FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Masumizu, T Noda, Y Mori, A Packer, L AF Masumizu, T Noda, Y Mori, A Packer, L TI Electron spin resonance assay of ascorbyl radical generation in mouse hippocampal slices during and after kainate-induced seizures SO BRAIN RESEARCH PROTOCOLS LA English DT Article DE ascorbyl radical; kainate-induced seizure; superoxide anion radical; hippocampus; zonisamide ID TEMPORAL-LOBE EPILEPSY; KAINIC ACID; RAT-BRAIN; DAMAGE AB As an index of oxidative status, we analyzed ascorbyl radical generation during and after kainate-induced seizures in mouse hippocampus, using an ESR spectrometer equipped with a special tissue-type quartz cell. A specific doublet ESR spectrum was observed after seizures, and the g value and the hyperfine coupling constant (hfcc) of the spectrum were identical with those of ascorbyl radical itself. Antiepileptic zonisamide inhibited the generation of ascorbyl radical accompanying the seizures. (c) 2005 Elsevier B.V. All rights reserved. C1 JEOL Ltd, Tokyo 1968558, Japan. Sojo Univ, Fac Pharmaceut Sci, Kumamoto 8600082, Japan. NHLBI, NIH, Bethesda, MD 20892 USA. Okayama Univ, Okayama 7008558, Japan. Univ So Calif, Los Angeles, CA 90089 USA. RP Masumizu, T (reprint author), JEOL Ltd, Tokyo 1968558, Japan. EM masumizu@ph.sojo-u.ac.jp NR 15 TC 10 Z9 12 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1385-299X J9 BRAIN RES PROTOC JI Brain Res. Protoc. PD DEC PY 2005 VL 16 IS 1-3 BP 65 EP 69 DI 10.1016/j.brainreprot.2005.10.001 PG 5 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 998XX UT WOS:000234354300009 PM 16297657 ER PT J AU Kiyatkin, EA AF Kiyatkin, EA TI Brain hyperthermia as physiological and pathological phenomena SO BRAIN RESEARCH REVIEWS LA English DT Review DE brain; metabolism; cerebral blood flow; brain temperature; hyperthermia; metabolic neural activation; arousal; behavior; physical exercise; hot and humid environment; addictive drug; emotional stress; neuronal injury; neurotoxicity ID CEREBRAL-BLOOD-FLOW; LOCALIZED THERMAL-CHANGES; TEGMENTAL AREA NEURONS; CENTRAL-NERVOUS-SYSTEM; FREELY MOVING ANIMALS; HEART-RATE; MALE-RATS; 3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA; PROLONGED EXERCISE; UNRESTRAINED RATS AB Although brain metabolism consumes high amounts of energy and is accompanied by intense heat production, brain temperature is usually considered a stable, tightly "regulated" homeostatic parameter. Current research, however, revealed relatively large and rapid brain temperature fluctuations (3-4 degrees C) in animals during various normal, physiological, and behavioral activities at stable ambient temperatures. This review discusses these data and demonstrates that physiological brain hyperthermia has an intra-brain origin.. resulting from enhanced neural metabolism and increased intra-brain heat production. Therefore, brain temperature is an important physiological parameter that both reflects alterations in metabolic neural activity and affects various neural functions. This work also shows that brain hyperthermia may be induced by various drugs of abuse that cause metabolic brain activation and impair heat dissipation. While individual drugs (i.e., heroin, cocaine, methamphetamine, MDMA) have specific, dose-dependent effects on brain and body temperatures, these effects are strongly modulated by an individual's activity state and environmental conditions, and change dramatically during the development of drug self-administration. Thus, brain thermorecording may provide new information on the central effects of various addictive drugs, drug-activity-environment interactions in mediating drugs' adverse effects, and alterations in metabolic neural activity associated with the development of drug-seeking and drug-taking behavior. While ambient temperatures and impairment of heat dissipation may also affect brain temperature, these environmental conditions strongly potentiate thermal effects of psychomotor stimulant drugs, resulting in pathological brain overheating. Since hyperthermia exacerbates drug-induced toxicity and is destructive to neural cells and brain functions, use of these drugs under activated conditions that restrict heat loss may pose a significant health risk, resulting in both acute life-threatening complications and chronic destructive CNS changes. Published by Elsevier B.V. C1 Natl Inst Drug Abuse Intramural Res