuse, and Inflammation: Building Collaborative Research Activities SO JOURNAL OF NEUROIMMUNE PHARMACOLOGY LA English DT Review DE NeuroAIDS; drug abuse; HIV; SIV; inflammation; brain AB Neurological complications of human immunodeficiency virus (HIV) infection are a public health problem despite the availability of active antiretroviral therapies. The neuropathogenesis of HIV infection revolves around a complex cascade of events that include viral infection and glial immune activation, monocyte-macrophage brain infiltration, and secretion of a host of viral and cellular inflammatory and neurotoxic molecules. Although there is evidence that HIV-infected drug abusers experience more severe neurological disease, the biological basis for this finding is unknown. A scientific workshop organized by the National Institute on Drug Abuse (NIDA) was held on March 23-24, 2006 to address this question. The goal of the meeting was to bring together basic science and clinical researchers who are experts in NeuroAIDS, glial immunity, drugs of abuse, and/or pharmacology in order to find new approaches to understanding interactions between drug abuse and neuroAIDS. The format of the meeting was designed to stimulate open discussion and forge new multidisciplinary research collaborations. This report includes transcripts of active discussions and short presentations from invited participants. The presentations were separated into sections that included: Glial Biology, Inflammation, and HIV; Pharmacology, Neurotoxicology, and Neuroprotection; NeuroAIDS and Virology; and Virus-Drug and Immune-Drug Interactions. Research priorities were identified. Additional information about this meeting is available through links from the NIDA AIDS Research Program website (http://www.nida.nih.gov/about/organization/arp/arp-websites.htm). C1 [Berman, Joan W.] Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10461 USA. [Carson, Monica J.] Univ Calif Riverside, Div Biomed Sci, Riverside, CA 92521 USA. [Chang, Linda] Univ Hawaii, Med Ctr, John A Burns Sch Med, Honolulu, HI 96816 USA. [Cox, Brian M.] Uniformed Serv Univ Hlth Sci, Dept Pharmacol, Bethesda, MD 20814 USA. [Fox, Howard S.] Scripps Inst, Mol & Integrat Neurosci Dept, La Jolla, CA 92037 USA. [Gonzalez, R. Gilberto] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hanson, Glen R.] Univ Utah, Med Ctr, Dept Pharmacol & Toxicol, Salt Lake City, UT 84132 USA. [Fox, Howard S.] La Jolla Canc Res Fdn, La Jolla, CA 92037 USA. [Hauser, Kurt F.] Univ Kentucky, Coll Med, Dept Anat & Neurobiol, Lexington, KY 40536 USA. [Hauser, Kurt F.] Univ Kentucky, Coll Med, Lucille P Markey Canc Ctr, Lexington, KY 40536 USA. [Ho, Wen-Zhe] Univ Penn, Med Ctr, Dept Pediat, Philadelphia, PA 19104 USA. [Hong, Jau-Shyong] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. [Major, Eugene O.] Natl Inst Neurol Disorders & Stroke, Bethesda, MD 20892 USA. [Maragos, William F.] Univ Kentucky, Coll Med, Dept Neurol, Lexington, KY 41287 USA. [Masliah, Eliezer] Univ Calif San Diego, Med Ctr, Dept Neurosci, La Jolla, CA 92093 USA. [McArthur, Justin C.; Nath, Avindra] Johns Hopkins Sch Med, Dept Neurol, Bethesda, MD 20205 USA. [Miller, Diane B.] Ctr Dis Control NIOSH, Toxicol & Mol Biol Branch, Morgantown, WV 30333 USA. [O'Callaghan, James P.] Ctr Dis Control NIOSH, Mol Neurotoxicol Lab, Morgantown, WV USA. [Persidsky, Yuri] Univ Nebraska, Med Ctr, Dept Pharmacol & Expt Neurosci, Omaha, NE 68198 USA. [Power, Christopher] Univ Alberta, Dept Med, Edmonton, AB T2N 4N1, Canada. [Rogers, Thomas J.] Temple Univ, Sch Med, Fels Inst, Philadelphia, PA 19104 USA. [Royal, Walter, III] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. RP Berman, JW (reprint author), Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10461 USA. EM berman@aecom.yu.edu; monica.carson@ucr.edu; lchang@hawaii.edu; bcox@usuhs.mil; hsfox@scripps.edu; rggonzalez@partners.org; glen.hanson@hsc.utah.edu; khauser@uky.edu; ho@email.chop.edu; hong3@niehs.nih.gov; majorg@ninds.nih.gov; Maragos@uky.edu; emasliah@ucsd.edu; jm@welchlink.welch.jhu.edu; dum6@cdc.gov; anath1@jhmi.edu; jdo5@cdc.gov; ypersids@unmc.edu; chris.power@ualberta.ca; rogerst@temple.edu; wroyal@som.umaryland.edu RI Power, Christopher/C-7181-2013; O'Callaghan, James/O-2958-2013; OI Fox, Howard/0000-0003-2032-374X FU NINDS NIH HHS [R01 NS039508, R01 NS045735] NR 126 TC 16 Z9 16 U1 3 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1557-1890 J9 J NEUROIMMUNE PHARM JI J. Neuroimmune Pharm. PD DEC PY 2006 VL 1 IS 4 BP 351 EP 399 DI 10.1007/s11481-006-9048-9 PG 49 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA V04MX UT WOS:000207063600001 PM 18040811 ER PT J AU Wickremaratchi, MM Momeni, P Hardy, J Neal, J Morris, HR AF Wickremaratchi, M. M. Momeni, P. Hardy, J. Neal, J. Morris, H. R. TI Genetic and pathological heterogeneity of familial fronto-temporal dementia in Wales: A study of 6 families SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Meeting Abstract CT Spring Meeting of the Association-of-British-Neurologists CY APR 19-21, 2006 CL Brighton, ENGLAND SP Assoc British Neurol C1 Univ Wales Hosp, Dept Neurol, Univ Cardiff Wales, Cardiff, Wales. NIA, Neurogenet Lab, Bethesda, MD 20892 USA. Univ Wales Hosp, Dept Pathol, Cardiff, Wales. NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2006 VL 77 IS 12 MA 033 BP 1394 EP 1394 PG 1 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 106WR UT WOS:000242133200062 ER PT J AU Pomeroy, IM Jordan, EK Frank, J Matthews, PM Esiri, MM AF Pomeroy, I. M. Jordan, E. K. Frank, J. Matthews, P. M. Esiri, M. M. TI Neurodegeneration in a marmoset model of multiple sclerosis SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Meeting Abstract CT Spring Meeting of the Association-of-British-Neurologists CY APR 19-21, 2006 CL Brighton, ENGLAND SP Assoc British Neurol C1 Univ Oxford, Dept Clin Neurol, Oxford, England. NIH, Lab Diagnost Radiol Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2006 VL 77 IS 12 MA 060 BP 1399 EP 1399 PG 1 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 106WR UT WOS:000242133200089 ER PT J AU Depboylu, C Elden, LE Schafer, MKH Reinhart, TA Mitsuya, H Schall, TJ Weihe, E AF Depboylu, Candan Elden, Lee E. Schaefer, Martin K.-H. Reinhart, Todd A. Mitsuya, Hiroaki Schall, Thomas J. Weihe, Eberhard TI Fractalkine expression in the rhesus monkey brain during lentivirus infection and its control by 6-chloro-2 ',3 '-dideoxyguanosine SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article; Proceedings Paper CT 32nd Annual Meeting of the Society-for-Neuroscience CY NOV 02-07, 2002 CL ORLANDO, FL SP Soc Neurosci DE antiretroviral treatment; chemokine; gliosis; infiltration; neuro-AIDS; neuroinflammation ID SIMIAN IMMUNODEFICIENCY VIRUS; HIV-1 ASSOCIATED DEMENTIA; CENTRAL-NERVOUS-SYSTEM; ENHANCED EXPRESSION; RAT-BRAIN; CHEMOKINE; ENCEPHALITIS; RECEPTOR; ACTIVATION; MICROGLIA AB Existing data concerning the role of the delta-chemokine fractalkine (CX3CL1) and its receptor (CX3CR1) in lentivirus-induced encephalitis are limited and controversial. We explored, by quantitative in situ hybridization and immunohistochemistry, the cell-specific changes of CX3CL1 and CX3CR1 in rhesus macaque brain during simian immunodeficiency virus (SIV) infection and antiretroviral treatment. Neuronal expression of CX3CL1 was significantly reduced in cortex and striatum of AIDS-diseased monkeys as compared with uninfected and asymptomatic SIV-infected monkeys. CX3CL1 mRNA was increased in some endothelial cells and newly induced in astrocytes and macrophages focally in areas of SIV burden and inflammatory infiltrates. In most CX3CL1-positive astrocytes and macrophages, the transcription factor NF-kappa B was translocated to the nucleus. CX3CR1 was upregulated in scattered, nodule, and giant cell-forming microglia/macrophages and mononuclear infiltrates close to CX3CL1-induced cells in the brain. Treatment of AIDS monkeys with the central nervous system-permeant 6-chloro-2',3'-dideoxyguanosine fully reversed SIV burden, productive inflammation, nuclear NF-kappa B translocation as well as focal induction of CX3CL1 in astrocytes and macrophages and downregulation in neurons. In contrast, diffuse CX3CR1-positive microgliosis and GFAP-positive astrogliosis were partially reversed by 6-chloro-2',3'-dideoxyguanosine. Thus, focally induced CX3CL1 may be a target for therapeutic intervention to limit ongoing inflammatory infiltration into brain in lentivirus infection. C1 Univ Marburg, Inst Anat & Cell Biol, Dept Mol Neurosci, D-35032 Marburg, Germany. Univ Marburg, Dept Neurol, Ctr Nervous Dis, Marburg, Germany. NIMH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Dept Infect Dis & Microbiol, Pittsburgh, PA USA. NCI, Div Canc Treatment, NIH, Bethesda, MD 20892 USA. ChemoCentryx, Div Discovery Biol & Mol Pharmacol, San Carlos, CA USA. RP Weihe, E (reprint author), Univ Marburg, Inst Anat & Cell Biol, Dept Mol Neurosci, Robert Koch Str 8, D-35032 Marburg, Germany. EM weihe@staff.uni-marburg.de OI Eiden, Lee/0000-0001-7524-944X NR 42 TC 6 Z9 6 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD DEC PY 2006 VL 65 IS 12 BP 1170 EP 1180 PG 11 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 126MM UT WOS:000243517000009 PM 17146291 ER PT J AU Paydarfar, D Forger, DB Clay, JR AF Paydarfar, David Forger, Daniel B. Clay, John R. TI Noisy inputs and the induction of on-off switching behavior in a neuronal pacemaker SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID ALKALINE INTRACELLULAR PH; CENTRAL-NERVOUS-SYSTEM; SQUID GIANT-AXONS; ELECTROPHYSIOLOGICAL PROPERTIES; OSCILLATIONS; INFORMATION; FREQUENCY; MEMBRANE; DYNAMICS; INACTIVATION AB Neuronal oscillators can function as bistable toggle switches, flipping between quiescence and rhythmic firing in response to an input stimulus. In theory, such switching should be sensitive to small noisy inputs if the bistable states are in close proximity, which we test here using a perfused squid axon preparation. We find that small noisy stimulus currents induce a multitude of paths between two nearby stable states: repetitive firing and quiescence. The pattern of on-off switching of the pacemaker depends on the intensity, spectral properties, and phase angle of stimulus current fluctuations. Analysis by spike-triggered averaging of the stimulus currents near the transitions reveals that sinusoidal stimuli timed antiphase or in phase with repetitive firing correlates with switching of the pacemaker off or on, respectively. Our results reveal a distinct form of bistability in which noise can either silence pacemaker activity, trigger repetitive firing, or induce sporadic burst patterns similar to those recorded in a variety of normal and pathological neurons. C1 Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA 01655 USA. Univ Massachusetts, Sch Med, Dept Physiol, Worcester, MA 01655 USA. Marine Biol Lab, Woods Hole, MA 02543 USA. Univ Michigan, Math Biol Res Grp, Dept Math, Ann Arbor, MI 48109 USA. NINDS, NIH, Bethesda, MD 20892 USA. RP Paydarfar, D (reprint author), Univ Massachusetts, Sch Med, Dept Neurol, 55 Lake Ave N, Worcester, MA 01655 USA. EM david.paydarfar@umassmed.edu RI Forger, Daniel/C-5552-2015 OI Forger, Daniel/0000-0001-7581-4031 FU Intramural NIH HHS NR 50 TC 39 Z9 39 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 EI 1522-1598 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD DEC PY 2006 VL 96 IS 6 BP 3338 EP 3348 DI 10.1152/jn.00486.2006 PG 11 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 107NH UT WOS:000242177800051 PM 16956993 ER PT J AU Matveev, V Bertram, R Sherman, A AF Matveev, Victor Bertram, Richard Sherman, Arthur TI Residual bound Ca2+ can account for the effects of Ca2+ buffers on synaptic facilitation SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID PRESYNAPTIC CALCIUM DYNAMICS; SHORT-TERM ENHANCEMENT; TRANSMITTER RELEASE; NEUROTRANSMITTER RELEASE; NEUROMUSCULAR FACILITATION; GRANULE-CELL; TIME-COURSE; TERMINALS; NEURONS; SATURATION AB Facilitation is a transient stimulation- induced increase in synaptic response, a ubiquitous form of short- term synaptic plasticity that can regulate synaptic transmission on fast time scales. In their pioneering work, Katz and Miledi and Rahamimoff demonstrated the dependence of facilitation on presynaptic Ca2+ influx and proposed that facilitation results from the accumulation of residual Ca2+ bound to vesicle release triggers. However, this bound Ca2+ hypothesis appears to contradict the evidence that facilitation is reduced by exogenous Ca2+ buffers. This conclusion led to a widely held view that facilitation must depend solely on the accumulation of Ca2+ in free form. Here we consider a more realistic implementation of the bound Ca2+ mechanism, taking into account spatial diffusion of Ca2+, and show that a model with slow Ca2+ unbinding steps can retain sensitivity to free residual Ca2+. We demonstrate that this model agrees with the facilitation accumulation time course and its biphasic decay exhibited by the crayfish inhibitor neuromuscular junction (NMJ) and relies on fewer assumptions than the most recent variants of the free residual Ca2+ hypothesis. Further, we show that the bound Ca2+ accumulation is consistent with Kamiya and Zucker's experimental results, which revealed that photolytic liberation of a fast Ca2+ buffer decreases the synaptic response within milliseconds. We conclude that Ca2+ binding processes with slow unbinding times (tens to hundreds of milliseconds) constitute a viable mechanism of synaptic facilitation at some synapses and discuss the experimental evidence for such a mechanism. C1 New Jersey Inst Technol, Dept Math Sci, Newark, NJ 07102 USA. Florida State Univ, Dept Math, Tallahassee, FL 32306 USA. Florida State Univ, Neurosci Program, Tallahassee, FL 32306 USA. Florida State Univ, Mol BioPhys Program, Tallahassee, FL 32306 USA. NIDDKD, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA. RP Matveev, V (reprint author), New Jersey Inst Technol, Dept Math Sci, Univ Hts, Newark, NJ 07102 USA. EM matveev@oak.njit.edu FU Intramural NIH HHS NR 46 TC 15 Z9 16 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD DEC PY 2006 VL 96 IS 6 BP 3389 EP 3397 DI 10.1152/jn.00101.2006 PG 9 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 107NH UT WOS:000242177800055 PM 16971687 ER PT J AU La Camera, G Rauch, A Thurbon, D Luscher, HR Senn, W Fusi, S AF La Camera, Giancarlo Rauch, Alexander Thurbon, David Luescher, Hans-R. Senn, Walter Fusi, Stefano TI Multiple time scales of temporal response in pyramidal and fast spiking cortical neurons SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID WEAKLY ELECTRIC FISH; IN-VIVO; FREQUENCY ADAPTATION; NEOCORTICAL NEURONS; NETWORK ACTIVITY; VISUAL-CORTEX; INTEGRATIVE PROPERTIES; SENSORIMOTOR CORTEX; PERSISTENT ACTIVITY; SENSORY ADAPTATION AB Neural dynamic processes correlated over several time scales are found in vivo, in stimulus-evoked as well as spontaneous activity, and are thought to affect the way sensory stimulation is processed. Despite their potential computational consequences, a systematic description of the presence of multiple time scales in single cortical neurons is lacking. In this study, we injected fast spiking and pyramidal (PYR) neurons in vitro with long-lasting episodes of step-like and noisy, in-vivo-like current. Several processes shaped the time course of the instantaneous spike frequency, which could be reduced to a small number (1-4) of phenomenological mechanisms, either reducing (adapting) or increasing (facilitating) the neuron's firing rate over time. The different adaptation/ facilitation processes cover a wide range of time scales, ranging from initial adaptation (< 10 ms, PYR neurons only), to fast adaptation (< 300 ms), early facilitation (0.5-1 s, PYR only), and slow (or late) adaptation (order of seconds). These processes are characterized by broad distributions of their magnitudes and time constants across cells, showing that multiple time scales are at play in cortical neurons, even in response to stationary stimuli and in the presence of input fluctuations. These processes might be part of a cascade of processes responsible for the power-law behavior of adaptation observed in several preparations, and may have far-reaching computational consequences that have been recently described. C1 Univ Bern, Inst Physiol, Bern, Switzerland. RP La Camera, G (reprint author), NIMH, Neuropsychol Lab, NIH, 49 Convent Dr, Bethesda, MD 20892 USA. EM lacamerag@mail.nih.gov RI Senn, Walter/D-6308-2014; Fusi, Stefano/E-9109-2011 OI Senn, Walter/0000-0003-3622-0497; Fusi, Stefano/0000-0002-3035-6652 NR 74 TC 49 Z9 50 U1 1 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD DEC PY 2006 VL 96 IS 6 BP 3448 EP 3464 DI 10.1152/jn.00453.2006 PG 17 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 107NH UT WOS:000242177800060 PM 16807345 ER PT J AU Chen, GJ Harvey, BK Shen, H Chou, J Victor, A Wang, Y AF Chen, Guann-Juh Harvey, Brandon K. Shen, Hui Chou, Jenny Victor, Adrienne Wang, Yun TI Activation of adenosine A3 receptors reduces ischemic brain injury in rodents SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE ischemia; stroke; adenosine; protection; apoptosis ID RAT CORTICAL-NEURONS; A(3) RECEPTOR; SYNAPTIC-TRANSMISSION; PROTECTS; A(3)-RECEPTORS; MEDIATE; AGONIST; HEART; A(1); MICE AB Adenosine A3 receptor (A3R) agonists have been shown to reduce cardiac and lung injury, but the protective roles of A3R agonists in the CNS are not well characterized. The protective effect of selective A3R agonist chloro-N-6-(3-iodo-benzyl)-adenosine-5'-N-methyluronamide (CI-IB-MECA) was first examined in primary cortical cultures. In cortical culture, CI-IB-MECA pretreatment antagonized the hypoxia-mediated decrease in cell viability. In vivo, Cl-IB-MECA or vehicle was given intracerebroventricularly or intravenously to anesthetized rats. Animals were subjected to focal cerebral ischemia induced by transient middle cerebral artery (MCA) ligation. Intracerebroventricular or repeated intravenous administration (i.e., at 165 min and 15 min before MCA ligation) of CI-IB-MECA did not alter blood pressure during ischemia but increased locomotor activity and decreased cerebral infarction 2 days after. In these animals, CI-IB-MECA also reduced the density of TUNEL labeling in the lesioned cortex. The possibility of endogeneous neuroprotection was further examined in A3R knockout mice. After MCA ligation, an increase in cerebral infarction was found in the A3R knockouts compared with the A3R wild-type controls, suggesting that A3Rs are tonically activated during ischemia. Additionally, intracerebroventricular pretreatment with Cl-IB-MECA decreased the size of infarction in the wild-type controls, but not in the A3R knockout animals, suggesting that Cl-IB-MECA-induced protection was mediated through the A3 receptors. Collectively, these data suggest that CI-IB-MECA reduced cerebral infarction through the activation of A3Rs and suppression of apoptosis. (c) 2006 Wiley-Liss, Inc. C1 NIDA, NIH, Baltimore, MD 21224 USA. Triserv Gen Hosp, Natl Def Med Ctr, Taipei, Taiwan. RP Wang, Y (reprint author), NIDA, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM ywang@intra.nida.nih.gov RI Harvey, Brandon/A-5559-2010 FU Intramural NIH HHS NR 20 TC 54 Z9 54 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD DEC PY 2006 VL 84 IS 8 BP 1848 EP 1855 DI 10.1002/jnr.21071 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 116SV UT WOS:000242823500022 PM 17016854 ER PT J AU Taylor, AN Rahman, SU Tio, DL Sanders, MJ Bando, JK Truong, AH Prolo, P AF Taylor, Anna N. Rahman, Shayan U. Tio, Delia L. Sanders, Matthew J. Bando, Jennifer K. Truong, Amy H. Prolo, Paolo TI Lasting neuroendocrine-immune effects of traumatic brain injury in rats SO JOURNAL OF NEUROTRAUMA LA English DT Article DE activity; body temperature; corticosterone; lipopolysaccharide; stress ID CORTICOTROPIN-RELEASING-FACTOR; PITUITARY-ADRENAL AXIS; CORTICAL IMPACT INJURY; CLOSED-HEAD INJURY; ALCOHOL-CONSUMPTION; TIME-SERIES; ETHANOL; RESPONSES; STRESS; FEVER AB Traumatic brain injury (TBI) is a principal cause of long-term physical, cognitive, behavioral, and social deficits in young adults, which frequently coexist with a high incidence of substance abuse disorders. However, few studies have examined the long-term effects of TBI on the neuroendocrine-immune system. TBI was induced in adult male rats under isoflurane anesthesia by cortical contusion injury with a pneumatic piston positioned stereotaxically over the left parietal cortex. Controls underwent sham surgery without injury. At 4 weeks post-injury, the plasma corticosterone response to 30-min restraint stress was significantly blunted in TBI rats compared to the sham controls. One week later, transmitters were implanted for continuous biotelemetric recording of body temperature and spontaneous locomotor activity. At 6 weeks post-injury, the febrile response to i.p. injection of the bacterial endotoxin, lipopolysaccharide (LPS; 50 mu g/kg), was significantly lower in TBI than in sham rats. At 8 weeks, swimming in the forced swim test was significantly less in TBI than sham rats. At 9 weeks, rats were rendered ethanol (EtOH) dependent by feeding an EtOH-containing liquid diet for 14 days. Cosine rhythmometry analysis of circadian body temperature Midline Estimating Statistic of Rhythm (MESOR), amplitudes, and acrophases indicated differential effects of EtOH and withdrawal in the two groups. Light- and dark-phase activity analysis indicated that TBI rats were significantly more active than the sham group, and that EtOH and withdrawal differentially affected their activity. Given the extensive interactions of the neuroendocrine-immune systems, these results demonstrate that TBI produces lasting dysregulation amidst the central substrates for allostasis and circadian rhythmicity. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Inst Brain Res, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Brain Injury Res Ctr, Los Angeles, CA 90095 USA. W Los Angeles Healthcare Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Div Neurosurg, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA. Marquette Univ, Dept Psychol, Milwaukee, WI 53233 USA. NIAID, LCMI, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Sch Dent, Div Oral Biol, Los Angeles, CA 90095 USA. RP Taylor, AN (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Inst Brain Res, 10833 Le Conte Ave,Box 951763, Los Angeles, CA 90095 USA. EM ataylor@mednet.ucla.edu NR 65 TC 12 Z9 12 U1 2 U2 6 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD DEC PY 2006 VL 23 IS 12 BP 1802 EP 1813 DI 10.1089/neu.2006.23.1802 PG 12 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 120AP UT WOS:000243056100008 PM 17184190 ER PT J AU Dixon, LB Subar, AF Wideroff, L Thompson, FE Kahle, LL Potischman, N AF Dixon, L. Beth Subar, Amy F. Wideroff, Louise Thompson, Frances E. Kahle, Lisa L. Potischman, Nancy TI Carotenoid and tocopherol estimates from the NCI diet history questionnaire are valid compared with multiple recalls and serum biomarkers SO JOURNAL OF NUTRITION LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRES; ALPHA-TOCOPHEROL; ADDITIONAL MEASUREMENTS; COMPOSITION DATABASE; BIOCHEMICAL MARKERS; WOMENS HEALTH; VITAMIN-E; PLASMA; ADULTS; CANCER AB To improve the measurement of usual dietary intake, the National Cancer Institute developed a cognitively based Diet History Questionnaire (DHQ), which has been validated against four 24-h dietary recalls (4 24-HR) for energy, macronutrients, and several vitamins and minerals. This analysis used data from The Eating at America's Table Study (EATS) to determine the validity of estimates for carotenoids and tocopherols from the DHQ. Over the course of a year, 163 participants provided 1 or 2 blood samples and completed the DHQ and 4 24-HR. For both the DHO and the 4 24-HR, crude correlations between serum and diet were modest to strong for the provitamin A carotenoids (a-carotene, beta-carotene, beta-cryptoxanthin), low to modest for lycopene, and very low for lutein. The individual dietary tocopherols were weakly correlated with the serum tocopherols, but vitamin E from food and dietary supplements was strongly and positively correlated with serum a-tocopherol and strongly and inversely correlated with serum gamma-tocopherol for both instruments. Adjustment for energy, BMI, smoking status, serum total cholesterol, and serum triacylglycerol did not appreciably change the correlations. Using the method of triads, validity coefficients for the DHQ were comparable to the 4 24-HR and were especially strong for alpha-carotene, beta-cryptoxanthin, lutein + zeaxanthin, and total vitamin E in men and gamma-tocopherol and total vitamin E in women. In this study, there was no advantage of 2 blood samples over 1, suggesting reasonably stable ranking of individuals for these biomarkers, which is important for large epidemiologic studies that typically obtain only 1 blood sample for biomarker status. C1 NYU, Dept Nutr Food Studies & Publ Hlth, New York, NY USA. NCI, Div Canc Prevent & Populat Sci, Bethesda, MD 20892 USA. Informat Management Serv Inc, Silver Spring, MD USA. RP Dixon, LB (reprint author), NYU, Dept Nutr Food Studies & Publ Hlth, 550 1St Ave, New York, NY USA. EM beth.dixon@nyu.edu RI Hernandez, Jessica/G-6527-2011 NR 48 TC 27 Z9 27 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 DEC PY 2006 VL 136 IS 12 BP 3054 EP 3061 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 108ZH UT WOS:000242277200019 PM 17116719 ER PT J AU Summer, GJ Puntillo, KA Miaskowski, C Dina, OA Green, PG Levine, JD AF Summer, Gretchen J. Puntillo, Kathleen A. Miaskowski, Christine Dina, Olayinka A. Green, Paul G. Levine, Jon D. TI TrkA and PKC-epsilon in thermal burn-induced mechanical hyperalgesia in the rat SO JOURNAL OF PAIN LA English DT Article DE pain; inflammation; mechanical hyperalgesia model; nerve growth factor; protein kinase; C-epsilon ID NERVE GROWTH-FACTOR; PROTEIN-KINASE-C; NOCICEPTION PAW TEST; SECONDARY HYPERALGESIA; INFLAMMATORY PAIN; SIGNALING PATHWAYS; ADULT-RAT; INJURY; SENSITIZATION; MICE AB Although mechanical hyperalgesia associated with medical procedures is the major source of severe pain in burn-injured patients, little is known about its underlying mechanism. One reason for this has been the lack of a model for mechanical hyperalgesia at the site of injury. We have modified an established partial-thickness burn model in the rat to produce long-lasting primary mechanical hyperalgesia, which is present from the first measurement at 0.5 h, reaches a maximum at 3 days, and is still significant after 7 days. Because nerve growth factor (NGF), which is elevated in burn-injured tissue, produces mechanical hyperalgesia and activates protein kinase C (PKC)-epsilon, a key mediator in inflammatory and neuropathic pain, we used this model to evaluate the role of the NGF receptor, tyrosine-receptor kinase A (TrkA), and PKC-epsilon in burn-induced primary mechanical hyperalgesia. Intrathecal administration of antisense oligodeoxynucleotides to TrkA and PKC-epsilon, starting 3 days before inducing a burn injury, caused dose-related decrease of burn-induced primary mechanical hyperalgesia. In addition, intradermal injection of a PKC-epsilon-selective inhibitor eliminated hyperalgesia. Our model provides a method to elucidate the underlying mechanism of burn-injury pain as well as to screen for targets for novel analgesic treatments of this important clinical condition. Perspective: This manuscript presents the first model of thermal injury-induced mechanical hyperalgesia which mimics prolonged duration of clinical burn injury pain. We also perform proof of concept experiments demonstrating that our model provides a method to elucidate the mechanism of this important clinical condition. (c) 2006 by the American Pain Society. C1 Univ Calif San Francisco, Sch Nursing, Dept Physiol Nursing, San Francisco, CA 94143 USA. Univ Calif San Francisco, NIH, Pain Ctr, San Francisco, CA 94143 USA. Univ Calif San Francisco, Sch Dent, Dept Oral & Maxillofacial Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Div Neurosci, Biomed Sci Program, San Francisco, CA 94143 USA. RP Summer, GJ (reprint author), C-522-Box 0440 521 Parnassus Ave, San Francisco, CA 94143 USA. EM gretchen.summer@ucsf.edu RI Green, Paul/C-5943-2011 FU NIDCR NIH HHS [R01-DE08973]; NINR NIH HHS [5 F31 NR07474] NR 60 TC 33 Z9 34 U1 0 U2 5 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD DEC PY 2006 VL 7 IS 12 BP 884 EP 891 DI 10.1016/j.jpain.2006.04.009 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 121WQ UT WOS:000243188100003 PM 17157774 ER PT J AU McKenzie, FE Wongsrichanalai, C Magill, AJ Forney, JR Permpanich, B Lucas, C Erhart, LM O'Meara, WP Smith, DL Sirichaisinthop, J Gasser, RA AF McKenzie, F. Ellis Wongsrichanalai, Chansuda Magill, Alan J. Forney, J. Russ Permpanich, Barnyen Lucas, Carmen Erhart, Laura M. O'Meara, Wendy P. Smith, David L. Sirichaisinthop, Jeeraphat Gasser, Robert A., Jr. TI Gametocytemia in Plasmodium vivax and Plasmodium falciparum infections SO JOURNAL OF PARASITOLOGY LA English DT Article ID RISK-FACTORS; SEVERE MALARIA; WESTERN KENYA; CARRIAGE; THAILAND; TRANSMISSION; DIAGNOSIS; CHILDREN; DEVICES; AREA AB Two expert research microscopists, each blinded to the other's reports, diagnosed single-species malaria infections in 2,141 adults presenting at outpatient malaria clinics in Tak Province, Thailand, and Iquitos, Peru, in May-August 1998, May-July 1999, and May-June 2001. Plasmodium vivax patients with gametocytemia had higher fever and higher parasitemia than those without gametocytemia; temperature correlated with parasitemia in the patients with gametocytemia. Plasmodium falciparum patients with gametocytemia had lower fever than those without gametocytemia, but similar parasitemia; temperature correlated with parasitemia in the patients without gametocytemia. Hematologic data in Thailand in 2001 showed lower platelet counts in P. vivax patients with gametocytemia than in the P. vivax patients without gametocytemia, whereas P. falciparum patients with gametocytemia had similar platelet counts but lower red blood cell counts, hemoglobin levels, hematocrit levels, and higher lymphocyte counts than patients without gametocytemia. C1 NIH, Fogart Int Ctr, Bethesda, MD 20892 USA. RP McKenzie, FE (reprint author), NIH, Fogart Int Ctr, Bldg 10, Bethesda, MD 20892 USA. EM em225k@nih.gov RI Smith, David/L-8850-2013 OI Smith, David/0000-0003-4367-3849 FU Intramural NIH HHS [Z99 TW999999] NR 29 TC 17 Z9 17 U1 0 U2 5 PU AMER SOC PARASITOLOGISTS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 0022-3395 J9 J PARASITOL JI J. Parasitol. PD DEC PY 2006 VL 92 IS 6 BP 1281 EP 1285 DI 10.1645/GE-911R.1 PG 5 WC Parasitology SC Parasitology GA 132RL UT WOS:000243959800021 PM 17304807 ER PT J AU Wendler, D Varna, S AF Wendler, David Varna, Sumeeta TI Minimal risk in pediatric research SO JOURNAL OF PEDIATRICS LA English DT Editorial Material ID PERIPHERAL INTRAVENOUS CATHETERS; STANDARD; SAFETY; TRANSFUSION; EFFICACY; CHILDREN; BENEFIT C1 NIH, Dept Clin Bioeth, Ctr Clin, Bethesda, MD 20892 USA. RP Wendler, D (reprint author), NIH, Dept Clin Bioeth, Ctr Clin, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM dwendler@nih.gov NR 30 TC 15 Z9 15 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD DEC PY 2006 VL 149 IS 6 BP 855 EP 861 DI 10.1016/j.jpeds.2006.08.064 PG 7 WC Pediatrics SC Pediatrics GA 122QW UT WOS:000243242500027 PM 17137907 ER PT J AU Offenbacher, S Lin, DM Strauss, R McKaig, R Irving, J Barros, SP Moss, K Barrow, DA Hefti, A Beck, JD AF Offenbacher, Steven Lin, Dongming Strauss, Robert McKaig, Rosemary Irving, Joanna Barros, Silvana P. Moss, Kevin Barrow, David A. Hefti, A. Beck, James D. TI Effects of periodontal therapy during pregnancy on periodontal status, biologic parameters, and pregnancy outcomes: A pilot study SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE bacteria; periodontitis; pregnancy; prematurity; therapy ID LOW-BIRTH-WEIGHT; SERUM INFLAMMATORY MARKERS; PRETERM BIRTH; RISK-FACTOR; DISEASE; WOMEN; INTERLEUKIN-6; INFECTION; PREECLAMPSIA; ASSOCIATION AB Background: Few studies have examined the potential effects of periodontal treatment during pregnancy on pregnancy outcomes, periodontal status, and inflammatory biomarkers. Methods: A randomized, delayed -treatment, controlled pilot trial was conducted to evaluate the effects of second -trimester scaling and root planing and the use of a sonic toothbrush on the rate of preterm delivery (< 37 weeks gestation). Secondary outcome measures included changes in periodontal status, levels of eight oral pathogens, levels of gingival crevicular fluid (GCF) interleukin-1 beta (IL-1 beta), prostaglandin E-2 (PGE(2)), 8-isoprostane (8-iso), and IL-6, and serum levels of IL-6, soluble intercellular adhesion molecule I (sICAM1), 8-isoprostane, soluble glycoprotein 130 (sGP130), IL-6 soluble receptor (IL-6sr), and C-reactive protein (CRP). Logistic regression models were used to test for effects of treatment on preterm delivery. Secondary outcomes were analyzed by analysis of covariance adjusting for subject baseline values. Results: Periodontal intervention resulted in a significantly decreased incidence odds ratio (OR) for preterm delivery (OR = 0.26; 95% confidence interval = 0.08 to 0.85), adjusting for baseline periodontal status which was unbalanced after randomization. Pregnancy without periodontal treatment was associated with significant increases in probing depths, plaque scores, GCF IL-1 beta, and GCF IL-6 levels. Intervention resulted in significant improvements in clinical status (attachment level, probing depth, plaque, gingivitis, and bleeding on probing scores) and significant decreases in levels of Prevotella, nigrescens and Prevotella intermedia, serum IL-6sr, and GCF IL-1 beta. Conclusions: Results from this pilot study (67 subjects) provide further evidence supporting the potential benefits of periodontal treatment on pregnancy outcomes. Treatment was safe, improved periodontal health, and prevented periodontal disease progression. Preliminary data show a 3.8-fold reduction in the rate of preterm delivery, a decrease in periodontal pathogen load, and a decrease in both GCF IL-1 beta and serum markers of IL-6 response. However, further studies will be needed to substantiate these early findings. C1 Univ N Carolina, Dept Obstet & Gynecol, Chapel Hill, NC 27515 USA. Univ N Carolina, Dept Periodontol, Ctr Oral & Syst Dis, Chapel Hill, NC 27515 USA. NIAID, NIH, Bethesda, MD 20892 USA. N Carolina Wake Cty Hlth Dept, Raleigh, NC USA. Univ N Carolina, Ctr Oral Syst Dis, Chapel Hill, NC 27515 USA. RP Offenbacher, S (reprint author), Univ N Carolina, Dept Periodontol, Ctr Oral & Syst Dis, Chapel Hill, NC 27515 USA. EM steve_offenbacher@dentistry.unc.edu FU NCRR NIH HHS [RR-00046]; NIDCR NIH HHS [DE-012453] NR 31 TC 95 Z9 98 U1 0 U2 5 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 DEC PY 2006 VL 77 IS 12 BP 2011 EP 2024 DI 10.1092/jop.2006.060047 PG 14 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 130LO UT WOS:000243801300011 PM 17209786 ER PT J AU Manian, N Papadakis, AA Strauman, TJ Essex, MJ AF Manian, Nanmathi Papadakis, Alison A. Strauman, Timothy J. Essex, Marilyn J. TI The development of children's ideal and ought self-guides: Parenting, temperament, and individual differences in guide strength SO JOURNAL OF PERSONALITY LA English DT Article ID MOTHERS PERSONALITY; SOCIAL-DEVELOPMENT; NEGATIVE AFFECT; EARLY-CHILDHOOD; BEHAVIOR; SOCIALIZATION; DETERMINANTS; DISCREPANCY; PATTERNS; SYSTEMS AB Regulatory focus theory (RFT; Higgins, 1997) predicts that individual differences in the strength of promotion (ideal) and prevention (ought) orientations emerge from patterns of parent/child interactions that emphasize making good things happen versus keeping bad things from happening. This article examines the development of individual differences in the strength of children's promotion and prevention goals and presents selected findings from three studies exploring the origins of regulatory focus. We found a three-factor structure for parenting behaviors that differentiated between the presence/absence of positive outcomes versus the presence/absence of negative outcomes in two different data sets and validated that factor structure by examining its associations with maternal temperament. In turn, the parenting factors predicted individual differences in children's orientations to ideal and ought guides, and those associations were moderated by individual differences in child temperament. C1 NICHD, Bethesda, MD 20892 USA. Duke Univ, Durham, NC 27706 USA. Univ Wisconsin, Madison, WI 53706 USA. RP Manian, N (reprint author), NICHD, Suite 8030,6705 Rockledge Dr, Bethesda, MD 20892 USA. EM maniann@mail.nih.gov RI Papadakis, Alison/A-9482-2009 NR 86 TC 24 Z9 24 U1 0 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3506 J9 J PERS JI J. Pers. PD DEC PY 2006 VL 74 IS 6 BP 1619 EP 1645 DI 10.1111/j.1467-6494.2006.00422.x PG 27 WC Psychology, Social SC Psychology GA 101WZ UT WOS:000241773300005 PM 17083660 ER PT J AU Park, JY Kang, HW Moon, HJ Huh, SU Jeong, SW Soldatov, NM Lee, JH AF Park, Jin-Yong Kang, Ho-Won Moon, Hyung-Jo Huh, Sung-Un Jeong, Seong-Woo Soldatov, Nikolai M. Lee, Jung-Ha TI Activation of protein kinase C augments T-type Ca2+ channel activity without changing channel surface density SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID CALCIUM-CHANNELS; XENOPUS-OOCYTES; N-TYPE; DEPENDENT MODULATION; HIPPOCAMPAL-NEURONS; SKELETAL-MUSCLE; SENSORY NEURONS; NA+ CHANNELS; PKC ISOZYME; K+ CHANNEL AB T-type Ca2+ channels play essential roles in numerous cellular processes. Recently, we reported that phorbol-12-myristate-13-acetate (PMA) potently enhanced the current amplitude of Ca(v)3.2 T-type channels reconstituted in Xenopus oocytes. Here, we have compared PMA modulation of the activities of Ca(v)3.1, Ca(v)3.2 and Ca(v)3.3 channels, and have investigated the underlying mechanism. PMA augmented the current amplitudes of the three T-type channel isoforms, but the fold stimulations and time courses differed. The augmentation effects were not mimicked by 4 alpha-PMA, an inactive stereoisomer of PMA, but were abolished by preincubation with protein kinase C (PKC) inhibitors, indicating that PMA augmented T-type channel currents via activation of oocyte PKC. The stimulation effect on Ca(v)3.1 channel activity by PKC was mimicked by endothelin when endothelin receptor type A was coexpressed with Ca(v)3.1 in the Xenopus oocyte system. Pharmacological studies combined with fluorescence imaging revealed that the surface density of Ca(v)3.1 T-type channels was not significantly changed by activation of PKC. The PKC effect on Ca(v)3.1 was localized to the cytoplasmic II-III loop using chimeric channels with individual cytoplasmic loops of Ca(v)3.1 replaced by those of Ca(v)2.1. C1 Sogang Univ, Dept Life Sci, Seoul 121742, South Korea. Sogang Univ, Interdisciplinary Program Biotechnol, Seoul 121742, South Korea. Yonsei Univ, Coll Med, Dept Physiol, Wonju, Kangwon Do, South Korea. Yonsei Univ, Coll Med, Inst Basic Med Sci, Wonju, Kangwon Do, South Korea. NIA, Baltimore, MD 21224 USA. RP Lee, JH (reprint author), Sogang Univ, Dept Life Sci, Shinsu Dong, Seoul 121742, South Korea. EM jhleem@sogang.ac.kr NR 65 TC 40 Z9 41 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD DEC 1 PY 2006 VL 577 IS 2 BP 513 EP 523 DI 10.1113/jphysiol.2006.117440 PG 11 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 108LI UT WOS:000242240900005 PM 17008378 ER PT J AU Cannick, GF Horowitz, AM Reed, SG Drury, TF Day, TA AF Cannick, GF Horowitz, AM Reed, SG Drury, TF Day, TA TI Opinions of South Carolina dental Students toward tobacco use interventions SO JOURNAL OF PUBLIC HEALTH DENTISTRY LA English DT Article; Proceedings Paper CT 82nd General Session of the International-Association-for-Dental-Research/American-Association-for-D ental-Research CY MAR 10-13, 2004 CL Honolulu, HI SP Int Assoc Dent Res, Amer Assoc Dent Res DE students, dental; tobacco use cessation ID PHARYNGEAL CANCER; CARE PROVIDERS; SMOKING; PERIODONTITIS; PREVENTION; KNOWLEDGE; DENTISTS AB Objectives: Tobacco use accounts for 75 percent of oral cancer deaths in the United States. One objective of Healthy People 2010 is to increase the percentage of dentists who provide smoking cessation counseling. However, studies of dentists have shown that the majority feel inadequately prepared to do so. The objective of this study was to determine the opinions of dental students at the Medical University of South Carolina (MUSC) regarding the provision of tobacco use interventions for patients. Methods: In 2002, 163 students were administered a written questionnaire which included questions about tobacco use interventions (response rate = 80 percent). Opinion items were analyzed using factor analysis, Fisher's Exact Test, and ANOVA(a <= 0.025). Results: While 89 percent of students agreed that dentists should be trained to provide tobacco cessation education, only 39 percent thought that they themselves were adequately trained. Students' opinions toward the role and training of dentists in providing tobacco use interventions differed by academic year. Only 14.1 percent of dental students were quite or very confident in their ability to help patients to stop smoking. Conclusions: This study indicates that although MUSC dental students support tobacco cessation training for dentists, the majority responded that they are not adequately trained and are not comfortable providing tobacco cessation education to patients. A comprehensive tobacco prevention and cessation program is indicated for the objective of Healthy People 2010 to be met. C1 Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. Med Univ S Carolina, Coll Grad Studies, Dept Biostat Bioinformat & Epidemiol, Charleston, SC 29425 USA. Med Univ S Carolina, Coll Dent Med, Dept Stomatol, Charleston, SC USA. Med Univ S Carolina, Coll Med, Dept Otolaryngol Head & Neck Surg, Charleston, SC USA. RP Horowitz, AM (reprint author), Natl Inst Dent & Craniofacial Res, NIH, 45 Ctr Dr,Room 4As-37A, Bethesda, MD 20892 USA. EM alice.horowitz@nih.gov NR 29 TC 20 Z9 20 U1 0 U2 0 PU AAPHD NATIONAL OFFICE PI PORTLAND PA 3760 SW LYLE COURT, PORTLAND, OR 97221 USA SN 0022-4006 J9 J PUBLIC HEALTH DENT JI J. Public Health Dent. PD WIN PY 2006 VL 66 IS 1 BP 44 EP 48 DI 10.1111/j.1752-7325.2006.tb02550.x PG 5 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA 021VI UT WOS:000236013600007 PM 16570750 ER PT J AU Duma, D Jewell, CM Cidlowski, JA AF Duma, Danielle Jewell, Christine M. Cidlowski, John A. TI Multiple glucocorticoid receptor isoforms and mechanisms of post-translational modification SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article; Proceedings Paper CT 17th International Symposium of the Journal-of-Steroid-Biochemistry-and-Molecular-Biology