Program, Cellular Neurobiol Branch, DHHS, NIH, Baltimore, MD 21224 USA. RP Natl Inst Drug Abuse Intramural Res Program, Cellular Neurobiol Branch, DHHS, NIH, 5500 Nathan Shock, Baltimore, MD 21224 USA. EM ekiyatki@intra.nida.nih.gov NR 195 TC 66 Z9 66 U1 0 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0173 EI 1872-6321 J9 BRAIN RES REV JI Brain Res. Rev. PD DEC 1 PY 2005 VL 50 IS 1 BP 27 EP 56 DI 10.1016/j.brainresrev.2005.04.001 PG 30 WC Neurosciences SC Neurosciences & Neurology GA 994UW UT WOS:000234057700004 PM 15890410 ER PT J AU Santen, RJ Lobenhofer, EK Afshari, CA Bao, Y Song, RX AF Santen, RJ Lobenhofer, EK Afshari, CA Bao, Y Song, RX TI Adaptation of estrogen-regulated genes in long-term estradiol deprived MCF-7 breast cancer cells SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE estradiol; estrogen; breast cancer; MCF-7 cells; cellular adaptation ID HORMONE-INDEPENDENT GROWTH; DNA-REPLICATION FORK; NF-KAPPA-B; C-MYC; ADAPTIVE HYPERSENSITIVITY; KINASE-ACTIVITY; FACTOR-ALPHA; RECEPTOR; EXPRESSION; PROTEIN AB First line treatment of hormone dependent breast cancer initially causes tumor regression but later results in adaptive changes and tumor re-growth. Responses to second line treatments occur but tumors again begin to progress after a period of 12-18 months. In depth understanding of the adaptive process would allow the identification of targets to abrogate the development of hormonal resistance and prolong the efficacy of endocrine therapy. We have developed a model system to examine adaptive changes in human MCF-7 breast cancer cells. Upon deprivation of estradiol for a prolonged period of time, a maneuver analogous to surgical oophorectomy in pre-menopausal women and use of aromatase inhibitors in post-menopausal patients, tumor cells adapt and become hypersensitive to estradiol. We reasoned that the expression pattern of multiple genes would change in response to estradiol deprivation and that cDNA microarrays would provide an efficient means of assessing these changes. Accordingly, we examined the transcriptional responses to estradiol in long-term estradiol deprived (LTED) MCF-7 cells with a cDNA microarray containing 1901 known genes and ESTs. To assess the changes induced by long-term estradiol deprivation, we compared the effects of estradiol administration in LTED cells with those in MCF-7 cells, which we had previously reported, and confirmed with real time PCR using the parental and LTED cells. Seven genes and one EST were induced by estradiol in LTED but not in wild type MCF-7 cells, whereas ten genes were down-regulated by estradiol only in LTED cells. The expression of seven genes increased concurrently and five decreased in response to estradiol in both cell types. From these observations, we generated testable hypotheses regarding several genes including DKFZP, RAP-1, ribosomal protein S6, and TM4SF1. Based upon the known functions of these genes and the patterns of observed changes, we postulate that divergent regulation of these genes may contribute to the different biologic responses to estrogen in these cell lines. These results provide targets for further mechanistic studies in our experimental system. Our findings indicate that long-term estradiol deprivation causes expression changes in multiple genes and emphasizes the complexity of the process of cellular adaptation. C1 Univ Virginia Hlth Syst, Div Endocrinol, Charlottesville, VA 22908 USA. Natl Inst Environm Hlth Sci, Natl Ctr Toxicogenom, Res Triangle Pk, NC USA. Icoria Inc, Res Triangle Pk, NC USA. Amgen Inc, Thousand Oaks, CA 91320 USA. Univ Virginia Hlth Syst, Dept Microbiol, Charlottesville, VA USA. RP Santen, RJ (reprint author), Univ Virginia Hlth Syst, Div Endocrinol, POB 801416, Charlottesville, VA 22908 USA. EM mn7f@virginia.edu NR 73 TC 20 Z9 20 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2005 VL 94 IS 3 BP 213 EP 223 DI 10.1007/s10549-005-5776-4 PG 11 WC Oncology SC Oncology GA 986XV UT WOS:000233483900004 PM 16258703 ER PT J AU Webster, RG Brain, KL Wilson, RH Grem, JL Vincent, A AF Webster, RG Brain, KL Wilson, RH Grem, JL Vincent, A TI Oxaliplatin induces hyperexcitability at motor and autonomic neuromuscular junctions through effects on voltage-gated sodium channels SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE oxaliplatin; neuromyotonia; neurotoxicity; hyperexcitability; carbamazepine; beta-pompilidotoxin; voltage-activated Na+ channels; neuromuscular junction ID MOUSE VAS-DEFERENS; COLORECTAL-CANCER; SYMPATHETIC VARICOSITIES; TRANSMITTER RELEASE; NERVE TERMINALS; CALCIUM; BINDING; RAT; PHARMACOKINETICS; NEUROMYOTONIA AB 1 Oxaliplatin, an effective cytotoxic treatment in combination with 5-fluorouracil for colorectal cancer, is associated with sensory, motor and autonomic neurotoxicity. Motor symptoms include hyperexcitability while autonomic effects include urinary retention, but the cause of these side-effects is unknown. We examined the effects on motor nerve function in the mouse hemidiaphragni and on the autonomic system in the vas deferens. 2 In the mouse diaphragm, oxaliplatin (0.5 mM) induced multiple endplate potentials (EPPs) following a single stimulus, and was associated with an increase in spontaneous miniature EPP frequency. In the vas deferens, spontaneous excitatory junction potential frequency was increased after 30 min exposure to oxaliplatin; no changes in resting Ca2+ concentration in nerve terminal varicosities were observed, and recovery after stimuli trains was unaffected. 3 In both tissues, an oxaliplatin-induced increase in spontaneous activity was prevented by the voltage-gated Na+ channel blocker tetrodotoxin (TTX). Carbamazepine (0.3 mm) also prevented multiple EPPs and the increase in spontaneous activity in both tissues. In diaphragm, beta-pompilidotoxin (100 mu M), which slows Na+ channel inactivation, induced multiple EPPs similar to oxaliplatin's effect. By contrast, blockers of K+ channels (4-aminopyridine and apamin) did not replicate oxaliplatin-induced hyperexcitability in the diaphragm. 4 The prevention of hyperexcitability by TTX blockade implies that oxaliplatin acts on nerve conduction rather than by effecting repolarisation. The similarity between beta-pompilidotoxin and oxaliplatin suggests that alteration of voltage-gated Na+ channel kinetics is likely to underlie the acute neurotoxic actions of oxaliplatin. C1 John Radcliffe Hosp, Weatherall Inst Mol Med, Neurosci Grp, Oxford OX3 9DS, England. Univ Oxford, Dept Pharmacol, Oxford OX1 3QT, England. NCI, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Webster, RG (reprint author), John Radcliffe Hosp, Weatherall Inst Mol Med, Neurosci Grp, Oxford OX3 9DS, England. EM richard.webster@imm.ox.ac.uk OI Brain, Keith/0000-0002-0906-7012 FU Wellcome Trust [074128] NR 46 TC 69 Z9 70 U1 0 U2 0 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 2005 VL 146 IS 7 BP 1027 EP 1039 DI 10.1038/sj.bjp.0706407 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 990LR UT WOS:000233745100015 PM 16231011 ER PT J AU Rosenheck, R Stroup, S Keefe, RSE McEvoy, J Swartz, M Perkins, D Hsiao, J Shumway, M Lieberman, J AF Rosenheck, R Stroup, S Keefe, RSE McEvoy, J Swartz, M Perkins, D Hsiao, J Shumway, M Lieberman, J TI Measuring outcome priorities and preferences in people with schizophrenia SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article ID QUALITY-OF-LIFE; CLINICAL ANTIPSYCHOTIC TRIALS; EFFECTIVENESS CATIE PROJECT; RATING-SCALE; RECOVERY AB Background Measures have not taken account of the relative importance patients place on various outcomes. Aims To construct and evaluate a multidimensional, preference-weighted mental health index. Method Each of over 1200 patients identified the relative importance of improvement in six domains: social life, energy, work, symptoms, confusion and side-effects. A mental health index was created in which measures of well-being in these six domains were weighted for their personal importance. Results The strongest preference was placed on reducing confusion and the least on reducing side-effects. There was no significant difference between the unweighted and preference-weighted mental health status measures and they had similar correlations with global health status measures, Patients with greater preference for functional activities Such as work had less preference for medical model goals such as reducing symptoms and had less symptoms. Conclusions A preference-weighted mental health index demonstrated no advantage over an unweighted index. Declaration of interest None. C1 VA Connecticut Hlth Care Syst, NE Program Evaluat Ctr 182, West Haven, CT 06516 USA. W Haven & Yale Univ, NE Program Evaluat Ctr, New Haven, CT USA. Univ N Carolina, Chapel Hill, NC USA. Duke Univ, Durham, NC USA. NIMH, Bethesda, MD 