CY MAY 31-JUN 03, 2006 CL Seefeld, AUSTRIA SP Journal Steroid Biochem & Mol Biol DE glucocorticoid receptor; isoforms; post-translational modification ID NUCLEAR HORMONE-RECEPTORS; BETA-ISOFORM; ARGININE METHYLATION; HISTONE METHYLATION; IN-VIVO; PROTEIN; GENE; PHOSPHORYLATION; EXPRESSION; CELLS AB Glucocorticoids regulate diverse physiological effects in virtually every organ and tissue in the body. Glucocorticoid actions are mediated through the glucocorticoid receptor (GR), a ligand-dependent transcriptional factor that activates or represses gene transcription. Since, the cloning of the human GR in 1985, research efforts have been focused on describing the mechanism of action exerted by one of the GR isoforms, GR alpha. However, recent studies from our lab and others have suggested that multiple isoforms of hGR are generated from one single gene and one mRNA species by the mechanisms of alternative RNA splicing and alternative translation initiation. These isoforms display diverse cytoplasm-to-nucleus trafficking patterns and distinct transcription activities. In addition, this new information predicts that each hGR protein can be subjected to a variety of post-translational modifications, such as phosphorylation, sumoylation and ubiquitination. The nature and degree of post-translational modification, as well as subcellular localization, may differentially modulate stability and function among the GR isoforms in different tissues providing an additional important mechanism for regulation of GR action. We outline the recent advances made in identifying the processes that generate and modify multiple GR isoforms and the post-translational modifications that contribute to the increasing diversity in the glucocorticoid signaling pathway. (c) 2006 Published by Elsevier Ltd. C1 NIEHS, Lab Signal Transduct, Mol Endocrinol Grp, NIH, Res Triangle Pk, NC 27709 USA. RP Cidlowski, JA (reprint author), NIEHS, Lab Signal Transduct, Mol Endocrinol Grp, NIH, POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM cidlows1@niehs.nih.gov NR 78 TC 141 Z9 147 U1 2 U2 11 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 DEC PY 2006 VL 102 IS 1-5 SI SI BP 11 EP 21 DI 10.1016/j.jsbmb.2006.09.009 PG 11 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 117LS UT WOS:000242875300003 PM 17070034 ER PT J AU Shah, BH Baukal, AJ Chen, HD Shah, AB Catt, KJ AF Shah, Bukhtiar H. Baukal, Albert J. Chen, Hung-Dar Shah, Ali B. Catt, Kevin J. TI Mechanisms of endothelin-1-induced MAP kinase activation in adrenal glomerulosa cells SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article; Proceedings Paper CT 17th International Symposium of the Journal-of-Steroid-Biochemistry-and-Molecular-Biology CY MAY 31-JUN 03, 2006 CL Seefeld, AUSTRIA SP Journal Steroid Biochem & Mol Biol DE endothelin-1; adrenal glomerulosa cells; EGF; MAP kinase; Src kinase; CREB; RSK-1 ID EPIDERMAL-GROWTH-FACTOR; EGF-RECEPTOR TRANSACTIVATION; PROTEIN-COUPLED RECEPTORS; ANGIOTENSIN-II ACTIVATION; SRC TYROSINE KINASE; ALDOSTERONE SECRETION; SIGNALING PATHWAYS; LYSOPHOSPHATIDIC ACID; CARDIAC-HYPERTROPHY; REGULATED KINASE-1 AB G protein-coupled receptors (GPCRs) such as angiotensin II, bradykinin and endothelin-1 (ET-1) are critically involved in the regulation of adrenal function, including aldosterone production from zona glomerulosa cells. Whereas, substantial data are available on the signaling mechanisms of ET-1 in cardiovascular tissues, such information in adrenal glomerulosa cells is lacking. Bovine adrenal glomerulosa (BAG) cells express receptors for endothelin-1 (ET-1) and their stimulation caused phosphorylation of Src (at Tyr416), proline-rich tyrosine kinase (Pyk2 at Tyr402). extracellularly regulated signal kinases (ERK1/2), and their dependent proteins, p90 ribosomal S6 kinase (RSK-1) and CREB. ET-1 elicited these responses predominantly through activation of a G(i)-linked cascade with a minor contribution from the G(q)/PKC pathway. Whereas, selective inhibition of EGF-R kinase with AG1478 caused complete inhibition of EGF-induced ERK/RSK-1/CREB activation, it caused only partial reduction (30-40%) of such ET-1-induced responses. Consistent with this, inhibition of matrix metalloproteinases (MMPs) with GM6001 reduced ERK1/2 activation by ET-1, consistent with partial involvement of the MMP-dependent EGF-R activation in this cascade. Activation of ERK/RSK-1/CREB by both ET-1 and EGF was abolished by inhibition of Src, indicating its central role in ET-1 signaling in BAG cells. Moreover, the signaling characteristics of ET-1 in cultured BAG cells closely resembled those observed in clonal adrenocortical H295R cells. The ET-I-induced proliferation of BAG and H295 R cells was much smaller than that induced by Ang II or FGF. These data demonstrate that ET-1 causes ERK/RSK-1/CREB phosphorylation predominantly through activation of G(i) and Src, with a minor contribution from MMP-dependent EGF-R transactivation. (c) 2006 Elsevier Ltd. All rights reserved. C1 NICHD, ERRB, NIH, Bethesda, MD 20892 USA. RP Catt, KJ (reprint author), NICHD, ERRB, NIH, Bld 49,Rm 6A36, Bethesda, MD 20892 USA. EM cattk@mail.nih.gov FU Intramural NIH HHS [Z99 HD999999, ZIA HD000184-31, Z01 HD000193-23, ZIA HD000193-24, Z01 HD000184-29, ZIA HD000193-25, Z01 HD000193-22, ZIA HD000184-32, Z01 HD000184-30] NR 54 TC 14 Z9 14 U1 0 U2 2 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 DEC PY 2006 VL 102 IS 1-5 SI SI BP 79 EP 88 DI 10.1016/j.jsbmb.2006.09.026 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 117LS UT WOS:000242875300010 PM 17113976 ER PT J AU Heinz, AJ Epstein, DH Schroeder, JR Singleton, EG Heishman, SJ Preston, KL AF Heinz, Adrienne J. Epstein, David H. Schroeder, Jennifer R. Singleton, Edward G. Heishman, Stephen J. Preston, Kenzie L. TI Heroin and cocaine craving and use during treatment: Measurement validation and potential relationships SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article; Proceedings Paper CT 29th Annual Association-for-Medical-Evaluation-and-Research-in-Substance-Abuse Conference CY OCT, 2005 CL Washington, DC SP Assoc Med Evaluat & Res Substance Abuse DE craving; cocaine; heroin; treatment; measure ID DEPENDENT VOLUNTEERS; INITIAL VALIDATION; SMOKING RELAPSE; DRUG-USE; QUESTIONNAIRE; ABUSERS; TOBACCO; REINFORCEMENT; WITHDRAWAL; VALIDITY AB Although commonly assessed with unidimensional scales, craving has been suggested to be multifaceted and to have a complex relationship with drug use and relapse. This study assessed the consistency and predictive validity of unidimensional and multidimensional craving scales. At the beginning of a 12-week outpatient treatment trial, opiate users (n = 101) and cocaine users (n = 72) completed unidimensional visual analog scales (VASs) assessing "want," "need," and "craving" and multidimensional 14- and 45-item versions of the Cocaine Craving Questionnaire (CCQ) or Heroin Craving Questionnaire (HCQ). Spearman correlations between the VASs and the first-order factors from the 45-item CCQ/HCQ were.20-.40, suggesting that the two types of assessment were not redundant. Treatment dropout and intreatment drug use were more frequently predicted by scores on the 14- or 45-item CCQ than by VAS ratings. Results suggest that the CCQ/ HCQ and the 14-item CCQ provide information that unidimensional VASs do not. (c) 2006 Elsevier Inc. All rights reserved. C1 NIDA, Clin Pharmacol & Therapeut Branch, Intramural Res Program, Baltimore, MD 21224 USA. RP Heinz, AJ (reprint author), 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM heinza@intra.nida.nih.gov RI Preston, Kenzie/J-5830-2013; OI Preston, Kenzie/0000-0003-0603-2479; Singleton, Edward G./0000-0003-3442-877X FU Intramural NIH HHS NR 35 TC 34 Z9 34 U1 2 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD DEC PY 2006 VL 31 IS 4 BP 355 EP 364 DI 10.1016/j.jsat.2006.05.009 PG 10 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 105TU UT WOS:000242056000005 PM 17084789 ER PT J AU Danforth, DN Abati, A Filie, A Prindiville, SA Palmieri, D Simon, R Ried, T Steeg, PS AF Danforth, David N., Jr. Abati, Andrea Filie, Armando Prindiville, Shiela A. Palmieri, Diane Simon, Richard Ried, Thomas Steeg, Patricia S. TI Combined breast ductal lavage and ductal endoscopy for the evaluation of the high-risk breast: A feasibility study SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Article DE chemoprevention; breast cytology; high-risk breast epithelium; ductal sampling ID IN-SITU HYBRIDIZATION; CANCER; NIPPLE; TISSUE; WOMEN; CYTOLOGY; FLUID; HETEROZYGOSITY; EPITHELIUM; ANEUSOMY AB Background and Objectives: Evaluation of the ductal epithelium of the breast at increased risk for breast cancer is needed to define the carcinogenic pathway, for risk assessment, and to improve selection of women for chemoprevention therapy. We studied the feasibility of combining breast ductal endoscopy with ductal lavage in the high-risk contralateral breast of women with ipsilateral breast cancer for the evaluation of high-risk ducts and acquisition of ductal epithelial cells for analysis. Methods: Breast ducts were studied by ductal lavage and ductal endoscopy, and epithelial cell content studied cytologically and quantitatively. Results: Twenty-five subjects and 44 ducts, including 22 (50.0%) which did not produce nipple aspirate fluid (NAF), were studied. Cellular atypia was present in five subjects. Ductal endoscopy was performed on 1 or more ducts in 24 subjects. Structural changes were noted in 63.6% of the ducts, most commonly fibrous stranding or bridging. Ductal sampling with endoscopic brush and coil sampling devices provided additional cellular samples of relatively pure ductal epithelial content (>= 91% purity) in 8/11 subjects. Conclusions: Breast ductal endoscopy combined with ductal lavage represents a feasible approach for characterizing the ducts and ductal epithelium of the high-risk breast, especially in a research setting. C1 NCI, Surg Branch, CCR, NIH, Bethesda, MD 20892 USA. NCI, Lab Cytopathol, CCR, NIH, Bethesda, MD 20892 USA. NCI, Canc Genet Branch, CCR, NIH, Bethesda, MD 20892 USA. NCI, Mol Pharmacol Lab, CCR, NIH, Bethesda, MD 20892 USA. NCI, Biometr Res Branch, CCR, NIH, Bethesda, MD 20892 USA. RP Danforth, DN (reprint author), NCI, Surg Branch, CCR, NIH, Bldg 10,Rm 4-5764, Bethesda, MD 20892 USA. EM david_danforth@nih.gov RI Palmieri, Diane/B-4258-2015 FU Intramural NIH HHS NR 33 TC 11 Z9 11 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD DEC 1 PY 2006 VL 94 IS 7 BP 555 EP 564 DI 10.1002/jso.20650 PG 10 WC Oncology; Surgery SC Oncology; Surgery GA 108ES UT WOS:000242223700005 PM 17048242 ER PT J AU Vitiello, B Rohde, P Silva, S Wells, K Casat, C Waslick, B Simons, A Reinecke, M Weller, E Kratochvil, C Walkup, J Pathak, S Robins, M March, J AF Vitiello, Benedetto Rohde, Paul Silva, Susan Wells, Karen Casat, Charles Waslick, Bruce Simons, Anne Reinecke, Mark Weller, Elizabeth Kratochvil, Christopher Walkup, John Pathak, Sanjeev Robins, Michele March, John CA TADS Team TI Functioning and quality of life in the Treatment for Adolescents with Depression Study (TADS) SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE depression; treatment; functioning; impairment ID NATION OUTCOME SCALES; INTERPERSONAL PSYCHOTHERAPY; CONTROLLED-TRIAL; CHILDREN; FLUOXETINE; SERTRALINE; EFFICACY; DISORDER; HONOSCA; PLACEBO AB Objective: To test whether 12-week treatment of major depression improved the level of functioning, global health, and quality of life of adolescents. Method: The Treatment for Adolescents With Depression Study was a multisite, randomized clinical trial of fluoxetine, cognitive-behavioral therapy (CBT), their combination (COMB), or clinical management with placebo in 439 adolescents with major depression. Functioning was measured with the Children's Global Assessment Scale (CGAS), global health with the Health of the Nation Outcome Scales for Children and Adolescents (HoNOSCA), and quality of life with the Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q). Random-effects regression models were applied to the data. Results: Compared with placebo, COMB was effective on the CGAS (p <.0001), HoNOSCA (p < 05), and PQ-LES-Q (p <.001), whereas fluoxetine was superior to placebo on the CGAS only (p <.05). COMB was superior to fluoxetine on the CGAS (p <.05) and PQ-LES-Q (p =.001). Fluoxetine was superior to CBT on the CGAS (p <.01). CBT monotherapy was not statistically different from the placebo group on any of the measures assessed. Treatment effects were mediated by improvement in depressive symptoms measured on the Child Depression Rating Scale-Revised. Conclusions: The combination of fluoxetine and CBT was effective in improving functioning, global health, and quality of life in depressed adolescents. Fluoxetine monotherapy improved functioning. C1 NIMH, Bethesda, MD 20892 USA. RP Vitiello, B (reprint author), NIMH, Room 7147,6001 Execut Blvd, Bethesda, MD 20892 USA. EM bvitiell@mail.nih.gov FU DS NIH HHS [98-DS-0008]; NIMH NIH HHS [N01 MH80008] NR 26 TC 67 Z9 67 U1 2 U2 7 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 DEC PY 2006 VL 45 IS 12 BP 1419 EP 1426 DI 10.1097/01.chi.0000242229.52646.6e PG 8 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 111XL UT WOS:000242489100004 PM 17135987 ER PT J AU Maggio, M Lauretani, F Ceda, GP Bandinelli, S Basaria, S Ble, A Egan, J Paolisso, G Najjar, S Metter, EJ Valenti, G Guralnik, JM Ferrucci, L AF Maggio, Marcello Lauretani, Fulvio Ceda, Gian Paolo Bandinelli, Stefania Basaria, Shehzad Ble, Alessandro Egan, Josephine Paolisso, Giuseppe Najjar, Samer Metter, E. Jeffrey Valenti, Giorgio Guralnik, Jack M. Ferrucci, Luigi TI Association between hormones and metabolic syndrome in older Italian men SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE SHBG; testosterone; hormonal dysregulation; older men; metabolic syndrome ID ENDOGENOUS SEX-HORMONES; BINDING GLOBULIN LEVELS; INSULIN SENSITIVITY; ELDERLY-WOMEN; TESTOSTERONE; LEPTIN; SERUM; PREVALENCE; RESISTANCE; INCHIANTI AB OBJECTIVES: To determine whether low levels of testosterone, sex hormone binding globulin (SHBG), insulin-like growth factor-1 (IGF-1), and dehydroepiandrosterone sulfate (DHEAS) and high levels of cortisol and leptin would be associated with metabolic syndrome (MS). DESIGN: Cross-sectional. SETTING: Population-based sample of older Italian men. PARTICIPANTS: Four hundred fifty-two men aged 65 and older enrolled in the Invecchiare in Chianti (InCHIANTI) study. MEASUREMENTS: Complete data on testosterone, cortisol, DHEAS, SHBG, fasting insulin, IGF-1 and leptin. MS was defined according to Adult Treatment Panel III criteria. RESULTS: MS was present in 73 men (15.8% of the sample). After adjusting for confounders, total testosterone (P <.05) and log (SHBG) (P <.001) were inversely associated, whereas log (leptin) was positively associated with MS (P <.001). Independent of age, log (SHBG) was positively associated with high-density lipoprotein cholesterol (P <.05) and negatively associated with abdominal obesity (P <.001) and triglycerides (P <.001). Log (leptin) was significantly associated with each component of MS. Cortisol, DHEAS, free and bioavailable testosterone, and IGF-I were not associated with MS. Having three or more hormones in the lower (for hormones lower in MS) or the upper (for hormones higher in MS) quartile was associated with three times the risk of being affected by MS (odds ratio = 2.8, 95% confidence interval = 1.3-6.9) (P=.005), compared with not having this condition. CONCLUSION: Total testosterone and SHBG are negatively and leptin is positively associated with MS in older men. Whether specific patterns of hormonal dysregulation predict the development of MS should be tested in longitudinal studies. C1 NIA, Clin Res Branch, Baltimore, MD USA. NIA, Lab Cardiovasc Sci, Baltimore, MD USA. Tuscany Reg Hlth Agcy, Florence, Italy. Univ Parma, Sch Endocrinol, Sect Geriatr, Dept Internal Med & Biomed Sci, Parma, Italy. Geriatr Rehabil Unit, Florence, Italy. Johns Hopkins Univ, Sch Med, Bayview Med Ctr, Div Endocrinol,Dept Med, Baltimore, MD USA. Univ Naples, Dept Geriatr Med & Metab Dis 2, Naples, Italy. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD USA. RP Maggio, M (reprint author), Harbor Hosp, NIA ASTRA, NIH, 3001 S Hanover St, Baltimore, MD 21225 USA. EM maggiom@grc.nia.nih.gov RI Perez , Claudio Alejandro/F-8310-2010; Lauretani, Fulvio/K-5115-2016; OI Perez , Claudio Alejandro/0000-0001-9688-184X; Paolisso, Giuseppe/0000-0002-2137-455X; Lauretani, Fulvio/0000-0002-5287-9972; Ceda, Gian Paolo/0000-0002-9648-8295 FU Intramural NIH HHS [Z99 AG999999] NR 37 TC 56 Z9 57 U1 0 U2 2 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 DEC PY 2006 VL 54 IS 12 BP 1832 EP 1838 DI 10.1111/j.1532-5415.2006.00963.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 119FJ UT WOS:000242997900003 PM 17198487 ER PT J AU Barrett, HH Myers, KJ Devaney, N Dainty, C AF Barrett, Harrison H. Myers, Kyle J. Devaney, Nicholas Dainty, Christopher TI Objective assessment of image quality. IV. Application to adaptive optics SO JOURNAL OF THE OPTICAL SOCIETY OF AMERICA A-OPTICS IMAGE SCIENCE AND VISION LA English DT Article ID OBSERVER DETECTION PERFORMANCE; HOTELLING TRACE CRITERION; NOISE; COMPANION; MODEL; VARIABILITY; SPECKLES; SIGNALS; SYSTEMS; FILTERS AB The methodology of objective assessment, which defines image quality in terms of the performance of specific observers on specific tasks of interest, is extended to temporal sequences of images with random point spread functions and applied to adaptive imaging in astronomy. The tasks considered include both detection and estimation, and the observers are the optimal linear discriminant (Hotelling observer) and the optimal linear estimator (Wiener). A general theory of first- and second-order spatiotemporal statistics in adaptive optics is developed. It is shown that the covariance matrix can be rigorously decomposed into three terms representing the effect of measurement noise, random point spread function, and random nature of the astronomical scene. Figures of merit are developed, and computational methods are discussed. (c) 2006 Optical Society of America. C1 Univ Arizona, Coll Opt Sci, Tucson, AZ 85724 USA. Univ Arizona, Dept Radiol, Tucson, AZ 85724 USA. NIBIB, CDRH, Lab Assessment Med Imaging Syst, Rockville, MD 20850 USA. Natl Univ Ireland Univ Coll Galway, Dept Phys, Galway, Ireland. RP Barrett, HH (reprint author), Univ Arizona, Coll Opt Sci, Tucson, AZ 85724 USA. EM hhb@email.arizona.edu; kyle.myers@fda.hhs.gov; nicholas.devaney@nuigalway.ie; c.dainty@nuigalway.ie FU NIBIB NIH HHS [P41 EB002035, P41 EB002035-08, R37 EB000803, R37 EB000803-16] NR 61 TC 26 Z9 26 U1 0 U2 3 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1084-7529 J9 J OPT SOC AM A JI J. Opt. Soc. Am. A-Opt. Image Sci. Vis. PD DEC PY 2006 VL 23 IS 12 BP 3080 EP 3105 DI 10.1364/JOSAA.23.003080 PG 26 WC Optics SC Optics GA 109RN UT WOS:000242326400011 PM 17106464 ER PT J AU Yeow, WS Baras, A Chua, A Nguyen, DM Sehgal, SS Schrump, DS Nguyen, DM AF Yeow, Wen-Shuz Baras, Aris Chua, Alex Nguyen, Duc M. Sehgal, Shailen S. Schrump, David S. Nguyen, Dao M. TI Gossypol, a phytochemical with BH3-mimetic property, sensitizes cultured thoracic cancer cells to Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article; Proceedings Paper CT 86th Annual Meeting of the American-Association-for-Thoracic-Surgery CY APR 29-MAY 03, 2006 CL Philadelphia, PA SP Amer Assoc Thorac Surg ID TRAIL-INDUCED APOPTOSIS; BCL-X-L; IN-VIVO; APO2L/TRAIL; INHIBITOR; PROTEINS; MALIGNANCIES; MECHANISMS; RESISTANCE; DEATH AB Objectives: Chemotherapeutic agents sensitize cancer cells to Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL) via recruitment of the mitochondria-dependent activation of caspase and induction of apoptosis. This study was designed to evaluate whether gossypol, a phytochemical compound with BH3-mimetic property that functions as an inhibitor of Bcl2/BclXL, would sensitize cultured thoracic cancer cells to this death-inducing ligand. Methods: Cancer cell lines from the lung (H460, H322), the esophagus (TE2, TE12), and the pleura (H290, H211) or primary normal cells were treated with gossypol + Apo2L/TRAIL combinations. Cell viability and apoptosis were evaluated by (4,5-dimethylthiazo-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) assays, respectively. Caspase 9 and 3 specific proteolytic activity in combination-treated cells was determined by fluorometric enzymatic assay. Results: Gossypol, selectively cytotoxic to cancer cells and not primary normal cells, significantly sensitized thoracic cancer cells to Apo2L/TRAIL as indicated by 1.5-to more than 10-fold reduction of Apo2L/TRAIL 50% inhibitory concentration values in cells treated with gossypol + Apo2L/TRAIL combinations. Whereas less than 20% of cancer cells exposed to either gossypol (5 mu mol/L) or Apo2L/TRAIL (20 ng/mL) were dead, more than 90% of cells treated with the drug combinations were apoptotic. Combination-induced cytotoxicity and apoptosis was completely abrogated either by overexpression of Bcl2 or by the selective caspase 9 inhibitor. This combination was not toxic to normal cells. Conclusion: Gossypol profoundly sensitizes thoracic cancer cells to the cytotoxic effect of Apo2L/TRAIL via activation of the mitochondria- dependent death signaling pathway. This study provides evidence for the profound anticancer activity of this drug combination and should be further evaluated as a novel targeted molecular therapeutic for thoracic cancers. C1 NCI, Sect Thorac Oncol, Surg Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Nguyen, DM (reprint author), Room 4W-4-3940,10 Ctr Dr, Bethesda, MD 20892 USA. EM dao_nguyen@nih.gov FU Intramural NIH HHS NR 23 TC 26 Z9 27 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD DEC PY 2006 VL 132 IS 6 BP 1356 EP U17 DI 10.1016/j.jtcvs.2006.07.025 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 113VN UT WOS:000242626200018 PM 17140955 ER PT J AU Colina, CM Venkateswarlu, D Duke, R Perera, L Pedersen, LG AF Colina, C. M. Venkateswarlu, D. Duke, R. Perera, L. Pedersen, L. G. TI What causes the enhancement of activity of factor VIIa by tissue factor? SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Letter ID COAGULATION-FACTOR; BLOOD-COAGULATION; CRYSTAL-STRUCTURE; ACTIVATION; DOMAIN; IDENTIFICATION; RESIDUES; COFACTOR; COMPLEX; BINDING C1 Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA. NCAT, Dept Chem, Greensboro, NC USA. NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. RP Pedersen, LG (reprint author), Univ N Carolina, Dept Chem, Campus Box 3290, Chapel Hill, NC 27599 USA. EM lee_pedersen@unc.edu RI perera, Lalith/B-6879-2012; Pedersen, Lee/E-3405-2013; Venkateswarlu, Divi/K-1815-2014 OI perera, Lalith/0000-0003-0823-1631; Pedersen, Lee/0000-0003-1262-9861; Venkateswarlu, Divi/0000-0003-2481-7480 FU Intramural NIH HHS; NHLBI NIH HHS [HL-06350] NR 19 TC 5 Z9 5 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1538-7933 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD DEC PY 2006 VL 4 IS 12 BP 2726 EP 2729 DI 10.1111/j.1538-7836.2006.02222.x PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 104IB UT WOS:000241951000037 PM 17002651 ER PT J AU Cooper, GS Parks, CG Schur, PS Fraser, PA AF Cooper, Glinda S. Parks, Christine G. Schur, Peter S. Fraser, Patricia A. TI Occupational and environmental associations with antinuclear antibodies in a general population sample SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; AUTOANTIBODIES; RISK; CONCORDANCE; PREVALENCE; EXPOSURE; DISEASE; SILICA; TWINS AB Antinuclear antibodies are a hallmark feature of the autoimmune disease systemic lupus erythematosus, and can occur many years before onset of symptoms. The objective of this study was to examine the association between exposures and high-titer antinuclear antibodies in the general population (i.e., people who do not have lupus or other systemic autoimmune diseases). Serum was collected from 266 population-based controls who had been frequency-matched to the age and gender distribution of lupus cases in a 60-county study area in the southeastern United States. A detailed occupational history was collected using a structured interview; information was also collected on hair dye use. Antinuclear antibodies were assayed using HEp-2 cells as substrate. Logistic regression was used to estimate the odds ratio (OR) as a measure of association between exposures and high-titer antinuclear antibody levels, adjusting for age, gender, and race. High-titer antinuclear antibodies (>= 1:160) were observed in 21 subjects (8%). A twofold increased prevalence of high-titer antinuclear antibodies was seen with some occupational exposures (silica dust, pesticides, and sunlight), although none of these individual estimates were statistically significant. The association seen with use of hair dyes was weaker (OR 1.4). There was a suggestion of a dose response with a combined measure based on the summation of exposures (ORs of 1.7, 2.1, and 5.9 for 1, 2, and >= d 3 exposures). These data suggest that occupational exposures may influence the expression of antinuclear antibodies. Larger studies addressing these exposures may provide insights into the mechanisms by which various environmental factors affect the development of autoantibodies and the progression to clinical disease. C1 Natl Inst Environm Hlth Sci, Dept Hlth & Human Serv, NIH, Durham, NC USA. NIOSH, Morgantown, WV USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Cooper, GS (reprint author), NIEHS, Epidemiol Branch, MD A3-05,POB 12233, Res Triangle Pk, NC 27709 USA. EM gscooper1@gmail.com OI Parks, Christine/0000-0002-5734-3456 FU Intramural NIH HHS; NIEHS NIH HHS [ES10295, ES10457] NR 17 TC 15 Z9 17 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1528-7394 J9 J TOXICOL ENV HEAL A JI J. Toxicol. Env. Health Part A PD DEC 1 PY 2006 VL 69 IS 23 BP 2063 EP 2069 DI 10.1080/15287390600746165 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 097HV UT WOS:000241438900001 PM 17060093 ER PT J AU Lee, SJ Choyke, LT Locklin, JK Wood, BJ AF Lee, S. Justin Choyke, Lynda T. Locklin, Julia K. Wood, Bradford J. TI Use of hydrodissection to prevent nerve and muscular damage during radiofrequency ablation of kidney tumors SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID RENAL-CELL CARCINOMA AB Muscular complications are uncommon but have been reported after radiofrequency (RF) ablation of renal tumors. Ablation of renal lesions near the psoas muscle may result in paresthesia in the distribution of the genitofemoral nerve. The present report describes a case of sensory and muscular dysfunction after RF ablation of a renal lesion lying on top of the psoas muscle that was treated without hydrodissection. To prevent this complication, hydrodissection was effectively used in two other patients during RF ablation of lesions abutting or in close proximity to the psoas muscle. C1 NCI, Dept Diagnost Radiol, Ctr Clin, Urol Oncol Branch,NIH, Bethesda, MD 20892 USA. RP Locklin, JK (reprint author), NCI, Dept Diagnost Radiol, Ctr Clin, Urol Oncol Branch,NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM locklinj@cc.nih.gov FU Intramural NIH HHS [Z99 CL999999] NR 5 TC 31 Z9 31 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD DEC PY 2006 VL 17 IS 12 BP 1967 EP 1969 DI 10.1097/01.RVI.0000248829.49442.0E PG 3 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 123FK UT WOS:000243281500015 PM 17185695 ER PT J AU Neeman, Z Dromi, SA Sarin, S Wood, BJ AF Neeman, Ziv Dromi, Sergio A. Sarin, Shawn Wood, Bradford J. TI CT fluoroscopy shielding: Decreases in scattered radiation for the patient and operator SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID INTERVENTIONAL PROCEDURES; COMPUTED-TOMOGRAPHY; PERSONNEL; EXPOSURE; GUIDANCE; DEVICE; TIME; HAND AB PURPOSE: High-radiation exposure occurs during computed tomographic (CT) fluoroscopy. Patient and operator doses during thoracic and abdominal interventional procedures were studied in the present experiment, and a novel shielding device to reduce exposure to the patient and operator was evaluated. MATERIALS AND METHODS: With a 16-slice CT scanner in CT fluoroscopy mode (120 kVp, 30 mA), surface dosimetry was performed on adult and pediatric phantoms. The shielding was composed of tungsten antimony in the form of a lightweight polymer sheet. Doses to the patient were measured with and without shielding for thoracic and abdominal procedures. Doses to the operator were recorded with and without phantom, gantry, and table shielding in place. Double-layer lead-free gloves were used by the operator during the procedures. RESULTS: Tungsten antimony shielding adjacent to the scan plane resulted in a maximum dose reduction of 92.3% to the patient. Maximum 85.6%, 93.3%, and 85.1% dose reductions were observed for the operator's torso, gonads, and hands, respectively. The use of double-layer lead-free gloves resulted in a maximum radiation dose reduction of 97%. CONCLUSIONS: Methods to reduce exposure during CT fluoroscopy are effective and should be searched for. Significant reduction in radiation doses to the patient and operator can be accomplished with tungsten antimony shielding. C1 NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. RP Neeman, Z (reprint author), NIH, Dept Diagnost Radiol, Ctr Clin, Bldg 10,Room 1C 660,10 Ctr Dr, Bethesda, MD 20892 USA. EM zneeman@cc.nih.gov FU Intramural NIH HHS [Z99 CL999999] NR 26 TC 27 Z9 28 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD DEC PY 2006 VL 17 IS 12 BP 1999 EP 2004 DI 10.1097/01.RVI.0000244847.63204.5F PG 6 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 123FK UT WOS:000243281500019 PM 17185699 ER PT J AU Tilton, JC Johnson, AJ Luskin, MR Manion, MM Yang, J Adelsberger, JW Lempicki, RA Hallahan, CW McLaughlin, M Mican, JM Metcalf, JA Iyasere, C Connors, M AF Tilton, John C. Johnson, Alison J. Luskin, Marlise R. Manion, Maura M. Yang, Jun Adelsberger, Joseph W. Lempicki, Richard A. Hallahan, Claire W. McLaughlin, Mary Mican, JoAnn M. Metcalf, Julia A. Iyasere, Christiana Connors, Mark TI Diminished production of monocyte proinflammatory cytokines during human immunodeficiency virus viremia is mediated by type I interferons SO JOURNAL OF VIROLOGY LA English DT Article ID CD8(+) T-CELLS; PLASMACYTOID DENDRITIC CELLS; IMMUNE RESTORATION DISEASE; HIV-INFECTED INDIVIDUALS; NECROSIS-FACTOR-ALPHA; ANTIRETROVIRAL THERAPY; HIV-1-INFECTED SUBJECTS; PROLIFERATIVE CAPACITY; HOMOSEXUAL MEN; CD4(+) AB The effect of human immunodeficiency virus (HIV) infection and high-level HIV replication on the function of monocytes was investigated. HIV-positive patients had elevated levels of spontaneous production of some or all of the monocyte proinflammatory cytokines measured (interleukin-1 beta [IL-1 beta], IL-6, and tumor necrosis factor alpha [TNF-alpha]) compared to uninfected controls. In patients on therapy with high frequencies of monocytes producing proinflammatory cytokines, this frequency was diminished in the context of viremia during an interruption of therapy. Diminished production of proinflammatory cytokines during viremia was restored by culture with autologous CD4(+) T cells or monocytes from an on-therapy time point or lipopolysaccharide (LPS). Microarray analysis demonstrated that diminished monocyte production of proinflammatory cytokines was correlated with elevated type I interferon-stimulated gene transcripts. The addition of exogenous alpha 2A interferon diminished the spontaneous production of IL-1 beta, IL-6, and TNF-alpha but did not affect responses to LPS, recapitulating the changes observed for HIV-viremic patients. These results suggest that monocyte function is diminished during high-level HIV viremia and that this effect is mediated by chronic stimulation by type I interferons. This effect on monocytes during viremia may play a role in diminished innate or adaptive immune system functions in HIV-infected patients. In addition, the restoration of these functions may also play a role in some immune reconstitution syndromes observed during initiation of therapy. C1 NIAID, LIR, NIH, Bethesda, MD 20892 USA. SAIC Frederick Inc, Serv Clin Program, Frederick, MD USA. RP Connors, M (reprint author), NIAID, LIR, NIH, Bldg 10,Rm 11B-09,10 Ctr Dr,MSC 1876, Bethesda, MD 20892 USA. EM mconnors@niaid.nih.gov RI Lempicki, Richard/E-1844-2012 OI Lempicki, Richard/0000-0002-7059-409X FU NCI NIH HHS [N01 CO 12400, N01CO12400] NR 57 TC 42 Z9 42 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 DEC PY 2006 VL 80 IS 23 BP 11486 EP 11497 DI 10.1128/JVI.00324-06 PG 12 WC Virology SC Virology GA 108ED UT WOS:000242222200007 PM 17005663 ER PT J AU Govindasamy, L Padron, E McKenna, R Muzyczka, N Kaludov, N Chiorini, JA Agbandje-McKenna, M AF Govindasamy, Lakshmanan Padron, Eric McKenna, Robert Muzyczka, Nicholas Kaludov, Nikola Chiorini, John A. Agbandje-McKenna, Mavis TI Structurally mapping the diverse phenotype of adeno-associated virus serotype 4 SO JOURNAL OF VIROLOGY LA English DT Article ID HEPARAN-SULFATE PROTEOGLYCAN; CENTRAL-NERVOUS-SYSTEM; HUMAN PARVOVIRUS B19; SIALIC-ACID BINDING; HUMAN GENE-THERAPY; EFFICIENT TRANSDUCTION; TYPE-2 CAPSIDS; MINUTE VIRUS; INTRAMUSCULAR INJECTION; MUTATIONAL ANALYSIS AB The adeno-associated viruses (AAVs) can package and deliver foreign DNA into cells for corrective gene delivery applications. The AAV serotypes have distinct cell binding, transduction, and antigenic characteristics that have been shown to be dictated by the capsid viral protein (VP) sequence. To understand the contribution of capsid structure to these properties, we have determined the crystal structure of AAV serotype 4 (AAV4), one of the most diverse serotypes with respect to capsid protein sequence and antigenic reactivity. Structural comparison of AAV4 to AAV2 shows conservation of the core beta strands (beta B to beta I) and helical (alpha A) secondary structure elements, which also exist in all other known parvovirus structures. However, surface loop variations (I to IX), some containing compensating structural insertions and deletions in adjacent regions, result in local topological differences on the capsid surface. These include AAV4 having a deeper twofold depression, wider and rounder protrusions surrounding the threefold axes, and a different topology at the top of the fivefold channel from that of AAV2. Also, the previously observed "valleys" between the threefold protrusions, containing AAV2's heparin binding residues, are narrower in AAV4. The observed differences in loop topologies at subunit interfaces are consistent with the inability of AAV2 and AAV4 VPs to combine for mosaic capsid formation in efforts to engineer novel tropisms. Significantly, all of the surface loop variations are associated with amino acids reported to affect receptor recognition, transduction, and anticapsid antibody reactivity for AAV2. This observation suggests that these capsid regions may also play similar roles in the other AAV serotypes. C1 Univ Florida, Coll Med, Dept Biochem & Mol Biol, Ctr Struct Biol,McKnight Brain Inst, Gainesville, FL 32610 USA. Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL 32610 USA. Univ Florida, Coll Med, Powell Gene Therapy Ctr, Gainesville, FL 32610 USA. NIDCR, NIH, Bethesda, MD 20892 USA. RP Agbandje-McKenna, M (reprint author), Univ Florida, Coll Med, Dept Biochem & Mol Biol, Ctr Struct Biol,McKnight Brain Inst, Gainesville, FL 32610 USA. EM mckenna@ufl.edu FU Intramural NIH HHS; NHLBI NIH HHS [P01 HL 51811, P01 HL051811] NR 71 TC 83 Z9 84 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2006 VL 80 IS 23 BP 11556 EP 11570 DI 10.1128/JVI.01536-06 PG 15 WC Virology SC Virology GA 108ED UT WOS:000242222200013 PM 16971437 ER PT J AU Wessels, E Duijsings, D Lanke, KHW van Dooren, SHJ Jackson, CL Melchers, WJG van Kuppeveld, FJM AF Wessels, Els Duijsings, Daniel Lanke, Kjerstin H. W. van Dooren, Sander H. J. Jackson, Catherine L. Melchers, Willem J. G. van Kuppeveld, Frank J. M. TI Effects of picornavirus 3A proteins on protein transport and GBF1-dependent COP-I recruitment SO JOURNAL OF VIROLOGY LA English DT Article ID MOUTH-DISEASE VIRUS; TO-GOLGI TRANSPORT; HEPATITIS-A VIRUS; COXSACKIEVIRUS 2B PROTEIN; PORE COMPLEX COMPOSITION; ENDOPLASMIC-RETICULUM; MEMBRANE ASSOCIATION; POLIOVIRUS INFECTION; EXCHANGE FACTOR; VIRAL PROTEIN AB The 3A protein of the coxsackievirus B3 (CVB3), an enterovirus that belongs to the family of the picorna-viruses, inhibits endoplasmic reticulum-to-Golgi transport. Recently, we elucidated the underlying mechanism by showing that CVB3 3A interferes with ADP-ribosylation factor I (Arf1)-dependent COP-1 recruitment to membranes by binding and inhibiting the function of GBF1, a guanine nucleotide exchange factor that is required for the activation of Arf1 (E. Wessels et al., Dev. Cell 11:191-201, 2006). Here, we show that the 3A protein of poliovirus, another enterovirus, is also able to interfere with COP-1 recruitment through the same mechanism. No interference with protein transport or COP-I recruitment was observed for the 3A proteins of any of the other picornaviruses tested here (human rhinovirus [HRV], encephalomyocarditis virus, foot-and-mouth disease virus, and hepatitis A virus). We show that the 3A proteins of HRV, which are the most closely related to the enteroviruses, are unable to inhibit COP-I recruitment, due to a reduced ability to bind GBF1. When the N-terminal residues of the HRV 3A proteins are replaced by those of CVB3 3A, chimeric proteins are produced that have gained the ability to bind GBF1 and, by consequence, to inhibit protein transport. These results show that the N terminus of the CVB3 3A protein is important for binding of GBF1 and its transport-inhibiting function. Taken together, our data demonstrate that the activity of the enterovirus 3A protein to inhibit GBF1-dependent COP-1 recruitment is unique among the picornaviruses. C1 Radboud Univ Nijmegen, Med Ctr, Dept Med Microbiol, Nijmegen Ctr Mol Life Sci, NL-6500 HB Nijmegen, Netherlands. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP van Kuppeveld, FJM (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Med Microbiol, Nijmegen Ctr Mol Life Sci, POB 9101, NL-6500 HB Nijmegen, Netherlands. EM f.vankuppeveld@ncmls.ru.nl RI Jackson, Catherine/A-3421-2013; Melchers, Willem/C-8819-2015 OI Jackson, Catherine/0000-0002-0843-145X; Melchers, Willem/0000-0002-5446-2230 NR 51 TC 60 Z9 67 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 DEC PY 2006 VL 80 IS 23 BP 11852 EP 11860 DI 10.1128/JVI.01225-06 PG 9 WC Virology SC Virology GA 108ED UT WOS:000242222200040 PM 17005635 ER PT J AU Garfinkel, DJ Stefanisko, KM Nyswaner, KM Moore, SP Oh, J Hughes, SH AF Garfinkel, David J. Stefanisko, Karen M. Nyswaner, Katherine M. Moore, Sharon P. Oh, Jangsuk Hughes, Stephen H. TI Retrotransposon suicide: Formation of Ty1 circles and autointegration via a central DNA flap SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CENTRAL POLYPURINE TRACT; NUCLEAR-LOCALIZATION SIGNAL; TERMINAL REPEAT CIRCLES; SACCHAROMYCES-CEREVISIAE; REVERSE TRANSCRIPTION; IN-VITRO; RETROVIRAL INFECTION; TN10 TRANSPOSITION; STRAND TRANSFER AB Despite their evolutionary distance, the Saccharomyces cerevisiae retrotransposon Ty1 and retroviruses use similar strategies for replication, integration, and interactions with their hosts. Here we examine the formation of circular Ty1 DNA, which is comparable to the dead-end circular products that arise during retroviral infection. Appreciable levels of circular Ty1 DNA are present with one-long terminal repeat (LTR) circles and deleted circles comprising major classes, while two-LTR circles are enriched when integration is defective. One-LTR circles persist when homologous recombination pathways are blocked by mutation, suggesting that they result from reverse transcription. Ty1 autointegration events readily occur, and many are coincident with and dependent upon DNA flap structures that result from DNA synthesis initiated at the central polypurine tract. These results suggest that Ty1-specific mechanisms minimize copy number and raise the possibility that special DNA structures are a targeting determinant. C1 NCI, Gene Regulat & Chromosome Biol Lab, Ft Detrick, MD 21702 USA. NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. RP Garfinkel, DJ (reprint author), NCI, Gene Regulat & Chromosome Biol Lab, POB B, Ft Detrick, MD 21702 USA. EM garfinke@ncifcrf.gov NR 88 TC 12 Z9 12 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 DEC PY 2006 VL 80 IS 24 BP 11920 EP 11934 DI 10.1128/JVI.01483-06 PG 15 WC Virology SC Virology GA 113SP UT WOS:000242617900003 PM 17005648 ER PT J AU Majerciak, V Yamanegi, K Zheng, ZM AF Majerciak, Vladimir Yamanegi, Koji Zheng, Zhi-Ming TI Gene. structure and expression of Kaposi's sarcoma-associated herpesvirus ORF56, ORF57, ORF58, and ORF59 SO JOURNAL OF VIROLOGY LA English DT Article ID PRIMARY EFFUSION LYMPHOMA; EPSTEIN-BARR-VIRUS; VIRAL-DNA POLYMERASE; MESSENGER-RNA; CELL-LINE; TRANSCRIPTIONAL ANALYSIS; PROCESSIVITY FACTOR; BZIP PROTEIN; K-BZIP; HUMAN-HERPESVIRUS-8 AB Though similar to those of herpesvirus saimiri and Epstein-Barr virus (EBV), the Kaposi's sarcoma-associated herpesvirus (KSHV) genome features more splice genes and encodes many genes with bicistronic or polycistronic transcripts. In the present study, the gene structure and expression of KSHV ORF56 (primase), ORF57 (MTA), ORF58 (EBV BMRF2 homologue), and ORF59 (DNA polymerase processivity factor) were analyzed in butyrate-activated KSHV+ JSC-1 cells. ORF56 was expressed at low abundance as a bicistronic ORF56/57 transcript that utilized the same intron, with two alternative branch points, as ORF57 for its RNA splicing. ORF56 was transcribed from two transcription start sites, nucleotides (nt) 78994 (minor) and 79075 (major), but selected the same poly(A) signal as ORF57 for RNA polyadenylation. The majority of ORF56 and ORF57 transcripts were cleaved at nt 83628, although other nearby cleavage sites were selectable. On the opposite strand of the viral genome, colinear ORF58 and ORF59 were transcribed from different transcription start sites, nt 95821 (major) or 95824 (minor) for ORF58 and nt 96790 (minor) or 96794 (major) for ORF59, but shared overlapping poly(A) signals at nt 94492 and 94488. Two cleavage sites, at nt 94477 and nt 94469, could be equally selected for ORF59 polyadenylation, but only the cleavage site at nt 94469 could be selected for ORF58 polyadenylation without disrupting the ORF58 stop codon immediately upstream. ORF58 was expressed in low abundance as a monocistronic transcript, with a long 5' untranslated region (UTR) but a short 3' UTR, whereas ORF59 was expressed in high abundance as a bicistronic transcript, with a short 5' UTR and a long 3' UTR similar to those of polycistronic ORF60 and ORF62. Both ORF56 and ORF59 are targets of ORF57 and were up-regulated significantly in the presence of ORF57, a posttranscriptional regulator. C1 NCI, HIV & AIDS Malignancy Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Zheng, ZM (reprint author), NCI, HIV & AIDS Malignancy Branch, Canc Res Ctr, NIH, 10 Ctr Dr,Rm 10 S255,MSC-1868, Bethesda, MD 20892 USA. EM zhengt@exchange.nih.gov FU Intramural NIH HHS NR 48 TC 36 Z9 36 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2006 VL 80 IS 24 BP 11968 EP 11981 DI 10.1128/JVI.01394-06 PG 14 WC Virology SC Virology GA 113SP UT WOS:000242617900007 PM 17020939 ER PT J AU Ou, W Silver, J AF Ou, Wu Silver, Jonathan TI Stoichiometry of murine leukemia virus envelope protein-mediated fusion and its neutralization SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODY; RETROVIRAL TRANSMEMBRANE PROTEIN; MEMBRANE-FUSION; HETERO-OLIGOMERIZATION; HIV-1 ENVELOPE; CELL-FUSION; TYPE-1; GLYCOPROTEIN; GP41; 2F5 AB Envelope glycoproteins (Envs) of retroviruses form trimers that mediate fusion between viral and cellular membranes and are the targets for neutralizing antibodies. Understanding in detail how Env trimers mediate membrane fusion, and how antibodies interfere with this process, is a fundamental problem in biology with practical implications for the development of antiviral drugs and vaccines. We investigated the stoichiometry of Env-mediated fusion and its inhibition by antibody by inserting an epitope from human immunodeficiency virus for a neutralizing antibody (2F5) into the surface (SU) or transmembrane (TM) protein of murine leukemia virus Env, along with point mutations that abrogate SU and TM function but complement one another. We transfected various combinations of these Env genes and investigated Env-mediated cell fusion and its inhibition by 2F5 antibody. Our results showed that heterotrimers with one functional SU molecule were fusion competent in complementation experiments and that one antibody molecule was sufficient to inactivate the fusion function of a trimer when its epitope was in functional SU or TM. 2F5 antibody could also neutralize trimers with the 2F5 epitope in nonfunctional SU or TM, but less efficiently. C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Silver, J (reprint author), Bldg 4,Room 336,4 Ctr Dr, Bethesda, MD 20892 USA. EM jsilver@nih.gov NR 50 TC 2 Z9 2 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 DEC PY 2006 VL 80 IS 24 BP 11982 EP 11990 DI 10.1128/JVI.01318-06 PG 9 WC Virology SC Virology GA 113SP UT WOS:000242617900008 PM 17035325 ER PT J AU Oliphant, T Nybakken, GE Engle, M Xu, Q Nelson, CA Sukupolvi-Petty, S Marri, A Lachmi, BE Olshevsky, U Fremont, DH Pierson, TC Diamond, MS AF Oliphant, Theodore Nybakken, Grant E. Engle, Michael Xu, Qing Nelson, Christopher A. Sukupolvi-Petty, Soila Marri, Anantha Lachmi, Bat-El Olshevsky, Udy Fremont, Daved H. Pierson, Theodore C. Diamond, Michael S. TI Antibody recognition and neutralization determinants on domains I and II of West Nile virus envelope protein SO JOURNAL OF VIROLOGY LA English DT Article ID BORNE ENCEPHALITIS-VIRUS; HUMANIZED MONOCLONAL-ANTIBODY; DENGUE HEMORRHAGIC-FEVER; E-GLYCOPROTEIN; DEPENDENT ENHANCEMENT; MEMBRANE-FUSION; TYPE-2 VIRUSES; INFECTION; MICE; EPITOPES AB Previous studies have demonstrated that monoclonal antibodies (MAbs) against an epitope on the lateral surface of domain III (DIII) of the West Nile virus (WNV) envelope (E) strongly protect against infection in animals. Herein, we observed significantly less efficient neutralization by 89 MAbs that recognized domain I (DI) or II (DII) of WNV E protein. Moreover, in cells expressing Fc gamma receptors, many of the DI- and DII-specific MAbs enhanced infection over a broad range of concentrations. Using yeast surface display of E protein variants, we identified 25 E protein residues to be critical for recognition by Dl- or DII-specific neutralizing MAbs. These residues cluster into six novel and one previously characterized epitope located on the lateral ridge of DI, the linker region between DI and DIII, the hinge interface between DI and DII, and the lateral ridge, central interface, dimer interface, and fusion loop of DII. Approximately 45% of DI-DII-specific MAbs showed reduced binding with mutations in the highly conserved fusion loop in DII: 85% of these (34 of 40) cross-reacted with the distantly related dengue virus (DENV). In contrast, MAbs that bound the other neutralizing epitopes in DI and DII showed no apparent cross-reactivity with DENV E protein. Surprisingly, several of the neutralizing epitopes were located in solvent-inaccessible positions in the context of the available pseudoatomic model of WNV. Nonetheless, DI and DII MAbs protect against WNV infection in mice, albeit with lower efficiency than DIII-specific neutralizing MAbs. C1 Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. NIH, Viral Dis Lab, Viral Pathogenesis Sect, Bethesda, MD 20892 USA. Israel Inst Biol Res, Dept Infect Dis, IL-70450 Ness Ziona, Israel. RP Diamond, MS (reprint author), Washington Univ, Sch Med, Dept Med, 660 S Euclid Ave,Box 8051, St Louis, MO 63110 USA. EM diamond@borcim.wustl.edu FU Intramural NIH HHS; NIAID NIH HHS [AI061373, U01 AI061373, U54 AI057160] NR 65 TC 160 Z9 169 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2006 VL 80 IS 24 BP 12149 EP 12159 DI 10.1128/JVI.01732-06 PG 11 WC Virology SC Virology GA 113SP UT WOS:000242617900027 PM 17035317 ER PT J AU Mejia, AF Culp, TD Cladel, NM Balogh, KK Budgeon, LR Buck, CB Christensen, ND AF Mejia, Andres F. Culp, Timothy D. Cladel, Nancy M. Balogh, Karla K. Budgeon, Lynn R. Buck, Christopher B. Christensen, Neil D. TI Preclinical model to test human papillomavirus virus (HPV) capsid vaccines in vivo using infectious HPV/cottontail rabbit papillomavirus chimeric papillomavirus particles SO JOURNAL OF VIROLOGY LA English DT Article ID CONTROLLED-TRIAL; YOUNG-WOMEN; IMMUNIZATION; TYPE-16; NEUTRALIZATION; EFFICACY; PROTEIN; CANCER; SERA AB A human papillomavirus (HPV) vaccine consisting of virus-like particles (VLPs) was recently approved for human use. It is generally assumed that VLP vaccines protect by inducing type-specific neutralizing antibodies. Preclinical animal models cannot be used to test for protection against HPV infections due to species restriction. We developed a model using chimeric HPV capsid/cottontail rabbit papillomavirus (CRPV) genome particles to permit the direct testing of HPV VLP vaccines in rabbits. Animals vaccinated with CRPV, HPV type 16 (HPV-16), or HPV-11 VLPs were challenged with both homologous (CRPV capsid) and chimeric (HPV-16 capsid) particles. Strong type-specific protection was observed, demonstrating the potential application of this approach. C1 Penn State Univ, Coll Med, Gittlen Canc Res Fdn, Hershey, PA 17033 USA. Penn State Univ, Coll Med, Dept Microbiol & Immunol, Hershey, PA 17033 USA. NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. RP Christensen, ND (reprint author), Penn State Univ, Coll Med, Gittlen Canc Res Fdn, 500 Univ Dr, Hershey, PA 17033 USA. EM ndc1@psu.edu OI Buck, Christopher/0000-0003-3165-8094 NR 16 TC 24 Z9 26 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 DEC PY 2006 VL 80 IS 24 BP 12393 EP 12397 DI 10.1128/JVI.01583-06 PG 5 WC Virology SC Virology GA 113SP UT WOS:000242617900051 PM 17005666 ER PT J AU Krantz, DS Olson, MB Francis, JL Phankao, C Merz, CNB Sopko, G Vido, DA Shaw, LJ Sheps, DS Pepine, CJ Matthews, KA AF Krantz, David S. Olson, Marian B. Francis, Jennifer L. Phankao, Carolyn Bairey Merz, C. Noel Sopko, George Vido, Diane A. Shaw, Leslee J. Sheps, David S. Pepine, Carl J. Matthews, Karen A. CA WISE Investigators TI Anger, hostility, and cardiac symptoms in women with suspected coronary artery disease: The Women's Ischemia Syndrome Evaluation (WISE) study SO JOURNAL OF WOMENS HEALTH LA English DT Article ID NHLBI-SPONSORED WISE; HEART-DISEASE; CHRONIC PAIN; A BEHAVIOR; CAROTID ATHEROSCLEROSIS; POSTMENOPAUSAL WOMEN; MYOCARDIAL-ISCHEMIA; SOCIAL SUPPORT; RISK-FACTORS; CHEST PAIN AB Objective: To determine the relationship of anger and hostility to angiographic coronary artery disease (CAD), symptoms, and functional status among women with suspected CAD. Methods: Data were collected from 636 women with suspected CAD referred for diagnostic angiography in the Women's Ischemia Syndrome Evaluation (WISE) Study. CAD was assessed as angiographic presence/absence of disease (>= 50% stenosis in any epicardial coronary artery). Hostility/anger, angina, symptoms, and functional status were assessed by the Cook-Medley Hostility Inventory, Spielberger Anger Expression Scale, cardiovascular symptom history, and the Duke Activity Status Index. Results: Logistic regression revealed that anger-out (i.e., aggressive behavior in response to angry feelings) was independently associated with the presence/absence of angiographic CAD (OR=1.09, CI 1.01-1.17). Anger and hostility were higher among women reporting increased cardiovascular symptoms. In women without angiographic CAD, those with nonanginal cardiac symptoms had the highest anger-out, anger expression, hostile affect, and aggressive responding scores, and those with typical angina reported the lowest functional status. Among women with CAD, functional status was lowest in women with atypical angina. Conclusions: Among women with suspected CAD, anger-out scores were associated with the presence of angiographic CAD. Anger/hostility traits were associated with increased symptoms, particularly with nonanginal chest pain in women without angiographic CAD. Relationships among psychosocial factors, cardiac symptoms, and angiographic CAD are potentially important in the management of women with suspected CAD. C1 Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, Bethesda, MD 20814 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. Cedars Sinai Med Ctr, Cedars Sinai Res Inst, Dept Med, Div Cardiol, Los Angeles, CA 90048 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. NHLBI, Div Heart & Vasc Dis, NIH, Bethesda, MD 20892 USA. Allegheny Gen Hosp, Dept Med, Pittsburgh, PA 15212 USA. Atlanta Cardiovasc Res Inst, Atlanta, GA USA. Univ Florida, Dept Med, Div Cardiol, Gainesville, FL USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. RP Krantz, DS (reprint author), Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM dskrantz@usuhs.mil RI Krantz, David/L-5364-2015 OI Krantz, David/0000-0002-1671-1355 FU NHLBI NIH HHS [N01-HV-68161, N01-HV-68162, N01-HV-68163, N01-HV-68164, U01 HL649141, U01HL649241]; PHS HHS [U0164829] NR 42 TC 27 Z9 29 U1 1 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD DEC PY 2006 VL 15 IS 10 BP 1214 EP 1223 DI 10.1089/jwh.2006.15.1214 PG 10 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 126GB UT WOS:000243499500013 PM 17199462 ER PT J AU Harrenstien, LA Finnegan, MV Woodford, NL Mansfield, KG Waters, WR Bannantine, JP Paustian, ML Garner, MM Bakke, AC Peloquin, CA Phillips, TM AF Harrenstien, Lisa A. Finnegan, Mitchell V. Woodford, Nina L. Mansfield, Kristin G. Waters, W. Ray Bannantine, John P. Paustian, Michael L. Garner, Michael M. Bakke, Antony C. Peloquin, Charles A. Phillips, Terry M. TI Mycobacterium avium in pygmy rabbits (Brachylagus idahoensis): 28 cases SO JOURNAL OF ZOO AND WILDLIFE MEDICINE LA English DT Article DE Brachylagus idahoensis; cell-mediated immunity; mycobacteriosis; Mycobacterium avium complex; pygmy rabbit ID IMMUNOAFFINITY CAPILLARY-ELECTROPHORESIS; POLYMERASE-CHAIN-REACTION; DENDROLAGUS-MATSCHIEI; EASTERN WASHINGTON; FASTING CONDITIONS; COMPLEX INFECTION; OSTEOMYELITIS; PARATUBERCULOSIS; DIAGNOSIS; PHARMACOKINETICS AB The Columbia basin subpopulation of pygmy rabbit Brachylagus idahoensis was listed as endangered by the United States Fish and Wildlife Service in November 2001, and no pygmy rabbits have been seen in the wild since spring 2002. Captive propagation efforts have attempted to increase population size in preparation for reintroduction of animals into central Washington. Disseminated mycobacteriosis due to Mycobacterium avium has been the most common cause of death of adult captive pygmy rabbits. Between June 2002 and September 2004, mycobacteriosis was diagnosed in 28 captive adult pygmy rabbits (representing 29% of the captive population), in contrast to 18 adult pygmy rabbits dying of all other causes in the same time period. Antemortem and postmortem medical records were evaluated retrospectively to describe the clinical course of mycobacteriosis in pygmy rabbits, physical examination findings, and diagnostic test results in the diagnosis of mycobacteriosis in pygmy rabbits. Various treatment protocols, possible risk factors for mortality. and recommendations for prevention of mycobacteriosis were evaluated also. Compromised cell-mediated immunity appears to be the best explanation at this time for the observed high morbidity and mortality from mycobacterial infections in pygmy rabbits. C1 Oregon Zoo, Portland, OR 97221 USA. Washington State Univ, Coll Vet Med, Off Campus Veterinarian, Pullman, WA 99164 USA. Washington Dept Fish & Wildlife, Spokane, WA 99216 USA. USDA ARS, Natl Anim Dis Ctr, Bacterial Dis Livestock Res Unit, Ames, IA 50010 USA. NW ZooPath, Monroe, WA 98272 USA. Oregon Hlth Sci Univ, Dept Pathol & Med, Portland, OR 97239 USA. Natl Jewish Med & Res Ctr, Dept Med, Denver, CO 80206 USA. Univ Colorado, Sch Pharm, Denver, CO 80206 USA. Univ Colorado, Sch Med, Denver, CO 80206 USA. NIH, Bethesda, MD 20892 USA. RP Harrenstien, LA (reprint author), Oregon Zoo, 4001 SW Canyon Rd, Portland, OR 97221 USA. OI Bannantine, John/0000-0002-5692-7898 NR 46 TC 8 Z9 8 U1 0 U2 3 PU AMER ASSOC ZOO VETERINARIANS PI MEDIA PA 6 NORTH PENNELL ROAD, MEDIA, PA 19063 USA SN 1042-7260 J9 J ZOO WILDLIFE MED JI J. Zoo Wildl. Med. PD DEC PY 2006 VL 37 IS 4 BP 498 EP 512 DI 10.1638/05-002.1 PG 15 WC Veterinary Sciences SC Veterinary Sciences GA 124KS UT WOS:000243367300008 PM 17315435 ER PT J AU Inouye, SK Ferrucci, L AF Inouye, Sharon K. Ferrucci, Luigi TI Elucidating the pathophysiology of delirium and the interrelationship of delirium and dementia SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Editorial Material ID MEDICAL INPATIENTS; ELDERLY-PATIENTS; OLDER PERSONS; CARE C1 Hebrew SeniorLife, Aging Brain Ctr, Inst Aging Res, Boston, MA 02131 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02115 USA. NIA, Clin Res Branch, Baltimore, MD 21224 USA. RP Inouye, SK (reprint author), Hebrew SeniorLife, Aging Brain Ctr, Inst Aging Res, 1200 Ctr St, Boston, MA 02131 USA. EM agingbraincenter@hrca.harvard.edu FU Intramural NIH HHS [Z99 AG999999]; NIA NIH HHS [R21 AG025193, P60AG00812, K24 AG000949, R21AG025193, K24AG00949, P50AG005134, P50 AG005134] NR 22 TC 46 Z9 49 U1 1 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD DEC PY 2006 VL 61 IS 12 BP 1277 EP 1280 PG 4 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 129AR UT WOS:000243701300008 PM 17234820 ER PT J AU Miller, FG Joffe, S AF Miller, Franklin G. Joffe, Steven TI Evaluating the therapeutic misconception SO KENNEDY INSTITUTE OF ETHICS JOURNAL LA English DT Article ID PLACEBO-CONTROLLED TRIALS; INFORMED-CONSENT; RESEARCH PARTICIPANTS; CLINICAL-TRIALS AB The "therapeutic misconception," described by Paul Appelbaum and colleagues more than 20 years ago, refers to the tendency of participants in clinical trials to confuse the design and conduct of research with personalized medical care. Although the "therapeutic misconception" has become a term of art in research ethics, little systematic attention has been devoted to the ethical significance of this phenomenon. This article examines critically the way in which Appelbaum and colleagues formulate what is at stake in the therapeutic misconception, paying particular attention to assumptions and implications that clinical trial participation disadvantages research participants as compared with receiving standard medical care. After clarifying the ethical significance of the therapeutic misconception with respect to the decision making of patients, we offer policy recommendations for obtaining informed consent to participation in clinical trials. C1 NIH, Unit Clin Res, Dept Clin Bioeth, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Miller, FG (reprint author), NIH, Unit Clin Res, Dept Clin Bioeth, Bldg 10, Bethesda, MD 20892 USA. OI Joffe, Steven/0000-0002-0667-7384 NR 20 TC 30 Z9 30 U1 1 U2 1 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 1054-6863 J9 KENNEDY INST ETHIC J JI Kennedy Inst. Ethics J. PD DEC PY 2006 VL 16 IS 4 BP 353 EP 366 DI 10.1353/ken.2006.0025 PG 14 WC Ethics; Philosophy; Social Issues SC Social Sciences - Other Topics; Philosophy; Social Issues GA 119TU UT WOS:000243037300003 PM 17847601 ER PT J AU Friedman, EA Friedman, AL Eggers, P AF Friedman, E. A. Friedman, A. L. Eggers, P. TI End-stage renal disease in diabetic persons: Is the pandemic subsiding? SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT Meeting on Novel and Evolving Treatment Approaches to Manage Chronic Kidney Disease CY MAY 05-06, 2006 CL Brooklyn, NY DE diabetes; nephropathy; pandemic; renoprotection; hypertension; end-stage renal disease ID CHRONIC KIDNEY-DISEASE; CARDIOVASCULAR RISK; BLOOD-GLUCOSE; REGISTER; TYPE-1; TRIAL AB Analysis of data compiled by the United States Renal Data System and the National Health Interview Survey as reported in the Centers for Disease Control and Prevention's Weekly Morbidity and Mortality Report indicates that between 1990 and 2002, there has been a sharp decline in incidence rate of the number of persons with diabetes who develop end-stage renal disease. Although it is comforting to practitioners to attribute this improvement to a widely advocated regimen of renoprotection, consisting of careful regulation of hypertensive blood pressure, improved glycemic control, and lifestyle modification, evidence for this causal relationship is appearing only now. There is need to clarify the source of this epidemiologic change that will lessen the projected burden on medical and socioeconomic resources in the immediate future. C1 Suny Downstate Med Ctr, Dept Med, Brooklyn, NY 11203 USA. Yale Univ, Sch Med, Dept Surg, New Haven, CT 06510 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Friedman, EA (reprint author), Suny Downstate Med Ctr, Dept Med, Brooklyn, NY 11203 USA. EM elifriedmn@aol.com NR 26 TC 8 Z9 8 U1 0 U2 0 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 DEC PY 2006 VL 70 SU 104 BP S51 EP S54 DI 10.1038/sj.ki.5001978 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 109YR UT WOS:000242346000012 ER PT J AU Noh, MY Jo, YH Oh, SH Kim, DH Park, HJ Kim, I Barillas-Mury, C Kim, HC Lee, WJ Lee, IH Seo, SJ Kang, SW Lee, YS Kho, WG Kang, SS Han, YS AF Noh, Mi Young Jo, Yong Hun Oh, Seung Han Kim, Dong Hyun Park, Hee Jung Kim, Iksoo Barillas-Mury, Carolina Kim, Heung Chul Lee, Won-Ja Lee, In Hee Seo, Sook Jae Kang, Se Won Lee, Yong Seok Kho, Weon-Gyu Kang, Sang Sun Han, Yeon Soo TI Cloning and subcellular localization of a serpin containing nuclear export signal from the Korean malaria vector, Anopheles sinensis SO KOREAN JOURNAL OF GENETICS LA English DT Article DE Anopheles sinensis; Plasmodium berghei; serpin; midgut; apoptosis; time bomb model ID PLASMODIUM-BERGHEI; MIDGUT CELLS; NUCLEOCYTOPLASMIC DISTRIBUTION; INVASION; GAMBIAE; PROTEIN; OVEREXPRESSION; PATHWAY; SUMO AB Anopheles sinensis is known to play a critical role in malaria transmission and re-emergence in the areas near the Demilitarized Zone (DMZ) of Korea. However, no study on Plasmodium-midgut interactions using A. sinensis has been reported. Here, we describe the cloning and dynamic subcellular localization of the orthologue of Anopheles gambiae (AgSRPN10), isoform RCM from Anopheles sinensis (AnsiSRPN-10). AnsiSRPN10 mRNA is expressed in embryoes, and is almost undetectable in 4(th) instar larvae. It increases transiently in pupae and is most abundant in adult females. Expression is higher in the abdomen and the midgut compared to the thorax and ovary. It is induced in response to laminarin and Actinomycin-D. AnsiSRPN10 protein does not contain a consensus nuclear localization signal (NLS), but has a putative nuclear export signal (NES) and small ubiquitin-like modifier (SUMO) modification site. It is present mainly in the nucleus of healthy midgut cells, but translocates from the nucleus to the cytosol in Plasmodium-invaded cells. AnsiSRPN10 expression increases as midgut cells undergo apoptosis, indicating that the epithelial responses to P. berghei invasion are conserved across different anopheline species. AnsiSRPN10 is a useful marker of Plasmodium-induced apoptosis in midgut. To our knowledge, this is the first report on A. sinensis innate immunity in the context of Time Bomb model. C1 Chonnam Natl Univ, Coll Agr & Life Sci, Dept Agr Biol, Kwangju 500757, South Korea. NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. USA, Med Detachment 5, Med Command 18th, Seoul 96205, South Korea. Korea Ctr Dis Control & Prevent, Dept Med Entomol, Seoul 122701, South Korea. Inje Univ, Coll Med, PICR, Dept Parasitol & Malariol, Pusan 614735, South Korea. Inje Univ, Frontier Inje Res Sci & Technol, Pusan 614735, South Korea. RP Han, YS (reprint author), Chonnam Natl Univ, Coll Agr & Life Sci, Dept Agr Biol, Kwangju 500757, South Korea. EM hanys@chonnam.ac.kr NR 27 TC 2 Z9 4 U1 0 U2 0 PU GENETICS SOC KOREA PI SEOUL PA SEOUL NATL UNIV, DEPT BIOLOGY, COLL EDUCATION, SINLIMDONG SAN 56-1, KWANAKGU, SEOUL 151-742, SOUTH KOREA SN 0254-5934 J9 KOREAN J GENETIC JI Korean J. Genet. PD DEC PY 2006 VL 28 IS 4 BP 433 EP 441 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 130BF UT WOS:000243773300015 ER PT J AU Reddy, V Khan, AI Remaley, AT Wians, FH AF Reddy, Vtkrarn Khan, Adil I. Remaley, Alan T. Wians, Frank H., Jr. TI Update on point-of-surgery testing SO LABMEDICINE LA English DT Review ID SURGICAL-MANAGEMENT; PARATHYROID-HORMONE; ASSAY; INSULINOMAS AB In the approximately 10-year period since the introduction of intra-operative parathyroid hormone testing, a variety of hormones have proven to be valuable tools in the surgical management of patients with various types of resectable tumors. To what extent the current list of hormones/markers performed intra-operatively will expand will be related, in part, to the speed with which new hormones/tumor markers are identified that meet the criteria indicated below for useful markers in point-of-surgery testing (POST). With the exception of intra-operative parathyroid hormone (loPTH) testing, testing for the other hormones indicated below is performed at specialized centers using either modified commercial ("hormone brew") or research uses only (RUO) assays. C1 Univ Texas, SW Med Ctr, Dept Pathol, Dallas, TX 75235 USA. NIH, Dept Lab Med, Bethesda, MD 20892 USA. RP Reddy, V (reprint author), Univ Texas, SW Med Ctr, Dept Pathol, Dallas, TX 75235 USA. NR 12 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 DEC PY 2006 VL 37 IS 12 BP 754 EP 756 DI 10.1309/AMONN9GH76WOLHNV PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 111AM UT WOS:000242422800009 ER PT J AU Cross, AJ Lim, U AF Cross, Amanda J. Lim, Unhee TI The role of dietary factors in the epidemiology of non-Hodgkin's lymphoma SO LEUKEMIA & LYMPHOMA LA English DT Review DE diet; non-Hodgkin's lymphoma; cancer; epidemiology; review ID FOOD FREQUENCY QUESTIONNAIRE; DRINKING-WATER NITRATE; VITAMIN SUPPLEMENT USE; ONE-CARBON METABOLISM; BODY-MASS INDEX; ALCOHOL-CONSUMPTION; CANCER-RISK; UNITED-STATES; MALIGNANT-LYMPHOMA; PHYSICAL-ACTIVITY AB The incidence of non-Hodgkin's lymphoma (NHL) has risen dramatically over recent decades and, despite some known risk factors, such as compromised immunity, the etiology of NHL and the reasons for most of this increase are unknown. Dietary components may be a common and critical source of immunologic antigens and promoters, which needs to be incorporated more in the etiologic research of NHL. To date, epidemiologic evidence suggests that obesity and fat intake, in particular saturated or animal fat, may increase the risk of NHL; whereas whole-grains, vegetables and moderate consumption of alcohol may be inversely associated with NHL risk. Much of the current evidence is obtained from case-control studies, which are subject to dietary recall bias; therefore, this area of research requires further study within prospective cohorts with detailed dietary information and with a large number of cases to examine disease sub-type heterogeneity. C1 NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD 20852 USA. RP Cross, AJ (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD 20852 USA. EM crossa@mail.nih.gov NR 116 TC 24 Z9 24 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD DEC PY 2006 VL 47 IS 12 BP 2477 EP 2487 DI 10.1080/10428190600932927 PG 11 WC Oncology; Hematology SC Oncology; Hematology GA 117IN UT WOS:000242866700011 PM 17169793 ER PT J AU Nathan, PC Whitcomb, T Wolters, PL Steinberg, SM Balis, FM Brouwers, P Hunsberger, S Feusner, J Sather, H Miser, J Odom, LF Poplack, D Reaman, G Bleyer, WA AF Nathan, Paul C. Whitcomb, Trish Wolters, Pamela L. Steinberg, Seth M. Balis, Frank M. Brouwers, Pim Hunsberger, Sally Feusner, James Sather, Harland Miser, James Odom, Lorrie F. Poplack, David Reaman, Gregory Bleyer, W. Archie TI Very high-dose methotrexate (33.6 g/m(2)) as central nervous system preventive therapy for childhood acute lymphoblastic leukemia: results of National Cancer Institute/Children's Cancer Group trials CCG-191P, CCG-134P and CCG-144P SO LEUKEMIA & LYMPHOMA LA English DT Article DE leukemia; lymphocytic; acute; methotrexate; child; intelligence tests ID ACUTE LYMPHOCYTIC-LEUKEMIA; PEDIATRIC-ONCOLOGY-GROUP; LONG-TERM SURVIVORS; CRANIAL IRRADIATION; INTRAVENOUS METHOTREXATE; INTERMEDIATE-RISK; PROPHYLACTIC CHEMOTHERAPY; INTRATHECAL METHOTREXATE; CEREBROSPINAL-FLUID; FOLLOW-UP AB Between 1977 and 1991, the Children's Cancer Group and the National Cancer Institute conducted three trials of very high-dose methotrexate (33.6 g/m(2); VHD-MTX) in place of cranial radiation (CRT) as central nervous system (CNS) preventive therapy, and assessed efficacy, acute toxicity and long-term neurocognitive outcome. CCG-191P compared VHD-MTX to CRT plus intrathecal methotrexate (IT-MTX) in 181 patients and demonstrated equivalent survival. However, patients treated with CRT had poorer performance on neurocognitive testing over time. CCG-134P evaluated the addition of intensified systemic and intrathecal therapy to VHD-MTX in 128 patients with high-risk acute lymphoblastic leukemia ( ALL) and demonstrated reduced CNS relapse compared to the CCG-191P trial, but equivalent survival. CCG-144P compared VHD-MTX to IT-MTX alone in 175 patients with average-risk ALL and demonstrated equivalent survival. VHD-MTX was associated with significant toxicities, particularly neutropenia, transient hepatic dysfunction and sepsis. VHD-MTX achieved similar survival to other CNS-directed therapies without the long-term impact on intelligence, but with substantial acute toxicities. C1 NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. NCI, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. Med Illness Counseling Ctr, Bethesda, MD USA. Childrens Reg Med Ctr, Seattle, WA USA. Childrens Hosp No Calif, Oakland, CA USA. Childrens Oncol Grp, Arcadia, CA USA. Childrens Hosp, Columbus, OH 43205 USA. Childrens Hosp, Denver, CO 80218 USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. RP Balis, FM (reprint author), NCI, Pediat Oncol Branch, NIH, 10 Ctr Dr,Bldg 10 CRC,Room 3-2571, Bethesda, MD 20892 USA. EM balisf@mail.nih.gov FU Intramural NIH HHS; NCI NIH HHS [CA13539, N01-SC-07006]; PHS HHS [HHSN261200477004C] NR 50 TC 23 Z9 25 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD DEC PY 2006 VL 47 IS 12 BP 2488 EP 2504 DI 10.1080/10428190600942769 PG 17 WC Oncology; Hematology SC Oncology; Hematology GA 117IN UT WOS:000242866700012 PM 17169794 ER PT J AU Reynolds, HY AF Reynolds, Herbert Y. TI Medical volunteering: Giving something back SO LUNG LA English DT Article DE health care volunteers; indigent care; senior and retired care givers; general health problems AB A national health issue is how to provide medical care for the large number of people who are uninsured or do not qualify for medical coverage. Establishing free health clinics staffed by volunteer health professionals is one approach that is increasing, but this alone will not solve this societal problem. Many volunteer health care providers are needed, and more senior and retired physicians might be recruited. However, practicing general, not subspeciality, medicine in an unfamiliar surrounding with different patient demands may seem intimidating and anxiety producing. However, a conducive clinical environment and working with other volunteer health care staff may alleviate these feelings and make medical volunteering very enjoyable. The Mercy Health Clinic in Montgomery County, Maryland, has had this effect on us who volunteer there and care for its needy patients. C1 NHLBI, DLD, Rockledge Ctr 2, Bethesda, MD 20892 USA. RP Reynolds, HY (reprint author), NHLBI, DLD, Rockledge Ctr 2, 6701 Rockledge Dr, Bethesda, MD 20892 USA. EM reynoldh@mail.nih.gov NR 4 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0341-2040 J9 LUNG JI Lung PD DEC PY 2006 VL 184 IS 6 BP 369 EP 371 DI 10.1007/s00408-006-0028-x PG 3 WC Respiratory System SC Respiratory System GA 111OU UT WOS:000242463600011 PM 17086461 ER PT J AU Thompson, RB McVeigh, ER AF Thompson, Richard B. McVeigh, Elliot R. TI Cardiorespiratory-resolved magnetic resonance imaging: Measuring respiratory modulation of cardiac function SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE MRI; breathing; respiration; phase contrast; SSFP; radial ID PHASE-CONTRAST; BLOOD-FLOW; CINE MRI; MOTION AB A technique for cardiac- and respiratory-resolved MRI is described. A retrospectively gated-segmented acquisition scheme similar to that used in conventional cine cardiac imaging was used to collect image data that spanned both the cardiac and respiratory cycles. Raw k-space data were regridded in a cardiorespiratory phase space to allow image reconstruction at target cardiac and respiratory phases. The approach can be applied with various k-space trajectories and pulse sequences, and was implemented in this study with both a Cartesian steady-state free precession (SSFP) sequence and a radial phase-contrast (PC) pulse sequence. Free-breathing short-axis SSFP images of the heart were reconstructed at multiple respiratory and cardiac phases to illustrate separation of cardiac and respiratory motion without artifacts. A respiratory-resolved radial PC experiment was used to quantify the volumetric flow rates in the inferior vena cava (IVC), pulmonary artery (PA), and aorta (Ao) in five free-breathing normal volunteers and a positive-pressure ventilated dog. Total flow (ml/min) in each vessel was quantified as a function of respiratory phase (peak/minimum output = 1.85 +/- 0.29 (IVC), 1.36 +/- 0.15 (PA), 1.24 +/- 0.09 (Ao)). Peak flow occurred during inspiration for the IVC and PA, and during expiration for the Ao, and there was a complete pattern reversal for the positive-pressure ventilated dog. C1 Univ Alberta, Dept Biomed Engn, Edmonton, AB T6G 2V2, Canada. NIH, Cardiac Energet Lab, Bethesda, MD 20892 USA. RP Thompson, RB (reprint author), Univ Alberta, Dept Biomed Engn, Edmonton, AB T6G 2V2, Canada. EM richard.thompson@ualberta.ca RI Thompson, Richard/E-9821-2011 FU Intramural NIH HHS [Z01 HL004608-08] NR 16 TC 18 Z9 18 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 DEC PY 2006 VL 56 IS 6 BP 1301 EP 1310 DI 10.1002/mrm.21075 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 110OO UT WOS:000242388400015 PM 17058205 ER PT J AU Baio, G Fabbi, M de Totero, D Ferrini, S Cilli, M Derchi, LE Neumaier, CE AF Baio, G. Fabbi, M. de Totero, D. Ferrini, S. Cilli, M. Derchi, L. E. Neumaier, C. E. TI Magnetic resonance imaging at 1.5T with immunospecific contrast agent in vitro and in vivo in a xenotransplant model SO MAGNETIC RESONANCE MATERIALS IN PHYSICS BIOLOGY AND MEDICINE LA English DT Article DE iron oxide particle; cell-specific MRI; in vivo small animal MRI; targeted contrast material; lymphoma ID SUPERPARAMAGNETIC IRON-OXIDE; RAT-BRAIN; LYMPHOMA; TRACKING; LIVER AB Object: Demonstrating the feasibility of magnetic resonance imaging (MRI) at 1.5 T of ultrasmall particle iron oxide (USPIO)-antibody bound to tumor cells in vitro and in a murine xenotransplant model. Methods: Human D430B cells or Raji Burkitt lymphoma cells were incubated in vitro with different amounts of commercially available USPIO-anti-CD20 antibodies and cell pellets were stratified in a test tube. For in vivo studies, D430B cells and Raji lymphoma cells were inoculated subcutaneously in immunodeficient mice. MRI at 1.5 T was performed with T1-weighted three-dimensional fast field echo sequences (17/4.6/13 degrees) and T2-weighted three-dimensional fast-field echo sequences (50/12/7 degrees). For in vivo studies MRI was performed before and 24 h after USPIO-anti-CD20 administration. Results: USPIO-anti-CD20-treated D430B cells, showed a dose-dependent decrease in signal intensity (SI) on T2*-weighted images and SI enhancement on T1-weighted images in vitro. Raji cells showed lower SI changes, in accordance to the fivefold lower expression of CD20 on Raji with respect to D430B cells. In vivo 24 h after USPIO-anti-CD20 administration, both tumors showed an inhomogeneous decrease of SI on T2*-weighted images and SI enhancement on T1-weighted images. Conclusions: MRI at 1.5 T is able to detect USPIO-antibody conjugates targeting a tumor-associated antigen in vitro and in vivo. C1 Natl Canc Inst, Dept Diagnost Imaging, IST, I-16100 Genoa, Italy. Univ Genoa, DICMI Radiol, I-16100 Genoa, Italy. Natl Canc Inst, Lab Immunol Therapy, IST, I-16100 Genoa, Italy. Natl Canc Inst, Anim Facil, IST, I-16100 Genoa, Italy. RP Neumaier, CE (reprint author), Natl Canc Inst, Dept Diagnost Imaging, IST, Largo Rosanna Benzi 10, I-16100 Genoa, Italy. EM carlo.neumaier@istge.it RI Fabbi, Marina/I-1290-2012; Baio, Gabriella/M-7621-2015; OI Baio, Gabriella/0000-0002-8397-5318; Ferrini, Silvano/0000-0001-7254-2616 NR 16 TC 15 Z9 16 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0968-5243 J9 MAGN RESON MATER PHY JI Magn. Reson. Mat. Phys. Biol. Med. PD DEC PY 2006 VL 19 IS 6 BP 313 EP 320 DI 10.1007/s10334-006-0059-6 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 138UX UT WOS:000244389900004 PM 17160691 ER PT J AU Santos, PE Piontelli, E Shea, YR Galluzzo, ML Holland, SM Zelazko, ME Rosenzweig, SD AF Santos, P. E. Piontelli, E. Shea, Y. R. Galluzzo, M. L. Holland, S. M. Zelazko, M. E. Rosenzweig, S. D. TI Penicillium piceum infection: diagnosis and successful treatment in chronic granulomatous disease SO MEDICAL MYCOLOGY LA English DT Article DE pulmonary nodule; osteomyelitis; voriconazole; surgery; fine needle aspirate ID MARNEFFEI; ASPERGILLUS; FUNGI AB Infections due to Penicillium species other than P. marneffei are rare. We identified a boy with X-linked chronic granulomatous disease (X-CGD) with a pulmonary nodule and adjacent rib osteomyelitis caused by Penicillium piceum. The only sign of infection was an elevated sedimentation rate. P piceum was isolated by fine needle aspirate and from excised infected tissues. Surgical removal and one year of voriconazole treatment were very well tolerated and led to complete recovery. Microbiological, microscopic and molecular studies support the fungal diagnosis. P. piceum should be considered as a relevant pathogen immunocompromised patients. C1 Hosp Pediat J P Garran, Serv Inmunol, Microbiol Lab, RA-1244 Buenos Aires, DF, Argentina. Univ Valparaiso, Escuela Med, Catedra Micol, Valparaiso, Chile. NIH, Ctr Clin, Dept Lab Med, Microbiol Serv, Bethesda, MD USA. Hosp Pediat J P Garrahan, Serv Anat Patol, Buenos Aires, DF, Argentina. NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD USA. Hosp Pediat JP Garrahan, Serv Inmunol, Buenos Aires, DF, Argentina. RP Rosenzweig, SD (reprint author), Hosp Pediat J P Garran, Serv Inmunol, Microbiol Lab, Combate Pozos 1881, RA-1244 Buenos Aires, DF, Argentina. EM srosenzweig@garrahan.gov.ar FU FIC NIH HHS [R01TW006644]; Intramural NIH HHS NR 18 TC 17 Z9 17 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1369-3786 J9 MED MYCOL JI Med. Mycol. PD DEC PY 2006 VL 44 IS 8 BP 749 EP 753 DI 10.1080/13693780600967089 PG 5 WC Infectious Diseases; Mycology; Veterinary Sciences SC Infectious Diseases; Mycology; Veterinary Sciences GA 135KB UT WOS:000244151400008 PM 17127632 ER PT J AU Varma, A Wu, SX Guo, NR Liao, WQ Lu, GX Li, AS Hu, YL Bulmer, G Kwon-Chung, KJ AF Varma, Ashok Wu, Shaoxi Guo, Ningru Liao, Wanqing Lu, Guxia Li, Anshen Hu, Yonglin Bulmer, Glenn Kwon-Chung, Kyung J. TI Identification of a novel gene, URE2, that functionally complements a urease-negative clinical strain of Cryptococcus neoformans SO MICROBIOLOGY-SGM LA English DT Article ID CHROMOSOME SCAFFOLD PROTEIN; CAPSULE-ASSOCIATED GENE; PRESUMPTIVE IDENTIFICATION; 2 VARIETIES; VIRULENCE; TRANSFORMATION; ACTIVATION; MARKER; FAMILY; CONDENSATION AB A urease-negative serotype A strain of Cryptococcus neoformans (B-4587) was isolated from the cerebrospinal fluid of an immunocompetent patient with a central nervous system infection. The URE1 gene encoding urease failed to complement the mutant phenotype. Urease-positive clones of B-4587 obtained by complementing with a genomic, library of strain H99 harboured an episomal plasmid containing DNA inserts with homology to the sudA gene of Aspergillus nidulans. The gene harboured by these plasmids was named URE2 since it enabled the transformants; to grow on media containing urea as the sole nitrogen source while the transformants with an empty vector failed to grow. Transformation of strain B-4587 with a plasmid construct containing a truncated version of the URE2 gene failed to complement the urease-negative phenotype. Disruption of the native URE2 gene in a wild-type serotype A strain H99 and a serotype D strain LP1 of C. neoformans resulted in the inability of the strains to grow on media containing urea as the sole nitrogen source, suggesting that the URE2 gene product is involved in the utilization of urea by the organism. Virulence in mice of the urease-negative isolate B-4587, the urease-positive transformants containing the wild-type copy of the URE2 gene, and the urease-negative vector-only transformants was comparable to that of the H99 strain of C. neoformans regardless of the infection route. Virulence of the URE2 disruption stain of H99 was slightly reduced compared to the wildtype strain in the intravenous model but was significantly attenuated in the inhalation model. These results indicate that the importance of urease activity in pathogenicity varies depending on the strains of C. neoformans used and/or the route of infection. Furthermore, this study shows that complementation cloning can serve as a useful tool to functionally identify genes such as URE2 that have otherwise been annotated as hypothetical proteins in genomic databases. C1 NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. Chinese Acad Med Sci, Inst Dermatol, Beijing 100037, Peoples R China. Peking Union Med Coll, Beijing, Peoples R China. Second Mil Med Univ, Zhangzhen Hosp, Shanghai 200003, Peoples R China. Zhenyi Med Coll, Zhenyi, Peoples R China. RP Kwon-Chung, KJ (reprint author), NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, NIH, Bldg 10,Room 11C304, Bethesda, MD 20892 USA. EM june_kwon-chung@nih.gov FU Intramural NIH HHS NR 37 TC 9 Z9 9 U1 0 U2 4 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1350-0872 J9 MICROBIOL-SGM JI Microbiology-(UK) PD DEC PY 2006 VL 152 BP 3723 EP 3731 DI 10.1099/mic.2006/00133-0 PN 12 PG 9 WC Microbiology SC Microbiology GA 122DL UT WOS:000243205800027 PM 17159224 ER PT J AU Sa, JM Yamamoto, MM Fernandez-Becerra, C de Azevedo, MF Papakrivos, J Naude, B Wellems, TE del Portillo, HA AF Sa, Juliana Martha Yamamoto, Marcio M. Fernandez-Becerra, Carmen de Azevedo, Mauro Ferreira Papakrivos, Janni Naude, Bronwen Wellems, Thomas E. del Portillo, Hernando A. TI Expression and function of pvcrt-o, a Plasmodium vivax ortholog of pfcrt, in Plasmodium falciparum and Dictyostelium discoideum SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE malaria; chloroquine resistance; Plasmodium vivax; Plasmodium falciparum; Dictyostelium discoideum; transgenic lines; pfcrt; pvcrt-o; luciferase; transgene expression ID DRUG/METABOLITE TRANSPORTER SUPERFAMILY; CHLOROQUINE RESISTANCE TRANSPORTER; TRANSMEMBRANE PROTEIN PFCRT; IN-VITRO; MALARIA PARASITES; BLOOD STAGES; MUTATIONS; SENSITIVITY; MECHANISM; VERAPAMIL AB Chloroquine resistance in Plasmodium vivax threatens the use of this drug as first-line treatment for millions of people infected each year worldwide. Unlike Plasmodium falciparum, in which chloroquine resistance is associated with mutations in the pfcrt gene encoding a digestive vacuole transmembrane protein, no point mutations have been associated with chloroquine resistance in the P. vivax ortholog gene, pvcrt-o (also called pvcg10). However, the question remains whether pvcrt-o can affect chloroquine response independent of mutations. Since R vivax cannot be cultured in vitro, we used two heterologous expression systems to address this question. Results from the first system, in which chloroquine sensitive P. falciparum parasites were transformed with pvcrt-o, showed a 2.2-fold increase in chloroquine tolerance with pvcrt-o expression under a strong promoter; this effect was reversed by verapamil. In the second system, wild type pvcrt-o or a mutated form of the gene was expressed in Dicryostelium discoideum. Forms of PvCRT-o engineered to express either lysine or threonine at position 76 produced a verapamil-reversible reduction of chloroquine accumulation in this system to similar to 60% of that in control cells. Our data support an effect of PvCRT-o on chloroquine transport and/or accumulation by P. vivax, independent of the K76T amino acid substitution. (c) 2006 Elsevier B.V. All rights reserved. C1 Univ Sao Paulo, Inst Ciencias Biomed, Dept Parasitol, BR-05508900 Sao Paulo, Brazil. NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA. Univ Cape Town, Div Pharmacol, ZA-7925 Cape Town, South Africa. RP del Portillo, HA (reprint author), Univ Sao Paulo, Inst Ciencias Biomed, Dept Parasitol, Av Lineu Prestes 1374, BR-05508900 Sao Paulo, Brazil. EM hernando@icb.usp.br RI Fernandez Becerra, Carmen/L-2069-2014; del Portillo, Hernando /L-2131-2014; Azevedo, Mauro/H-6180-2012 OI Fernandez Becerra, Carmen/0000-0001-5154-0013; del Portillo, Hernando /0000-0002-5278-3452; Azevedo, Mauro/0000-0002-5233-2037 NR 36 TC 27 Z9 31 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD DEC PY 2006 VL 150 IS 2 BP 219 EP 228 DI 10.1016/j.molbiopara.2006.08.006 PG 10 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA 111TF UT WOS:000242476900011 PM 16987557 ER PT J AU