20892 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Rosenheck, R (reprint author), VA Connecticut Hlth Care Syst, NE Program Evaluat Ctr 182, 950 Campbell Ave, West Haven, CT 06516 USA. EM Robert.Rosenheck@Yale.edu RI Stroup, Thomas/F-9188-2014 OI Stroup, Thomas/0000-0002-3123-0672 FU NIMH NIH HHS [N01 MH 90001] NR 26 TC 40 Z9 43 U1 0 U2 1 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON SW1X 8PG, ENGLAND SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD DEC PY 2005 VL 187 BP 529 EP 536 DI 10.1192/bjp.187.6.529 PG 8 WC Psychiatry SC Psychiatry GA 992CH UT WOS:000233861500007 PM 16319405 ER PT J AU Shibusawa, Y Takeuchi, N Shindo, H Ito, Y AF Shibusawa, Y Takeuchi, N Shindo, H Ito, Y TI Separation of phospholipids from hen egg yolk by high-speed countercurrent chromatography SO BUNSEKI KAGAKU LA Japanese DT Article DE countercurrent chromatography; two or three-phase systems; hen egg yolk phospholipids; partition coefficient ID LIQUID PARTITION CHROMATOGRAPHY; COIL PLANET CENTRIFUGE; HUMAN-BRAIN LIPIDS; SOLID SUPPORT; PURIFICATION; GLYCOLIPIDS; EXTRACTION; DCC AB Phospholipids were fractionated by high-speed counter-current chromatography in a one-step operation from about 0.75 g of hen egg yolk using a type J-multilayer coil planet centrifuge. The partition coefficients values of phospholipids were measured in several two or three-solvent systems. The separation of phospholipids was performed with a two-phase solvent system composed of chloroform/n-heptane/n-butanol/methanol/60% acetic acid (2: 3: 2: 3: 5) by eluting the lower phase at a flow-rate of 1.0 ml/min. The phospholipids in each fraction were characterized by thin-layer chromatography. C1 Tokyo Univ Pharm & Life Sci, Div Struct Biol & Analyt Sci, Hachioji, Tokyo 1920392, Japan. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Shibusawa, Y (reprint author), Tokyo Univ Pharm & Life Sci, Div Struct Biol & Analyt Sci, 1432-1 Horinouchi, Hachioji, Tokyo 1920392, Japan. NR 23 TC 3 Z9 3 U1 0 U2 8 PU JAPAN SOC ANALYTICAL CHEMISTRY PI TOKYO PA 26-2 NISHIGOTANDA 1 CHOME SHINAGAWA-KU, TOKYO, 141, JAPAN SN 0525-1931 J9 BUNSEKI KAGAKU JI Bunseki Kagaku PD DEC PY 2005 VL 54 IS 12 BP 1149 EP 1154 DI 10.2116/bunsekikagaku.54.1149 PG 6 WC Chemistry, Analytical SC Chemistry GA 994NA UT WOS:000234037300003 ER PT J AU Haggstrom, DA Quale, C Smith-Bindman, R AF Haggstrom, DA Quale, C Smith-Bindman, R TI Differences in the quality of breast cancer care among vulnerable populations SO CANCER LA English DT Article DE breast cancer; therapy; African Americans; Hispanic Americans; Asian Americans; physician's practice patterns; women's health ID SEER-MEDICARE DATA; CONSERVING SURGERY; CLAIMS DATA; CARCINOMA TREATMENT; TREATMENT PATTERNS; RACIAL-DIFFERENCES; RADIATION-THERAPY; TUMOR RECURRENCE; POOLED-ANALYSIS; LUNG-CANCER AB BACKGROUND. It is unknown whether differences in the quality of breast cancer care among women from racial and ethnic minority groups, the elderly, and rural areas have changed over time across the continuum of care. METHODS. The linked Surveillance, Epidemiology, and End Results-Medicare database identified 22,701 women ages 66-79 years diagnosed with early stage breast cancer from 1992-1999. Multiple breast cancer processes of care were measured, including breast-conserving surgery, radiation therapy, documentation of estrogen receptor status, surveillance mammography, and a combined measure of "adequate care". RESULTS. African-American and Hispanic women were significantly less likely to receive adequate care than White women in unadjusted comparisons (54.7% and 58.0% vs. 68.4% for African-American and Hispanic vs. White women) and adjusted comparisons (adjusted odds ratio [AOR] 0.67; 95% confidence interval [95% CII 0.59-0.76, and AOR 0.77; 95% CI 0.66-0.90 for African-American and Hispanic women, respectively). The proportion of Asian/Pacific Islander women receiving adequate care was similar to White women. When considering only women diagnosed with breast cancer from 1997-1999, African-American women remained less likely than White women to receive adequate care (AOR 0.63; 95% CI 0.50-0.79). Women ages 75-79 years were less likely to receive adequate care compared with women ages 66-69 years (AOR 0.74; 95% CI 0.69-0.80), and women from rural (vs. metropolitan) areas were less likely to receive adequate care (AOR 0.81; 95% Cl 0.73-0.89). CONCLUSIONS. The quality of breast cancer care is lower among vulnerable populations across the continuum of care, and many of these differences have not improved in more recent years. C1 NCI, Canc Prevent Fellowship Program, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Haggstrom, DA (reprint author), Execut Plaza N,Room 4009C,6130 Execut Blvd, Bethesda, MD 20892 USA. EM haggstrd@mail.nih.gov FU NCI NIH HHS [CA86032]; PHS HHS [1 D14 HP001 78-01] NR 37 TC 63 Z9 63 U1 1 U2 2 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 2005 VL 104 IS 11 BP 2347 EP 2358 DI 10.1002/cncr.21443 PG 12 WC Oncology SC Oncology GA 985ZX UT WOS:000233419200007 PM 16211547 ER PT J AU Rowland, JH Baker, F AF Rowland, JH Baker, F TI Introduction: Resilience of cancer survivors across the lifespan SO CANCER LA English DT Editorial Material ID BREAST-CANCER C1 NCI, Off Canc Survivorship, Bethesda, MD 20892 USA. Amer Canc Soc, Behav Res Ctr, Atlanta, GA 30329 USA. RP Rowland, JH (reprint author), NCI, Off Canc Survivorship, 6116 Execut Blvd,Suite 404, Bethesda, MD 20892 USA. EM rowlandj@mail.nih.gov NR 27 TC 33 Z9 34 U1 1 U2 6 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 2005 VL 104 IS 11 SU S BP 2543 EP 2548 DI 10.1002/cncr.21487 PG 6 WC Oncology SC Oncology GA 988DL UT WOS:000233571700001 PM 16258940 ER PT J AU Stanton, AL Ganz, PA Rowland, JH Meyerowitz, BE Krupnick, JL Sears, SR AF Stanton, AL Ganz, PA Rowland, JH Meyerowitz, BE Krupnick, JL Sears, SR TI Promoting adjustment after treatment for cancer SO CANCER LA English DT Article; Proceedings Paper CT Conference on Cancer Survivorship - Resilience Across the Lifespan CY JUN 02-04, 2002 CL Washington, DC SP NCI, Amer Canc Soc DE cancer; survivorship; quality of life; reentry ID QUALITY-OF-LIFE; STAGE BREAST-CANCER; PSYCHOLOGICAL DISTRESS; CONTROLLED-TRIAL; PROSTATE-CANCER; 1ST YEAR; WOMEN; PREVALENCE; DIAGNOSIS; OUTCOMES AB The transition from the period of diagnosis and medical treatment of cancer to survivorship (i.e., the reentry phase) is an understudied phase in the cancer trajectory. The objectives of this report were 1) to illustrate several adaptive tasks of the reentry phase, 2) to provide examples of research on factors that predict positive adjustment during this phase, and 3) to discuss interventions that address the adaptive tasks of early cancer survivorship. Although the pertinent empirical literature is scarce, accounts from cancer survivors, healthcare professionals, and qualitative researchers converge to suggest several themes in adaptive tasks during reentry. Drawing from the authors' work and that of others, the authors have described common expectancies held by many individuals approaching reentry (e.g., "I shouldn't need support"), typical concerns during this phase (e.g., concern over cancer recurrence), and personal and contextual factors that can facilitate and hinder adjustment. Promising psychosocial interventions have been developed for individuals in the reentry period. Continued research will be necessary to characterize this important phase of cancer survivorship. C1 Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Publ Hlth, Div Canc Prevent & Control Res, Los Angeles, CA USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA USA. NCI, Off Canc Survivorship, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Dept Psychiat, Washington, DC USA. Vet Adm Palo Alto Hlth Care Syst, Psychol Serv, Palo Alto, CA USA. RP Stanton, AL (reprint author), Univ Calif Los Angeles, Dept Psychol, 1285 Franz Hall,Box 951563, Los Angeles, CA 90095 USA. EM astanton@ucla.edu FU NCI NIH HHS [R01 CA63028] NR 48 TC 87 Z9 88 U1 7 U2 12 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 2005 VL 104 IS 11 SU S BP 2608 EP 2613 DI 10.1002/cncr.21246 PG 6 WC Oncology SC Oncology GA 988DL UT WOS:000233571700009 PM 16247779 ER PT J AU Ballas, MS Dennis, PA AF Ballas, MS Dennis, PA TI A slow disengagement from platinum-based chemotherapy for patients with advanced non-small cell lung cancer SO CANCER BIOLOGY & THERAPY LA English DT Article DE lung cancer; platinum-based chemotherapy; clinical trials ID ANTICANCER AGENTS; II TRIAL; PHASE-I; PACLITAXEL; IRINOTECAN; COMBINATION; LINES AB A Slow Disengagement from Platinum-Based Chemotherapy for Patients with Advanced Non-Small Cell Lung Cancer. C1 Natl Canc Inst, Ctr Canc Res, Med Oncol Branch, Bethesda, MD USA. RP Dennis, PA (reprint author), NCI