Smoak, K Cidlowski, JA AF Smoak, Kathleen Cidlowski, John A. TI Glucocorticoids regulate tristetraprolin synthesis and posttranscriptionally regulate tumor necrosis factor alpha inflammatory signaling SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID AU-RICH ELEMENTS; MESSENGER-RNA DEGRADATION; PROTEIN-KINASE P38; GROWTH-FACTOR-BETA; GENE-EXPRESSION; MOLECULAR-MECHANISMS; BINDING PROTEINS; TNF-ALPHA; RECEPTOR; CELLS AB Glucocorticoids are used to treat various inflammatory disorders, but the mechanisms underlying these actions are incompletely understood. The zinc finger protein tristetraprolin (TTP) destabilizes several proinflammatory cytokine mRNAs by binding to AU-rich elements within their 3' untranslated regions, targeting them for degradation. Here we report that glucocorticoids induce the synthesis of TTP mRNA and protein in A549 lung epithelial cells and in rat tissues. Dexamethasone treatment leads to a sustained induction of TTP mRNA expression that is abrogated by RU486. Glucocorticoid induction of TTP mRNA is also blocked by actinomycin D but not by cycloheximide, suggesting a transcriptional mechanism which has been confirmed by transcription run-on experiments. The most widely characterized TTP-regulated gene is the AU-rich tumor necrosis factor alpha (TNF-alpha) gene. Dexamethasone represses TNF-alpha mRNA in A549 cells and decreases luciferase expression of a TNF-alpha 3' untranslated region reporter plasmid in an orientation-dependent manner. Small interfering RNAs to TTP significantly prevent this effect, and a cell line stably expressing a short-hairpin RNA to TTP conclusively establishes that TTP is critical for dexamethasone inhibition of TNF-alpha mRNA expression. These studies provide the molecular evidence for glucocorticoid regulation of human TTP and reflect a novel inductive anti-inflammatory signaling pathway for glucocorticoids that acts via posttranscriptional mechanisms. C1 NIEHS, Lab Signal Transduct, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. RP Cidlowski, JA (reprint author), NIEHS, Lab Signal Transduct, Dept Hlth & Human Serv, NIH, Bldg 101, Res Triangle Pk, NC 27709 USA. EM cidlowski@niehs.nih.gov FU Intramural NIH HHS NR 40 TC 91 Z9 93 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 DEC PY 2006 VL 26 IS 23 BP 9126 EP 9135 DI 10.1128/MCB.00679-06 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 107XG UT WOS:000242203700039 PM 16982682 ER PT J AU Lai, WS Parker, JS Grissom, SF Stumpo, DJ Blackshear, PJ AF Lai, Wi S. Parker, Joel S. Grissom, Sherry F. Stumpo, Deborah J. Blackshear, Perry J. TI Novel mRNA targets for tristetraprolin (TTP) identified by global analysis of stabilized transcripts in TTP-deficient fibroblasts SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ZINC-FINGER PROTEINS; AU-RICH ELEMENTS; GENE-EXPRESSION; TNF-ALPHA; BINDING; DEADENYLATION; DEGRADATION; SEQUENCE; DATABASE; TURNOVER AB Tristetraprolin (TTP) is a tandem CCCH zinc finger protein that was identified through its rapid induction by mitogens in fibroblasts. Studies of TTP-deficient mice and cells derived from them showed that TTP could bind to certain AU-rich elements in mRNAs, leading to increases in the rates of mRNA deadenylation and destruction. Known physiological target mRNAs for TTP include tumor necrosis factor alpha, granulocyte-macrophage colony-stimulating factor, and interieukin-2 beta. Here we used microarray analysis of RNA from wild-type and TTP-deficient fibroblast cell lines to identify transcripts with different decay rates, after serum stimulation and actinomycin D treatment. Of 250 mRNAs apparently stabilized in the absence of TTP, 23 contained two or more conserved TTP binding sites; nine of these appeared to be stabilized on Northern blots. The most dramatically affected transcript encoded the protein Ier3, recently implicated in the physiological control of blood pressure. The Ier3 transcript contained several conserved TTP binding sites that could bind TTP directly and conferred TTP sensitivity to the mRNA in cell transfection studies. These studies have identified several new, physiologically relevant TTP target transcripts in fibroblasts; these target mRNAs encode proteins from a variety of functional classes. C1 NIEHS, Neurobiol Lab, Res Triangle Pk, NC 27709 USA. NIEHS, Microarray Grp, Res Triangle Pk, NC 27709 USA. NIEHS, Off Clin Res, Res Triangle Pk, NC 27709 USA. Constella Grp, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA. RP Blackshear, PJ (reprint author), NIEHS, Neurobiol Lab, A2-05,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM Black009@niehs.nih.gov FU Intramural NIH HHS NR 41 TC 149 Z9 151 U1 0 U2 7 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 DEC PY 2006 VL 26 IS 24 BP 9196 EP 9208 DI 10.1128/MCB.00945-06 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 117FV UT WOS:000242859200005 PM 17030620 ER PT J AU Mor-Vaknin, N Punturieri, A Sitwala, K Faulkner, N Legendre, M Khodadoust, MS Kappes, F Ruth, JH Koch, A Glass, D Petruzzelli, L Adams, BS Markovitz, DM AF Mor-Vaknin, Nirit Punturieri, Antonello Sitwala, Kajal Faulkner, Neil Legendre, Maureen Khodadoust, Michael S. Kappes, Ferdinand Ruth, Jeffrey H. Koch, Alisa Glass, David Petruzzelli, Lilli Adams, Barbara S. Markovitz, David M. TI The DEK nuclear autoantigen is a secreted chemotactic factor SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID JUVENILE RHEUMATOID-ARTHRITIS; ACUTE MYELOID-LEUKEMIA; PROTEIN-KINASE CK2; PUTATIVE ONCOPROTEIN DEK; CELL-DERIVED EXOSOMES; CAN FUSION GENE; ANTINUCLEAR ANTIBODY; CASEIN KINASE-2; SYNOVIAL-FLUID; MESSENGER-RNA AB The nuclear DNA-binding protein DEK is an autoantigen that has been implicated in the regulation of transcription, chromatin architecture, and mRNA processing. We demonstrate here that DEK is actively secreted by macrophages and is also found in synovial fluid samples from patients with juvenile arthritis. Secretion of DEK is modulated by casein kinase 2, stimulated by interieukin-8, and inhibited by dexamethasone and cyclosporine A, consistent with a role as a proinflammatory molecule. DEK is secreted in both a free form and in exosomes, vesicular structures in which transcription-modulating factors such as DEK have not previously been found. Furthermore, DEK functions as a chemotactic factor, attracting neutrophils, CD8(+) T lymphocytes, and natural killer cells. Therefore, the DEK autoantigen, previously described as a strictly nuclear protein, is secreted and can act as an extracellular chemoattractant, suggesting a direct role for DEK in inflammation. C1 Univ Michigan, Med Ctr, Dept Internal Med, Div Infect Dis, Ann Arbor, MI 48109 USA. Univ Michigan, Med Ctr, Dept Internal Med, Div Pulm Med, Ann Arbor, MI 48109 USA. Univ Michigan, Med Ctr, Dept Internal Med, Div Rheumatol, Ann Arbor, MI 48109 USA. Univ Michigan, Med Ctr, Dept Internal Med, Div Hematol & Oncol, Ann Arbor, MI 48109 USA. Univ Michigan, Med Ctr, Dept Pediat, Div Rheumatol, Ann Arbor, MI 48109 USA. Univ Michigan, Med Ctr, Program Immunol, Ann Arbor, MI 48109 USA. Univ Michigan, Med Ctr, Mol & Cellular Biol Program, Ann Arbor, MI 48109 USA. NHLBI, Div Lung Dis, Bethesda, MD 20892 USA. Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. RP Markovitz, DM (reprint author), Univ Michigan, Med Ctr, Dept Internal Med, Div Infect Dis, 5220 MSRB 3,1150 W Med Ctr Dr, Ann Arbor, MI 48109 USA. EM dmarkov@umich.edu RI Kappes , Ferdinand /H-4445-2014; OI Kappes, Ferdinand/0000-0002-0369-0065 FU NCI NIH HHS [T32 CA088784, T32CA88784-03]; NCRR NIH HHS [M01 RR000042, M01-RR00042]; NHLBI NIH HHS [HL58694]; NIAID NIH HHS [AI40987, R01 AI040987]; NIAMS NIH HHS [5 P30 AR48310-02, AR48267, AR49907, P30 AR048310, R01 AR048267, R03 AR049907]; NIGMS NIH HHS [T32 GM007863, T32 GM07863] NR 71 TC 42 Z9 44 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 2006 VL 26 IS 24 BP 9484 EP 9496 DI 10.1128/MCB.01030-06 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 117FV UT WOS:000242859200029 PM 17030615 ER PT J AU Chen, RB Holmes, EC AF Chen, Rubing Holmes, Edward C. TI Avian influenza virus exhibits rapid evolutionary dynamics SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE avian influenza virus; relaxed molecular clock; emerging virus; H5N1; coalescent ID MULTIPLE SEQUENCE ALIGNMENT; A VIRUSES; NONSTRUCTURAL GENES; SUBSTITUTION; PATTERNS; ECOLOGY; MATRIX; ORIGIN; BIRDS AB Influenza A viruses from wild aquatic birds, their natural reservoir species, are thought to have reached a form of stasis, characterized by low rates of evolutionary change. We tested this hypothesis by estimating rates of nucleotide substitution in a diverse array of avian influenza viruses (AIV) and allowing for rate variation among lineages. The rates observed were extremely high, at > 10(-3) substitutions per site, per year, with little difference among wild and domestic host species or viral subtypes and were similar to those seen in mammalian influenza A viruses. Influenza A virus therefore exhibits rapid evolutionary dynamics across its host range, consistent with a high background mutation rate and rapid replication. Using the same approach, we also estimated that the common ancestors of the hemagglutinin and neuraminidase sequences of AIV arose within the last 3,000 years, with most intrasubtype diversity emerging within the last 100 years and suggestive of a continual selective turnover. C1 Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Chen, RB (reprint author), Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. EM ech15@psu.edu RI Chen, Rubing/F-2314-2011; Chen, Rubing/A-2276-2010; OI Holmes, Edward/0000-0001-9596-3552 NR 24 TC 114 Z9 120 U1 4 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0737-4038 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD DEC PY 2006 VL 23 IS 12 BP 2336 EP 2341 DI 10.1093/molbev/msl102 PG 6 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 104JT UT WOS:000241955400012 PM 16945980 ER PT J AU Yan, Y Lu, Y Wang, M Vikis, H Yao, R Wang, Y Lubet, RA You, M AF Yan, Ying Lu, Yan Wang, Min Vikis, Haris Yao, Ruisheng Wang, Ylan Lubet, Ronald A. You, Ming TI Effect of an epidermal growth factor receptor inhibitor in mouse models of lung cancer SO MOLECULAR CANCER RESEARCH LA English DT Article ID NF-KAPPA-B; TYROSINE KINASE; ZD1839 IRESSA(TM); CELL-DEATH; GEFITINIB; MUTATIONS; THERAPY; TUMORS; EXPRESSION; PATHWAYS AB Gefitinib (Iressa, ZD1839) is a potent high-affinity competitive tyrosine kinase inhibitor aimed primarily at epidermal growth factor receptor (EGFR). Inhibitors in this class have recently been approved for clinical use in the treatment of advanced non-small cell lung cancer as monotherapy following failure of chemotherapy. We examined the efficacy of gefitinib on lung turnorigenesis in mouse models using both postinitiation and progression protocols. Gefitinib was given at a dose of 200 mg/kg body weight (i.g.) beginning either 2 or 12 weeks following carcinogen initiation. In the postinitiation protocol, gefitinib significantly inhibited both tumor multiplicity (similar to 70%) and tumor load (similar to 90%) in A/J or p53-mutant mice (P < 0.0001). Interestingly, gefitinib was also highly effective against lung carcinogenesis in the progression protocol when individual animals already have multiple preinvasive lesions in the lung. Gefitinib exhibited similar to 60% inhibition of tumor multiplicity and similar to 80% inhibition of tumor load when compared with control mice (both P < 0.0001). These data show that gefitinib is a potent chemopreventive agent in both wild-type and p53-mutant mice and that a delayed administration was still highly effective. Analyses of mutations in the EGFR and K-ras genes in lung tumors from either control or treatment groups showed no mutations in EGFR and consistent mutation in K-ras. Using an oligonucleotide array on control and gefitinib-treated lesions showed that gefitinib treatment failed to alter the activity or the expression level of EGFR. In contrast, gefitinib treatment significantly altered the expression of a series of genes involved in cell cycle, cell proliferation, cell transformation, angiogenesis, DNA synthesis, cell migration, immune responses, and apoptosis. Thus, gefitinib showed highly promising chemopreventive and chemotherapeutic activity in this mouse model of lung carcinogenesis. 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 Agent Dev Res Grp, Bethesda, MD 20892 USA. RP You, M (reprint author), Washington Univ, Sch Med, Dept Surg, Campus Box 8109,660 S Euclid Ave, St Louis, MO 63110 USA. EM youm@wudosis.wustl.edu NR 34 TC 25 Z9 25 U1 0 U2 1 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 DEC PY 2006 VL 4 IS 12 BP 971 EP 981 DI 10.1158/1541-7786.MCR-06-0086 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 120VA UT WOS:000243113100008 PM 17189387 ER PT J AU Tsai, WS Yeow, WS Chua, A Reddy, RM Nguyen, DM Schrump, DS Nguyen, DM AF Tsai, Wilson S. Yeow, Wen-Shuz Chua, Alex Reddy, Rishindra M. Nguyen, Duc M. Schrump, David S. Nguyen, Dao M. TI Enhancement of Apo2L/TRAIL-mediated cytotoxicity in esophageal cancer cells by cisplatin SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID APOPTOSIS-INDUCING LIGAND; TRAIL-INDUCED APOPTOSIS; TARGETING DEATH RECEPTORS; CYTOCHROME-C; EXTRINSIC PATHWAYS; CASPASE ACTIVATION; DECOY RECEPTORS; LEUKEMIA-CELLS; NECROSIS; CHEMOTHERAPY AB Although expressing adequate levels of functional tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors DR4/DR5, significant proportion of cancer cells exhibit resistance to the cytotoxic effect of this ligand. Exposure of Apo2L/TRAIL-refractory cancer cells to cytotoxic chemotherapeutic agents enhances their sensitivity to Apo2L/TRAIL cytotoxicity. This study aims to elucidate the molecular mechanism responsible for the cisplatin-mediated enhancement of Apo2L/TRAIL sensitivity in cultured esophageal cancer cells. Exposure of cancer cells to sublethal concentrations of cisplatin resulted in profound potentiation of their susceptibility to Apo2L/TRAIL cytotoxicity as indicated by 2- to > 20-fold reduction in Apo2L/TRAIL IC50 values. Significant activation of caspase-8, caspase-9, and caspase-3 was observed only in cells treated with cisplatin/Apo2L/TRAIL combination and not in those exposed to either agent alone. More importantly, activation of these key caspases was significantly abrogated by overexpression of Bcl2 or by the selective caspase-9 inhibitor. This observation strongly suggested that caspase-8 activation in cells treated with the cisplatin/Apo2L/TRAIL combination was secondary to the mitochondria-mediated amplification feedback loop and activation of the executioner caspase-3 was dependent on the recruitment of the intrinsic pathway characteristic of the type 11 cell. Profound combination-mediated cytotoxicity and induction of apoptosis was completely suppressed either by Bcl2 overexpression or by inhibition of caspase-9 activity, which conclusively pointed to the essential role of the mitochondria-dependent death signaling cascade in this process. Cisplatin sensitizes esophageal cancer cells to Apo2L/TRAIL cytotoxicity by potentiation of the mitochondria-dependent death signaling pathway that leads to amplification of caspase activation, particularly caspase-8, by the feedback loop to efficiently induce apoptosis. C1 NCI, Sect Thorac Oncol, Surg Branch, Canc Res Ctr,NIH, Bethesda, MD 20892 USA. RP Nguyen, DM (reprint author), NCI, Sect Thorac Oncol, Surg Branch, Canc Res Ctr,NIH, Room 4-4W-3940,10 Ctr Dr, Bethesda, MD 20892 USA. EM Dao_Nguyen@nih.gov; Dao_Nguyen@nih.gov FU Intramural NIH HHS NR 53 TC 30 Z9 32 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 DEC PY 2006 VL 5 IS 12 BP 2977 EP 2990 DI 10.1158/1535-7163.MCT-05-0514 PG 14 WC Oncology SC Oncology GA 122UO UT WOS:000243252800004 PM 17172403 ER PT J AU Sordet, O Goldman, A Pommier, Y AF Sordet, Olivier Goldman, Abby Pommier, Yves TI Topoisomerase II and tubulin inhibitors both induce the formation of apoptotic topoisomerase I cleavage complexes SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID MEDIATED DNA-DAMAGE; MITOCHONDRIAL-FUNCTION; HYDROGEN-PEROXIDE; OXYGEN RADICALS; CELL-DEATH; DISRUPTION; GENERATION; DRUGS AB Topoisomerase 1 (Top1) is a ubiquitous enzyme that removes DNA supercoiling generated during transcription and replication. Top 1 can be trapped on DNA as cleavage complexes by the anticancer drugs referred to as Top1 inhibitors as well as by alterations of the DNA structure. We reported recently that Top1 cleavage complexes (Top1cc) are trapped during apoptosis induced by arsenic trioxide and staurosporine. In the present study, we generalize the occurrence of apoptotic Top 1 cc in response to anticancer drugs, which by themselves do not directly interact with Top1: the topoisomerase 11 inhibitors etoposide, doxorubicin, and amsacrine, and the tubulin inhibitors vinblastine and Taxol. In all cases, the Top1cc form in the early phase of apoptosis and persist throughout the apoptotic process. Their formation is prevented by the caspase inhibitor benzyloxycarbonyl -Val -Ala-DL-Asp(OMe)-fluoromethylketone and the antioxidant N-acetyl-L-Cysteine. We propose that the trapping of Top1cc is a general process of programmed cell death, which is caused by alterations of the DNA structure (oxidized bases and strand breaks) induced by caspases and reactive oxygen species. C1 NCI, Canc Res Ctr, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. RP Pommier, Y (reprint author), NCI, Canc Res Ctr, Mol Pharmacol Lab, NIH, Bldg 37,room 5068, Bethesda, MD 20892 USA. EM pommier@nih.gov RI Sordet, Olivier/M-3271-2014 FU Intramural NIH HHS NR 35 TC 16 Z9 17 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2006 VL 5 IS 12 BP 3139 EP 3144 DI 10.1158/1535-7163/MCT-06-0463 PG 6 WC Oncology SC Oncology GA 122UO UT WOS:000243252800021 PM 17172417 ER PT J AU Takahashi, Y Lavigne, JA Hursting, SD Chandramouli, GVR Perkins, SN Kim, YS Wang, TTY AF Takahashi, Yoko Lavigne, Jackie A. Hursting, Stephen D. Chandramouli, Gadisetti V. R. Perkins, Susan N. Kim, Young S. Wang, Thomas T. Y. TI Molecular signatures of soy-derived phytochemicals in androgen-responsive prostate cancer cells: A comparison study using DNA microarray SO MOLECULAR CARCINOGENESIS LA English DT Article DE equol; isoflavone; microarray; prostate cancer; prevention ID EPITHELIAL-CELLS; MCF-7 CELLS; SIGNALING PATHWAYS; JAPANESE MEN; IN-VITRO; GENISTEIN; GROWTH; EXPRESSION; KINASE; CYCLE AB The present study utilized microarray technology as a tool to elucidate the molecular signatures of soy-derived phytochemicals in the human androgen-responsive prostate cancer cell line LNCaP. Global gene expression pattern analysis of LNCaP cells exposed to 0, 1, 5, or 25 mu M of the soy-derived phytochemicals equol and daidzein were conducted and compared. The data were further compared with previously generated data from exposure of LNCaP cells to the same doses of genistein, a soy isoflavone. Multidimensional scaling (MDS) analyses of the expression patterns suggest that these compounds exerted differential effects on gene expression in LNCaP cells. Further examination of specific gene changes revealed that these compounds differentially modulated genes in multiple cellular pathways, including the cell-cycle pathway genes. However, the three compounds also exerted similar effect on genes belonging to several other important cellular pathways. A universal effect of the three compounds on androgen-responsive genes, IGF-1 pathway gene, and MAP kinase-related pathway gene was observed. These results provide the foundation for establishing molecular signatures for equol, daidzein, and genistein. Moreover, these results also allow for the identification of candidate mechanism(s) by which soy phytochemicals and soy may act in prostate cancer cells. (c) 2006 Wiley-Liss, Inc. C1 USDA, Beltsville Human Nutr Res Ctr, Agr Res Serv, Phtonutr Lab, Beltsville, MD 20705 USA. Natl Food Res Inst, Tsukuba, Ibaraki 305, Japan. NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. RP Wang, TTY (reprint author), USDA, Beltsville Human Nutr Res Ctr, Agr Res Serv, Phtonutr Lab, Bldg 307C,Room 132, Beltsville, MD 20705 USA. NR 56 TC 18 Z9 19 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD DEC PY 2006 VL 45 IS 12 BP 943 EP 956 DI 10.1002/mc.20247 PG 14 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 114GE UT WOS:000242653900005 PM 16865672 ER PT J AU Henriquez, S Tapia, A Quezada, M Vargas, M Cardenas, H Rios, M Salvatierra, AM Croxatto, H Orihuela, P Zegers-Hochschild, F Munroe, DJ Velasquez, L AF Henriquez, S. Tapia, A. Quezada, M. Vargas, M. Cardenas, H. Rios, M. Salvatierra, A. M. Croxatto, H. Orihuela, P. Zegers-Hochschild, F. Munroe, D. J. Velasquez, L. TI Deficient expression of monoamine oxidase A in the endometrium is associated with implantation failure in women participating as recipients in oocyte donation SO MOLECULAR HUMAN REPRODUCTION LA English DT Article DE monoamine oxidase A; endometrium; implantation failure; implantation window; oocyte donation ID GENE-EXPRESSION; RECEPTIVITY; INFERTILITY; WINDOW AB Successful implantation depends both on the quality of the embryo and on the endometrial receptivity. The latter depends on progesterone-induced changes in gene expression, a process that has been characterized by microarray analysis. One of the genes whose transcription appears to be enhanced during the receptive period is monoamine oxidase A (MAO-A). Our first objective was to confirm the increased expression of MAO-A in the endometrium during the receptive phase of spontaneous normal cycles using real time PCR and immunofluorescence. The second objective was to examine the endometrial expression of MAO-A during the receptive phase induced by exogenous estradiol (E-2) and progesterone in patients whose endometrium was shown to have been either receptive or non-receptive to embryo implantation in repeated cycles of oocyte donation. Results showed that MAO-A transcript levels increased between the pre-receptive (LH+3) and receptive phase (LH+7) in all spontaneous cycles examined, with a median increase of 25-fold. Immunofluorescent labelling demonstrated MAO-A localization to the glandular and luminal epithelium with an increasing positive score between LH+3 and LH+7. Conversely, prior failure of embryo implantation was associated with a 29-fold decrease in MAO-A mRNA levels and a substantial reduction in MAO-A protein immunofluorescent label score. These results show a strong association between endometrial receptivity and MAO-A expression in the endometrial epithelium, suggesting an important role for this enzyme in normal implantation. C1 Univ Santiago Chile, Lab Inmunol Reprod, Santiago, Chile. Inst Chileno Med Reprod, Santiago, Chile. Millenium Inst Fundamental & Appl Biol, Santiago, Chile. Clin Las Condes, Santiago, Chile. NCI, SAIC Frederick, Lab Mol Technol, Frederick, MD 21701 USA. RP Velasquez, L (reprint author), Alamaeda 3363,Casilla 40,Correo 33, Santiago, Chile. EM lvelasqu@lauca.usach.cl FU NCI NIH HHS [N01-CO-12400] NR 24 TC 16 Z9 18 U1 0 U2 1 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 DEC PY 2006 VL 12 IS 12 BP 749 EP 754 DI 10.1093/molehr/gal082 PG 6 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA 108XI UT WOS:000242272100004 PM 17020906 ER PT J AU Adams, CD Schnurr, B Skoko, D Marko, JF Reznikoff, WS AF Adams, Christian D. Schnurr, Bernhard Skoko, Dunja Marko, John F. Reznikoff, William S. TI Tn5 transposase loops DNA in the absence of Tn5 transposon end sequences SO MOLECULAR MICROBIOLOGY LA English DT Article ID CLEAVAGE SYNAPTIC COMPLEX; ACTIVE-SITE; BINDING; RECOMBINATION; MUTANTS; PROTEIN; MULTIMERIZATION; IDENTIFICATION; INTERMEDIATE; ARCHITECTURE AB Transposases mediate transposition first by binding specific DNA end sequences that define a transposable element and then by organizing protein and DNA into a highly structured and stable nucleoprotein 'synaptic' complex. Synaptic complex assembly is a central checkpoint in many transposition mechanisms. The Tn5 synaptic complex contains two Tn5 transposase subunits and two Tn5 transposon end sequences, exhibits extensive protein-end sequence DNA contacts and is the node of a DNA loop. Using single-molecule and bulk biochemical approaches, we found that Tn5 transposase assembles a stable nucleoprotein complex in the absence of Tn5 transposon end sequences. Surprisingly, this end sequence-independent complex has structural similarities to the synaptic complex. This complex is the node of a DNA loop; transposase dimerization and DNA specificity mutants affect its assembly; and it likely has the same number of proteins and DNA molecules as the synaptic complex. Furthermore, our results indicate that Tn5 transposase preferentially binds and loops a subset of non-Tn5 end sequences. Assembly of end sequence-independent nucleoprotein complexes likely plays a role in the in vivo downregulation of transposition and the cis-transposition bias of many bacterial transposases. C1 Univ Wisconsin, Dept Biochem, Madison, WI 53706 USA. Univ Illinois, Dept Phys, Chicago, IL 60607 USA. NYU, Sch Med, Dept Pathol, New York, NY 10016 USA. NYU, Sch Med, Skirball Inst Biomol Med, New York, NY 10016 USA. NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Northwestern Univ, Dept Biochem Mol Biol & Cell Biol, Evanston, IL 60208 USA. Northwestern Univ, Dept Phys & Astron, Evanston, IL 60208 USA. RP Reznikoff, WS (reprint author), Univ Wisconsin, Dept Biochem, 433 Babcock Dr, Madison, WI 53706 USA. EM reznikoff@biochem.wisc.edu FU NIGMS NIH HHS [R21-GM-71019-1, GM 50692] NR 48 TC 9 Z9 9 U1 2 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 DEC PY 2006 VL 62 IS 6 BP 1558 EP 1568 DI 10.1111/j.1365-2958.2006.05471.x PG 11 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 108JU UT WOS:000242236900007 PM 17074070 ER PT J AU Fekete, RA Venkova-Canova, T Park, K Chattoraj, DK AF Fekete, Richard A. Venkova-Canova, Tatiana Park, Kyusung Chattoraj, Dhruba K. TI IHF-dependent activation of P1 plasmid origin by DnaA SO MOLECULAR MICROBIOLOGY LA English DT Article ID INTEGRATION HOST FACTOR; ESCHERICHIA-COLI BINDS; REPLICATION ORIGIN; INITIATOR PROTEIN; CHROMOSOMAL ORIGIN; ATP-BINDING; IN-VITRO; BENT DNA; GENE; HU AB In bacteria, many DNA-protein interactions that initiate transcription, replication and recombination require the mediation of DNA architectural proteins such as IHF and HU. For replication initiation, plasmid P1 requires three origin binding proteins: the architectural protein HU, a plasmid-specific initiator, RepA, and the Escherichia coli chromosomal initiator, DnaA. The two initiators bind in the origin of replication to multiple sites, called iterons and DnaA boxes respectively. We show here that all five known DnaA boxes can be deleted from the plasmid origin provided the origin is extended by about 120 bp. The additional DNA provides an IHF site and most likely a weak DnaA binding site, because replacing the putative site with an authentic DnaA box enhanced plasmid replication in an IHF-dependent manner. IHF most likely brings about interactions between distally bound DnaA and RepA by bending the intervening DNA. The role of IHF in activating P1 origin by allowing DnaA binding to a weak site is reminiscent of the role the protein plays in initiating the host chromosomal replication. C1 NCI, Biochem Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Chattoraj, DK (reprint author), NCI, Biochem Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM chattoraj@nih.gov NR 54 TC 5 Z9 5 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD DEC PY 2006 VL 62 IS 6 BP 1739 EP 1751 DI 10.1111/j.1365-2958.2006.05479.x PG 13 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 108JU UT WOS:000242236900020 PM 17087773 ER PT J AU Dabydeen, DA Burnett, JC Bai, RL Verdier-Pinard, P Hickford, SJH Pettit, GR Blunt, JW Munro, MHG Gussio, R Hamel, E AF Dabydeen, Donnette A. Burnett, James C. Bai, Ruoli Verdier-Pinard, Pascal Hickford, Sarah J. H. Pettit, George R. Blunt, John W. Munro, Murray H. G. Gussio, Rick Hamel, Ernest TI Comparison of the activities of the truncated halichondrin B analog NSC 707389 (E7389) with those of the parent compound and a proposed binding site on tubulin SO MOLECULAR PHARMACOLOGY LA English DT Article ID BOVINE BRAIN TUBULIN; ANTITUMOR POLYETHER MACROLIDES; MACROCYCLIC KETONE ANALOGS; ANTIMITOTIC AGENTS; MARINE SPONGE; VINCA DOMAIN; ANTINEOPLASTIC AGENTS; COMMON PHARMACOPHORE; HOMOHALICHONDRIN-B; BETA-TUBULIN AB The complex marine natural product halichondrin B was compared with NSC 707389 (E7389), a structurally simplified, synthetic macrocyclic ketone analog, which has been selected for clinical trials in human patients. NSC 707389 was invariably more potent than halichondrin B in its interactions with tubulin. Both compounds inhibited tubulin assembly, inhibited nucleotide exchange on beta-tubulin, and were noncompetitive inhibitors of the binding of radiolabeled vinblastine and dolastatin 10 to tubulin. Neither compound seemed to induce an aberrant tubulin assembly reaction, as occurs with vinblastine (tight spirals) or dolastatin 10 (aggregated rings and spirals). We modeled the two compounds into a shared binding site on tubulin consistent with their biochemical properties. Of the two tubulin structures available, we selected for modeling the complex of a stathmin fragment with two tubulin heterodimers with two bound colchicinoid molecules and a single bound vinblastine between the two heterodimers (Nature (Lond) 435:519-522, 2005). Halichondrin B and NSC 707389 fit snugly between the two heterodimers adjacent to the exchangeable site nucleotide. Fitting the compounds into this site, which was also close to the vinblastine site, resulted in enough movement of amino acid residues at the vinblastine site to cause the latter compound to bind less well to tubulin. The model suggests that halichondrin B and NSC 707389 most likely form highly unstable, small aberrant tubulin polymers rather than the massive stable structures observed with vinca alkaloids and antimitotic peptides. C1 NCI, Toxicol & Pharmacol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,HIH, Ft Detrick, MD 21702 USA. NCI, Informat Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,HIH, Ft Detrick, MD 21702 USA. SAIC Frederick, Target Based Drug Discovery Grp, Frederick, MD USA. Univ Canterbury, Dept Chem, Christchurch 1, New Zealand. Arizona State Univ, Canc Res Inst, Tempe, AZ 85287 USA. Arizona State Univ, Dept Chem, Tempe, AZ 85287 USA. RP Hamel, E (reprint author), NCI, Toxicol & Pharmacol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,HIH, Bldg 469,Room 104, Ft Detrick, MD 21702 USA. EM hamele@mail.nih.gov OI Blunt, John/0000-0003-4053-4376; Verdier-Pinard, Pascal/0000-0002-6149-6578 FU NCI NIH HHS [N01-1-CO-12400] NR 39 TC 68 Z9 69 U1 0 U2 3 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 DEC PY 2006 VL 70 IS 6 BP 1866 EP 1875 DI 10.1124/mol.106.026641 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 106XQ UT WOS:000242135700005 PM 16940412 ER PT J AU Nicodemus, KK Luna, A Vakkalanka, R Goldberg, T Egan, M Straub, RE Weinberger, DR AF Nicodemus, K. K. Luna, A. Vakkalanka, R. Goldberg, T. Egan, M. Straub, R. E. Weinberger, D. R. TI Further evidence for association between ErbB4 and schizophrenia and influence on cognitive intermediate phenotypes in healthy controls SO MOLECULAR PSYCHIATRY LA English DT Letter ID RISK; SUSCEPTIBILITY C1 NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. RP Nicodemus, KK (reprint author), NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. EM weinberd@mail.nih.gov RI Luna, Alain/F-4888-2012 NR 10 TC 60 Z9 63 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 DEC PY 2006 VL 11 IS 12 BP 1062 EP 1065 DI 10.1038/sj.mp.4001878 PG 4 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 110ZH UT WOS:000242419600001 PM 17130882 ER PT J AU Harold, D Paracchini, S Scerri, T Dennis, M Cope, N Hill, G Moskvina, V Walter, J Richardson, AJ Owen, MJ Stein, JF D Green, E O'Donovan, MC Williams, J Monaco, AP AF Harold, D. Paracchini, S. Scerri, T. Dennis, M. Cope, N. Hill, G. Moskvina, V. Walter, J. Richardson, A. J. Owen, M. J. Stein, J. F. D Green, E. O'Donovan, M. C. Williams, J. Monaco, A. P. TI Further evidence that the KIAA0319 gene confers susceptibility to developmental dyslexia SO MOLECULAR PSYCHIATRY LA English DT Article DE reading disability; susceptibility locus; genetic association; KIAA0319; DCDC2; epistasis ID QUANTITATIVE-TRAIT LOCUS; CHROMOSOME 6P INFLUENCES; READING-DISABILITY; ASSOCIATION; LINKAGE; DISEQUILIBRIUM; FAMILIES; GENOME; DCDC2 AB The DYX2 locus on chromosome 6p22.2 is the most replicated region of linkage to developmental dyslexia ( DD). Two candidate genes within this region have recently been implicated in the disorder: KIAA0319 and DCDC2. Variants within DCDC2 have shown association with DD in a US and a German sample. However, when we genotyped these specific variants in two large, independent UK samples, we obtained only weak, inconsistent evidence for their involvement in DD. Having previously found evidence that variation in the KIAA0319 gene confers susceptibility to DD, we sought to refine this genetic association by genotyping 36 additional SNPs in the gene. Nine SNPs, predominantly clustered around the first exon, showed the most significant association with DD in one or both UK samples, including rs3212236 in the 5' flanking region (P=0.00003) and rs761100 in intron 1 (P=0.0004). We have thus refined the region of association with developmental dyslexia to putative regulatory sequences around the first exon of the KIAA0319 gene, supporting the presence of functional mutations that could affect gene expression. Our data also suggests a possible interaction between KIAA0319 and DCDC2, which requires further testing. C1 Cardiff Univ, Dept Med Psychol, Cardiff CF14 4XN, Wales. Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA. Cardiff Univ, Biostat & Bioinformat Unit, Cardiff, Wales. Univ Oxford, Dept Physiol, Oxford, England. RP Williams, J (reprint author), Cardiff Univ, Dept Med Psychol, Henry Wellcome Bldg,Heath Pk, Cardiff CF14 4XN, Wales. EM williamsj@cardiff.ac.uk RI Monaco, Anthony/A-4495-2010; turton, miranda/F-4682-2011; OI Monaco, Anthony/0000-0001-7480-3197; O'Donovan, Michael/0000-0001-7073-2379; Paracchini, Silvia/0000-0001-9934-8602; Harold, Denise/0000-0001-5195-0143; Escott-Price, Valentina/0000-0003-1784-5483 FU Intramural NIH HHS; Medical Research Council [G9810900]; Wellcome Trust NR 37 TC 101 Z9 103 U1 1 U2 8 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 DEC PY 2006 VL 11 IS 12 BP 1085 EP 1091 DI 10.1038/sj.mp.4001904 PG 7 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 110ZH UT WOS:000242419600006 PM 17033633 ER PT J AU Chen, PS Peng, GS Li, G Yang, S Wu, X Wang, CC Wilson, B Lu, RB Gean, PW Chuang, DM Hong, JS AF Chen, P-S Peng, G-S Li, G. Yang, S. Wu, X. Wang, C-C Wilson, B. Lu, R-B Gean, P-W Chuang, D-M Hong, J-S TI Valproate protects dopaminergic neurons in midbrain neuron/glia cultures by stimulating the release of neurotrophic factors from astrocytes SO MOLECULAR PSYCHIATRY LA English DT Article DE BDNF; GDNF; valproate; astrocytes; dopaminergic neurons; neurotrophic effects ID HISTONE DEACETYLASE INHIBITION; SUBSTANTIA-NIGRA; IN-VIVO; INDUCED DEGENERATION; HUNTINGTONS-DISEASE; PARKINSONS-DISEASE; CEREBRAL-ISCHEMIA; MOOD STABILIZERS; MUSCULAR-ATROPHY; APOPTOTIC DEATH AB Valproate (VPA), one of the mood stabilizers and antiepileptic drugs, was recently found to inhibit histone deacetylases (HDAC). Increasing reports demonstrate that VPA has neurotrophic effects in diverse cell types including midbrain dopaminergic (DA) neurons. However, the origin and nature of the mediator of the neurotrophic effects are unclear. We have previously demonstrated that VPA prolongs the survival of midbrain DA neurons in lipopolysaccharide (LPS)-treated neuron-glia cultures through the inhibition of the release of pro-inflammatory factors from microglia. In this study, we report that VPA upregulates the expression of neurotrophic factors, including glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) from astrocytes and these effects may play a major role in mediating VPA-induced neurotrophic effects on DA neurons. Moreover, VPA pretreatment protects midbrain DA neurons from LPS or 1-methyl-4-phenylpyridinium (MPP+)induced neurotoxicity. Our study identifies astrocyte as a novel target for VPA to induce neurotrophic and neuroprotective actions in rat midbrain and shows a potential new role of cellular interactions between DA neurons and astrocytes. The neurotrophic and neuroprotective effects of VPA also suggest a utility of this drug for treating neurodegenerative disorders including Parkinson's disease. Moreover, the neurotrophic effects of VPA may contribute to the therapeutic action of this drug in treating bipolar mood disorder that involves a loss of neurons and glia in discrete brain areas. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. Natl Cheng Kung Univ, Inst Basic Med Sci, Tainan 70101, Taiwan. Natl Cheng Kung Univ, Coll Med, Dept Psychiat, Tainan 70101, Taiwan. Tri Serv Gen Hosp, Dept Neurol, Natl Def Med Ctr, Taipei, Taiwan. Dalian Med Univ, Dept Physiol, Dalian, Peoples R China. Kaohsiung Med Univ, Coll Med, Dept Anat, Kaohsiung, Taiwan. Natl Cheng Kung Univ, Coll Med, Dept Pharmacol, Tainan 70101, Taiwan. NIMH, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA. RP Hong, JS (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233,MD F1-01, Res Triangle Pk, NC 27709 USA. EM hong3@niehs.nih.gov NR 60 TC 201 Z9 210 U1 3 U2 16 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 DEC PY 2006 VL 11 IS 12 BP 1116 EP 1125 DI 10.1038/sj.mp.4001893 PG 10 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 110ZH UT WOS:000242419600010 PM 16969367 ER PT J AU Fukuda, T Ahearn, M Roberts, A Mattaliano, RJ Zaal, K Ralston, E Plotz, PH Raben, N AF Fukuda, Tokiko Ahearn, Meghan Roberts, Ashley Mattaliano, Robert J. Zaal, Kristien Ralston, Evelyn Plotz, Paul H. Raben, Nina TI Autophagy and mistargeting of therapeutic enzyme in skeletal muscle in Pompe disease SO MOLECULAR THERAPY LA English DT Article DE acid alpha-glucosidase; lysosome; autophagy; live cultured myofibers; glycogen storage; enclocytosis; enzyme replacement therapy; lipofuscin ID ACID ALPHA-GLUCOSIDASE; REPLACEMENT THERAPY; GLYCOGEN-STORAGE; OXIDATIVE STRESS; CLINICAL-TRIAL; NATURAL COURSE; MOUSE MODEL; INFANTILE; RECOMBINANT; CELLS AB Enzyme replacement therapy (ERT) became a reality for patients with Pompe disease, a fatal cardiomyopathy and skeletal muscle myopathy caused by a deficiency of glycogen-degrading lysosomal enzyme acid alpha-glucosidase (GAA). The therapy, which relies on receptor-mediated endocytosis of recombinant human GAA (rhGAA), appears to be effective in cardiac muscle, but less so in skeletal muscle. We have previously shown a profound disturbance of the lysosomal degradative pathway (autophagy) in therapy-resistant muscle of GAA knockout mice (KO). Our findings here demonstrate a progressive age-dependent autophagic buildup in addition to enlargement of glycogen-filled lysosomes in multiple muscle groups in the KO. Trafficking and processing of the therapeutic enzyme along the endocytic pathway appear to be affected by the autophagy. Confocal microscopy of live single muscle fibers exposed to fluorescently labeled rhGAA indicates that a significant portion of the endocytosed enzyme in the KO was trapped as a partially processed form in the autophagic areas instead of reaching its target-the lysosomes. A fluid-phase endocytic marker was similarly mistargeted and accumulated in vesicular structures within the autophagic areas. These findings may explain why ERT often falls short of reversing the disease process and point toward new avenues for the development of pharmacological intervention. C1 NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. NIAMSD, Light Imaging Sect, Off Sci & Technol, NIH, Bethesda, MD 20892 USA. Genzyme Corp, Cell & Prot Therapeut R&D, Framingham, MA 01701 USA. RP Raben, N (reprint author), NIAMS, NIH, 9000 Rockville Pike,Clin Ctr Bldg 10-9N244, Bethesda, MD 20892 USA. EM rabenn@aarb.niams.nih.gov FU Intramural NIH HHS [Z01 AR041099-16] NR 38 TC 93 Z9 96 U1 1 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD DEC PY 2006 VL 14 IS 6 BP 831 EP 839 DI 10.1016/j.ymthe.2006.08.009 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 115GR UT WOS:000242723300009 PM 17008131 ER PT J AU Ross, GW Abbott, RD Petrovitch, H Tanner, CM Davis, DG Nelson, J Markesbery, WR Hardman, J Masaki, K Launer, L White, LR AF Ross, G. Webster Abbott, Robert D. Petrovitch, Helen Tanner, Caroline M. Davis, Daron G. Nelson, James Markesbery, William R. Hardman, John Masaki, Kamal Launer, Lenore White, Lon R. TI Association of olfactory dysfunction with incidental Lewy bodies SO MOVEMENT DISORDERS LA English DT Article DE olfaction; Lewy bodies; epidemiology; Parkinson's disease ID IDIOPATHIC PARKINSONS-DISEASE; SMELL IDENTIFICATION TEST; BRAIN; IMPAIRMENT; RELATIVES; DOPAMINE; HYPOSMIA; MIDLIFE; SPECT; STAGE AB Olfactory dysfunction is found in early Parkinson's disease (PD) and in asymptomatic relatives of PD patients. Incidental Lewy bodies (ILB), the presence of Lewy bodies in the brains of deceased individuals without a history of PD or dementia during life, are thought to represent a presymptomatic stage of PD. If olfactory dysfunction were associated with the presence of ILB, this would suggest that olfactory deficits may precede clinical PD. The purpose of this study was to determine the association of olfactory dysfunction during late life with ILB in the substantia nigra or locus ceruleus. Olfaction was assessed during the 1991-1994 and 1994-1996 examinations of elderly Japanese-American men participating in the longitudinal Honolulu-Asia Aging Study. Among those who later died and underwent a standardized postmortem examination, brains were examined for Lewy bodies in the substantia nigra and the locus ceruleus with hematoxylin and eosin stain. Lewy bodies in the brains of individuals without clinical PD or dementia were classified as ILB. There were 164 autopsied men without clinical PD or dementia who had olfaction testing during one of the examinations. Seventeen had ILB. The age-adjusted percent of brains with ILB increased from 1.8% in the highest tertile of odor identification to 11.9% in the mid-tertile to 17.4% in the lowest tertile (P = 0.019 in test for trend). Age-adjusted relative odds of ILB for the lowest versus the highest tertile was 11.0 (P = 0.02). Olfactory dysfunction is associated with ILB. If incidental Lewy bodies represent presymptomatic stage of PD, olfactory testing may be a useful screening tool to identify those at high risk for developing PD. (C) 2006 Movement Disorder Society. C1 Vet Affairs Pacific Isl Hlth Care Syst, Honolulu, HI USA. Univ Hawaii, John A Burns Sch Med, Dept Med, Honolulu, HI 96822 USA. Univ Hawaii, John A Burns Sch Med, Dept Geriatr Med, Honolulu, HI 96822 USA. Pacific Hlth Res Inst, Honolulu, HI 96813 USA. Kuakini Med Ctr, Honolulu Asia Aging Study, Honolulu, HI USA. Univ Virginia, Sch Med, Div Biostat & Epidemiol, Charlottesville, VA 22908 USA. Parkinsons Inst, Sunnyvale, CA USA. Univ Kentucky, Med Ctr, Dept Pathol, Lexington, KY 40536 USA. Univ Kentucky, Med Ctr, Dept Neurol, Lexington, KY 40536 USA. Univ Hawaii, John A Burns Sch Med, Dept Pathol, Honolulu, HI 96822 USA. NIA, NIH, Bethesda, MD 20892 USA. RP Ross, GW (reprint author), Pacific Hlth Res Inst, 846 S Hotel St,Suite 307, Honolulu, HI 96813 USA. EM wross@phrihawaii.org FU Intramural NIH HHS; NIA NIH HHS [1 U01 AG19349-01, 5 R01 AG017155-04]; NINDS NIH HHS [5 R01 NS041265-04] NR 37 TC 95 Z9 99 U1 0 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 DEC PY 2006 VL 21 IS 12 BP 2062 EP 2067 DI 10.1002/mds.21076 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 121LI UT WOS:000243158700004 PM 16991138 ER PT J AU Battaglia, F Ghilardi, MF Quartarone, A Bagnato, S Girlanda, P Hallett, M AF Battaglia, Fortunato Ghilardi, Maria Felice Quartarone, Angelo Bagnato, Sergio Girlanda, Paolo Hallett, Mark TI Impaired long-term potentiation-like plasticity of the trigeminal blink reflex circuit in Parkinson's disease SO MOVEMENT DISORDERS LA English DT Article DE LTP; Parkinson's disease; blink reflex ID STRIATAL SYNAPTIC PLASTICITY; HYPEREXCITABILITY; EXPLANATION; LEVODOPA AB We investigated the hypothesis that Parkinsons's disease (PD) is associated with abnormal plasticity of the neuronal circuits mediating blink reflex. We induced long-term potentiation (LTP)-like plasticity in trigeminal wide dynamic range neurons of the blink reflex circuit by pairing an high-frequency train of electrical stimuli over the right supraorbital nerve (SO) coincident with the R2 response elicited by a preceding SO stimulus. The facilitation of the R2 response after the induction protocol was markedly decreased in patients relative to controls. Treatment with dopaminergic drugs normalized the LTP-like plasticity of the R2 response. We conclude that nigrostriatal denervation disrupts LTP-like plasticity in the trigeminal reflex circuit. (C) 2006 Movement Disorder Society. C1 CUNY, Sch Med, Dept Physiol & Pharmacol, New York, NY 10031 USA. Univ Messina, Inst Neurosci Psychiat & Anaesthesiol Sci, I-98100 Messina, Italy. NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. RP Battaglia, F (reprint author), CUNY, Sch Med, Dept Physiol & Pharmacol, 138th St & Convent Ave,D-210, New York, NY 10031 USA. EM fb@med.cuny.edu OI GIRLANDA, Paolo/0000-0002-7152-2290; QUARTARONE, Angelo/0000-0003-1485-6590; Bagnato, Sergio/0000-0002-6289-1887 NR 15 TC 14 Z9 14 U1 0 U2 0 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 DEC PY 2006 VL 21 IS 12 BP 2230 EP 2233 DI 10.1002/mds.21138 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 121LI UT WOS:000243158700038 PM 17078045 ER PT J AU Openshaw, H Atkins, HL Chen, JT de Bittencourt, PRM Griffith, LM Kerr, DA Khoury, SA Muraro, PA Nash, RA Saccardi, R AF Openshaw, H. Atkins, H. L. Chen, J. T. de Bittencourt, P. R. M. Griffith, L. M. Kerr, D. A. Khoury, S. A. Muraro, P. A. Nash, R. A. Saccardi, R. TI Multiple sclerosis conference synopsis and discussion: cellular therapy for treatment of autoimmune diseases (October 2005) SO MULTIPLE SCLEROSIS LA English DT Article DE cyclophosphamide; hematopoietic cell transplantation; immunosuppression; multiple sclerosis ID TRANSPLANTATION AB At a conference held in October 2005, participants presented studies on high dose immunosuppression with hematopoietic cell transplant (HCT) for multiple sclerosis (MS), including neuro-immunological and magnetic resonance imaging (MRI) mechanistic approaches, clinical registry reports, and ongoing or newly-designed protocols. A discussion panel considered questions on how to define success, timing of controlled clinical trials, difficulty in patient recruitment, and future direction of high dose therapy. C1 City Hope Natl Med Ctr, Dept Neurol, Duarte, CA 91010 USA. Ottawa Hosp, Blood & Bone Marrow Transplant Program, Ottawa, ON, Canada. Montreal Neurol Hosp & Inst, McConnell Brain Imaging Ctr, Montreal, PQ H3A 2B4, Canada. Unidade Neurol Clin, Curitiba, Parana, Brazil. NIAID, NIH, Div Allergy Immunol & Transplantat, Bethesda, MD 20892 USA. Johns Hopkins Univ Hosp, Dept Neurol, Baltimore, MD 21287 USA. Harvard Univ, Dept Neurol, Boston, MA 02115 USA. NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. Univ Florence, Careggi Hosp, Bone Marrow Transplantat Unit, I-50121 Florence, Italy. RP Openshaw, H (reprint author), City Hope Natl Med Ctr, Dept Neurol, 1500 E Duarte Rd, Duarte, CA 91010 USA. EM hopenshaw@coh.org RI KERR, Douglas /B-9270-2008; OI Muraro, Paolo/0000-0002-3822-1218 NR 5 TC 1 Z9 1 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 J9 MULT SCLER JI Mult. Scler. PD DEC PY 2006 VL 12 IS 6 BP 824 EP 825 DI 10.1177/1352458506070943 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 127WM UT WOS:000243617000021 PM 17263013 ER PT J AU Ingraham, SE Lynch, RA Surti, U Rutter, JL Buckler, AJ Khan, SA Menon, AG Lepont, P AF Ingraham, Susan E. Lynch, Roy A. Surti, Urvashi Rutter, Joni L. Buckler, Alan J. Khan, Sohaib A. Menon, Anil G. Lepont, Pierig TI Identification and characterization of novel human transcripts embedded within HMGA2 in t(12;14)(q15;q24.1) uterine leiomyoma SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE HMGA2; uterine leiomyorna; embedded transcripts; novel laminin receptor; chromosomal translocation; non-coding RNA ID STEROID-HORMONE RECEPTORS; BREAKPOINT CLUSTER REGION; SOFT-TISSUE TUMORS; MESENCHYMAL TUMORS; HMGIC GENE; CHROMOSOMAL-ABERRATIONS; NONCODING RNAS; DNA-BINDING; EXPRESSION; SEQUENCES AB The high mobility group A2 protein (HMGA2) has been implicated in the pathogenesis of mesenchymal tumors such as leiomyoma, lipoma and hamartoma. HMGA2 was pinpointed by mapping the breakpoints in the chromosomal translocations in 12q15, especially the t(12;14) that is commonly seen in uterine leiomyoma. It is generally assumed that altered expression of HMGA2 is an early event in the pathway to tumor formation. Here, we show evidence that three novel transcripts, A15, 136 and D12 are located within the HMGA2 gene itself and are transcribed from the opposite strand. These embedded transcripts are expressed at 6-20-fold higher levels in tumors compared to matched myometrium from the same patients. We estimate that the domain of increased expression extends 500 kb on chromosome 12q15, and encompasses the majority of t(12;14) translocation breakpoints. However, a corresponding domain of consistently altered expression is not seen on chromosome 14 or outside of the chromosome 12 multiple aberration region. These data suggest that t(I 2; 14) breakpoints contribute to the pathogenesis of uterine leiomyoma by interrupting a complex regulation of HMGA2 and other genes embedded within and around it. We also discovered a novel laminin receptor gene, transcribed from the opposite strand, within the promoter region of HMGA2. Although the roles for these embedded transcripts are still unknown, preliminary data suggest that they are members of the family of non-coding RNA and that they may play an important role in the pathology of uterine leiomyoma. (c) 2006 Elsevier B.V. All rights reserved. C1 Univ Cincinnati, Dept Anat Cell Biol & Neurosci, Cincinnati, OH 45267 USA. Univ Cincinnati, Dept Mol Genet Biochem & Microbiol, Cincinnati, OH 45267 USA. Univ Pittsburgh, Dept Cellular & Mol Pathol, Pittsburgh, PA 15213 USA. NIDA, NIH, Bethesda, MD 20892 USA. Novartis Inst Biomed Res, Cambridge, MA 02139 USA. RP Khan, SA (reprint author), Univ Cincinnati, Dept Anat Cell Biol & Neurosci, Cincinnati, OH 45267 USA. EM sohaib.khan@uc.edu RI Ingraham, Susan/B-4565-2012; OI Rutter, Joni/0000-0002-6502-2361 FU NCI NIH HHS [T32-CA059268, R01-CA67315]; NICHD NIH HHS [HD29773] NR 46 TC 9 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD DEC 1 PY 2006 VL 602 IS 1-2 BP 43 EP 53 DI 10.1016/j.mrfmmm.2006.07.007 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 112XX UT WOS:000242562400006 PM 17045619 ER PT J AU Shaughnessy, DT Schaaper, RA Umbach, DA DeManni, DA AF Shaughnessy, Daniel T. Schaaper, Roel A. Umbach, David A. DeManni, David A. TI Inhibition of spontaneous mutagenesis by vanillin and cinnamaldehyde in Escherichia coli: Dependence on recombinational repair SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE antimutagens; DNA repair; recombination; vanillin; cinnamaldehyde ID CHINESE-HAMSTER-CELLS; SPONTANEOUS MUTATION; DROSOPHILA-MELANOGASTER; MAMMALIAN-CELLS; STRAND BREAKS; SOMATIC-CELLS; DNA-DAMAGE; V79 CELLS; LACI GENE; UV-LIGHT AB Vanillin (VAN) and cinnamaldehyde (CIN) are dietary antimultagens that effectively inhibit both induced and spontaneous mutations. We have shown previously that VAN and CIN reduced the spontaneous mutant frequency in Salmonella TA104 (hisG428, rfa, Delta uvrB, pKM101) by. approximately 50% and that both compounds significantly reduced mutations at GC sites but not at AT sites. Previous studies have suggested that VAN and CIN may reduce mutations in bacterial model systems by modulating DNA repair pathways, particularly by enhancing recombinational repair. To further explore the basis for inhibition of spontaneous mutation by VAN and CIN, we have determined the effects of these compounds on survival and mutant frequency in five Escherichia coli strains derived from the wild-type strain NR9102 with different DNA repair backgrounds. At nontoxic doses, both VAN and CIN significantly reduced mutant frequency in the wild-type strain NR9102, in the nucleotide excision repair-deficient strain NR1 1634 (uvrB), and in the recombination-proficient but SOS-deficient strain NR1 1475 (recA430). In contrast, in the recombination-deficient and SOS-deficient strain NR1 1317 (recA56), both VAN and CIN not only failed to inhibit the spontaneous mutant frequency but actually increased the mutant frequency. In the mismatch repair-defective strain NR9319 (mutL), only CIN was antimutagenic. Our results show that the antimutagenicity of VAN and CIN against spontaneous mutation required the RecA recombination function but was independent of the SOS and nucleotide excision repair pathways. Thus, we propose the counterintuitive notion that these antimutagens actually produce a type of DNA damage that elicits recombinational repair (but not mismatch, SOS, or nucleotide excision repair), which then repairs not only the damage induced by VAN and CIN but also other DNA damage-resulting in an antimutagenic effect on spontaneous mutation. (c) 2006 Elsevier B.V. All rights reserved. C1 US EPA, Div Environm Carcinogenesis, NHEERL, Res Triangle Pk, NC 27711 USA. Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. Natl Inst Environm Hlth Sci, Genet Mol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. Natl Inst Environm Hlth Sci, Biostat Branch, NIH, DHHS, Res Triangle Pk, NC 27709 USA. RP DeManni, DA (reprint author), US EPA, Div Environm Carcinogenesis, NHEERL, Res Triangle Pk, NC 27711 USA. EM demarini.david@epa.gov FU Intramural NIH HHS; PHS HHS [TAXP012655] NR 42 TC 24 Z9 25 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD DEC 1 PY 2006 VL 602 IS 1-2 BP 54 EP 64 DI 10.1016/j.mrfmmm.2006.08.006 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 112XX UT WOS:000242562400007 PM 16999979 ER PT J AU Tycko, R AF Tycko, R. TI Molecular structure of amyloid and prion fibrils: Insights from solid state NMR SO NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 NIH, NIDDK, Chem Phys Lab, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1549-9634 EI 1549-9642 J9 NANOMED-NANOTECHNOL JI Nanomed.-Nanotechnol. Biol. Med. PD DEC PY 2006 VL 2 IS 4 BP 271 EP 271 DI 10.1016/j.nano.2006.10.012 PG 1 WC Nanoscience & Nanotechnology; Medicine, Research & Experimental SC Science & Technology - Other Topics; Research & Experimental Medicine GA 120VR UT WOS:000243115000018 ER PT J AU Lippel, PH Teague, EC McNeil, SE AF Lippel, P. H. Teague, E. C. McNeil, S. E. TI Health and medicine in the national nanotechnology initiative SO NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 NCI, Nanotechnol Characterizat Lab, Natl Nanotechnol Coordinating Off, Arlington, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1549-9634 EI 1549-9642 J9 NANOMED-NANOTECHNOL JI Nanomed.-Nanotechnol. Biol. Med. PD DEC PY 2006 VL 2 IS 4 BP 283 EP 283 DI 10.1016/j.nano.2006.10.032 PG 1 WC Nanoscience & Nanotechnology; Medicine, Research & Experimental SC Science & Technology - Other Topics; Research & Experimental Medicine GA 120VR UT WOS:000243115000055 ER PT J AU Fisher, R AF Fisher, R. TI NIH Roadmap on basic nanomedicine SO NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 NIH, NEI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1549-9634 EI 1549-9642 J9 NANOMED-NANOTECHNOL JI Nanomed.-Nanotechnol. Biol. Med. PD DEC PY 2006 VL 2 IS 4 BP 289 EP 289 DI 10.1016/j.nano.2006.10.068 PG 1 WC Nanoscience & Nanotechnology; Medicine, Research & Experimental SC Science & Technology - Other Topics; Research & Experimental Medicine GA 120VR UT WOS:000243115000070 ER PT J AU Heetderks, W AF Heetderks, W. TI Nanomedicine and nanotechnology research at the NIBIB and the NIH SO NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 NIH, Natl Inst Biomed Imaging & Bioengn, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1549-9634 EI 1549-9642 J9 NANOMED-NANOTECHNOL JI Nanomed.-Nanotechnol. Biol. Med. PD DEC PY 2006 VL 2 IS 4 BP 300 EP 301 DI 10.1016/j.nano.2006.10.102 PG 2 WC Nanoscience & Nanotechnology; Medicine, Research & Experimental SC Science & Technology - Other Topics; Research & Experimental Medicine GA 120VR UT WOS:000243115000101 ER PT J AU Sipe, JD AF Sipe, J. D. TI The extracellular matrix: amyloidosis, tissue engineering and regenerative medicine SO NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 NIH, Ctr Sci Review, Musculoskeletal Tissue Engn Study Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1549-9634 EI 1549-9642 J9 NANOMED-NANOTECHNOL JI Nanomed.-Nanotechnol. Biol. Med. PD DEC PY 2006 VL 2 IS 4 BP 300 EP 300 DI 10.1016/j.nano.2006.10.101 PG 1 WC Nanoscience & Nanotechnology; Medicine, Research & Experimental SC Science & Technology - Other Topics; Research & Experimental Medicine GA 120VR UT WOS:000243115000100 ER PT J AU Patri, AK AF Patri, A. K. TI Preclinical assessment of dendrimer platform for biomedical applications SO NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 Natl Canc Inst, Nanotechnol Characterizat Lab, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1549-9634 EI 1549-9642 J9 NANOMED-NANOTECHNOL JI Nanomed.-Nanotechnol. Biol. Med. PD DEC PY 2006 VL 2 IS 4 BP 308 EP 308 DI 10.1016/j.nano.2006.10.123 PG 1 WC Nanoscience & Nanotechnology; Medicine, Research & Experimental SC Science & Technology - Other Topics; Research & Experimental Medicine GA 120VR UT WOS:000243115000121 ER PT J AU Edgar, R Barrett, T AF Edgar, Ron Barrett, Tanya TI NCBI GEO standards and services for microarray data SO NATURE BIOTECHNOLOGY LA English DT Letter ID MIAME C1 Natl Ctr Biotechnol Informat, Natl Lib Med, NIH, Bethesda, MD 20892 USA. RP Edgar, R (reprint author), Natl Ctr Biotechnol Informat, Natl Lib Med, NIH, 45 Ctr Dr, Bethesda, MD 20892 USA. EM geo@ncbi.nlm.nih.gov FU Intramural NIH HHS [NIH0010394446]; PHS HHS [NIH0010394446] NR 6 TC 61 Z9 65 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD DEC PY 2006 VL 24 IS 12 BP 1471 EP 1472 DI 10.1038/nbt1206-1471 PG 2 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 116IL UT WOS:000242795800010 PM 17160034 ER PT J AU De la Fuente, R Baumann, C Fan, T Schmidtmann, A Dobrinski, I Muegge, K AF De La Fuente, Rabindranath Baumann, Claudia Fan, Tao Schmidtmann, Anja Dobrinski, Ina Muegge, Kathrin TI Lsh is required for meiotic chromosome synapsis and retrotransposon silencing in female germ cells SO NATURE CELL BIOLOGY LA English DT Article ID SNF2 FAMILY; MOUSE; GENE; MICE; DNA; HETEROCHROMATIN; ELEMENTS; OOCYTES; LOCALIZATION; METHYLATION AB Lymphoid specific helicase (Lsh) is a major epigenetic regulator that is essential for DNA methylation and transcriptional silencing of parasitic elements in the mammalian genome(1,2). However, whether Lsh is involved in the regulation of chromatin-mediated processes during meiosis is not known. Here, we show that Lsh is essential for the completion of meiosis and transcriptional repression of repetitive elements in the female gonad. Oocytes from Lsh knockout mice exhibit demethylation of transposable elements and tandem repeats at pericentric heterochromatin, as well as incomplete chromosome synapsis associated with persistent RAD51 foci and gamma H2AX phosphorylation. Failure to load crossover-associated foci results in the generation of non-exchange chromosomes. The severe oocyte loss observed and lack of ovarian follicle formation, together with the patterns of Lsh nuclear compartmentalization in the germ line, demonstrate that Lsh has a critical and previously unidentified role in epigenetic gene silencing and maintenance of genomic stability during female meiosis. C1 Univ Penn, Sch Vet Med, Female Germ Cell Biol Grp, Dept Clin Studies,Ctr Anim Transgenesis & Germ Ce, Kennett Sq, PA 19348 USA. NCI, Mol Immunoregulat Lab, SAIC Basic Res Program, Frederick, MD 21701 USA. RP De la Fuente, R (reprint author), Univ Penn, Sch Vet Med, Female Germ Cell Biol Grp, Dept Clin Studies,Ctr Anim Transgenesis & Germ Ce, 382 W St Rd,Kennett Sq, Kennett Sq, PA 19348 USA. EM rfuente@vet.upenn.edu RI Dobrinski, Ina/A-1095-2007 FU NCRR NIH HHS [RR17359]; NICHD NIH HHS [HD042740]; PHS HHS [N01-C0-12400] NR 30 TC 80 Z9 82 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD DEC PY 2006 VL 8 IS 12 BP 1448 EP U85 DI 10.1038/ncb1513 PG 10 WC Cell Biology SC Cell Biology GA 110ZJ UT WOS:000242419800022 PM 17115026 ER PT J AU Muranski, P Boni, A Wrzesinski, C Citrin, DE Rosenberg, SA Childs, R Restifo, NP AF Muranski, Pawel Boni, Andrea Wrzesinski, Claudia Citrin, Deborah E. Rosenberg, Steven A. Childs, Richard Restifo, Nicholas P. TI Increased intensity lymphodepletion and adoptive immunotherapy - how far can we go? SO NATURE CLINICAL PRACTICE ONCOLOGY LA English DT Review DE adoptive cell transfer; immunodepletion; lymphodepletion; melanoma; T lymphocytes ID TOTAL-BODY IRRADIATION; CD8(+) T-CELLS; BONE-MARROW-TRANSPLANTATION; VERSUS-HOST-DISEASE; TREATMENT-RELATED MORTALITY; DIAGNOSED MULTIPLE-MYELOMA; ACUTE MYELOGENOUS LEUKEMIA; ACTIVATED KILLER CELLS; METASTATIC MELANOMA; IN-VIVO AB In a recent clinical trial involving patients with metastatic melanoma, immunosuppressive conditioning with fludarabine and cyclophosphamide resulted in a 50% response rate in robust long-term persistence of adoptively transferred T cells. Experimental findings indicate that lymphodepletion prior to adoptive transfer of tumor-specific T lymphocytes plays a key role in enhancing treatment efficacy by eliminating regulatory T cells and competing elements of the immune system ('cytokine sinks'). Newly emerging animal data suggest that more profound lymphoablative conditioning with autologous hematopoetic stem-cell rescue might further enhance treatment results. Here we review recent advances in adoptive immunotherapy of solid tumors and discuss the rationale for lymphodepleting conditioning. We also address safety issues associated with translating experimental animal results of total lymphoid ablation into clinical practice. C1 NHLBI, Clin Res Ctr, NIH, Stem Cell Allogene Transplant Unit,Hematol Branch, Bethesda, MD 20892 USA. NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Restifo, NP (reprint author), NHLBI, Clin Res Ctr, NIH, Stem Cell Allogene Transplant Unit,Hematol Branch, Room 3-5762, Bethesda, MD 20892 USA. EM restifo@nih.gov RI Wrzesinski, Claudia/A-3077-2008; Restifo, Nicholas/A-5713-2008; Muranski, Pawel/E-5572-2010; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999] NR 115 TC 151 Z9 155 U1 2 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1743-4254 J9 NAT CLIN PRACT ONCOL JI Nat. Clin. Pract. Oncol. PD DEC PY 2006 VL 3 IS 12 BP 668 EP 681 DI 10.1038/ncponc0666 PG 14 WC Oncology SC Oncology GA 115BR UT WOS:000242710100008 PM 17139318 ER PT J AU Cao, L Finkel, T AF Cao, Liu Finkel, Toren TI Cancer gets the Chk'ered flag SO NATURE MEDICINE LA English DT Editorial Material ID ONCOGENE-INDUCED SENESCENCE; DNA-DAMAGE RESPONSE; TUMORIGENESIS; P53; INSTABILITY; P16(INK4A); ACTIVATION; BARRIER; MYC AB Certain oncogenes seem to be able to trigger cellular senescence and growth arrest, thereby holding cancer at bay. Two new studies suggest that oncogenes trigger senescence through activation of a pathway initially described as sensing DNA damage. C1 NHLBI, US Natl Inst Hlth, Bethesda, MD 20892 USA. RP Cao, L (reprint author), NHLBI, US Natl Inst Hlth, 10 Ctr Dr, Bethesda, MD 20892 USA. EM finkelt@nih.gov NR 14 TC 0 Z9 1 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD DEC PY 2006 VL 12 IS 12 BP 1354 EP 1356 DI 10.1038/nm1206-1354 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 113SS UT WOS:000242618200012 PM 17151689 ER PT J AU Brenchley, JM Price, DA Schacker, TW Asher, TE Silvestri, G Rao, S Kazzaz, Z Bornstein, E Lambotte, O Altmann, D Blazar, BR Rodriguez, B Teixeira-Johnson, L Landay, A Martin, JN Hecht, FM Picker, LJ Lederman, MM Deeks, SG Douek, DC AF Brenchley, Jason M. Price, David A. Schacker, Timothy W. Asher, Tedi E. Silvestri, Guido Rao, Srinivas Kazzaz, Zachary Bornstein, Ethan Lambotte, Olivier Altmann, Daniel Blazar, Bruce R. Rodriguez, Benigno Teixeira-Johnson, Leia Landay, Alan Martin, Jeffrey N. Hecht, Frederick M. Picker, Louis J. Lederman, Michael M. Deeks, Steven G. Douek, Daniel C. TI Microbial translocation is a cause of systemic immune activation in chronic HIV infection SO NATURE MEDICINE LA English DT Article ID IMMUNODEFICIENCY-VIRUS-INFECTION; T-CELL DEPLETION; COMBINATION ANTIRETROVIRAL THERAPY; INFLAMMATORY-BOWEL-DISEASE; VERSUS-HOST-DISEASE; TOLL-LIKE RECEPTORS; GASTROINTESTINAL-TRACT; TYPE-1 INFECTION; SIV INFECTION; INTESTINAL PERMEABILITY AB Chronic activation of the immune system is a hallmark of progressive HIV infection and better predicts disease outcome than plasma viral load, yet its etiology remains obscure. Here we show that circulating microbial products, probably derived from the gastrointestinal tract, are a cause of HIV-related systemic immune activation. Circulating lipopolysaccharide, which we used as an indicator of microbial translocation, was significantly increased in chronically HIV-infected individuals and in simian immunodeficiency virus (SIV)-infected rhesus macaques (P <= 0.002). We show that increased lipopolysaccharide is bioactive in vivo and correlates with measures of innate and adaptive immune activation. Effective antiretroviral therapy seemed to reduce microbial translocation partially. Furthermore, in nonpathogenic SIV infection of sooty mangabeys, microbial translocation did not seem to occur. These data establish a mechanism for chronic immune activation in the context of a compromised gastrointestinal mucosal surface and provide new directions for therapeutic interventions that modify the consequences of acute HIV infection. C1 NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. Univ Penn, Dept Pathol, Philadelphia, PA 19104 USA. NIAID, Lab Anim Med, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Dept Infect Dis, London W12 0NN, England. Univ Minnesota, Dept Pediat, Div Hematol Oncol & Blood & Marrow Transplantat, Minneapolis, MN 55455 USA. Case Western Reserve Univ, Cleveland, OH 44016 USA. Univ Hosp Cleveland, Cleveland, OH 44016 USA. Rush Med Coll, Dept Immunol & Microbiol, Chicago, IL 60612 USA. Univ Calif San Francisco, San Francisco, CA 90210 USA. Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Portland, OR 97006 USA. RP Douek, DC (reprint author), NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. EM ddouek@mail.nih.gov RI Price, David/C-7876-2013; Rodriguez, Benigno/C-3365-2009; OI Price, David/0000-0001-9416-2737; Rodriguez, Benigno/0000-0001-9736-7957; Altmann, Daniel/0000-0002-2436-6192 FU Intramural NIH HHS; Medical Research Council [G108/441]; NCRR NIH HHS [M01-RR0083-37, RR-00165]; NIAID NIH HHS [AI066998, AI 25879, AI 36219, AI 38858, AI052745, AI41531, P30 AI27763, R0I AI052755]; NIMH NIH HHS [P30 MH62246] NR 50 TC 1690 Z9 1741 U1 18 U2 114 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD DEC PY 2006 VL 12 IS 12 BP 1365 EP 1371 DI 10.1038/nm1511 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 113SS UT WOS:000242618200016 PM 17115046 ER PT J AU Capell, BC Collins, FS AF Capell, Brian C. Collins, Francis S. TI Human laminopathies: nuclei gone genetically awry SO NATURE REVIEWS GENETICS LA English DT Review ID HUTCHINSON-GILFORD-PROGERIA; FAMILIAL PARTIAL LIPODYSTROPHY; DREIFUSS MUSCULAR-DYSTROPHY; ENCODING LAMIN A/C; A-TYPE LAMINS; CAUSE AUTOSOMAL-DOMINANT; CHROMATIN BINDING-SITE; C-TERMINAL DOMAIN; PRELAMIN-A; DILATED CARDIOMYOPATHY AB Few genes have generated as much recent interest as LMNA, LMNB1 and LMNB2, which encode the components of the nuclear lamina. Over 180 mutations in these genes are associated with at least 13 known diseases - the laminopathies. In particular, the study of LMNA, its products and the phenotypes that result from its mutation have provided important insights into subjects ranging from transcriptional regulation, the cell biology of the nuclear lamina and mechanisms of ageing. Recent studies have begun the difficult task of correlating the genotypes of laminopathies with their phenotypes, and potential therapeutic strategies using existing drugs, modified oligonucleotides and RNAi are showing real promise for the treatment of these diseases. C1 NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. RP Collins, FS (reprint author), NHGRI, Genome Technol Branch, NIH, 50 S Dr MSC8004, Bethesda, MD 20892 USA. EM fc23a@nih.gov OI Capell, Brian/0000-0002-7036-8359 NR 127 TC 276 Z9 286 U1 2 U2 31 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0056 J9 NAT REV GENET JI Nat. Rev. Genet. PD DEC PY 2006 VL 7 IS 12 BP 940 EP 952 DI 10.1038/nrg1906 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 106TT UT WOS:000242125100014 PM 17139325 ER PT J AU Weston, MC Schuck, P Ghosal, A Rosenmund, C Mayer, ML AF Weston, Matthew C. Schuck, Peter Ghosal, Alokesh Rosenmund, Christian Mayer, Mark L. TI Conformational restriction blocks glutamate receptor desensitization SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID LIGAND-BINDING CORE; RECOMBINANT KAINATE RECEPTORS; AMPA RECEPTOR; CRYSTAL-STRUCTURES; 3-DIMENSIONAL STRUCTURE; STRUCTURAL BASIS; POINT MUTATION; ION CHANNELS; ACTIVATION; MECHANISMS AB Desensitization is a universal feature of ligand-gated ion channels. Using the crystal structure of the GluR2 L483Y mutant channel as a guide, we attempted to build non-desensitizing kainate-subtype glutamate receptors. Success was achieved for GluR5, GluR6 and GluR7 with intermolecular disulfide cross-links but not by engineering the dimer interface. Crystallographic analysis of the GluR6 Y490C L752C dimer revealed relaxation from the active conformation, which functional studies reveal is not sufficient to trigger desensitization. The equivalent non-desensitizing cross-linked GluR2 mutant retained weak sensitivity to a positive allosteric modulator, which had no effect on GluR2 L483Y. These results establish that the active conformation of AMPA and kainate receptors is conserved and further show that their desensitization requires dimer rearrangements, that subtle structural differences account for their diverse functional properties and that the ligand-binding core dimer is a powerful regulator of ion-channel activity. C1 NICHHD, Lab Cellular & Mol Neurophysiol, Porter Neurosci Res Ctr, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. NICHHD, Div Bioengn & Phys Sci, Porter Neurosci Res Ctr, NIH,Dept Hlth & Human Serv,Off Res Serv, Bethesda, MD 20892 USA. RP Mayer, ML (reprint author), NICHHD, Lab Cellular & Mol Neurophysiol, Porter Neurosci Res Ctr, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM mayerm@mail.nih.gov RI Mayer, Mark/H-5500-2013; OI Schuck, Peter/0000-0002-8859-6966; Rosenmund, Christian/0000-0002-3905-2444 FU Intramural NIH HHS; NIGMS NIH HHS [T32 GM008507] NR 49 TC 79 Z9 81 U1 4 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 DEC PY 2006 VL 13 IS 12 BP 1120 EP 1127 DI 10.1038/nsmb1178 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 114GV UT WOS:000242655600019 PM 17115050 ER PT J AU Lam-Himlin, D Espey, MG Perry, G Smith, MA Castellani, RJ AF Lam-Himlin, Dora Espey, Michael G. Perry, George Smith, Mark A. Castellani, Rudy J. TI Malignant glioma progression and nitric oxide SO NEUROCHEMISTRY INTERNATIONAL LA English DT Article DE nitric oxide; nitric oxide synthase; glioma; glioblastoma multiforme ID GROWTH-FACTOR RECEPTOR; ASTROCYTIC BRAIN-TUMORS; HIGH-GRADE GLIOMAS; GLIOBLASTOMA-MULTIFORME; GENE AMPLIFICATION; NERVOUS-SYSTEM; P53 MUTATIONS; SECONDARY GLIOBLASTOMAS; SUPPRESSOR GENES; CHROMOSOME 10Q AB Glioblastoma multiforme, the most common of the malignant gliomas, carries a dismal prognosis in spite of the most aggressive therapy and recent advances in molecular pathways of glioma progression. Although it has received relatively little attention in the setting of malignant gliomas, nitric oxide metabolism may be intimately associated with the disease process. Interestingly, nitric oxide has both physiological roles (e.g., neurotransmitter-like activity, stimulation of cyclic GMP), and pathophysiological roles (e.g., neoplastic transformation,. tumor neovascularization, induction of apoptosis, free radical damage). Moreover, whether nitric oxide is neuroprotective or neurotoxic in a given disease state, or whether it enhances or diminishes chemotherapeutic efficacy in malignant neoplasia, is unresolved. This review discusses the multifaceted activity of nitric oxide with particular reference to malignant gliomas. (c) 2006 Elsevier Ltd. All rights reserved. C1 Univ Maryland, Dept Pathol, Baltimore, MD 21201 USA. NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA. Univ Texas, Coll Sci, San Antonio, TX 78285 USA. RP Castellani, RJ (reprint author), Univ Maryland, Dept Pathol, 22 S Greene St, Baltimore, MD 21201 USA. EM rcastellani@som.umaryland.edu RI Smith, Mark/A-9053-2009; Castellani, Rudy/A-9555-2009; Perry, George/A-8611-2009 OI Perry, George/0000-0002-6547-0172 NR 63 TC 27 Z9 27 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0197-0186 J9 NEUROCHEM INT JI Neurochem. Int. PD DEC PY 2006 VL 49 IS 8 BP 764 EP 768 DI 10.1016/j.neuint.2006.07.001 PG 5 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 108VH UT WOS:000242266800008 PM 16971023 ER PT J AU Yu, CH Manry, MT Li, J Narasimha, PL AF Yu, Changhua Manry, Michael T. Li, Jiang Narasimha, Pramod Lakshmi TI An efficient hidden layer training method for the multilayer perceptron SO NEUROCOMPUTING LA English DT Article; Proceedings Paper CT 8th Brazilian Symposium on Neural Networks CY SEP 29-OCT 01, 2004 CL Sao Luis, BRAZIL SP Brazilian Comp Soc, Int Neural Networks Soc , SIG INNS Brazil Special Interest Grp DE hidden weight optimization (HWO); convergence; hidden layer error function; saturation; adaptive learning factor ID BACKPROPAGATION ALGORITHM; NEURAL-NETWORK; ERROR FUNCTION; SATURATION AB The output-weight-optimization and hidden-weight-optimization (OWO-HWO) training algorithm for the multilayer perceptron alternately solves linear equations for output weights and reduces a separate hidden layer error function with respect to hidden layer weights. Here, three major improvements are made to OWO-HWO. First, a desired net function is derived. Second, using the classical mean square error, a weighted hidden layer error function is derived which de-emphasizes net function errors that correspond to saturated activation function values. Third, an adaptive learning factor based on the local shape of the error surface is used in hidden layer training. Faster learning convergence is experimentally verified, using three training data sets. (c) 2006 Elsevier B.V. All rights reserved. C1 FastVDO LLC, Columbia, MD 21046 USA. Univ Texas, Dept Elect Engn, Arlington, TX 76019 USA. NIH, Dept Radiol, Ctr Clin, Bethesda, MD 20892 USA. RP Yu, CH (reprint author), FastVDO LLC, Columbia, MD 21046 USA. EM ychmailuta@yahoo.com NR 30 TC 11 Z9 11 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-2312 J9 NEUROCOMPUTING JI Neurocomputing PD DEC PY 2006 VL 70 IS 1-3 BP 525 EP 535 DI 10.1016/j.neucom.2005.11.008 PG 11 WC Computer Science, Artificial Intelligence SC Computer Science GA 113MP UT WOS:000242602300050 ER PT J AU Deckers, RHR van Gelderen, P Ries, M Barret, O Duyn, JH Ikonomidou, VN Fukunaga, M Glover, GH de Zwart, JA AF Deckers, Roel H. R. van Gelderen, Peter Ries, Mario Barret, Olivier Duyn, Jeff H. Ikonomidou, Vasiliki N. Fukunaga, Masaki Glover, Gary H. de Zwart, Jacco A. TI An adaptive filter for suppression of cardiac and respiratory noise in MRI time series data SO NEUROIMAGE LA English DT Article DE physiologic noise; artifacts; filtering; temporal stability; fMRI ID FUNCTIONAL MRI; HUMAN BRAIN; FMRI; FLUCTUATION; REGRESSION; REDUCTION AB The quality of MRI time series data, which allows the study of dynamic processes, is often affected by confounding sources of signal fluctuation, including the cardiac and respiratory cycle. An adaptive filter is described, reducing these signal fluctuations as long as they are repetitive and their timing is known. The filter, applied in image domain, does not require temporal oversampling of the artifact-related fluctuations. Performance is demonstrated for suppression of cardiac and respiratory artifacts in 10-minute brain scans on 6 normal volunteers. Experimental parameters resemble a typical fMRI experiment (17 slices; 1700 ms TR). A second dataset was acquired at a rate well above the Nyquist frequency for both cardiac and respiratory cycle (single slice; 100 ins TR), allowing identification of artifacts specific to the cardiac and respiratory cycles, aiding assessment of filtering performance. Results show significant reduction in temporal standard deviation (SDt) in all subjects. For an 6 datasets with 1700 ms TR combined, the filtering method resulted in an average reduction in SDt of 9.2% in 2046 voxels substantially affected by respiratory artifacts, and 12.5% for the 864 voxels containing substantial cardiac artifacts. The maximal SDt reduction achieved was 52.7% for respiratory and 55.3% for cardiac filtering. Performance was found to be at least equivalent to the previously published RETROICOR method. Furthermore, the interaction between the filter and fMRI activity detection was investigated using Monte Carlo simulations, demonstrating that filtering algorithms introduce a systematic error in the detected BOLD-related signal change if applied sequentially. It is demonstrated that this can be overcome by combining physiological artifact filtering and detection of BOLD-related signal changes simultaneously. Visual fMRI data from 6 volunteers were analyzed with and without the filter proposed here. Inclusion of the cardio-respiratory regressors in the design matrix yielded a 4.6% t-score increase and 4.0% increase in the number of significantly activated voxels. (c) 2006 Elsevier Inc. All rights reserved. C1 NINDS, LFMI, Adv MRI Sect, NIH, Bethesda, MD 20892 USA. Eindhoven Univ Technol, Dept Biomed Engn, Biomed NMR, NL-5600 MB Eindhoven, Netherlands. Univ Bordeaux 2, CNRS, ERT, F-33076 Bordeaux, France. Stanford Univ, Sch Med, Radiol Sci Lab, Palo Alto, CA 94304 USA. RP de Zwart, JA (reprint author), NINDS, LFMI, Adv MRI Sect, NIH, Bldg 10,Rm BID-728,MSC 1065, Bethesda, MD 20892 USA. EM Jacco.deZwart@nih.gov RI Duyn, Jozef/F-2483-2010; Fukunaga, Masaki/F-6441-2013; Deckers, Roel/J-7749-2015 OI Fukunaga, Masaki/0000-0003-1010-2644; Deckers, Roel/0000-0001-5281-2949 FU Intramural NIH HHS; NCRR NIH HHS [P41 RR009784]; PHS HHS [P41 09784] NR 21 TC 50 Z9 50 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD DEC PY 2006 VL 33 IS 4 BP 1072 EP 1081 DI 10.1016/j.neuroimage.2006.08.006 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 108TU UT WOS:000242262900006 PM 17011214 ER PT J AU Wang, J Coolen, LM Brown, JL Usdin, TB AF Wang, Jing Coolen, Lique M. Brown, Jennifer L. Usdin, Ted B. TI Neurons containing tuberoinfundibular peptide of 39 residues are activated following male sexual behavior SO NEUROPEPTIDES LA English DT Article DE mating behavior; immediate early gene; Fos; subparafascicular nucleus ID SUBPARAFASCICULAR THALAMIC NUCLEUS; MEDIAL PREOPTIC AREA; MALE-RAT BRAIN; 39 RESIDUES; FOS IMMUNOREACTIVITY; COPULATORY-BEHAVIOR; LESIONS; CONNECTIONS; TEGMENTUM; AMYGDALA AB Tuberoinfundibular peptide of 39 residues (TIP39)-immunoreactive (IR) neurons are present in the medial subdivision of the parvocellular subparafascicular thalamic nucleus (mSPFp) where ejaculation-specific Fos expression is localized. The mSPFp is reciprocally connected to the medial preoptic area (MPOA), bed nucleus of the stria terminalis (BNST) and the medial nucleus of the amygdala (Me), all of which are critical for the regulation of male sexual behavior. The mSPFp also receives galanin and enkephalin containing projections from a region in the lumbar spinal cord, thought to be a central ejaculation center. Therefore, we hypothesized that TIP39 neurons in the mSPFp may be part of the neuronal circuitry activated by male sexual behavior. To test this hypothesis, we examined induction of Fos in TIP39 containing neurons in the mSPFp following male sexual behavior. Mating-induced Fos expression was evaluated in sexually experienced male rats under four experimental conditions: animals that (1) remained in their home cage without any interaction with females, (2) interacted with stimulus females and displayed intromission without ejaculation, (3) displayed one ejaculation, or (4) displayed 2 ejaculations. We found that Fos was induced in TIP39-IR neurons in the mSPFp in male rats following ejaculation but much less so following intromission without ejaculation. This suggests that TIP39-IR neurons in the mSPFp are part of the afferent circuits that process genital-somatosensory information related to ejaculation, and which contribute to mating and mating-induced changes in reproductive behavior. C1 NIMH, Genet Lab, Bethesda, MD 20892 USA. Univ Cincinnati, Dept Cell Biol Neurobiol & Anat, Cincinnati, OH 45267 USA. Univ Western Ontario, Dept Physiol & Pharmacol, London, ON N6A 5C1, Canada. Univ Western Ontario, Dept Anat & Cell Biol, London, ON N6A 5C1, Canada. RP Usdin, TB (reprint author), NIMH, Genet Lab, Bethesda, MD 20892 USA. EM usdint@mail.nih.gov FU NIMH NIH HHS [MH 60781] NR 29 TC 8 Z9 8 U1 1 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4179 J9 NEUROPEPTIDES JI Neuropeptides PD DEC PY 2006 VL 40 IS 6 BP 403 EP 408 DI 10.1016/j.npep.2006.08.003 PG 6 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 118LK UT WOS:000242943600002 PM 17056109 ER PT J AU Adermark, L Lovinger, DM AF Adermark, Louise Lovinger, David M. TI Ethanol effects on electrophysiological properties of astrocytes in striatal brain slices SO NEUROPHARMACOLOGY LA English DT Article DE alcohol; astroglia; gap junction; GFAP; patch clamp; whole cell ID RAT-HEART-CELLS; ABSTINENT ALCOHOLICS; CORTICAL ASTROCYTES; PRIMARY CULTURES; GAP-JUNCTIONS; GLIAL CONTROL; CHANNELS; SYNAPTOGENESIS; COMMUNICATION; PERMEABILITY AB Ethanol (EtOH) is known to alter neuronal physiology, but much less is known about the actions of this drug on glial function. To this end, we examined acute effects of ethanol on resting and voltage-activated membrane currents in striatal astrocytes using rat brain slices. Ten minutes exposure to 50 mM EtOH reduced slope conductance by 20%, increased input resistance by 25% and decreased capacitance by 38% but did not affect resting membrane potential. Current generated by a hyperpolarizing pulse was inhibited in a concentration dependent manner in passive astrocytes, while no significant EtOH effect was observed in complex astrocytes or neurons. The EtOH effect was blocked when intracellular KCl was replaced with CsCl, but not during chelation of intracellular calcium with BAPTA. During blockage of gap junction coupling with high intracellular CaCl2 or extracellular carbenoxolone the EtOH effect persisted but was reduced. Interestingly, EtOH effects were largely irreversible when gap junctions were open, but were fully reversible when gap junctions were closed. Ethanol also reduced the spread to other cells of Lucifer Yellow dye from individual glia filled via the patch pipette. These data suggest that EtOH inhibits a calcium-insensitive potassium channel, most likely a passive potassium channel, but also affects gap junction coupling in a way that is sustained after ethanol withdrawal. Astrocytes play a critical role in brain potassium homeostasis, and therefore EtOH effects on astrocytic function could influence neuronal activity. Published by Elsevier Ltd. C1 NIAAA, Sect Synapt Pharmacol, Lab Integrat Neurosci, NIH, Bethesda, MD 20892 USA. RP Lovinger, DM (reprint author), NIAAA, Sect Synapt Pharmacol, Lab Integrat Neurosci, NIH, 5625 Fishers Lane,TS-13, Bethesda, MD 20892 USA. EM lovindav@mail.nih.gov RI Adermark, Louise/D-2297-2014 OI Adermark, Louise/0000-0002-7165-9908 FU Intramural NIH HHS NR 46 TC 15 Z9 16 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD DEC PY 2006 VL 51 IS 7-8 BP 1099 EP 1108 DI 10.1016/j.neuropharm.2006.05.035 PG 10 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 117VV UT WOS:000242902300001 PM 16938316 ER PT J AU Wood, SK Verhoeven, RE Savit, AZ Rice, KC Fischbach, PS Woods, JH AF Wood, Susan K. Verhoeven, Robert E. Savit, Aaron Z. Rice, Kenner C. Fischbach, Peter S. Woods, James H. TI Facilitation of cardiac vagal activity by CRF-RI antagonists during swim stress in rats SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE CRF antagonists; antalarmin; astressin B; R121919; cardiac vagal activity; swim stress ID CORTICOTROPIN-RELEASING-FACTOR; HEART-RATE-VARIABILITY; MAJOR DEPRESSION; FACTOR RECEPTORS; WATER IMMERSION; IN-VIVO; ANTALARMIN; RESPONSES; ANXIETY; ADRENOCORTICOTROPIN AB Exposure to stressors that elicit fear and feelings of hopelessness can cause severe vagal activation leading to bradycardia, syncope, and sudden death. These phenomena though documented, are difficult to diagnose, treat clinically, and prevent. Therefore, an animal model incorporating these cardiovascular conditions could be useful. The present study examined 'sinking' during a 2-h swim stress, a phenomenon that occurs in 50% of rats during 25 degrees C water exposure. Concurrent measurements of body temperature, immobility, heart rate (HR), and PR interval (a measure of vagal activity) were