Navy Med Oncol, 8901 Wisconsin Ave,Bldg 8,Rm 5101, Bethesda, MD 20889 USA. EM pd85f@nih.gov NR 14 TC 0 Z9 0 U1 0 U2 0 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 2005 VL 4 IS 12 BP 1316 EP 1317 PG 2 WC Oncology SC Oncology GA 022GV UT WOS:000236044400012 PM 16434876 ER PT J AU Stoddard, AM Fagan, P Sorensen, G Hunt, MK Frazier, L Girod, K AF Stoddard, AM Fagan, P Sorensen, G Hunt, MK Frazier, L Girod, K TI Reducing cigarette smoking among working adolescents: Results from the SMART study SO CANCER CAUSES & CONTROL LA English DT Article DE adolescents; randomized trial; smoking; worksite ID PREVENTION PROJECT; HUTCHINSON SMOKING; HEALTH; EDUCATION AB Objective: The SMART Teens Against the Risks of Tobacco Study was designed to test the feasibility and efficacy of tobacco control intervention methods for employed teens. Methods: A randomized controlled pilot study tested the efficacy of a behavioral intervention delivered between September, 1999, and August, 2000. Baseline and final survey data were collected on 560 teens in four intervention and five control stores. Results: Although smoking prevalence decreased and intention to quit increased more among teens in the intervention stores compared to those in the control stores, the differences were not statistically significant. Conclusions: The worksite holds promise as a possible venue for tobacco prevention and cessation interventions for youth although further research is needed to increase the efficacy of interventions for this setting. C1 New England Res Inst, Watertown, MA 02472 USA. NCI, Div Canc Control & Populat Sci, Tobacco Control Res Branch, Rockville, MD USA. Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, Boston, MA 02115 USA. Harvard Univ, Sch Med, Channing Lab, Boston, MA 02115 USA. RP Stoddard, AM (reprint author), New England Res Inst, 9 Galen St, Watertown, MA 02472 USA. EM astoddard@neriscience.com FU NINR NIH HHS [R01 NR04748] NR 20 TC 8 Z9 8 U1 1 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD DEC PY 2005 VL 16 IS 10 BP 1159 EP 1164 DI 10.1007/s10552-005-0353-z PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 979TL UT WOS:000232967600003 PM 16215865 ER PT J AU Rohrmann, S Paltoo, DN Platz, EA Hoffman, SC Comstock, GW Helzlsouer, KJ AF Rohrmann, S Paltoo, DN Platz, EA Hoffman, SC Comstock, GW Helzlsouer, KJ TI Association of vasectomy and prostate cancer among men in a Maryland cohort SO CANCER CAUSES & CONTROL LA English DT Article DE epidemiology; prostate cancer; risk; vasectomy ID UNITED-STATES MEN; RETROSPECTIVE COHORT; RECORD-LINKAGE; RISK; HEALTH; METAANALYSIS AB Objectives To evaluate the association of vasectomy with prostate cancer. Methods Participants were male members of the CLUE II cohort followed since 1989. On a questionnaire mailed in 1996, the men were asked if they had had a vasectomy and their age at vasectomy. Between 1996 and April 2004, 78 prostate cancer cases were confirmed among the 3373 men who were at least 35 years old at baseline and who completed the questions about vasectomy. Cox proportional hazards regression was used to estimate age-adjusted hazard ratios (HR) of prostate cancer. Results The HR for prostate cancer for men who had had a vasectomy was 2.03 (95% CI: 1.24-3.32). Risk of low-grade disease (HR=2.87; 95% CI 1.49-5.54), but not high-grade disease (HR=0.99; 95% CI 0.36-2.76), was higher in men who had had a vasectomy. No statistically significant associations were observed for low- or high-stage disease. The association for vasectomy was more pronounced in men who were 40 years at the time of vasectomy (HR=2.63; 95% CI 1.40-4.94) than in men who were younger at vasectomy. Conclusions The results from this prospective study suggest a positive association between vasectomy and prostate cancer, especially low-grade disease. C1 Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. NHLBI, Div Heart & Vasc Dis, NIH, Bethesda, MD 20892 USA. Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Johns Hopkins Med Inst, James Buchanan Brady Urol Inst, Baltimore, MD 21205 USA. RP Platz, EA (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St,Room E6138, Baltimore, MD 21205 USA. EM eplatz@jhsph.edu RI Rohrmann, Sabine/D-2113-2012 FU NCI NIH HHS [CA 08030]; NHLBI NIH HHS [HL 21670]; NIA NIH HHS [AG18033] NR 24 TC 15 Z9 16 U1 2 U2 5 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 2005 VL 16 IS 10 BP 1189 EP 1194 DI 10.1007/s10552-005-0304-8 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 979TL UT WOS:000232967600007 PM 16215869 ER PT J AU Cerhan, JR Bernstein, L Severson, RK Davis, S Colt, JS Blair, A Hartge, P AF Cerhan, JR Bernstein, L Severson, RK Davis, S Colt, JS Blair, A Hartge, P TI Anthropometrics, physical activity, related medical conditions, and the risk of non-Hodgkin lymphoma SO CANCER CAUSES & CONTROL LA English DT Article DE anthropometrics; diabetes; non-Hodgkin lymphoma; physical activity ID BODY-MASS INDEX; CANCER-RISK; DIABETES-MELLITUS; UNITED-STATES; US ADULTS; OLDER WOMEN; OBESITY; MORTALITY; COHORT; ASSOCIATION AB Background: Recent reports suggest that obesity, or conditions associated with obesity, might be risk factors for non-Hodgkin lymphoma (NHL), a cancer with dramatically increasing incidence in western countries over the last several decades. Physical inactivity increases the risk of obesity and of type 2 diabetes, but there are few data on the association of physical activity with risk of NHL. Methods: We evaluated these factors in a population-based case-control study conducted in Detroit, Iowa, Los Angeles, and Seattle from 1998 to 2000. Incident HIV-negative NHL cases aged 20-74 years were rapidly reported in each area (n = 1321). Controls were identified through random digit dialing and Medicare files, and were frequency matched to cases on sex, age, race, and study site (n = 1057). Risk factor data were collected by in-person interviews and self-administered questionnaires. Unconditional logistic regression was used to estimate the odds ratio (OR) and 95% confidence intervals (CI), adjusted for age, sex, race and study center. Results: High body mass index (OR = 1.73 for 35+ versus < 25 kg/m(2); 95% CI 1.15-2.59) and history of gallstones (OR = 1.95, 95% CI 1.11-3.40) were positively associated with diffuse NHL, but were not associated with follicular or all NHL combined. Height was positively associated with risk of all NHL combined (OR = 1.38 for > 70 versus < 65 inches; 95% CI 0.98-1.94), and positive associations were apparent for both diffuse and follicular NHL. Non-occupational physical activity was inversely associated with risk of all NHL combined (ORs with increasing level: 1, 0.75, 0.71, 0.55, 0.68; p-trend = 0.04) and for diffuse and follicular NHL. We observed no association of total energy intake, type 2 diabetes, or hypertension with risk of NHL. In a multivariable model to predict risk of diffuse NHL, BMI (OR = 2.15 for 35+ versus < 25 kg/m(2); 95% CI 1.09-4.25) and height (OR = 1.63 for 71+ versus < 65 inches; 95% CI 0.75-3.57) were positively associated with risk while physical activity was weakly and inversely associated risk (ORs with increasing level: 1, 0.76, 0.72, 0.78, 0.82; p-trend = 0.9). Conclusion: BMI and history of gallstones were positively associated with risk of diffuse NHL, supporting a role for obesity in this NHL subtype. Height was positively associated with NHL risk across subtypes, and suggests a role for early life nutrition in NHL risk. Non-occupational physical activity was only weakly and inversely associated with NHL risk after adjustment for obesity, height and alcohol use. C1 Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN 55905 USA. Univ Iowa, Iowa City, IA USA. Univ So Calif, Los Angeles, CA USA. Karmanos Canc Inst, Detroit, MI USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. NCI, Bethesda, MD 20892 USA. RP Cerhan, JR (reprint author), Mayo Clin, Coll Med, Dept Hlth Sci Res, 200 1st St SW, Rochester, MN 55905 USA. EM cerhan.james@mayo.edu OI Cerhan, James/0000-0002-7482-178X NR 64 TC 52 Z9 56 U1 4 U2 6 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 2005 VL 16 IS 10 BP 1203 EP 1214 DI 10.1007/s10552-005-0358-7 PG 12 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 979TL UT WOS:000232967600009 PM 16215871 ER PT J AU Glaze, ER Lambert, AL Smith, AC Page, JG Johnson, WD McCormick, DL Brown, AP Levine, BS Covey, JM Egorin, MJ Eiseman, JL Holleran, JL Sausville, EA Tomaszewski, JE AF Glaze, ER Lambert, AL Smith, AC Page, JG Johnson, WD McCormick, DL Brown, AP Levine, BS Covey, JM Egorin, MJ Eiseman, JL Holleran, JL Sausville, EA Tomaszewski, JE TI Preclinical toxicity of a geldanamycin analog, 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG), in rats and dogs: potential clinical relevance SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE 17-DMAG; 17-AAG; geldanamycin; preclinical studies; animal toxicity studies ID TISSUE DISTRIBUTION; PHARMACOKINETICS; NSC-707545; METABOLISM; HSP90 AB Purpose: 17-DMAG is a hydrophilic derivative of the molecular chaperone inhibitor 17-(allylamino)-17-demethoxygeldanamycin (17-AAG; NSC-330507), which is currently being evaluated for the treatment of cancer in clinical trials. 