made. Neither decreases in immobility nor variations in hypothermia during swim were correlated with sinking. Bradycardia was more severe in sinking rats (average minimum HR +/- SEM; 143 +/- 13 vs 247 +/- 14; p < 0.01), and PR interval was elevated (p < 0.0001). To examine potential modulation of vagal activity during stress, corticotropinrelasing factor (CRF) receptor antagonists (antalarmin, R121919 and astressin B), a glucocorticoid receptor antagonist (RU486), and a peripherally acting cholinergic antagonist (methylatropine nitrate) were administered. The centrally acting CRF antagonist, antalarmin (32 mg/kg), produced elongation of the PR interval (p < 0.0001), robust bradycardia (135 +/- 18; p < 0.001), and increased sinking (92%; p < 0.05), and methylatropine nitrate (3.2 mg/ kg) blocked these effects. Corroborating these data, two different CRF antagonists, R121919 (30 mg/kg) and astressin B (intracerebroventricular (i.c.v.), 0.03 mg/rat) increased sinking to 100%. RU486 (20 mg/kg) blocked HPA axis negative feedback and decreased percent sinking to 25%. From these studies, we concluded that sinking during a 2-h water exposure was a result of extreme vagal hyperactivity. Furthermore, stress- induced CRF release may serve to protect against elevated cardiac vagal activity. C1 Univ Michigan, Sch Med, Dept Pharmacol, Ann Arbor, MI 48109 USA. Earlham Coll, Dept Biol, Richmond, IN 47374 USA. NIDDK, Med Chem Lab, NIH, Bethesda, MD USA. RP Wood, SK (reprint author), Univ Michigan, Sch Med, Dept Pharmacol, 1301 MSRB 3, Ann Arbor, MI 48109 USA. EM howells@umich.edu OI Wood, Susan/0000-0001-5732-3335 FU NIDA NIH HHS [DA14349, R01 DA014349]; NIGMS NIH HHS [GM07767, T32 GM007767] NR 51 TC 11 Z9 12 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 IS 12 BP 2580 EP 2590 DI 10.1038/sj.npp.1301085 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 105QG UT WOS:000242046800003 PM 16710322 ER PT J AU Chen, SA O'Dell, LE Hoefer, ME Greenwell, TN Zorrilla, EP Koob, GF AF Chen, Scott A. O'Dell, Laura E. Hoefer, Michael E. Greenwell, Thomas N. Zorrilla, Eric P. Koob, George F. TI Unlimited access to heroin self-administration: Independent motivational markers of opiate dependence SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE escalation; circadian rhythm; food intake or feeding; meal pattern analysis; buprenorphine; naloxone ID INGESTIVE BEHAVIOR; FEEDING PATTERNS; DRUG-ADDICTION; DOSE-RESPONSE; RATS; BUPRENORPHINE; MORPHINE; WITHDRAWAL; COCAINE; REWARD AB The goal of the present study was to develop and validate an animal model of unlimited access to intravenous heroin self-administration combined with responding for food and water to characterize the transition to drug dependence. Male Wistar rats were allowed to lever press for heroin ( 60 mg/kg/0.1 ml infusion/s; fixed ratio 1; 20-s time out) and nosepoke for food and water in consecutive, daily 23-h sessions. Daily heroin intake increased over days, reaching significance by Day 14. Drug-taking increased across the circadian cycle, reflected as increases in both the nocturnal peak and diurnal nadir of heroin intake. Changes in the circadian pattern of food intake and meal patterning preceded and paralleled the changes in heroin intake. By Day 7, the circadian amplitude of feeding was blunted. Nocturnal intake decreased because rats consumed smaller and briefer meals. Diurnal intake increased due to increased meal frequency, whereas total daily food intake decreased. To control for time or experience in the self-administration boxes as a possible confound, rats with saline (no drug) tethers were tested and did not display significant changes in food intake pattern. Body weight gain slowed slightly in heroin rats relative to saline controls. Separate groups of rats revealed that significant physical dependence as measured by physical signs of opiate withdrawal following a naloxone injection (1.0 mg/kg, subcutaneous (s.c.)) was reached by Day 14. Significant increases in heroin intake could be produced using low doses of naloxone (0.003-0.03 mg/kg, s.c.) on days 28-31 of heroin access. After 6 weeks of heroin self-administration, rats injected with buprenorphine (0, 0.01, 0.04, and 0.2 mg/kg, s. c.) showed a dose-dependent reduction in heroin intake. Changes in the pattern of drug and food intake in the present unlimited heroin access model may serve as independent motivational markers for the transition to a drug- dependent state. C1 Scripps Res Inst, Mol & Integrat Neurosci Dept, La Jolla, CA USA. RP Chen, SA (reprint author), NIAAA, NIH, Lab Clin & Translat Studies, Sect Study Primate Models Psychopathol,Anim Ctr, POB 529,Bldg 112, Poolesville, MD 20837 USA. EM scott.chen@mail.nih.gov RI koob, george/P-8791-2016; OI Greenwell, Thomas/0000-0001-6069-0064 FU NIDA NIH HHS [DA04043, F32 DA15583]; NIDDK NIH HHS [DK64871] NR 72 TC 50 Z9 51 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 IS 12 BP 2692 EP 2707 DI 10.1038/sj.npp.1301008 PG 16 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 105QG UT WOS:000242046800014 PM 16452993 ER PT J AU Zeng, XM Chen, J Deng, XL Liu, Y Rao, MS Cadet, JL Freed, WJ AF Zeng, Xianmin Chen, Jia Deng, Xiaolin Liu, Ying Rao, Mahendra S. Cadet, Jean-Lud Freed, William J. TI An in vitro model of human dopaminergic neurons derived from embryonic stem cells: MPP(+) toxicity and GDNF neuroprotection SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE human embryonic stem cell; dopaminergic neuron; Parkinson's disease; MPP(+); GDNF ID VESICULAR MONOAMINE TRANSPORTER; NEUROTROPHIC FACTOR; PARKINSONS-DISEASE; CEREBRAL MICROVESSELS; SUBSTANTIA-NIGRA; DIFFERENTIATION; LINE; SYSTEM; RAT; 1-METHYL-4-PHENYLPYRIDINIUM AB Human embryonic stem cells (hESCs) can proliferate indefinitely yet also differentiate in vitro, allowing normal human neurons to be generated in unlimited numbers. Here, we describe the development of an in vitro neurotoxicity assay using human dopaminergic neurons derived from hESCs. We showed that the dopaminergic neurotoxin 1-methyl-4-phenylpyridinium (MPP(+)), which produces features of Parkinson's disease in humans, was toxic for hESC-derived dopaminergic neurons. Treatment with glial cell line-derived neurotrophic factor protected tyrosine hydroxylase-positive neurons against MPP(+)-induced apoptotic cell death and loss of neuronal processes as well as against the formation of intracellular reactive oxygen species. The availability of human dopaminergic neurons, derived from hESCs, therefore allows for the possibility of directly examining the unique features of human dopaminergic neurons with respect to their responses to pharmacological agents as well as environmental and chemical toxins. C1 NIDA, IRP, Cellular Neurobiol Res Branch, DHHS,NIH, Baltimore, MD USA. NIDA, IRP, Mol Neuropsychiat Res Branch, NIH,DHHS, Baltimore, MD USA. NIA, Lab Neurosci, DHHS, Baltimore, MD 21224 USA. Buck Inst, Novato, CA USA. RP Zeng, XM (reprint author), Buck Inst Age Res, 8001 Redwood Blvd, Novato, CA 94945 USA. EM xzeng@buckinstitute.org FU NIDA NIH HHS [Z01 DA000472-02] NR 50 TC 41 Z9 53 U1 3 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 IS 12 BP 2708 EP 2715 DI 10.1038/sj.npp.1301125 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 105QG UT WOS:000242046800015 PM 17109014 ER PT J AU Arrillaga-Romany, IC Mattay, VS Rasetti, R Alce, G Lazerow, A Premkumar, A Dean, C Goldberg, T Apud, JA Weinberger, DR AF Arrillaga-Romany, Isabel C. Mattay, Venkata S. Rasetti, Roberta Alce, Guilna Lazerow, Alan Premkumar, Ajay Dean, Claire Goldberg, Terry Apud, Jose A. Weinberger, Daniel R. TI Effects of modafinil on brain regions underlying cognitive and emotional information processing: An fMRI study in normal healthy volunteers SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NIH, NIMH, Clin Brain Disorders Branch, Genes Cognition & Psychosis Program, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S147 EP S148 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900400 ER PT J AU Austin, C AF Austin, Christopher TI The NIH molecular libraries initiative: Chemical tools for the neuropsychiatry in the Genome era SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S66 EP S66 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900197 ER PT J AU Barr, CS Schwandt, ML Lindell, SG Maestripieri, D Goldman, D Suomi, SJ Higley, JD Heilig, M AF Barr, Christina S. Schwandt, Melanie L. Lindell, Stephen G. Maestripieri, Dario Goldman, David Suomi, Stephen J. Higley, J. D. Heilig, Markus TI Association of a functional variant in the Mu-Opioid receptor gene (Oprm1 C77g) with attachment behavior in infant rhesus macaques SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NIH NIAAA, Sect Primate Models Psychopathol, Poolesville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S132 EP S132 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900362 ER PT J AU Carlson, PJ Neumeister, A Nugent, A Tinsley, R Kaplan, J Geraci, M Luckenbaugh, D Pine, D Charney, D Drevets, WC AF Carlson, Paul J. Neumeister, Alex Nugent, Allison Tinsley, Ruth Kaplan, Johanna Geraci, Marilla Luckenbaugh, David Pine, Daniel Charney, Dennis Drevets, Wayne C. TI Neurophysiological mechanisms in panic: Alterations of cerebral metabolism with yohimbine-induced panic attacks SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S212 EP S212 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900563 ER PT J AU Chen, JS Song, J Ji, YY Du, J Sei, YS Lipska, BK Lu, B Weinberger, DR AF Chen, Jingshan Song, Jian Ji, Yuanyuan Du, Jing Sei, Yoshi Lipska, Barbara K. Lu, Bai Weinberger, Daniel R. TI Orientation and cellular localization of membrane-bound catechol-o-methyltransferase in primary cultures of rat cortical neurons SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NIH, NIMH, Cognit & Psychosis Program, Bethesda, MD 20892 USA. RI Lu, Bai/A-4018-2012; Du, Jing/A-9023-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S239 EP S239 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900628 ER PT J AU Chen, SA Higley, JD Tolbert, SM Flint, WW Suomi, SJ Heilig, MA Barr, CS AF Chen, Scott A. Higley, J. D. Tolbert, Stephanie M. Flint, Wesley W. Suomi, Stephen J. Heilig, Markus A. Barr, Christina S. TI Effects of naltrexone on ethanol self-administration in rhesus macaques exposed to early-life stress SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NIH, Clin Lab & Translat Studies, Poolesville, MD USA. NIAAA, Poolesville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S204 EP S205 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900545 ER PT J AU Choi, SH Aid, S Bosetti, F AF Choi, Sang-Ho Aid, Saba Bosetti, Francesca TI The neuroinflammatory response and oxidative stress induced by acute intracerebroventricular administration of lipopolysaccharide are decreased in cyclooxygenase-1 deficient mice and increased in cyclooxygenase-2 deficient mice SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NIA, Brain Physiol & Metab Sect, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S190 EP S191 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900509 ER PT J AU Chong, VZ Thompson, M Webster, MJ Weickert, CS AF Chong, Victor Z. Thompson, Mia Webster, Maree J. Weickert, Cynthia Shannon TI Elevated ErbB4 protein in the prefrontal cortex of schizophrenic patients SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NIH, NIMH, CBDB, Minds Unit, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S256 EP S256 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900671 ER PT J AU Compton, WM O'Brien, CP Kiehl, KA Schwartz, R Metzner, JL Volkow, ND Palmer, L AF Compton, Wilson M. O'Brien, Charles P. Kiehl, Kent A. Schwartz, Robert Metzner, Jeffrey L. Volkow, Nora D. Palmer, Larry TI Research with prisoners: Ethics and opportunities SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 Natl Inst Drug Abuse, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S11 EP S11 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900035 ER PT J AU Dickstein, DP Van der Veen, JWC Knopf, L Pine, DS Leibenluft, E AF Dickstein, Daniel P. Van der Veen, Jan Willem C. Knopf, Lisa Pine, Daniel S. Leibenluft, Ellen TI Proton magnetic resonance spectroscopy in children and adolescents with severe mood dysregulation SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NIMH, Mood & Anxiety Disorder Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S104 EP S104 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900292 ER PT J AU Drgon, T AF Drgon, Tomas TI VMAT2: Imprinted alletic variation and roles in narcolepsy, vulnerability to amphetamine dependence and tetrabenazine responses SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NIDA, NIH IRP, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S49 EP S49 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900147 ER PT J AU Du, J Creson, T Wei, YL Gray, N Falke, C Wang, Y Blumenthal, R Yuan, PX Chen, G Manji, HK AF Du, Jing Creson, Thomas Wei, Yanling Gray, Neil Falke, Cynthia Wang, Yun Blumenthal, Rayah Yuan, Peixiong Chen, Guang Manji, Husseini K. TI Modulation of AMPA glutamate receptor trafficking in treatment of bipolar disorder: Involvement of antimanic effect in animal model SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NIH, NIMH, Mol Pathophysiol Lab, Bethesda, MD 20892 USA. RI Chen, Guang/A-2570-2017 NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S167 EP S167 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900450 ER PT J AU Ernst, M AF Ernst, Monique TI Behavioral and neural substrates of decision-making processes in adolescents as potential markers of risk for substance use SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S36 EP S37 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900109 ER PT J AU Fox, MA Jensen, CL Murphy, DL AF Fox, Meredith A. Jensen, Catherine L. Murphy, Dennis L. TI Mediation of exaggerated serotonin syndrome-like behaviors and temperature responses in serotonin transporter knockout mice by 5-HT1A and 5-HT7 serotonin receptors: A possible model and mechanism for differential human vulnerability to the serotonin syndrome SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NIMH, LCS, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NR 0 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 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S221 EP S222 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900586 ER PT J AU Gallardo, K Rapoport, J Shaw, P AF Gallardo, Kathy Rapoport, Judith Shaw, Philip TI Longitudinal mapping of lobar cerebral cortical asymmetry in children and adolescents with and without attention deficit hyperactivity disorder SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S211 EP S211 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900560 ER PT J AU Giedd, JN Lenroot, RK AF Giedd, Jay N. Lenroot, Rhoshel K. TI Longitudinal trajectories of brain development in healthy children and adolescents SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S67 EP S67 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900200 ER PT J AU Gogtay, N AF Gogtay, Nitin TI Brain development in children and adolescents with psychotic disorders: Insights from longitudinal neuroimaging and genetic studies SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RI Gogtay, Nitin/A-3035-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S67 EP S67 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900201 ER PT J AU Goldman, D Yuan, QP Enoch, MA Hu, XZ Murphy, D Kennedy, J Shen, PH Virkkunen, M Albaugh, B Hodgkinson, C Xu, K AF Goldman, David Yuan, Qiaoping Enoch, Mary-Anne Hu, Xian-zhang Murphy, Dennis Kennedy, James Shen, Pei-Hong Virkkunen, Matti Albaugh, Bernard Hodgkinson, Colin Xu, Ke TI Accessing addictions neurobiologies with a 130 gene, 1536 marker array SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NIAAA, NIH, Neurogenet Lab, Rockville, MD 20852 USA. RI Hodgkinson, Colin/F-9899-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S52 EP S53 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900158 ER PT J AU Goldstein, D AF Goldstein, David TI Pharmacogenetics - Lessons from anti-epileptic drugs SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 Natl Inst Drug Abuse, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S11 EP S11 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900034 ER PT J AU Grillon, C Avenevoli, S Cui, LH Merikangas, KR AF Grillon, Christian Avenevoli, Shelli Cui, Lihong Merikangas, Kathleen R. TI The effects of sex and pubertal status on the potentiated startle reflex SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NIMH, Unit Affect Psychophysiol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S82 EP S82 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900236 ER PT J AU Hall, FS Perona, MT Waters, S Sora, I Lesch, KP Murphy, DL Caron, M Uhl, GR AF Hall, Frank S. Perona, Maria T. Waters, Shonna Sora, Ichiro Lesch, Klaus-Peter Murphy, Dennis L. Caron, Marc Uhl, George R. TI The effects of DAT, SERT and NET gene knockout on behavior in animal models of depression SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NIDA, Mol Neurobio Branch, Baltimore, MD USA. RI Hall, Frank/C-3036-2013 OI Hall, Frank/0000-0002-0822-4063 NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S155 EP S156 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900420 ER PT J AU Hansson, AC Cippitelli, A Sommer, WH Fedeli, A Bjork, K Soverchia, L Terasmaa, A Massi, M Heilig, M Ciccocioppo, R AF Hansson, Anita C. Cippitelli, Andrea Sommer, Wolfgang H. Fedeli, Amalia Bjork, Karl Soverchia, Laura Terasmaa, Anton Massi, Maurizio Heilig, Markus Ciccocioppo, Roberto TI Variation at the rat Crhr1 locus and sensitivity to relapse into alcohol seeking induced by environmental stress SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 Natl Inst Hlth, Clin Lab & Translational Studies, Bethesda, MD USA. NIAAA, Bethesda, MD USA. RI Terasmaa, Anton/I-3312-2015 OI Terasmaa, Anton/0000-0002-5139-1764 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S73 EP S73 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900215 ER PT J AU Hardy, J AF Hardy, John TI Genome wide studies: Analyzing data beyond association and interpreting negative data SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NIH, NIA, Neurogenet Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S10 EP S11 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900033 ER PT J AU Kleinman, JE Weickert, CS Law, AJ Lipska, BK Hyde, TM Straub, R Cassano, H Weinberger, DR AF Kleinman, Joel E. Weickert, Cynthia S. Law, Amanda J. Lipska, Barbara K. Hyde, Thomas M. Straub, Richard Cassano, Hope Weinberger, Daniel R. TI Postmortem brain studies in schizophrenics and controls: Splice variants and isoforms SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 CBDB, NIMH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S6 EP S7 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900020 ER PT J AU Leibenluft, E Rich, B Brotman, M McClure, E Roberson-Nay, R Dickstein, D Berghorst, L Pine, D AF Leibenluft, Ellen Rich, Brendan Brotman, Melissa McClure, Erin Roberson-Nay, Roxann Dickstein, Daniel Berghorst, Lisa Pine, Daniel TI Amygdala deficits in bipolar disorder vs. anxiety disorders: It's all about context SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RI Brotman, Melissa/H-7409-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S22 EP S23 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900070 ER PT J AU Lenroot, R Schmitt, JE Sarah, O Wallace, GL Neale, MC Lerch, JP Giedd, JN AF Lenroot, Rhoshel Schmitt, James E. Sarah, Ordaz Wallace, Gregory L. Neale, Michael C. Lerch, Jason P. Giedd, Jay N. TI Heritability of cortical thickness during childhood and adolescence SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NIMH, Bethesda, MD 20892 USA. RI Giedd, Jay/A-3080-2008; Neale, Michael/B-1418-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S209 EP S209 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900555 ER PT J AU Lindell, SG Schwandt, ML Suomi, SJ Goldman, D Heilig, M Higley, JD Barr, CS AF Lindell, Stephen G. Schwandt, Melanie L. Suomi, Stephen J. Goldman, David Heilig, Markus Higley, J. D. Barr, Christina S. TI Variation in the rhNPY promoter region is associated with anxiety and behavioral pathology in infant Rhesus macaques SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NIH, NIAAA, LCTS, Poolesville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S232 EP S232 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900611 ER PT J AU Lipsky, RH Hu, XZ McMahon, FJ Buervenich, S Rush, AJ Charney, D Wilson, AF Sorant, AJ Panpanicolaou, GJ Fava, M Trivedi, MH Wisniewski, S Laje, G Manji, H AF Lipsky, Robert H. Hu, Xian-Zhang McMahon, Francis J. Buervenich, Silvia Rush, A. John Charney, Dennis Wilson, Alexander F. Sorant, Alexa J. Panpanicolaou, George J. Fava, Maurizio Trivedi, Madhukar H. Wisniewski, Steven Laje, Gonzalo Manji, Husseini TI Identification of genes influencing citalopram treatment response in the STAR*D trial SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NIAAA, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S23 EP S24 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900073 ER PT J AU Lu, B AF Lu, Bai TI BDNF synthesis and processing pathways relevant to cellular mechanisms of schizophrenia pathogenesis SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NICHD, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S34 EP S34 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900103 ER PT J AU Lu, L Shaham, Y AF Lu, Lin Shaham, Yavin TI Roles of BDNF within the mesolimbic dopamine system in cocaine craving and relapse SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NIH, Natl Inst Drug Abuse, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S4 EP S5 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900014 ER PT J AU Manji, H Du, J Chen, G AF Manji, Husseini Du, Jing Chen, Guang TI Signaling cascades regulate glutamatergically-mediated neural plasticity in critical limbic and reward circuits: Implications for the pathophysiology and treatment of bipolar disorder SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NIMH, LMP, Bethesda, MD USA. RI Chen, Guang/A-2570-2017 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S23 EP S23 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900071 ER PT J AU Marenco, S Siuta, M Kippenhan, JS Grodofsky, S Kohn, P Mervis, CB Morris, CA Weinberger, DR Meyer-Lindenberg, A Pierpaoli, C Berman, KF AF Marenco, Stefano Siuta, Michael Kippenhan, J. Shane Grodofsky, Sam Kohn, Philip Mervis, Carolyn B. Morris, Colleen A. Weinberger, Daniel R. Meyer-Lindenberg, Andreas Pierpaoli, Carlo Berman, Karen F. TI Altered white matter in Williams syndrome: Preliminary findings with DTI SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. RI Marenco, Stefano/A-2409-2008; Pierpaoli, Carlo/E-1672-2011; Meyer-Lindenberg, Andreas/H-1076-2011 OI Marenco, Stefano/0000-0002-2488-2365; Meyer-Lindenberg, Andreas/0000-0001-5619-1123 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S219 EP S219 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900579 ER PT J AU McMahon, F AF McMahon, Francis TI Pharmacogenetics of treatment outcome and side effects in the STAR star D cohort SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S38 EP S39 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900115 ER PT J AU Merikangas, KR AF Merikangas, Kathleen R. TI Contribution of genetic epidemiologic approaches to complex disease etiology SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NIMH, Sect Dev Genet Epidemiol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S10 EP S10 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900031 ER PT J AU Meyer-Lindenberg, AS AF Meyer-Lindenberg, Andreas S. TI Impact of oxytocin on circuitry for social cognition and fear in humans SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 GCAP, NIMH, Bethesda, MD USA. RI Meyer-Lindenberg, Andreas/H-1076-2011 OI Meyer-Lindenberg, Andreas/0000-0001-5619-1123 NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S9 EP S9 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900028 ER PT J AU Nguyen, HN Villacreses, NE Chang, L Rapoport, SI AF Nguyen, Henry N. Villacreses, Nelly E. Chang, Lisa Rapoport, Stanley I. TI Imaging nicotine-initiated brain signal transduction via arachidonic acid in unanesthetized rats SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol ID METABOLISM C1 NIA, Brain Physiol Metab Sect, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S218 EP S219 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900578 ER PT J AU Pezawas, L Meyer-Lindenberg, A Goldman, AL Verchinski, BA Chen, G Kolachana, BS Egan, MF Mattay, VS Hariri, AR Weinberger, DR AF Pezawas, Lukas Meyer-Lindenberg, Andreas Goldman, Aaron L. Verchinski, Beth A. Chen, Gang Kolachana, Bhaskar S. Egan, Michael F. Mattay, Venkata S. Hariri, Ahmad R. Weinberger, Daniel R. TI Interactions of SERT & BDNF: A complex genetic model of depression SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol ID VAL66MET POLYMORPHISM; HUMAN-MEMORY; AMYGDALA C1 NIH, NIMH, GCAP, Bethesda, MD 20892 USA. RI Hariri, Ahmad/D-5761-2011; Meyer-Lindenberg, Andreas/H-1076-2011 OI Meyer-Lindenberg, Andreas/0000-0001-5619-1123 NR 5 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S171 EP S171 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900460 ER PT J AU Rao, JS Ertley, R DeMar, J Arnold, JT Lee, HJ Bazinet, R Rapoport, SI AF Rao, Jagadeesh S. Ertley, Renee DeMar, James Arnold, Julia T. Lee, Ho-Joo Bazinet, Richard Rapoport, Stanley I. TI Dietary n-3 polyunsaturated fatty acid deprivation in rats for 15 weeks decreases frontal cortex phosphorylated CREB, p38 MAPK activity and BDNF expression SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NIH, NIA, Bethesda, MD 20892 USA. RI Rao, Jagadeesh/C-1250-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S163 EP S163 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900440 ER PT J AU Rich, BA Berghorst, L Fromm, S Dickstein, D Brotman, M Pine, D Leibenluft, E AF Rich, Brendan A. Berghorst, Lisa Fromm, Stephen Dickstein, Daniel Brotman, Melissa Pine, Daniel Leibenluft, Ellen TI Neural connectivity in children with bipolar disorder: Impairment in the face emotion processing circuit SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NIMH, Mood & Anxiety Program, Bethesda, MD 20892 USA. RI Brotman, Melissa/H-7409-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S98 EP S98 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900277 ER PT J AU Rose, EJ Ross, TJ Salmeron, BJ Kurup, PK Stein, EA AF Rose, Emma J. Ross, Thomas J. Salmeron, Betty Jo Kurup, Pradeep K. Stein, Elliot A. TI The effect of acute cocaine on the brain response to the anticipation of monetary losses and gains SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NIDA, IRP, Neuroimaging Res Branch, Baltimore, MD USA. RI Stein, Elliot/C-7349-2008; Salmeron, Betty Jo/M-1793-2016 OI Salmeron, Betty Jo/0000-0003-1699-9333 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S201 EP S201 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900537 ER PT J AU Rothman, RB Murphy, DL Xu, H Godin, JA Dersch, CM Partilla, JS Tidgwell, K Schmidt, M Prisinzano, TE AF Rothman, Richard B. Murphy, Daniel L. Xu, Heng Godin, Jonathan A. Dersch, Christina M. Partilla, John S. Tidgwell, Kevin Schmidt, Matthew Prisinzano, Thomas E. TI Salvinorin A: Allosteric interactions at the mu opioid receptor SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NIH, NIDA, IRP, Clin Psychopharmacol Sect, Baltimore, MD USA. RI Prisinzano, Thomas/B-7877-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S137 EP S137 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900374 ER PT J AU Schwandt, ML Erickson, K Barr, CS Lindell, SG Suomi, SJ Higley, JD AF Schwandt, Melanie L. Erickson, Kristine Barr, Christina S. Lindell, Stephen G. Suomi, Stephen J. Higley, James D. TI Effects of early experience and lack of social support on the endocrine and behavioral responses of rhesus macaques (Macaca mulatta) to separation stress SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 Natl Inst Hlth, NIAAA, Lab Clin Translat Stud, Poolesville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S147 EP S147 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900398 ER PT J AU Shapiro, DI Marenco, S Goldberg, TE Cannon-Spoor, EH Egan, MF Weinberger, DR AF Shapiro, Daniel I. Marenco, Stefano Goldberg, Terry E. Cannon-Spoor, Eleanor H. Egan, Michael F. Weinberger, Daniel R. TI Premorbid adjustment and neuropsychological performance in a large cohort of schizophrenia and discordant siblings SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NIMH, CBDB, Washington, DC USA. RI Marenco, Stefano/A-2409-2008 OI Marenco, Stefano/0000-0002-2488-2365 NR 0 TC 1 Z9 1 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S119 EP S120 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900330 ER PT J AU Shaw, P Lerch, J Taylor, K Eckstrand, KL Evans, A Rapoport, JL Giedd, J AF Shaw, Philip Lerch, Jason Taylor, Kristen Eckstrand, Kristen L. Evans, Alan Rapoport, Judith L. Giedd, Jay TI Polymorphisms of the apolipoprotein E gene which alter risk for Alzheimer's disease also affect cortical morphology in children and adolescents SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NIMH, Bethesda, MD 20892 USA. RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S208 EP S209 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900554 ER PT J AU Sibley, DR Rex, E Rankin, M Cabrera, D AF Sibley, David R. Rex, Elizabeth Rankin, Michele Cabrera, David TI Ethanol potentiation of D1 dopamine receptor signaling can be mediated by protein kinase C in an isozyme-specific fashion SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NINDS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S128 EP S129 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900354 ER PT J AU Smith, EV Anderson, AL Chiang, N Elkashef, A Rawson, RA Kahn, R Pierce, V Li, SH Holmes, T Vocci, F Ling, W Haning, W McCann, M Mawhinney, J Campbell, J Weis, D Gorodetzky, C Carlton, B AF Smith, Edwina V. Anderson, Ann L. Chiang, Nora Elkashef, Ahmed Rawson, Richard A. Kahn, Roberta Pierce, Valerie Li, Shou-Hua Holmes, Tyson Vocci, Frank Ling, Walter Haning, William McCann, Michael Mawhinney, Joseph Campbell, Jan Weis, Dennis Gorodetzky, Charles Carlton, Barry TI Bupropion for the treatment of methamphetamine dependence SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 Natl Inst Hlth, DMPC, NIDA, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S71 EP S71 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900211 ER PT J AU Sommer, WH Rimondini, R Hansson, AC Heilig, M AF Sommer, Wolfgang H. Rimondini, Roberto Hansson, Anita C. Heilig, Markus TI CRH signaling and the dark side of addiction: Long-lasting hyper-reactivity to stress in animals with a history of ethanol dependence SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NIAAA, Lab Clin & Translat Studies, Bethesda, MD 20892 USA. NIH, Bethesda, MD USA. RI Rimondini, Roberto/B-2500-2010 OI Rimondini, Roberto/0000-0003-4099-513X NR 0 TC 1 Z9 2 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S208 EP S208 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900552 ER PT J AU Spinelli, S Schwandt, M Lindell, S Erickson, K Suomi, SJ Higley, JD Goldman, D Barr, C AF Spinelli, Simona Schwandt, Melanie Lindell, Stephen Erickson, Kristine Suomi, Stephen J. Higley, J. D. Goldman, David Barr, Christina TI Relationship between the 5HTTLPR polymorphism and behavior in Rhesus macaques during a separation paradigm SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NIH, NIAAA, Lab Clin & Translat Studies, Poolesville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S231 EP S232 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900610 ER PT J AU Stein, EA Gu, H Ross, TJ Salmeron, BJ Yang, YH AF Stein, Elliot A. Gu, Hong Ross, Thomas J. Salmeron, Betty Jo Yang, Yihong TI Reduced functional connectivity in cocaine users revealed by resting-state functional MRI SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NIDA, IRP, Neuroimaging Res Branch, Baltimore, MD USA. RI Stein, Elliot/C-7349-2008; Salmeron, Betty Jo/M-1793-2016 OI Salmeron, Betty Jo/0000-0003-1699-9333 NR 0 TC 1 Z9 1 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S201 EP S202 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900538 ER PT J AU Straub, RE AF Straub, Richard E. TI Dysbindin, MUTED, and BLOC1S2: Multiple susceptibility genes in the BLOC-1 complex implicates vesicular trafficking defects in schizophrenia SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NIH, NIMH, Cognit & Psychosis Program, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S33 EP S33 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900100 ER PT J AU Sunderland, T Mirza, N Dustin, I Putnam, KT Levy, JA Cohen, RM AF Sunderland, Trey Mirza, Nadeem Dustin, Irene Putnam, Karen T. Levy, James A. Cohen, Robert M. TI Are we ready for preventative trials in people "at risk"for dementia? SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S32 EP S33 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900099 ER PT J AU Tan, HY Chen, Q Goldberg, TE Mattay, VS Weinberger, DR Callicott, JH AF Tan, Hao Yang Chen, Qiang Goldberg, Terry E. Mattay, Venkata S. Weinberger, Daniel R. Callicott, Joseph H. TI Prefrontal dopaminergic modulation of updating but not retrieval in working memory - A fMRI study on the catechol-O-methyltransferase Val158Met polymorphism SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S89 EP S90 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900255 ER PT J AU Thorsell, A Cippitelli, A Ciccocioppo, R Heilig, M AF Thorsell, Annika Cippitelli, Andrea Ciccocioppo, Roberto Heilig, Markus TI Characterization of a novel brain penetrant, orally available corticotropin-releasing hormone receptor 1 (CRH-R1) antagonist for treatment of alcoholism SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NIAAA, LCTS, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S73 EP S74 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900217 ER PT J AU Uhl, GR AF Uhl, George R. TI Human genome scanning results support roles for mnemonic systems in addiction vulnerabilities SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NIDA, NIH IRP, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S64 EP S64 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900190 ER PT J AU Uhl, GR AF Uhl, George R. TI VMAT2: Parallels between data from heterozygous knockout mice and data examining influences of imprinted human haplotypes SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NIH IRP, NIDA, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S30 EP S30 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900091 ER PT J AU Verchinski, BA Honea, RA Pezawas, L Callicott, JH Kolachana, B Mattay, VS Weinberger, DR Meyer-Lindenberg, A AF Verchinski, Beth A. Honea, Robyn A. Pezawas, Lukas Callicott, Joseph H. Kolachana, Bhaskar Mattay, Venkata S. Weinberger, Daniel R. Meyer-Lindenberg, Andreas TI A voxel-based morphometry study of complex genetic interactions in catechol-O-methyltransferase (COMT) SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NIH, NIMH, Cognit & Psychosis Program, Bethesda, MD 20892 USA. RI Meyer-Lindenberg, Andreas/H-1076-2011 OI Meyer-Lindenberg, Andreas/0000-0001-5619-1123 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S84 EP S85 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900242 ER PT J AU Vocci, FJ AF Vocci, Frank J. TI Cognitive deficits in stimulant abusers: Types of deficits and their possible modulation SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NIDA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S43 EP S44 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900130 ER PT J AU Volkow, N Wang, GJ Newcorn, J Fowler, J Telang, F Solanto, M Logan, J Wong, C Ma, Y Swanson, JM AF Volkow, Nora Wang, Gene-Jack Newcorn, Jeffrey Fowler, Joanna Telang, Frank Solanto, Mary Logan, Jean Wong, Christopher Ma, Yernin Swanson, James M. TI Disrupted brain dopamine activity in ADHD: Comparison with that in addiction SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NIDA, NIH, DHHS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S37 EP S38 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900111 ER PT J AU Weinberger, DR Tan, HY Buckholtz, J Mattay, VS Straub, R Meyer-Lindenberg, A Goldberg, T Egan, MF Callicott, JH AF Weinberger, Daniel R. Tan, Hao-Yang Buckholtz, Joshua Mattay, Venkatta S. Straub, Richard Meyer-Lindenberg, Andreas Goldberg, Terry Egan, Michael F. Callicott, Joseph H. TI Genetic prediction of a schizophrenia intermediate phenotype related to cortical information processing SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NIMH, NIH, Genes Cognit & Psychosis Program, Bethesda, MD USA. RI Meyer-Lindenberg, Andreas/H-1076-2011 OI Meyer-Lindenberg, Andreas/0000-0001-5619-1123 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S16 EP S16 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900051 ER PT J AU Wendland, JR Jacobowitz, DM Elkahloun, AG Murphy, DL AF Wendland, Jens R. Jacobowitz, David M. Elkahloun, Abdel G. Murphy, Dennis L. TI Genome-wide profiling of amygdala, hippocampus, striatum and frontal cortex gene expression in mice with a targeted deletion of the serotonin transporter SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NIH, NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S166 EP S167 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900449 ER PT J AU Winslow, JT Noble, PL Sanchez, MM AF Winslow, James T. Noble, Pamela L. Sanchez, Mar M. TI Neuropetides associated with social and emotional deficits in rhesus macaques SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NIMH, IRP, Non Human Primate Core, Dickerson, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S9 EP S9 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900027 ER PT J AU Zarate, CA Singh, J Kronstein, P Carlson, P Luckenbaugh, D Yuan, PX Chen, G Manji, H AF Zarate, Carlos A. Singh, Jaskaran Kronstein, Phillip Carlson, Paul Luckenbaugh, David Yuan, Peixiong Chen, Guang Manji, Husseini TI Efficacy of a protein kinase C inhibitor in the treatment of acute mania: A double-blind, placebo-controlled study SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NIMH, Lab Mol Pathophysiol, Bethesda, MD 20892 USA. RI Chen, Guang/A-2570-2017 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S100 EP S100 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900281 ER PT J AU Zolkowska, D Baumann, MH Rothman, RB AF Zolkowska, Dorota Baumann, Michael H. Rothman, Richard B. TI Effect of chronic administration of fenfluramine and fluoxetine on fenfluramine-induced increases in plasma serotonin in rats SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 NIH, NIDA, IRP, Clin Psychopharmacol Sect, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S137 EP S138 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900375 ER PT J AU Karim, AA Hinterberger, T Richter, J Mellinger, J Neumann, N Flor, H Kubler, A Birbaumer, N AF Karim, Ahmed A. Hinterberger, Thilo Richter, Juergen Mellinger, Juergen Neumann, Nicola Flor, Herta Kuebler, Andrea Birbaumer, Niels TI Neural Internet: Web surfing with brain potentials for the completely paralyzed SO NEUROREHABILITATION AND NEURAL REPAIR LA English DT Article DE brain-computer interface (BCI); neuroprosthesis; slow cortical potentials (SCP); neurofeedback; amyotrophic lateral sclerosis (ALS); locked-in syndrome (LIS) ID LOCKED-IN SYNDROME; AMYOTROPHIC-LATERAL-SCLEROSIS; THOUGHT TRANSLATION DEVICE; COMPUTER INTERFACE BCI; MOVEMENT SIGNAL; COMMUNICATION; CORTEX AB Neural Internet is a new technological advancement in braincomputer interface research, which enables locked-in patients to operate a Web browser directly with their brain potentials. Neural Internet was successfully tested with a locked-in patient diagnosed with amyotrophic lateral sclerosis rendering him the first paralyzed person to surf the Internet solely by regulating his electrical brain activity. The functioning of Neural Internet and its clinical implications for motorimpaired patients are highlighted. C1 Univ Tubingen, Inst Med Psychol & Behav Neurobiol, D-72072 Tubingen, Germany. Int Max Planck Res Sch Neural & Behav Sci, Tubingen, Germany. Univ Tubingen, Dept Comp Engn, D-72072 Tubingen, Germany. Univ Heidelberg, Dept Clin & Cognit Neurosci, Cent Inst Mental Hlth, Mannheim, Germany. NINDS, NIH, Human Cort Physiol Unit, Bethesda, MD 20892 USA. RP Karim, AA (reprint author), Univ Tubingen, Inst Med Psychol & Behav Neurobiol, Gartenstr 29, D-72072 Tubingen, Germany. EM ahmed.karim@uni-tuebingen.de RI Karim, Ahmed/D-2503-2009; OI Flor, Herta/0000-0003-4809-5398; Kubler, Andrea/0000-0003-4876-0415 NR 35 TC 44 Z9 46 U1 0 U2 6 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 DEC PY 2006 VL 20 IS 4 BP 508 EP 515 DI 10.1177/1545968306290661 PG 8 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 105JY UT WOS:000242027400009 PM 17082507 ER PT J AU Bassett, DS Bullmore, ET AF Bassett, Danielle Smith Bullmore, Edward T. TI Small-world brain networks SO NEUROSCIENTIST LA English DT Review DE small-world network; graph theory; human brain functional networks; functional magnetic resonance imaging ID PRIMATE CEREBRAL-CORTEX; CORTICAL VISUAL-SYSTEM; FUNCTIONAL CONNECTIVITY; THEORETICAL NEUROANATOMY; SYNAPTIC CONNECTIVITY; EVOLVING NETWORKS; COMPLEX NETWORKS; ORGANIZATION; FREQUENCY; GRAPHS AB Many complex networks have a small-world topology characterized by dense local clustering or cliquishness of connections between neighboring nodes yet a short path length between any (distant) pair of nodes due to the existence of relatively few long-range connections. This is an attractive model for the organization of brain anatomical and functional networks because a small-world topology can support both segregated/specialized and distributed/integrated information processing. Moreover, small-world networks are economical, tending to minimize wiring costs while supporting high dynamical complexity. The authors introduce some of the key mathematical concepts in graph theory required for small-world analysis and review how these methods have been applied to quantification of cortical connectivity matrices derived from anatomical tract-tracing studies in the macaque monkey and the cat. The evolution of small-world networks is discussed in terms of a selection pressure to deliver cost-effective information-processing systems. The authors illustrate how these techniques and concepts are increasingly being applied to the analysis of human brain functional networks derived from electroencephalography/magnetoencephalography and fMRI experiments. Finally, the authors consider the relevance of small-world models for understanding the emergence of complex behaviors and the resilience of brain systems to pathological attack by disease or aberrant development. They conclude that small-world models provide a powerful and versatile approach to understanding the structure and function of human brain systems. C1 Univ Cambridge, Addenbrookes Hosp, Dept Psychiat, Brain Mapping Unit, Cambridge CB2 2QQ, England. Univ Cambridge, Dept Phys, Cavendish Lab, Cambridge CB2 1TN, England. NIMH, Unit Syst Neurosci Psychiat Genes, Cognit & Psychosis Program, NIH, Bethesda, MD USA. RP Bullmore, ET (reprint author), Univ Cambridge, Addenbrookes Hosp, Dept Psychiat, Brain Mapping Unit, Hills Rd, Cambridge CB2 2QQ, England. EM etb23@cam.ac.uk RI Bullmore, Edward/C-1706-2012 OI Bullmore, Edward/0000-0002-8955-8283 FU Medical Research Council [G0001354] NR 42 TC 772 Z9 800 U1 24 U2 134 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1073-8584 EI 1089-4098 J9 NEUROSCIENTIST JI Neuroscientist PD DEC PY 2006 VL 12 IS 6 BP 512 EP 523 DI 10.1177/1073858406293182 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 103WQ UT WOS:000241918300013 PM 17079517 ER PT J AU Jean Harry, G AF Jean Harry, G. TI Inflammation and repair in the aging brain: What a difference a decade makes. SO NEUROTOXICOLOGY LA English DT Meeting Abstract CT 23rd International Neurotoxicology Conference CY SEP 17-21, 2006 CL Little Rock, AR C1 NIH, NIEHS, Neurotoxicol Grp, Dept Hlth & Human Serv, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD DEC PY 2006 VL 27 IS 6 BP 1157 EP 1157 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 122FO UT WOS:000243211300052 ER PT J AU Kirshner, A AF Kirshner, Annette TI Translational medicine and the NIEHS Strategic Plan. SO NEUROTOXICOLOGY LA English DT Meeting Abstract CT 23rd International Neurotoxicology Conference CY SEP 17-21, 2006 CL Little Rock, AR C1 NIH, NIEHS, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD DEC PY 2006 VL 27 IS 6 BP 1173 EP 1174 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 122FO UT WOS:000243211300101 ER PT J AU Graham, AL Papandonatos, GD Bock, BC Cobb, NK Baskin-Sommers, A Niaura, R Abrams, DB AF Graham, Amanda L. Papandonatos, George D. Bock, Beth C. Cobb, Nathan K. Baskin-Sommers, Arielle Niaura, Raymond Abrams, David B. TI Internet- vs. telephone-administered questionnaires in a randomized trial of smoking cessation SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID NICOTINE DEPENDENCE; PARTNER SUPPORT; SOCIAL SUPPORT; WEIGHTED KAPPA; LIFE-SPAN; AGREEMENT; RELAPSE; WEB; INTERVENTION; ABSTINENCE AB The Internet offers a promising channel to conduct smoking cessation research. Among the advantages of Internet research are the ability to access large numbers of participants who might not otherwise participate in a cessation trial, and the ability to conduct research efficiently and cost-effectively. To leverage the opportunity of the Internet in clinical research, it is necessary to establish that measures of known validity used in research trials are reliable when administered via the Internet. To date, no published studies examine the psychometric properties of measures administered via the Internet to assess smoking variables and psychosocial constructs related to cessation (e.g., stress, social support, quit methods). The purpose of the present study was to examine the reliability of measures of previous quit methods, perceived stress, depression, social support for cessation, smoking temptations, alcohol use, perceived health status, and income when administered via the Internet. Participants in the present study were enrolled in a randomized controlled trial of the efficacy of Internet smoking cessation. Following baseline telephone assessment and randomization into the parent trial, participants were recruited to the reliability substudy. An e-mail was sent 2 days after the telephone assessment with a link to the Internet survey and instructions to complete the survey that day. Of the 297 individuals invited to participate, 213 completed the survey within I week. Results indicate that the internal consistency and test-retest reliability of the measures examined are comparable when self-administered via the Internet or when interviewer-administered via telephone. C1 Brown Univ, Sch Med, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA. Brown Univ, Miriam Hosp, Sch Med, Ctr Behav Med, Providence, RI USA. Brown Univ, Miriam Hosp, Sch Med, Ctr Prevent Med, Providence, RI USA. Brown Univ, Ctr Stat Sci, Providence, RI 02912 USA. Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. Brown Univ, Sch Med, Butler Hosp, Providence, RI 02912 USA. NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. RP Graham, AL (reprint author), Georgetown Univ, Med Ctr, Dept Oncol, 3300 Whitehaven St,NW,Suite 4100, Washington, DC 20007 USA. EM Amanda_Graham@brown.edu RI Papandonatos, George/J-2328-2014; OI Papandonatos, George/0000-0001-6770-932X; Baskin-Sommers, Arielle/0000-0001-6773-0508; Cobb, Nathan/0000-0003-4210-226X; Graham, Amanda/0000-0003-3036-9653 FU NCI NIH HHS [R01 CA104836-04, 5R01CA104836-02, R01 CA104836] NR 40 TC 28 Z9 28 U1 1 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD DEC PY 2006 VL 8 SU 1 BP S49 EP S57 DI 10.1080/14622200601045367 PG 9 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 132ZJ UT WOS:000243981100008 PM 17491171 ER PT J AU Graham, AL Bock, BC Cobb, NK Niaura, R Abrams, DB AF Graham, Amanda L. Bock, Beth C. Cobb, Nathan K. Niaura, Raymond Abrams, David B. TI Characteristics of smokers reached and recruited to an Internet smoking cessation trial: A case of denominators SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID DEPENDENCE; PROGRAM AB The Internet can deliver smoking cessation interventions to large numbers of smokers. Little is known about the feasibility, reach, or efficacy of Internet cessation interventions. Virtually no data exist on who enrolls in cessation programs or on differences between those who complete enrollment and those who do not. This paper reports recruitment and enrollment findings for the first 764 participants in an ongoing randomized controlled trial that tested the efficacy of a widely disseminated Internet smoking cessation service (www.QuitNet.com) alone and in conjunction with telephone counseling. Study participants were recruited through Internet search engines using an active user sampling protocol. During the first 16 weeks of the study, 28,297 individuals were invited. Of those, 11,147 accepted the invitation, 5,557 screened eligible, 3,614 were recruited, 1,489 provided online informed consent, and 764 were confirmed eligible and enrolled. Of those who were at least curious about a cessation trial (n=11,147), 6.9% enrolled. Of those who were eligible and recruited (n=3,614), 21.1% enrolled. Depending on the denominator selected, results suggest that 7% to 21% of smokers interested in cessation will enroll into a research trial. Internet recruitment provides unique challenges and opportunities for managing sample recruitment, analyzing sulisamples to determine generalizability, and understanding the characteristics of individuals who participate in online research. C1 Brown Univ, Ctr Alcohol & Addict Studies, Sch Med, Providence, RI 02912 USA. Brown Univ, Ctr Behav & Prevent Med, Sch Med, Miriam Hosp, Providence, RI 02912 USA. Massachusetts Gen Hosp, Pulm & Crit Care Univ, Boston, MA 02114 USA. Butler Hosp, Brown Med Sch, Providence, RI 02906 USA. NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. RP Graham, AL (reprint author), Georgetown Univ, Med Ctr, Dept Oncol, 3300 Whitehaven St,NW,Suite 4100, Washington, DC 20007 USA. EM Amanda_Graham@brown.edu OI Cobb, Nathan/0000-0003-4210-226X; Graham, Amanda/0000-0003-3036-9653 FU NCI NIH HHS [R01 CA104836-04, R01 CA104836, 5R01CA104836-02] NR 18 TC 48 Z9 48 U1 0 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD DEC PY 2006 VL 8 SU 1 BP S43 EP S48 DI 10.1080/14622200601042521 PG 6 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 132ZJ UT WOS:000243981100007 PM 17491170 ER PT J AU Stoddard, JL Augustson, EM Mabry, PL AF Stoddard, Jacqueline L. Augustson, Erik M. Mabry, Patricia L. TI The importance of usability testing in the development of an Internet-based smoking cessation treatment resource SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID WEB; PROGRAM; DESIGN; TASK AB It has been cogently argued that Web-based interventions hold substantial promise to deliver effective cessation to a wide audience. However, the potential effectiveness of a site is constrained by fundamental issues such as ease of navigation and structure of information, which impact a visitor's ability to find relevant information. Use of content and Web-design experts to assist in the development of cessation sites is a common approach. This approach, although highly useful, may fail to adequately identify problems that a more typical, target user would experience when visiting the site. Formal usability testing provides a user-centric approach to assessing a site's functionality. In this paper, we provide an example of this approach used in the development of a cessation Web site. C1 NCI, DCCPS, TCRB, Bethesda, MD 20892 USA. NCI, Sci Applicat Int Corp, Tobacco Control Res Branch, Bethesda, MD 20892 USA. RP Stoddard, JL (reprint author), NCI, DCCPS, TCRB, EPN RM 4039B,6130 Execut Blvd MSC7337, Bethesda, MD 20892 USA. EM stoddaja@mail.nih.gov NR 40 TC 12 Z9 12 U1 0 U2 5 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD DEC PY 2006 VL 8 SU 1 BP S87 EP S93 DI 10.1080/14622200601048189 PG 7 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 132ZJ UT WOS:000243981100012 PM 17491175 ER PT J AU Stoddard, JL Augustson, EM AF Stoddard, Jacqueline L. Augustson, Erik M. TI Smokers who use Internet and smokers who don't: Data from the Health Information and National Trends Survey (HINTS) SO NICOTINE & TOBACCO RESEARCH LA English DT Article AB Web-assisted tobacco interventions (WATI) have proliferated in recent years, but little is known about those such sites are reaching and those who might be reached in the future. A better understanding of factors that differentiate smokers who do and do not use the Internet could help developers of smoking cessation resources optimize the content and dissemination of resources to these two groups. Using the 2003 Health Information National Trends Survey (HINTS), a nationally representative survey of U.S. adults, we compared smokers using the Internet (n=728) with smokers not using the Internet (n=516) on demographics, smoking history, healthcare (status, care, access, and use), beliefs about lung cancer risks, and media preferences. Our results showed that compared with smokers not on the Internet, those using the Internet had a higher income and were more likely to be employed, despite having a younger age. Internet-connected smokers also reported less psychological distress, fewer barriers to healthcare, and a greater interest in quitting smoking. Preferences for media also differed by Internet status: Those on the Internet spent less time on television and more time with newspapers and magazines than those not on the Internet. These and other differences may assist the public health community with both the design and dissemination of resources to help smokers quit. C1 NCI, Tobacco Control Res Branch, DCCPS, BRP, Bethesda, MD 20892 USA. Sci Applicat Int Corp, Mclean, VA 22102 USA. NCI, MPH, DCCPS, BRP,Tobacco Control Res Branch, Bethesda, MD 20892 USA. RP Stoddard, JL (reprint author), NCI, Tobacco Control Res Branch, DCCPS, BRP, EPN-4040,6130 Execut Blvd, Bethesda, MD 20892 USA. EM stoddaja@mail.nih.gov NR 15 TC 23 Z9 23 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD DEC PY 2006 VL 8 SU 1 BP S77 EP S85 DI 10.1080/14622200601039147 PG 9 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 132ZJ UT WOS:000243981100011 PM 17491174 ER PT J AU Babu, MM Iyer, LM Balaji, S Aravind, L AF Babu, M. Madan Iyer, Lakshminarayan M. Balaji, S. Aravind, L. TI The natural history of the WRKY-GCM1 zinc fingers and the relationship between transcription factors and transposons SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DNA-BINDING DOMAIN; MULTIPLE SEQUENCE ALIGNMENT; SACCHAROMYCES-CEREVISIAE; REGULATORY NETWORKS; CANDIDA-ALBICANS; GENOMIC ANALYSIS; GENE-EXPRESSION; PAIRED DOMAIN; PSI-BLAST; PROTEIN AB WRKY and GCM1 are metal chelating DNA-binding domains (DBD) which share a four stranded fold. Using sensitive sequence searches, we show that this WRKY-GCM1 fold is also shared by the FLYWCH Zn-finger domain and the DBDs of two classes of Mutator-like element (MULE) transposases. We present evidence that they share a stabilizing core, which suggests a possible origin from a BED finger-like intermediate that was in turn ultimately derived from a C2H2 Zn-finger domain. Through a systematic study of the phyletic pattern, we show that this WRKY-GCM1 superfamily is a widespread eukaryote-specific group of transcription factors (TFs). We identified several new members across diverse eukaryotic lineages, including potential TFs in animals, fungi and Entamoeba. By integrating sequence, structure, gene expression and transcriptional network data, we present evidence that at least two major global regulators belonging to this superfamily in Saccharomyces cerevisiae (Rcs1p and Aft2p) have evolved from transposons, and attained the status of transcription regulatory hubs in recent course of ascomycete yeast evolution. In plants, we show that the lineage-specific expansion of WRKY-GCM1 domain proteins acquired functional diversity mainly through expression divergence rather than by protein sequence divergence. We also use the WRKY-GCM1 superfamily as an example to illustrate the importance of transposons in the emergence of new TFs in different lineages. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. MRC, Mol Biol Lab, Cambridge CB2 2QH, England. RP Babu, MM (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM madanm@mrc-lmb.cam.ac.uk; aravind@ncbi.nlm.nih.gov FU Intramural NIH HHS; Medical Research Council [MC_U105185859] NR 90 TC 88 Z9 92 U1 0 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD DEC PY 2006 VL 34 IS 22 BP 6505 EP 6520 DI 10.1093/nar/gkl888 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 121XY UT WOS:000243191500017 PM 17130173 ER PT J AU Gupta, R Sharma, S Doherty, KM Sommers, JA Cantor, SB Brosh, RM AF Gupta, Rigu Sharma, Sudha Doherty, Kevin M. Sommers, Joshua A. Cantor, Sharon B. Brosh, Robert M., Jr. TI Inhibition of BACH1 (FANCJ) helicase by backbone discontinuity is overcome by increased motor ATPase or length of loading strand SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DNA SUBSTRATE-SPECIFICITY; DDA HELICASE; BIOCHEMICAL-CHARACTERIZATION; UNZIPPING MECHANISM; HEXAMERIC HELICASE; STRUCTURAL BASIS; DAMAGE RESPONSE; NS3 HELICASE; BRCA1; PROTEIN AB The BRCA1 associated C-terminal helicase (BACH1) associated with breast cancer has been implicated in double strand break (DSB) repair. More recently, BACH1 (FANCJ) has been genetically linked to the chromosomal instability disorder Fanconi Anemia (FA). Understanding the roles of BACH1 in cellular DNA metabolism and how BACH1 dysfunction leads to tumorigenesis requires a comprehensive investigation of its catalytic mechanism and molecular functions in DNA repair. In this study, we have determined that BACH1 helicase contacts with both the translocating and the non-translocating strands of the duplex are critical for its ability to track along the sugar phosphate backbone and unwind dsDNA. An increased motor ATPase of a BACH1 helicase domain variant (M299I) enabled the helicase to unwind the backbone-modified DNA substrate in a more proficient manner. Alternatively, increasing the length of the 5' tail of the DNA substrate allowed BACH1 to overcome the backbone discontinuity, suggesting that BACH1 loading mechanism is critical for its ability to unwind damaged DNA molecules. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. Univ Massachusetts, Sch Med, Dept Canc Biol, Worcester, MA 01605 USA. RP Brosh, RM (reprint author), NIA, Lab Mol Gerontol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM broshr@grc.nia.nih.gov OI Sharma, Sudha/0000-0003-2765-2482 FU Intramural NIH HHS NR 42 TC 28 Z9 28 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD DEC PY 2006 VL 34 IS 22 BP 6673 EP 6683 DI 10.1093/nar/gkl964 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 121XY UT WOS:000243191500032 PM 17145708 ER PT J AU Young-Hyman, D Tanofsky-Kraff, M Yanovski, SZ Keil, M Cohen, ML Peyrot, M Yanovski, JA AF Young-Hyman, Deborah Tanofsky-Kraff, Marian Yanovski, Susan Z. Keil, Margaret Cohen, Marc L. Peyrot, Mark Yanovski, Jack A. TI Psychological status and weight-related distress in overweight or at-risk-for-overweight children SO OBESITY LA English DT Article DE psychological status; weight-related distress; children; gender; ethnicity ID AFRICAN-AMERICAN; OBESE CHILDREN; SELF-ESTEEM; DEPRESSIVE SYMPTOMS; PUBERTAL CHANGES; HEALTH-RISK; ADOLESCENTS; WOMEN; GIRLS; MEN AB Objective: To associate psychological status, weight-related distress, and weight status during childhood in overweight or at-risk-for-overweight children. Research Methods and Procedures: We associated self-report of depression, trait anxiety, and weight-related distress (body size dissatisfaction and weight-related peer teasing after controlling for the effects of weight) in 164 children (black 35%; age 11.9 +/- 2.5 years; girls 51%) who were overweight or at-high-risk-for-overweight and were not seeking weight loss. Results: Overall, heavier children reported more psychological and weight-related distress. Black children reported more anxiety and body size dissatisfaction than white children, despite equivalent weights. However, psychological distress was not significantly associated with weight in white children. Girls reported more weight-related distress than boys. Depression was associated with weight-related teasing in all predictive models, except in the model using only black subjects. Trait anxiely was associated with report of peer teasing when using all subjects. Depression was also significantly associated with children's report of body size dissatisfaction in models using all subjects, only girls, or white subjects, but not in analyses using only boys or black subjects. For boys peer teasing was associated with body size dissatisfaction. In models including only black children, depression and trait anxiety were not significantly associated with either report of peer teasing or body size dissatisfaction. Discussion: Regardless of race or sex, increasing weight is associated with emotional and weight-related distress in children. However, associations of psychological status, weight, and weight-related distress differ for girls and boys, and for black and white children. C1 Med Coll Georgia, Georgia Prevent Inst, Augusta, GA 30912 USA. NICHHD, Unit Growth & Obes, Bethesda, MD 20892 USA. NIDDK, NIH, Div Digest Dis & Nutr, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Young-Hyman, D (reprint author), Med Coll Georgia, Georgia Prevent Inst, HS 1640, Augusta, GA 30912 USA. EM dyounghyman@mail.mcg.edu RI Vollrath, Margarete/G-1297-2011 FU Intramural NIH HHS [Z01 HD000641-12, Z99 HD999999]; NICHD NIH HHS [Z01 HD000641] NR 43 TC 72 Z9 73 U1 1 U2 2 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 DEC PY 2006 VL 14 IS 12 BP 2249 EP 2258 DI 10.1038/oby.2006.264 PG 10 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 212OH UT WOS:000249606200018 PM 17189553 ER PT J AU Richter, HE Fielding, JR Bradley, CS Handa, VL Fine, P FitzGerald, MP Visco, A Wald, A Hakim, C Wei, JT Weber, AM AF Richter, Holly E. Fielding, Julia R. Bradley, Catherine S. Handa, Victoria L. Fine, Paul FitzGerald, Mary Pat Visco, Anthony Wald, Arnold Hakim, Christiane Wei, J. T. Weber, Anne M. CA Pelvic Floor Disorders Network TI Endoanal ultrasound findings and fecal incontinence symptoms in women with and without recognized anal sphincter tears SO OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 53rd Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 22-25, 2006 CL Toronto, CANADA SP Soc Gynecol Invest ID VAGINAL DELIVERY; PRIMARY REPAIR; ENDOSONOGRAPHY; 3RD-DEGREE; RISK; DEFECTS; RUPTURE; INJURY; DILATATION; DISRUPTION AB To estimate whether endoanal ultrasound findings are more prevalent in primiparous women with a history of anal sphincter tear than in women without this history and whether the findings are associated with fecal incontinence symptoms. METHODS: A total of 251 primiparous women at seven clinical sites underwent standardized ultrasound assessment of the internal and external anal sphincter 6-12 months after delivery. Participants were women in the three cohorts of the Childbirth and Pelvic Symptoms Study: 1) women with clinically evident third- or fourth-degree tear at vaginal delivery (n=106); 2) no tear at vaginal delivery (n=106); and 3) cesarean delivery without labor (n=39). Women completed the Fecal Incontinence Severity Index to assess fecal incontinence symptoms. RESULTS: Thirty-five percent of the sphincter tear group exhibited internal sphincter gaps compared with 3% of vaginal controls (odds ratio [OR] 18.4, 95% confidence interval [CI] 5.5-62.1) and 10% of cesarean controls. External sphincter gaps were identified in 51% of the tear group compared with 31% of vaginal controls (OR 2.3, 95% CI 1.3-4.0) and 28% of cesarean controls. In the tear group, fecal incontinence severity was greater in those with internal sphincter gaps compared with those with no internal sphincter gaps (Fecal Incontinence Severity Index score 6.6 +/- 8.3 compared with 3.3 +/- 6.1, P=.02), as well as in those with external sphincter gaps (6.1 +/- 8.4 compared with 2.7 +/- 5.0, P=.01), and greatest in those with both internal and external sphincter gaps compared with at least one gap not present (7.2 +/- 8.1 compared with 3.4 +/- 6.4, P=.003). CONCLUSION: Anal sphincter gaps detected by ultrasonography are prevalent in postpartum primiparous women with a history of sphincter tear and are associated with fecal incontinence severity. C1 Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35249 USA. Univ N Carolina, Dept Radiol, Chapel Hill, NC USA. Univ Iowa, Carver Coll Med, Dept Obstet & Gynecol, Iowa City, IA USA. Johns Hopkins Sch Med, Baltimore, MD USA. Baylor Coll Med, Houston, TX 77030 USA. Loyola Univ, Dept Obstet & Gynecol, Chicago, IL 60611 USA. Univ N Carolina, Dept Obstet & Gynecol, Chapel Hill, NC USA. Univ Pittsburgh, Med Ctr, Dept Med, Pittsburgh, PA USA. Magee Womens Hosp, Div Radiol, Pittsburgh, PA USA. Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA. NICHHD, Bethesda, MD 20892 USA. RP Richter, HE (reprint author), Univ Alabama, Dept Obstet & Gynecol, 620 20th St S,NHB 219, Birmingham, AL 35249 USA. EM hrichter@uabmc.edu RI Wei, John/E-8967-2012 FU NICHD NIH HHS [U01 HD41249, U10 HD041261, U10 HD41248, U10 HD41250, U10 HD41261, U10 HD41263, U10 HD41267, U10 HD41268, U10 HD41269]; NIDDK NIH HHS [K24 DK068389] NR 35 TC 36 Z9 36 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD DEC PY 2006 VL 108 IS 6 BP 1394 EP 1401 DI 10.1097/01.AOG.0000246799.53458.bc PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 171XX UT WOS:000246769800009 PM 17138772 ER PT J AU Cejtin, HE Kalinowski, A Bacchetti, P Taylor, RN Watts, DH Kim, S Massad, LS Preston-Martin, S Anastos, K Moxley, M Minkoff, HL AF Cejtin, Helen E. Kalinowski, Ann Bacchetti, Peter Taylor, Robert N. Watts, D. Heather Kim, Seijeoung Massad, L. Stewart Preston-Martin, Susan Anastos, Kathryn Moxley, Michael Minkoff, Howard L. TI Effects of human immunodeficiency virus on protracted amenorrhea and ovarian dysfunction SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID HIV-INFECTED WOMEN; NATURAL MENOPAUSE; ENDOCRINE FUNCTION; INTERAGENCY HIV; SERUM-ALBUMIN; AGE; SMOKING; PREDICTOR; SURVIVAL; OBESITY AB OBJECTIVE: To characterize ovarian failure and prolonged amenorrhea from other causes in women who are both human immunodeficiency virus (HIV) seropositive and seronegative. METHODS: This was a cohort study nested in the Women's Interagency HIV Study, a multicenter U.S. study of HIV infection in women. Prolonged amenorrhea was defined as no vaginal bleeding for at least 1 year. A serum follicle stimulating hormone more than 25 milli-International Units/mL and prolonged amenorrhea were used to define ovarian failure. Logistic regressions, chi(2), and t tests were performed to estimate relationships between HIV-infection and cofactors with both ovarian failure and amenorrhea from other causes. RESULTS: Results were available for 1,431 women (1,139 HIV seropositive and 292 seronegative). More than one half of the HIV positive women with prolonged amenorrhea of at least 1 year did not have ovarian failure. When adjusted for age, HIV seropositive women were about three times more likely than seronegative women to have prolonged amenorrhea without ovarian failure. Body mass index, serum albumin, and parity were all negatively associated with ovarian failure in HIV seropositive women. CONCLUSION: HIV serostatus is associated with prolonged amenorrhea. It is difficult to ascertain whether the cause of prolonged amenorrhea is ovarian in HIV-infected women without additional testing. C1 John H Stroger Hosp Cook Cty, Chicago, IL USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NICHHD, Bethesda, MD 20892 USA. So Illinois Univ, Springfield, IL USA. Univ So Calif, Los Angeles, CA USA. Lincoln Med & Mental Hlth Ctr, Bronx, NY USA. Georgetown Univ Hosp, Washington, DC 20007 USA. Maimonides Hosp, Brooklyn, NY 11219 USA. RP Cejtin, HE (reprint author), 1935 W Farwell, Chicago, IL 60626 USA. EM hcejlin@gmail.com FU NCRR NIH HHS [M01-RR00079, M01-RR00083]; NIAID NIH HHS [U01-AI-31834, U01-AI-34994, U01-AI-35004, U01-AI-42590, U01-AI-34989, U01-AI-34993]; NICHD NIH HHS [U01-HD-32632] NR 45 TC 32 Z9 34 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD DEC PY 2006 VL 108 IS 6 BP 1423 EP 1431 DI 10.1097/01.AOG.0000245442.29969.5c PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 171XX UT WOS:000246769800013 PM 17138776 ER PT J AU Ahlers, CM Figg, WD AF Ahlers, Christoph M. Figg, William D. TI Targeting metastatic prostate cancer: The search for innovative systemic therapies - The Berthold/Moore article reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material C1 NCI, Pharmacol Sect, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Ahlers, CM (reprint author), NCI, Pharmacol Sect, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 32 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD DEC PY 2006 VL 20 IS 14 BP 1792 EP + PG 3 WC Oncology SC Oncology GA V44BM UT WOS:000202978200008 ER PT J AU Vitale, S Cotch, MF Sperduto, R Ellwein, L AF Vitale, Susan Cotch, Mary Frances Sperduto, Robert Ellwein, Leon TI Costs of refractive correction of distance vision impairment in the United States, 1999-2002 SO OPHTHALMOLOGY LA English DT Article ID QUALITY-OF-LIFE; MEXICAN-AMERICAN POPULATION; ANGELES LATINO EYE; VISUAL IMPAIRMENT; PROYECTO VER; IMPACT; SELF; PREVALENCE; DISABILITY; BLINDNESS AB Objective: Correctable vision impairment caused by refractive error is common in the United States population. We estimated the direct costs of providing eyeglasses to all Americans (age >= 12) who need refractive correction to achieve good distance vision. Design: Cross-sectional study of a nationally representative sample of United States citizens. Participants: Participants in the 1999-2002 National Health and Nutrition Examination Survey (NHANES), age >= 12 years. The NHANES examines a nationally representative sample of the U.S. non institutionalized, civilian population. Methods: Presenting and corrected visual acuity data were obtained using an autorefractor from 13 211 (93.0%) of the 14 203 participants who visited the NHANES Mobile Examination Center in 1999 through 2002. Need for refractive correction was defined by current use of corrective lenses for distance vision, improvement to good visual acuity following autorefractor correction (using several cutpoints to define good visual acuity), or both. Main Outcome Measures: Estimates of direct cost for refractive correction (1 pair of complete eyeglasses and a refraction examination) were computed based on Centers for Medicare & Medicaid Services fee schedules for 2000 and also based on expenditure data from the Medical Expenditure Panel Survey. Results: The NHANES results indicate that > 110 million Americans could or do achieve normal vision with refractive correction. The annual direct cost of correcting distance vision impairment is at least $3.8 billion. Of this amount, $780 million represents the annual cost of providing distance vision correction for persons > age 65. Conclusions: Correctable vision impairment due to refractive error is common in the United States population. These cost estimates provide useful information for public health endeavors aimed at provision of refractive correction to those who need it. C1 NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20814 USA. RP Vitale, S (reprint author), NEI, Div Epidemiol & Clin Res, NIH, 5635 Fishers Lane,Suite 100, Bethesda, MD 20814 USA. EM sev@nei.nih.gov OI Cotch, Mary Frances/0000-0002-2046-4350 FU Intramural NIH HHS [Z01 EY000402-07, Z01 EY000402-06, Z99 EY999999, ZIA EY000402-08, ZIA EY000402-09, ZIA EY000402-10] NR 25 TC 74 Z9 77 U1 1 U2 9 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 DEC PY 2006 VL 113 IS 12 BP 2163 EP 2170 DI 10.1016/j.ophtha.2006.06.033 PG 8 WC Ophthalmology SC Ophthalmology GA 114KH UT WOS:000242664600006 PM 16996610 ER PT J AU Miller, AD Vigdorovich, V Strong, RK Fernandes, RJ Lerman, MI AF Miller, A. D. Vigdorovich, V. Strong, R. K. Fernandes, R. J. Lerman, M. I. TI Hyal2, where are you? SO OSTEOARTHRITIS AND CARTILAGE LA English DT Letter ID JAAGSIEKTE SHEEP RETROVIRUS; APE LEUKEMIA-VIRUS; NASAL TUMOR-VIRUS; ONCOGENIC TRANSFORMATION; RECEPTOR HYAL2; CELL-LINES; EXPRESSION; PROTEIN; ENTRY C1 Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98109 USA. Fred Hutchinson Canc Res Ctr, Mol & Cellular Biol Program, Seattle, WA 98109 USA. Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98109 USA. Univ Washington, Dept Orthopaed & Sports Med, Orthopaed Res Labs, Seattle, WA 98195 USA. NCI, Immunobiol Lab, Ctr Canc Res, Frederick, MD 21702 USA. RP Miller, AD (reprint author), Fred Hutchinson Canc Res Ctr, Div Human Biol, 1100 Fairview Ave N,Mailstop C2-023, Seattle, WA 98109 USA. EM dmiller@fhcrc.org OI Miller, Dusty/0000-0002-3736-3660 FU NIAMS NIH HHS [R03 AR052896] NR 13 TC 6 Z9 6 U1 0 U2 3 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1063-4584 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD DEC PY 2006 VL 14 IS 12 BP 1315 EP 1317 DI 10.1016/j.joca.2006.08.004 PG 3 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 116LV UT WOS:000242805300015 PM 16990026 ER PT J AU Frontera, WR Fuhrer, MJ Jette, AM Chan, L Cooper, RA Duncan, PW Kemp, JD Ottenbacher, KJ Peckham, PH Roth, EJ Tate, DG AF Frontera, WR Fuhrer, MJ Jette, AM Chan, L Cooper, RA Duncan, PW Kemp, JD Ottenbacher, KJ Peckham, PH Roth, EJ Tate, DG TI Rehabilitation medicine summit: Building research capacity executive summary SO OTJR-OCCUPATION PARTICIPATION AND HEALTH LA English DT Editorial Material AB The general objective of the "Rehabilitation Medicine Summit: Building Research Capacity" was to advance and promote research in medical rehabilitation by making recommendations to expand research capacity. The five elements of research capacity that guided the discussions were: (1) researchers; (2) research culture, environment, and infrastructure, (3) funding; (4) partnerships; and (5) metrics. The 100 participants included representatives of professional organizations, consumer groups, academic departments, researchers, governmental funding agencies, and the private sector. The small group discussions and plenary sessions generated an array of problems, possible solutions, and recommended actions. A post-summit, multi-organizational initiative is called to pursue the agendas outlined in this report. C1 Harvard Univ, Spaulding Rehabil Hosp, Sch Med, Cambridge, MA 02138 USA. NIH, Bethesda, MD 20892 USA. Boston Univ, Boston, MA 02215 USA. Univ Washington, Seattle, WA 98195 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Univ Florida, Gainesville, FL 32611 USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Rehabil Inst Chicago, Chicago, IL 60611 USA. Univ Michigan, Ann Arbor, MI 48109 USA. RP Frontera, WR (reprint author), Harvard Univ, Spaulding Rehabil Hosp, Sch Med, Cambridge, MA 02138 USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1539-4492 J9 OTJR-OCCUP PART HEAL JI OTJR-Occup. Particip. Health PD WIN PY 2006 VL 26 IS 1 BP 33 EP 38 PG 6 WC Rehabilitation SC Rehabilitation GA 002MA UT WOS:000234614400005 ER PT J AU Zenner, HP Pfister, M Birbaumer, N AF Zenner, Hans P. Pfister, Markus Birbaumer, Niels TI Tinnitus sensitization: Sensory and psychophysiological aspects of a new pathway of acquired centralization of chronic tinnitus SO OTOLOGY & NEUROTOLOGY LA English DT Article DE brain plasticity; facilitation; thresholds of auditory system; tinnitus associations ID STIMULUS-RESPONSE COMPATIBILITY; RETRAINING THERAPY; SELECTIVE ATTENTION; MODEL; LONG; HEMISPHERES; HABITUATION; PERCEPTION; DEPENDENCE; APLYSIA AB Objective: Acquired centralized tinnitus (ACT) is the most frequent form of chronic tinnitus. The proposed ACT sensitization (ACTS) assumes a peripheral initiation of tinnitus whereby sensitizing signals from the auditory system establish new neuronal connections in the brain. Consequently, permanent neurophysiological malfunction within the information-processing modules results. Successful treatment has to target these malfunctioning information processing. We present in this study the neurophysiological and psychophysiological aspects of a recently suggested neurophysiological model, which may explain the symptoms caused by central cognitive tinnitus sensitization. Although conditioned reflexes, as a causal agent of chronic tinnitus, respond to extinction procedures, sensitization may initiate a vicious circle of overexcitation of the auditory system, resisting extinction and habituation. Data Sources: We used the literature database as indicated under "References" covering English and German works. Study Selection: For the ACTS model we extracted neurophysiological hypotheses of the auditory stimulus processing and the neuronal connections of the central auditory system with other brain regions to explain the malfunctions of auditory information processing. The model does not assume information-processing changes specific for tinnitus but treats the processing of tinnitus signals comparable with the processing of other external stimuli. The model uses the extensive knowledge available on sensitization of perception and memory processes and highlights the similarities of tinnitus with central neuropathic pain. Data Extraction: Quality, validity, and comparability of the extracted data were evaluated by peer reviewing. Data Synthesis: Statistical techniques were not used. Conclusion: According to the tinnitus sensitization model, a tinnitus signal originates (as a type I-IV tinnitus) in the cochlea. In the brain, concerned with perception and cognition, the 1) conditioned associations, as postulated by the tinnitus model of Jastreboff, and the 2) unconditioned sensitized stimulus responses, as postulated in the present ACTS model, are actively connected with and attributed to the tinnitus signal. Attention to the tinnitus constitutes a typical undesired sensitized response. Some of the tinnitus-associated attributes may be called essential, unconditioned sensitization attributes. By a process called facilitation, the tinnitus' essential attributes are suggested to activate the tinnitus response. The result is an undesired increase in responsivity, such as an increase in attentional focus to the eliciting tinnitus stimulus. The mechanisms underlying sensitization are known as a specific nonassociative learning process producing a structural fixation of long-term facilitation at the synaptic level. This sensitization model may be important for the development of a sensitization-specific treatment if extinction procedures alone do not lead to satisfactory outcome. Inasmuch as this model considers sensitization as a nonassociative learning process based on cortical plasticity, it is reasonable to assume that this learning process can be altered by counteracting learning procedures. These counteracting learning procedures may consist of tinnitus-specific cognitive and behavioral procedures. C1 Univ Tubingen, Dept Otolaryngol, D-72076 Tubingen, Germany. Univ Tubingen, Dept Med Psychol & Behav Neurobiol, D-72076 Tubingen, Germany. Natl Inst Hlth, Human Cort Physiol Unit, Bethesda, MD USA. RP Zenner, HP (reprint author), Univ Tubingen, Dept Otolaryngol, Elfriede Aulhorn Str 5, D-72076 Tubingen, Germany. EM zenner@uni-tuebingen.de NR 68 TC 31 Z9 32 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD DEC PY 2006 VL 27 IS 8 BP 1054 EP 1063 DI 10.1097/01.mao.0000231604.64079.77 PG 10 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 111IS UT WOS:000242445300003 PM 17130796 ER PT J AU Gooding, HC Linnenbringer, EL Burack, J Roberts, JS Green, RC Biesecker, BB AF Gooding, Holly C. Linnenbringer, Erin L. Burack, Jeffrey Roberts, J. Scott Green, Robert C. Biesecker, Barbara B. TI Genetic susceptibility testing for Alzheimer disease: Motivation to obtain information and control as precursors to coping with increased risk SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE genetic testing; genetic counseling; Alzheimer disease risk; apolipoprotein E; appraisals of health threat ID 1ST-DEGREE RELATIVES; IMPACT; STRESS AB Objective: This study investigated appraisals, including motivation, and coping preferences for undergoing Apolipoprotein E (APOE) susceptibility testing for Alzheimer disease (AD). Methods: Participants were 60 adult children of individuals affected with AD enrolled in a trial investigating use and impact of APOE susceptibility testing. An exploratory qualitative study was undertaken in which participants were interviewed about their testing experience. Results: Most participants viewed genetic testing as providing valuable information that could help direct future health care decisions and meet their emotional concerns about living at increased risk. Participants related their motivation for genetic testing to their worries about developing AD, preference to seek information about health threats, and need to feel in control of their health. Results: Most participants viewed genetic testing as providing valuable information that could help direct future health care decisions and meet their emotional concerns about living at increased risk. Participants related their motivation for genetic testing to their worries about developing AD, preference to seek information about health threats, and need to feel in control of their health. Conclusion: Even without prevention or treatment options, genetic testing may be a useful coping strategy for some at-risk individuals. Practice implications: Once testing becomes clinically available, practitioners need to address the value and limitations of testing as well as appraisals and efforts to cope. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Univ Calif Berkeley, Sch Publ Hlth, Div Community Hlth & Human Dev, Berkeley, CA 94720 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Med, Genet Program, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA. RP Biesecker, BB (reprint author), Bldg 10,Room 10C101,10 Ctr Dr, Bethesda, MD 20892 USA. EM barbarab@nhgri.nih.gov FU Intramural NIH HHS NR 28 TC 28 Z9 28 U1 3 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD DEC PY 2006 VL 64 IS 1-3 BP 259 EP 267 DI 10.1016/j.pec.2006.03.002 PG 9 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 119LA UT WOS:000243012600032 PM 16860524 ER PT J AU Raju, TNK AF Raju, Tonse N. K. TI The problem of late-preterm (near-term) births: A workshop summary SO PEDIATRIC RESEARCH LA English DT Article ID GESTATIONAL-AGE; INFANTS BORN; WEIGHT; MORTALITY; NEWBORNS; OUTCOMES; CHILDREN; HEALTHY; RISK C1 NICHHD, Ctr Dev Biol & Perinatal Med, NIH, Bethesda, MD 20952 USA. RP Raju, TNK (reprint author), 6100 Executive Blvd,Room 4B03, Bethesda, MD 20952 USA. EM rajut@mail.nih.gov NR 19 TC 31 Z9 31 U1 0 U2 2 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 DEC PY 2006 VL 60 IS 6 BP 775 EP 776 DI 10.1203/01.pdr.0000246074.73342.1e PG 2 WC Pediatrics SC Pediatrics GA 108KT UT WOS:000242239400022 PM 17065577 ER PT J AU Gidding, SS Barton, BA Dorgan, JA Kimm, SYS Kwiterovich, PO Lasser, NL Robson, AM Stevens, VJ Van Horn, L Simons-Morton, DG AF Gidding, Samuel S. Barton, Bruce A. Dorgan, Joanne A. Kimm, Sue Y. S. Kwiterovich, Peter O. Lasser, Normal L. Robson, Alan M. Stevens, Victor J. Van Horn, Linda Simons-Morton, Denise G. TI Higher self-reported physical activity is associated with lower systolic blood pressure: The Dietary Intervention Study in Childhood (DISC) SO PEDIATRICS LA English DT Article DE blood pressure; physical fitness; cardiovascular disease ID BODY-MASS INDEX; CORONARY-HEART-DISEASE; RISK-FACTORS; CARDIOVASCULAR HEALTH; OBESE CHILDREN; EXERCISE; ADOLESCENCE; FITNESS; SCHOOL; GIRLS AB OBJECTIVE. Children participating in a dietary clinical trial were studied to (1) assess physical activity patterns in boys and girls longitudinally from late childhood through puberty and (2) determine the association of level of physical activity on systolic blood pressure, low-density lipoprotein cholesterol, and BMI. PATIENTS AND METHODS. In the Dietary Intervention Study in Childhood, a randomized clinical trial of a reduced saturated fat and cholesterol diet in 8- to 10-year-olds with elevated low-density lipoprotein, a questionnaire that determined time spent in 5 intensity levels of physical activity was completed at baseline and at 1 and 3 years. An estimated-metabolic-equivalent score was calculated for weekly activity; hours per week were calculated for intense activities. We hypothesized that weekly self-reported physical activity would be associated with lower systolic blood pressure, low-density lipoprotein, and BMI over 3 years. Longitudinal data analyses were performed for each outcome (systolic blood pressure, low-density lipoprotein, and BMI) by using generalized estimating equations with estimated- metabolic-equivalent score per week as the independent variable adjusted for visit, gender, and Tanner stage (BMI was included in models for systolic blood pressure and low-density lipoprotein). RESULTS. The initial study cohort comprised 663 youths (362 boys [mean age: 9.7 years] and 301 girls [mean age: 9.0 years), of whom 623 (94%) completed the 3-year visit. For every 100 estimated- metabolic-equivalent hours of physical activity, there was a decrease of 1.15 mm Hg of systolic blood pressure. There was a 1.28 mg/dL decline in low-density lipoprotein for a similar energy expenditure. For BMI, an analysis of intense physical activity showed that for every 10 hours of intense activity, there was a trend toward significance with a 0.2 kg/m(2) decrease. CONCLUSIONS. Children with elevated cholesterol levels who lead a more physically active lifestyle have lower systolic blood pressure and a trend toward lower lowdensity lipoprotein over a 3-year interval. Long-term participation in intense physical activity may reduce BMI as well. C1 Maryland Med Res Inst, Baltimore, MD 21210 USA. AI DuPont Childrens Hosp, Nemours Cardiac Ctr, Wilmington, DE USA. Thomas Jefferson Univ, Wilmington, DE USA. Maryland Med Res Inst, Baltimore, MD USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. Johns Hopkins Univ, Dept Pediat, Baltimore, MD 21218 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Internal Med, Newark, NJ 07103 USA. Childrens Hosp, Dept Nephrol, New Orleans, LA USA. Kaiser Permanente Ctr Hlth Res, Portland, OR USA. Northwestern Univ, Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. NHLBI, Bethesda, MD 20892 USA. RP Gidding, SS (reprint author), Maryland Med Res Inst, 600 Wyndhurst Ave, Baltimore, MD 21210 USA. EM sgidding@nemours.org; bbarton@mmri.org OI Barton, Bruce/0000-0001-7878-8895 FU NCRR NIH HHS [1 P20 RR020-173-01]; NHLBI NIH HHS [U01-HL37948, U01-HL37947, U01-HL37954, U01-HL37962, U01-HL37966, U01-HL37975, U01-HL38110] NR 31 TC 35 Z9 36 U1 0 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 DEC PY 2006 VL 118 IS 6 BP 2388 EP 2393 DI 10.1542/peds.2006-1785 PG 6 WC Pediatrics SC Pediatrics GA 111TX UT WOS:000242478900015 PM 17142523 ER PT J AU Williams, DE Cadwell, BL Cheng, YJ Gregg, EW Geiss, LS Engelgau, MM Narayan, KMV Imperatore, G Cowie, CC AF Williams, Desmond E. Cadwell, Betsy L. Cheng, Yiling J. Gregg, Edward W. Geiss, Linda S. Engelgau, Michael M. Narayan, K. M. Venkat Imperatore, Giuseppina Cowie, Catherine C. TI Low prevalence of impaired fasting glucose in obese adolescents from southern Europe - Reply SO PEDIATRICS LA English DT Letter C1 Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Diabet Translat, Atlanta, GA 30341 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Williams, DE (reprint author), Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Diabet Translat, Atlanta, GA 30341 USA. RI Narayan, K.M. Venkat /J-9819-2012 OI Narayan, K.M. Venkat /0000-0001-8621-5405 NR 4 TC 1 Z9 1 U1 0 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 DEC PY 2006 VL 118 IS 6 BP 2603 EP 2604 DI 10.1542/peds.2006-2571 PG 4 WC Pediatrics SC Pediatrics GA 111TX UT WOS:000242478900044 ER PT J AU Shudy, M de Almeida, ML Ly, S Landon, C Groft, S Jenkins, TL Nicholson, CE AF Shudy, Marysia de Almeida, Mary Lihinie Ly, Susan Landon, Christopher Groft, Stephen Jenkins, Tammara L. Nicholson, Carol E. TI Impact of pediatric critical illness and injury on families: A systematic literature review SO PEDIATRICS LA English DT Review DE critically ill children; siblings; injury; family impact; PICU ID TRAUMATIC BRAIN-INJURY; INTENSIVE-CARE-UNIT; CONGENITAL HEART-DISEASE; PARENTS STRESS RESPONSES; QUALITY-OF-LIFE; ILL CHILDREN; HELPING FAMILIES; YOUNG-CHILDREN; PSYCHOLOGICAL PREPARATION; HOSPITALIZATION AB OBJECTIVE. We sought to inform decision-making for children and families by describing what is known and remains unknown about the impact of childhood critical illness and injury on families. This report also was designed as a tool for research planning and design so that meaningful studies are performed and duplication is avoided. DESIGN. After a national scholarship competition and the identification of 3 medical student summer scholars, a literature search was conducted by using the National Library of Medicine and a PubMed keyword search system at the National Institutes of Health. RESULTS. A total of 115 reports were reviewed and assigned to the 5 following categories characterizing the impact of pediatric critical illness/injury on families: stressors, needs, specific domains (psychological, physical, social), coping, and interventions. The reports reviewed indicate that pediatric critical illness and injury is stressful for the entire family. The effects on parents, siblings, and marital cohesion were variably described. Needs of family members (eg, rest, nutrition, communication) were identified as being unmet in many studies. Permanent impact on siblings and marital relationships has been considered detrimental, but these conclusions are not adequately quantified in presently available studies. Reviewed reports minimally investigated cultural diversity, effects on fathers versus mothers, siblings, socioeconomic status, and financial burden. Studies were often anecdotal and included small sample sizes. Methodologic limitations were numerous and varied and seriously narrowed the significance of the studies we reviewed. The reports that we evaluated were largely limited to those of English-speaking families, white people, and married mothers. CONCLUSIONS. Future research should use more rigorous methods in the measurement of impact of childhood critical illness and injury on families. Families of critically ill and injured children would benefit from the practitioners of pediatric critical care acquiring enhanced knowledge and sensitivity about famliy communication and dynamics. C1 Univ Minnesota, Sch Med, New Brighton, MN 55112 USA. Med Coll Georgia, Augusta, GA 30912 USA. New York Med Coll, Valhalla, NY 10595 USA. Ventura Cty Med Ctr, Pediat Diagnost Ctr, Ventura, CA USA. NICHHD, Off Rare Dis, Off Director, NIH, Bethesda, MD 20892 USA. NICHHD, Natl Ctr Med Rehabil Res, NIH, Bethesda, MD 20892 USA. RP Shudy, M (reprint author), Univ Minnesota, Sch Med, 1694 14th Ave NW, New Brighton, MN 55112 USA. EM shud0014@umn.edu NR 110 TC 69 Z9 69 U1 1 U2 13 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 DEC PY 2006 VL 118 SU S BP S203 EP S218 DI 10.1542/peds.2006-0951B PG 16 WC Pediatrics SC Pediatrics GA 122BR UT WOS:000243201200001 PM 17142557 ER PT J AU Lee, CR North, KE Bray, MS Avery, CL Mosher, MJ Couper, DJ Coresh, J Folsom, AR Boerwinkle, E Heiss, G Zeldin, DC AF Lee, Craig R. North, Kari E. Bray, Molly S. Avery, Christy L. Mosher, Mary Jane Couper, David J. Coresh, Josef Folsom, Aaron R. Boerwinkle, Eric Heiss, Gerardo Zeldin, Darryl C. TI NOS3 polymorphisms, cigarette smoking, and cardiovascular disease risk: The Atherosclerosis Risk in Communities study SO PHARMACOGENETICS AND GENOMICS LA English DT Article DE coronary artery disease; endothelial nitric oxide synthase; polymorphism; smoking; stroke ID NITRIC-OXIDE SYNTHASE; COHORT; GENE; MICE AB Objective Endothelial nitric oxide synthase (NOS3) activity and cigarette smoking significantly influence endothelial function. We sought to determine whether cigarette smoking modified the association between NOS3 polymorphisms and risk of coronary heart disease or stroke. Methods All 1085 incident coronary heart disease cases, all 300 incident ischemic stroke cases, and 1065 reference individuals from the Atherosclerosis Risk in Communities. study were genotyped for the T-786C and E298D polymorphisms in NOS3. Using a case-cohort design, associations between genotype/haplotype and disease risk were evaluated by multivariable proportional hazards regression. Multiplicative scale interaction testing evaluated the influence of cigarette smoking history at baseline on these associations. Results In Caucasians, association between E298D genotype and risk of coronary heart disease was significantly modified by current smoking status (interaction P=0.013), with the highest risk observed in smokers carrying the variant D298 allele relative to nonsmokers carrying two E298 alleles (adjusted hazard rate ratio 2.07, 95% confidence interval 1.39-3.07). In African-Americans, association between T-786C genotype and risk of ischemic stroke was significantly modified by pack-year smoking history (interaction P=0.037), with the highest risk observed in >= 20 pack-year smokers carrying the variant C-786 allele relative to < 20 pack-year smokers carrying two T-786 alleles (adjusted hazard rate ratio 4.03, 95% confidence interval 1.54-10.6). Conclusions An interaction between the E298D and T-786C polymorphisms in NOS3, cigarette smoking, and risk of incident coronary heart disease and ischemic stroke events appears to exist, suggesting a potential complex interplay between genetic and environmental factors and cardiovascular disease risk. C1 Natl Inst Environm Hlth Sci, Div Intramural Res, Natl Inst Hlth, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Sch Pharm, Div Pharmacol & Expt Therapeut, Chapel Hill, NC USA. Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. Univ N Carolina, Sch Publ Hlth, Dept Biostat, Chapel Hill, NC USA. Baylor Coll Med, Childrens Nutr Res Ctr, Houston, TX 77030 USA. Univ Texas, Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA. Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. RP Zeldin, DC (reprint author), Natl Inst Environm Hlth Sci, Div Intramural Res, Natl Inst Hlth, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM zeldin@niehs.nih.gov OI Lee, Craig/0000-0003-3595-5301 FU Intramural NIH HHS [Z01 ES025034-13]; NHLBI NIH HHS [N01HC55020, N01-HC-55015, N01-HC-55018, N01-HC-55021, HL 074377, N01-HC-55016, N01-HC-55019, N01-HC-55022, N01HC55015, N01HC55018, N01HC55021, R01 HL074377, HL073366, N01-HC-55020, N01HC55022, R01 HL073366, N01HC55019, N01HC55016]; NIEHS NIH HHS [F32 ES012856-01, ES012856, F32 ES012856, F32 ES012856-02, F32 ES012856-03] NR 31 TC 22 Z9 22 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1744-6872 J9 PHARMACOGENET GENOM JI Pharmacogenet. Genomics PD DEC PY 2006 VL 16 IS 12 BP 891 EP 899 DI 10.1097/01.fpc.0000236324.96056.16 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA 115KZ UT WOS:000242734500006 PM 17108813 ER PT J AU Morton, LM Wang, SS Bergen, AW Chatterjee, N Kvale, P Welch, R Yeager, M Hayes, RB Chanock, SJ Caporaso, NE AF Morton, Lindsay M. Wang, Sophia S. Bergen, Andrew W. Chatterjee, Nilanjan Kvale, Paul Welch, Robert Yeager, Meredith Hayes, Richard B. Chanock, Stephen J. Caporaso, Neil E. TI DRD2 genetic variation in relation to smoking and obesity in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial SO PHARMACOGENETICS AND GENOMICS LA English DT Article DE alcohol consumption; dopamine; smoking; smoking cessation; obesity ID DOPAMINE-RECEPTOR GENE; DRUG-ADDICTION; NICOTINE PATCH; A1 ALLELE; BUPROPION; CESSATION; FOOD; AVAILABILITY; POLYMORPHISM; DEPENDENCE AB Objectives Cigarette smoking is the leading cause of morbidity and mortality worldwide. We investigated the association between smoking behavior and genetic variations in the D2 dopamine receptor (DRD2), which mediates nicotine dependence. To assess the specificity of genetic effects, we also investigated other reward-motivated characteristics (obesity, alcohol consumption). Methods Four single nucleotide polymorphisms in DRD2 were genotyped in 2374 participants selected randomly from the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial after stratifying by sex, age, and smoking status. Smoking, obesity, and alcohol consumption were assessed by questionnaire. Single nucleotide polymorphism and haplotype associations were estimated using odds ratios (ORs) and 95% confidence intervals derived from conditional logistic regression models, adjusted for race/ethnicity. Results DRD2 polymorphisms were associated with the risk of remaining a current smoker and obesity. Current smokers were more likely than former smokers to possess the variant TaqIA allele (rs#1 800497) in a dose-dependent model (ORCT = 1.2, ORTT = 1.5, P for linear trend = 0.007). The DRD2 haplotype T-C-T-A [TaqIA(C/T) - 957(T/C) - IVS6-83(G/T) - - 50977(A/G)] was more common among current than former smokers (OR = 1.3, P = 0.006), particularly among heavy smokers (21 + cigarettes per day; OR = 1.6, P = 0.006), and was more common among obese than normal weight individuals (OR = 1.4, P = 0.02). Conclusions Genetic variation in DRD2 is a modifier of the reward-motivated characteristics, smoking and obesity. As fewer than 15% of smokers who attempt to quit are able to maintain abstinence for greater than 3 months, our results support that DRD2 is an appropriate molecular target for smoking cessation treatments. Our results further support evaluation of DRD2 antagonists for obesity therapies. C1 NCI, Div Canc Epidemiol & Genet, DHHS, NIH, Rockville, MD 20852 USA. NCI, Core Genotyping Facil, Ctr Adv Technol, DHHS,NIH, Gaithersburg, MD USA. Henry Ford Hlth Syst, Detroit, MI USA. RP Morton, LM (reprint author), NCI, Div Canc Epidemiol & Genet, DHHS, NIH, 6120 Execut Blvd,EPS-550,MSC 7234, Rockville, MD 20852 USA. EM mortonli@mail.nih.gov RI Morton, Lindsay/B-5234-2015; OI Morton, Lindsay/0000-0001-9767-2310; Bergen, Andrew/0000-0002-1237-7644 FU Intramural NIH HHS NR 38 TC 32 Z9 33 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1744-6872 J9 PHARMACOGENET GENOM JI Pharmacogenet. Genomics PD DEC PY 2006 VL 16 IS 12 BP 901 EP 910 DI 10.1097/01.fpc.0000230417.20468.d0 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA 115KZ UT WOS:000242734500007 PM 17108814 ER PT J AU Flamant, F Baxter, JD Forrest, D Refetoff, S Samuels, H Scanlan, TS Vennstrom, B Samarut, J AF Flamant, Frederic Baxter, John D. Forrest, Douglas Refetoff, Samuel Samuels, Herbert Scanlan, Tom S. Vennstrom, Bjorn Samarut, Jacques TI International Union of Pharmacology. LIX. The pharmacology and classification of the nuclear receptor superfamily: Thyroid hormone receptors SO PHARMACOLOGICAL REVIEWS LA English DT Review ID TYPE-1 IODOTHYRONINE DEIODINASE; RETINOIC ACID RECEPTORS; LIGAND-BINDING DOMAIN; DEVELOPING RAT-BRAIN; GENE-EXPRESSION; ALPHA-GENE; POLYCHLORINATED-BIPHENYLS; TR-ALPHA; 3,5,3'-TRIIODOTHYRONINE BINDING; COACTIVATOR RECRUITMENT C1 Ecole Normale Super Lyon, CNRS, Lab Biol Mol, UMR 5665,INRALA913,IFR 128, F-69364 Lyon 07, France. Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Program Chem & Chem Biol, Dept Pharmaceut Chem, San Francisco, CA 94143 USA. NIDDKD, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Univ Chicago, Dept Med Pediat, Chicago, IL 60637 USA. NYU, Sch Med, Dept Pharmacol, New York, NY USA. NYU, Sch Med, Dept Med, New York, NY USA. Karolinska Inst, Dept Cell & Mol Biol, Stockholm, Sweden. RP Flamant, F (reprint author), Ecole Normale Super Lyon, CNRS, Lab Biol Mol, UMR 5665,INRALA913,IFR 128, 46 Allee Italie, F-69364 Lyon 07, France. EM frederic.flamant@ens-lyon.fr NR 100 TC 78 Z9 83 U1 4 U2 8 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 DEC PY 2006 VL 58 IS 4 BP 705 EP 711 DI 10.1124/pr.58.4.3 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 110JP UT WOS:000242374900003 PM 17132849 ER PT J AU Michalik, L Auwerx, J Berger, JP Chatterjee, VK Glass, CK Gonzalez, FJ Grimaldi, PA Kadowaki, T Lazar, MA O'Rahilly, S Palmer, CNA Plutzky, J Reddy, JK Spiegelman, BM Staels, B Wahli, W AF Michalik, Liliane Auwerx, Johan Berger, Joel P. Chatterjee, V. Krishna Glass, Christopher K. Gonzalez, Frank J. Grimaldi, Paul A. Kadowaki, Takashi Lazar, Mitchell A. O'Rahilly, Stephen Palmer, Colin N. A. Plutzky, Jorge Reddy, Janardan K. Spiegelman, Bruce M. Staels, Bart Wahli, Walter TI International Union of Pharmacology. LXI. Peroxisome proliferator-activated receptors SO PHARMACOLOGICAL REVIEWS LA English DT Review ID RETINOID-X-RECEPTOR; NUCLEAR HORMONE-RECEPTORS; LOW-DENSITY-LIPOPROTEIN; PPAR-ALPHA AGONIST; CAUSES INSULIN-RESISTANCE; POTENT ANTIDIABETIC THIAZOLIDINEDIONE; INHIBITS ADIPOCYTE DIFFERENTIATION; FOLLICULAR THYROID CARCINOMAS; PALMITOYLTRANSFERASE I GENE; DOMINANT-NEGATIVE MUTATIONS AB The three peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors of the nuclear hormone receptor superfamily. They share a high degree of structural homology with all members of the superfamily, particularly in the DNA-binding domain and ligand- and cofactor-binding domain. Many cellular and systemic roles have been attributed to these receptors, reaching far beyond the stimulation of peroxisome proliferation in rodents after which they were initially named. PPARs exhibit broad, isotype-specific tissue expression patterns. PPAR alpha is expressed at high levels in organs with significant catabolism of fatty acids. PPAR beta/delta has the broadest expression pattern, and the levels of expression in certain tissues depend on the extent of cell proliferation and differentiation. PPAR alpha is expressed as two isoforms, of which PPAR gamma 2 is found at high levels in the adipose tissues, whereas PPAR gamma 1 has a broader expression pattern. Transcriptional regulation by PPARs requires heterodimerization with the retinoid X receptor (RXR). When activated by a ligand, the dimer modulates transcription via binding to a specific DNA sequence element called a peroxisome proliferator response element (PPRE) in the promoter region of target genes. A wide variety of natural or synthetic compounds was identified as PPAR ligands. Among the synthetic ligands, the lipid-lowering drugs, fibrates, and the insulin sensitizers, thiazolidinediones, are PPAR alpha and PPAR gamma agonists, respectively, which underscores the important role of PPARs as therapeutic targets. Transcriptional control by PPAR/RXR heterodimers also requires interaction with coregulator complexes. Thus, selective action of PPARs in vivo results from the interplay at a given time point between expression levels of each of the three PPAR and RXR isotypes, affinity for a specific promoter PPRE, and ligand and cofactor availabilities. C1 Univ Lausanne, Ctr Integrat Genom, Natl Res Ctr Frontiers Genet, CH-1015 Lausanne, Switzerland. Inst Genet & Biol Mol & Cellulaire, Illkirch Graffenstaden, France. Merck Res Labs, Rahway, NJ USA. Univ Cambridge, Addenbrookes Hosp, Dept Med, Cambridge CB2 2QQ, England. Univ Calif Los Angeles, David Geffen Sch Med, Div Endocrinol Diabet & Hypertens, Los Angeles, CA USA. NCI, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA. Univ Nice Sophia Antipolis, INSERM, U636, Ctr Biochim,Unite Format & Rech Sci, Nice, France. Univ Tokyo, Grad Sch Med, Tokyo, Japan. Univ Penn, Sch Med, Div Endocrinol Diabet & Metab, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA. Univ Dundee, Ninewells Hosp & Med Sch, Biomed Res Ctr, Dundee DD1 9SY, Scotland. Harvard Univ, Sch Med, Div Cardiovasc, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Northwestern Univ, Feinberg Sch Med, Dept Pathol, Chicago, IL 60611 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Inst Pasteur, INSERM, Unite Rech 545, F-59019 Lille, France. RP Wahli, W (reprint author), Univ Lausanne, Ctr Integrat Genom, Natl Res Ctr Frontiers Genet, CH-1015 Lausanne, Switzerland. EM walter.wahli@unil.ch RI Palmer, Colin/C-7053-2008; Reddy, Jay/K-7200-2014; Wahli, Walter/B-1398-2009; OI Palmer, Colin/0000-0002-6415-6560; Reddy, Jay/0000-0003-4082-9254; Wahli, Walter/0000-0002-5966-9089; Staels, Bart/0000-0002-3784-1503 NR 294 TC 468 Z9 483 U1 5 U2 41 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 DEC PY 2006 VL 58 IS 4 BP 726 EP 741 DI 10.1124/pr.58.4.5 PG 16 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 110JP UT WOS:000242374900005 PM 17132851 ER PT J AU Dahlman-Wright, K Cavailles, V Fuqua, SA Jordan, VC Katzenellenbogen, JA Korach, KS Maggi, A Muramatsu, M Parker, MG Gustafsson, JA AF Dahlman-Wright, Karin Cavailles, Vincent Fuqua, Suzanne A. Jordan, V. Craig Katzenellenbogen, John A. Korach, Kenneth S. Maggi, Adriana Muramatsu, Masami Parker, Malcolm G. Gustafsson, Jan-Ake TI International Union of Pharmacology. LXIV. Estrogen receptors SO PHARMACOLOGICAL REVIEWS LA English DT Review ID BREAST-CANCER; BETA-GENE; MULTIPLE-SCLEROSIS; ALZHEIMERS-DISEASE; SELECTIVE LIGANDS; MOLECULAR-CLONING; ALPHA MUTATION; MESSENGER-RNA; ER-ALPHA; EXPRESSION C1 Karolinska Inst, Dept Biosci & Nutr, Huddinge, Sweden. INSERM, U540, Montpellier, France. Baylor Coll Med, Houston, TX 77030 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Univ Illinois, Urbana, IL 61801 USA. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. Univ Milan, Ctr Excellence Neurodegenerat Dis, Milan, Italy. Saitama Med Sch, Res Ctr Genom Med, Hidaka, Saitama, Japan. Univ London Imperial Coll Sci Technol & Med, Fac Med, Inst Reprod & Dev Biol, London, England. RP Dahlman-Wright, K (reprint author), Karolinska Inst, Dept Biosci & Nutr, SE-14186 Stockholm, Sweden. EM karin.dahlman-wright@biosci.ki.se RI Jordan, V. Craig/H-4491-2011; OI Korach, Kenneth/0000-0002-7765-418X NR 74 TC 251 Z9 259 U1 4 U2 25 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 DEC PY 2006 VL 58 IS 4 BP 773 EP 781 DI 10.1124/pr.58.4.8. PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 110JP UT WOS:000242374900008 PM 17132854 ER PT J AU Lu, NZ Wardell, SE Burnstein, KL Defranco, D Fuller, PJ Giguere, V Hochberg, RB McKay, L Renoir, JM Weigel, NL Wilson, EM McDonnell, DP Cidlowski, JA AF Lu, Nick Z. Wardell, Suzanne E. Burnstein, Kerry L. Defranco, Donald Fuller, Peter J. Giguere, Vincent Hochberg, Richard B. McKay, Lorraine Renoir, Jack-Michel Weigel, Nancy L. Wilson, Elizabeth M. McDonnell, Donald P. Cidlowski, John A. TI International Union of Pharmacology. LXV. The pharmacology and classification of the nuclear receptor superfamily: Glucocorticoid, mineralocorticoid, progesterone, and androgen receptors SO PHARMACOLOGICAL REVIEWS LA English DT Review ID INDEPENDENT PROSTATE-CANCER; LIGAND-BINDING DOMAIN; HUMAN NA/K ATPASE; COMPLEMENTARY-DNA; IN-VITRO; POSTTRANSCRIPTIONAL MECHANISMS; TRANSCRIPTIONAL REGULATION; DEOXYRIBONUCLEIC-ACID; FUNCTIONAL DIVERSITY; DEPRIVATION THERAPY C1 NIEHS, Mol Endocrinol Grp, Lab Signal Transduct, NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Durham, NC USA. Univ Miami, Miller Sch Med, Dept Mol & Cellular Pharmacol, Miami, FL 33152 USA. Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA 15261 USA. Prince Henrys Inst Med Res, Clayton, Vic, Australia. Royal Victoria Hosp, Mol Oncol Grp, Montreal, PQ H3A 1A1, Canada. Yale Univ, Sch Med, New Haven, CT USA. Bristol Myers Squibb Co, Immune Cell Funct Grp, Princeton, NJ USA. Univ Paris Sud, CNRS, UMR 8612, Chatenay Malabry, France. Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. Univ N Carolina, Dept Pediat, Chapel Hill, NC USA. Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC USA. RP Cidlowski, JA (reprint author), NIEHS, Mol Endocrinol Grp, Lab Signal Transduct, NIH,Dept Hlth & Human Serv, POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM cidlows1@niehs.nih.gov OI Giguere, Vincent/0000-0001-9567-3694; Fuller, Peter/0000-0002-0948-2072 NR 109 TC 171 Z9 179 U1 4 U2 23 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 DEC PY 2006 VL 58 IS 4 BP 782 EP 797 DI 10.1124/pr.58.4.9 PG 16 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 110JP UT WOS:000242374900009 PM 17132855 ER PT J AU Duncan, EA Rider, TR Jandacek, RJ Clegg, DJ Benoit, SC Tso, P Woods, SC AF Duncan, Elizabeth A. Rider, Therese R. Jandacek, Ronald J. Clegg, Deborah J. Benoit, Stephen C. Tso, Patrick Woods, Stephen C. TI The regulation of alcohol intake by melanin-concentrating hormone in rats SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE alcohol; melanin-concentrating hormone; progressive ratio; sucrose; food intake ID CONDITIONED INSULIN-SECRETION; LOCOMOTOR-ACTIVITY; ANTICIPATORY ACTIVITY; FEEDING-BEHAVIOR; FOOD-DEPRIVATION; GENE-EXPRESSION; PALATABLE MEAL; WATER-INTAKE; BODY-WEIGHT; ETHANOL AB Given into the brain, melanin-concentrating hormone (MCH) increases alcohol consumption, but the mechanism and physiological relevance of this effect are unclear. We hypothesized that endogenous MCH will enhance alcohol drinking and that MCH increases alcohol's reinforcing properties. An MCH receptor 1 (MCHR 1) antagonist, or saline was administered centrally alone, or preceding MCH or saline to rats trained to drink 10% alcohol using sucrose fading. Blocking MCHR 1 neither reduced alcohol intake (saline = 0.4 +/- 0.1 g, 30 mu g MCHR 1 antagonist = 0.4 +/- 0.1 g/kg alcohol), nor attenuated MCH-induced alcohol drinking (MCHR1 antagonist/saline = 0.7 +/- 0.1 g/kg, MCHR1 antagonist/MCH = 0.9 +/- 0.1 g/kg alcohol). Another cohort of rats was trained to lever press for alcohol on a progressive ratio schedule. MCH or saline was administered centrally and lever presses were measured. MCH had no effect prior to the break point, but increased total responding during the session (saline = 87.2 +/- 32.0, MCH = 315.4 +/- 61.0 presses). In conclusion, these data suggest that MCH augments alcohol drinking partly by enhancing the drug's reinforcing value. Further, endogenous MCH does not seem to regulate alcohol drinking, however because the antagonist failed to attenuate MCH-induced alcohol intake this conclusion is tentative. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Cincinnati, Dept Psychiat, Cincinnati, OH USA. Univ Cincinnati, Dept Pathol, Cincinnati, OH USA. RP Duncan, EA (reprint author), NIDA, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM duncanel@mail.nih.gov OI Duncan-Vaidya, Elizabeth/0000-0003-3622-8819 FU NIAAA NIH HHS [F31 AA015819-01, F31 AA015819]; NIDDK NIH HHS [T32 DK059803, R37 DK017844, T32 DK59803, T32 DK059803-05, R01 DK017844, R01 DK017844-29S1, DK17844] NR 39 TC 11 Z9 12 U1 0 U2 0 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 DEC PY 2006 VL 85 IS 4 BP 728 EP 735 DI 10.1016/j.pbb.2006.11.004 PG 8 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 138MC UT WOS:000244365700007 PM 17188345 ER PT J AU Mello, NK Negus, SS Rice, KC Mendelson, JH AF Mello, Nancy K. Negus, S. Stevens Rice, Kenner C. Mendelson, Jack H. TI Effects of the CRF1 antagonist antalarmin on cocaine self-administration and discrimination in rhesus monkeys SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE antalarmin; CRF1 antagonist; cocaine discrimination; cocaine self-administration; HPA axis ID CORTICOTROPIN-RELEASING-FACTOR; STRESS-INDUCED RELAPSE; HORMONE-RECEPTOR ANTAGONIST; INTRAVENOUS COCAINE; DRUG-ABUSE; BIOCHEMICAL MANIFESTATIONS; NONPEPTIDE ANTAGONIST; CIGARETTE-SMOKING; MOOD STATES; HPA AXIS AB Cocaine stimulates the rapid release of ACTH, and by inference, CRF in several species, suggesting that the HPA "stress" axis may contribute to the abuse-related effects of cocaine. The effects of a systemically-active CRF1 receptor antagonist, antalarmin, on cocaine self-administration and cocaine discrimination were examined in rhesus monkeys. Antalarmin's acute (1-10 mg/kg, IV) and chronic (3.2 mg/kg IV) effects on IV cocaine self-administration were studied. The acute effects of 3.2 mg/kg IV antalarmin on the cocaine self-administration dose-effect curve (0.001-0.10 mg/kg/inj) were also examined. The acute effects of antalarmin (5 and 10 mg/kg, IM) on the cocaine discrimination dose-effect curve (0.013-1.3 mg/kg) were examined. Antalarmin did not significantly decrease the reinforcing or the discriminative stimulus effects of cocaine. Acute antalarmin administration produced a dose-dependent but non-significant decrease in self-administration of 0.01 mg/kg/inj cocaine but did not alter the cocaine dose-effect curve. Chronic daily antalarmin treatment did not significantly decrease cocaine-maintained responding. Antalarmin did not significantly alter either the cocaine discrimination dose-effect curve or the time course of the cocaine-training dose. Antalarmin (10 mg/kg) produced sedation, suggesting that it was centrally active, however, it did not attenuate cocaine's abuse-related effects in rhesus monkeys. (c) 2006 Elsevier Inc. All rights reserved. C1 McLean Hosp, Alcohol & Drug Abuse Res Ctr, Belmont, MA 02478 USA. NIDA, Chem Biol Res Branch, NIH, Bethesda, MD 20892 USA. RP Mello, NK (reprint author), McLean Hosp, Alcohol & Drug Abuse Res Ctr, 115 Mill St, Belmont, MA 02478 USA. EM mello@mclean.harvard.edu FU Intramural NIH HHS; NIDA NIH HHS [P01-DA14528, K05-DA00101, K05-DA00064] NR 52 TC 13 Z9 13 U1 0 U2 0 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 DEC PY 2006 VL 85 IS 4 BP 744 EP 751 DI 10.1016/j.pbb.2006.11.008 PG 8 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 138MC UT WOS:000244365700009 PM 17182090 ER PT J AU Nelson, MI Simonsen, L Viboud, C Miller, MA Taylor, J George, KS Griesemer, SB Ghedi, E Sengamalay, NA Spiro, DJ Volkov, I Grenfell, BT Lipman, DJ Taubenberger, JK Holmes, EC AF Nelson, Martha I. Simonsen, Lone Viboud, Cecile Miller, Mark A. Taylor, Jill George, Kirsten St. Griesemer, Sara B. Ghedi, Elodie Sengamalay, Naomi A. Spiro, David J. Volkov, Igor Grenfell, Bryan T. Lipman, David J. Taubenberger, Jeffery K. Holmes, Edward C. TI Stochastic processes are key determinants of short-term evolution in influenza A virus SO PLOS PATHOGENS LA English DT Article ID HEMAGGLUTININ; REASSORTMENT; REVEALS; SITES AB Understanding the evolutionary dynamics of influenza A virus is central to its surveillance and control. While immune-driven antigenic drift is a key determinant of viral evolution across epidemic seasons, the evolutionary processes shaping influenza virus diversity within seasons are less clear. Here we show with a phylogenetic analysis of 413 complete genomes of human H3N2 influenza A viruses collected between 1997 and 2005 from New York State, United States, that genetic diversity is both abundant and largely generated through the seasonal importation of multiple divergent clades of the same subtype. These clades cocirculated within New York State, allowing frequent reassortment and generating genome-wide diversity. However, relatively low levels of positive selection and genetic diversity were observed at amino acid sites considered important in antigenic drift. These results indicate that adaptive evolution occurs only sporadically in influenza A virus; rather, the stochastic processes of viral migration and clade reassortment play a vital role in shaping short-term evolutionary dynamics. Thus, predicting future patterns of influenza virus evolution for vaccine strain selection is inherently complex and requires intensive surveillance, whole-genome sequencing, and phenotypic analysis. C1 Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. NIAID, NIH, Bethesda, MD 20892 USA. NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA. Inst Genom Res, Rockville, MD USA. NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Holmes, EC (reprint author), Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. EM ech15@psu.edu OI Simonsen, Lone/0000-0003-1535-8526; Holmes, Edward/0000-0001-9596-3552 FU PHS HHS [U50/CCU223671] NR 27 TC 118 Z9 128 U1 2 U2 16 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD DEC PY 2006 VL 2 IS 12 BP 1144 EP 1151 AR e125 DI 10.1371/journal.ppat.0020125 PG 8 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 122EY UT WOS:000243209700005 PM 17140286 ER PT J AU Barrientos, LG Matei, E Lasala, F Delgado, R Gronenborn, AM AF Barrientos, Laura G. Matei, Elena Lasala, Fatima Delgado, Rafael Gronenborn, Angela M. TI Dissecting carbohydrate-Cyanovirin-N binding by structure-guided mutagenesis: functional implications for viral entry inhibition SO PROTEIN ENGINEERING DESIGN & SELECTION LA English DT Article DE Cyanovirin-N; high-mannose oligosaccharides; mutant design; viral env glycoprotein; virucidal agent ID HIV-INACTIVATING PROTEIN; DOMAIN-SWAPPED DIMER; CIRCULAR-PERMUTED VARIANT; ANTIVIRAL ACTIVITY; CONTAINS 2; VIRUS; AFFINITY; GP120; SITES; NMR AB The HIV-inactivating protein Cyanovirin-N (CV-N) is a cyanobacterial lectin that exhibits potent antiviral activity at nanomolar concentrations by interacting with high-mannose carbohydrates on viral glycoproteins. To date there is no molecular explanation for this potent virucidal activity, given the experimentally measured micromolar affinities for small sugars and the problems encountered with aggregation and precipitation of high-mannose/CV-N complexes. Here, we present results for two CV-N variants, CV-N-mutDA and CV-N-mutDB, compare their binding properties with monomeric [P51G]CV-N (a stabilized version of wtCV-N) and test their in vitro activities. The mutations in CV-N-mutDA and CV-N-mutDB comprise changes in amino acids that alter the trimannose specificity of domain A(M) and abolish the sugar binding site on domain B-M, respectively. We demonstrate that carbohydrate binding via domain B-M is essential for antiviral activity, whereas alterations in sugar binding specificity on domain A(M) have little effect on envelope glycoprotein recognition and antiviral activity. Changes in A(M), however, affect the cross-linking activity of CV-N. Our findings augment and clarify the existing models of CV-N binding to N-linked glycans on viral glycoproteins, and demonstrate that the nanomolar antiviral potency of CV-N is related to the constricted and spatially crowded arrangement of the mannoses in the glycan clusters on viral glycoproteins and not due to CV-N induced virus particle agglutination, making CV-N a true viral entry inhibitor. C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Special Pathogens Branch, Div Viral & Rickettsial Dis, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. Hosp Univ 12 Octubre, Mol Microbiol Lab, Madrid, Spain. Univ Pittsburgh, Sch Med, Dept Biol Struct, Pittsburgh, PA 15260 USA. RP Barrientos, LG (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM lbarrientos1@cdc.gov; amg100@pitt.edu RI Delgado, Rafael/C-4910-2016; OI Delgado, Rafael/0000-0002-6912-4736; Gronenborn, Angela M/0000-0001-9072-3525 NR 31 TC 33 Z9 34 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1741-0126 J9 PROTEIN ENG DES SEL JI Protein Eng. Des. Sel. PD DEC PY 2006 VL 19 IS 12 BP 525 EP 535 DI 10.1093/protein/gzl040 PG 11 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 115EK UT WOS:000242717400001 PM 17012344 ER PT J AU Szyk, A Wu, ZB Tucker, K Yang, D Lu, WY Lubkowski, J AF Szyk, Agnieszka Wu, Zhibin Tucker, Kenneth Yang, De Lu, Wuyuan Lubkowski, Jacek TI Crystal structures of human alpha-defensins HNP4, HD5, and HD6 SO PROTEIN SCIENCE LA English DT Article DE human alpha-defensins; crystal structures; antimicrobial peptides; chemotaxis ID NATURAL PEPTIDE ANTIBIOTICS; ANTIMICROBIAL PEPTIDES; PROTEIN CRYSTALLOGRAPHY; ANTIBACTERIAL ACTIVITY; MAMMALIAN DEFENSINS; DISULFIDE ARRAY; HOST-DEFENSE; PANETH CELLS; REFINEMENT; REPLACEMENT AB Six alpha-defensins have been found in humans. These small arginine-rich peptides play important roles in various processes related to host defense, being the effectors and regulators of innate immunity as well as enhancers of adoptive immune responses. Four defensins, called neutrophil peptides 1 through 4, are stored primarily in polymorphonuclear leukocytes. Major sites of expression of defensins 5 and 6 are Paneth cells of human small intestine. So far, only one structure of human alpha-defensin (HNP3) has been reported, and the properties of the intestine defensins 5 and 6 are particularly poorly understood. In this report, we present the high-resolution X-ray structures of three human defensins, 4 through 6, supplemented with studies of their antimicrobial and chemotactic properties. Despite only modest amino acid sequence identity, all three defensins share their tertiary structures with other known alpha- and beta-defensins. Like HNP3 but in contrast to murine or rabbit alpha-defensins, human defensins 4-6 form characteristic dimers. Whereas antimicrobial and chemotactic activity of HNP4 is somewhat comparable to that of other human neutrophil defensins, neither of the intestinal defensins appears to be chemotactic, and for HD6 also an antimicrobial activity has yet to be observed. The unusual biological inactivity of HD6 may be associated with its structural properties, somewhat standing out when compared with other human alpha-defensins. The strongest cationic properties and unique distribution of charged residues on the molecular surface of HD5 may be associated with its highest bactericidal activity among human alpha-defensins. C1 NCI, Macromol Assembly Struct & Cell Signaling Sect, Frederick, MD 21702 USA. Univ Maryland, Inst Biotechnol, Inst Human Virol, Baltimore, MD 21201 USA. NCI, SAIC Frederick Inc, Opportunist Infect Lab, DCTD,DTP, Ft Detrick, MD 21702 USA. NCI, Mol Immunoregulat Lab, Frederick, MD 21702 USA. RP Lubkowski, J (reprint author), NCI, Macromol Assembly Struct & Cell Signaling Sect, 539, Frederick, MD 21702 USA. EM jacek@ncifcrf.gov RI Lu, Wuyuan/B-2268-2010 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400] NR 44 TC 102 Z9 112 U1 2 U2 5 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 DEC PY 2006 VL 15 IS 12 BP 2749 EP 2760 DI 10.1110/ps.062336606 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 110JE UT WOS:000242373700008 PM 17088326 ER PT J AU Xu, JS Mendrek, A Cohen, MS Monterosso, J Simon, S Brody, AL Jarvik, M Rodriguez, P Ernst, M London, ED AF Xu, Jiansong Mendrek, Adrianna Cohen, Mark S. Monterosso, John Simon, Sara Brody, Arthur L. Jarvik, Murray Rodriguez, Paul Ernst, Monique London, Edythe D. TI Effects of acute smoking on brain activity vary with abstinence in smokers performing the N-Back Task: A preliminary study SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE functional magnetic resonance imaging; tobacco; nicotine; working memory ID WORKING-MEMORY TASK; CIGARETTE-SMOKING; PREFRONTAL CORTEX; NICOTINE; 12-H; FMRI AB We previously reported that compared with a non-deprivation state, overnight abstinence from cigarette smoking was associated with higher brain activity in the left dorsolateral prefrontal cortex (L-DLPFC) during a low demanding working memory challenge, and little increase beyond this activity level during more taxing working memory conditions. In the present study, we aimed to assess how recent smoking (overnight abstinence vs. smoking ad libitum) influenced the effect of smoking a cigarette on brain activity related to a working memory challenge. Six smokers performed the N-Back working memory task during functional magnetic resonance imaging (fMRI) both before and after smoking a cigarette in each of two test sessions: one following overnight abstinence from smoking (similar to 13 h) and the other following ad libitum smoking. Task-related activity in L-DLPFC showed a significant interaction between the effects of acute smoking, test session, and task load. After overnight abstinence, post-smoking brain activity in L-DLPFC was lower than before smoking at low task load and higher at high task load; corresponding activity on a day of ad libitum smoking was higher at low load and lower at high task load after smoking during the session. These data suggest that the effect of acute smoking on working memory processing depends on recent prior smoking and task load. In particular, they provide preliminary evidence that functional efficiency of working memory is improved by smoking a cigarette during abstinence, while the effect of a cigarette in a non-deprived state varies with the nature and difficulty of the working memory challenge. This interaction merits further examination in larger studies specifically designed to consider this issue. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Biobehav Sci, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90024 USA. NIMH, Mood & Anxiety Disorders Res Program, Bethesda, MD 20892 USA. RP London, ED (reprint author), Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90024 USA. EM elondon@mednet.ucla.edu RI Cohen, Mark/C-6610-2011 OI Cohen, Mark/0000-0001-6731-4053 FU NCRR NIH HHS [M01 RR000865, MO1 RR 00865, RR08655]; NIDA NIH HHS [DA 13637, R01 DA014093, R01 DA014093.03, R01 DA015059, R01 DA020872, R01 DA020872-01, R01 DA020872-02, R21 DA 13627, R21 DA013627]; PHS HHS [R12169] NR 26 TC 37 Z9 42 U1 1 U2 9 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD DEC 1 PY 2006 VL 148 IS 2-3 BP 103 EP 109 DI 10.1016/j.pscychresns.2006.09.005 PG 7 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 117PR UT WOS:000242885800003 PM 17088048 ER PT J AU McClure, RK Phillips, I Jazayerli, R Barnett, A Coppola, R Weinberger, DR AF McClure, Robert K. Phillips, Ingrid Jazayerli, Roukan Barnett, Allan Coppola, Richard Weinberger, Daniel R. TI Regional change in brain morphometry in schizophrenia associated with antipsychotic treatment SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE schizophrenia; longitudinal volume change; morphometry ID CHILDHOOD-ONSET SCHIZOPHRENIA; VOXEL-BASED MORPHOMETRY; GRAY-MATTER; VOLUME CHANGES; TYPICAL ANTIPSYCHOTICS; EPISODE SCHIZOPHRENIA; NEUROLEPTIC TREATMENT; HALOPERIDOL TREATMENT; MESSENGER-RNA; BASAL GANGLIA AB The purpose of this pilot study was to: (1) determine if regional brain volume change occurs in schizophrenia patients during very short periods of withdrawal from, or stable treatment with, antipsychotics, and; (2) compare results of region-of-interest (ROI) to voxel-based morphometry (VBM) methods. In two small groups of schizophrenic inpatients, magnetic resonance imaging was performed before and after antipsychotic withdrawal, and at two time points during stable chronic antipsychotic treatment. Regional brain volumes were measured using ROI methods. Grey matter volume was measured with VBM. The medication withdrawal group showed no effect of treatment state or antipsychotic type on regional brain volumes with ROI analysis, but effects of both treatment state and antipsychotic type on grey matter volume were observed with VBM in right middle frontal, right medial frontal, right and left superior frontal, right cingulate, and fight superior temporal gyrii as well as in the right and left hippocampal gyrii. The chronic stable treatment group showed an effect of time on right caudate, left hippocampal, and total cerebrospinal fluid volumes with ROI analysis, while effects of both time and antipsychotic type were observed with VBM on grey matter volume in the left superior temporal lobe. No findings survived correction for multiple comparisons. A positive correlation between regional volume change and emerging psychopathology was demonstrated using ROI methods in the medication withdrawal group. Treatment state and emergent symptoms in schizophrenia patients were associated with regional volume change over very short time periods. Longitudinal regional brain volume change in schizophrenia patients is likely physiologic and therefore potentially reversible. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27510 USA. NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. George Washington Univ, Dept Psychiat, Washington, DC 20052 USA. RP McClure, RK (reprint author), Univ N Carolina, Dept Psychiat, CB 7160,Room 247,Wing C, Chapel Hill, NC 27510 USA. EM robert_mcclure@med.unc.edu NR 65 TC 57 Z9 57 U1 5 U2 7 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD DEC 1 PY 2006 VL 148 IS 2-3 BP 121 EP 132 DI 10.1016/j.pscychresns.2006.04.008 PG 12 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 117PR UT WOS:000242885800005 PM 17097276 ER EF