17-DMAG offers a potential advantage over 17- AAG because its aqueous solubility eliminates the need for complicated formulations that are currently used for administration of 17- AAG. In addition, 17- DMAG undergoes only limited metabolism compared to 17- AAG. The present results are from preclinical toxicity studies evaluating 17-DMAG in rats and dogs. Methods: Doses of 0, 2.4, 12 and 24 mg/m(2) per day were administered to rats, while dogs received doses of 0, 8 or 16 mg/m(2) per day. In both species, 17-DMAG was administered i.v. ( slow bolus for rats; 1-h infusion for dogs) daily for 5 days. An additional cohort of dogs received 16 mg/m(2) per day orally for 5 days. Clinical observations were noted, and standard hematology and clinical chemistry parameters were monitored. Selected tissues were evaluated microscopically for drug-related lesions. Tissue and plasma 17-DMAG concentrations were measured by HPLC/ MS at selected time-points on days 1 and 5. Results: Daily i.v. administration of 17-DMAG at doses of 24 mg/m(2) per day in rats or 16 mg/m(2) per day in dogs produced lethality on day 6, approximately 24 h following the last dose. Body weight loss was common in rats and dogs. Drug-related gastrointestinal, bone marrow and hepatic toxicities were also common in rats and dogs. Dogs also exhibited signs of renal and gallbladder toxicity. Plasma concentrations of 17-DMAG increased proportionately with dose in rats and disproportionately with dose in dogs. In rat tissues, however, only fourfold to sixfold increases in 17-DMAG concentrations were observed with a tenfold increase in dose. The highest concentrations of 17-DMAG were found in the liver of rats, with progressively lower concentrations in the spleen, lung, kidney and plasma. Regardless of the route of administration, higher drug concentrations were present in plasma ( rat and dog) and tissue ( rat) samples obtained on day 5 compared to those obtained on day 1. Although plasma concentrations decreased with time, 17-DMAG was still detected in dog plasma for at least 24 h after drug administration. Conclusions: With the recent approval of 17-DMAG for clinical use, the data generated from these preclinical studies will provide guidance to clinicians as they administer this drug to their patients. The MTD of 17-DMAG was 12 mg/m(2) per day in rats and 8 mg/m(2) per day in dogs; therefore, the recommended starting dose for phase I trial is 1.3 mg/m(2) per day for 5 days. Gastrointestinal and bone marrow toxicity were dose-limiting in rats, and gastrointestinal, renal, gallbladder and bone marrow toxicity were dose-limiting in dogs. All adverse effects were fully reversible in surviving animals after treatment was complete. C1 NCI, Toxicol & Pharmacol Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Rockville, MD 20852 USA. NCI, Dev Therapeut Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. So Res Inst, Birmingham, AL 35255 USA. IIT, Res Inst, Life Sci Grp, Chicago, IL 60616 USA. Univ Illinois, Toxicol Res Lab, Chicago, IL 60612 USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15213 USA. RP Glaze, ER (reprint author), NCI, Toxicol & Pharmacol Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Execut Plaza N,Room 8040, Rockville, MD 20852 USA. EM glazee@mail.nih.gov FU NCI NIH HHS [N01-CM-87103, P30CA47904, N01-CM-87102, N01-CM-87100, N01-CM-07106] NR 26 TC 77 Z9 81 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD DEC PY 2005 VL 56 IS 6 BP 637 EP 647 DI 10.1007/s00280-005-1000-9 PG 11 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 971HP UT WOS:000232375100012 PM 15986212 ER PT J AU Tiro, JA Vernon, SW Hyslop, T Myers, RE AF Tiro, JA Vernon, SW Hyslop, T Myers, RE TI Factorial validity and invariance of a survey measuring psychosocial correlates of colorectal cancer screening among African Americans and Caucasians SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID FECAL-OCCULT-BLOOD; CONFIRMATORY FACTOR-ANALYSIS; OF-FIT INDEXES; IMPROPER SOLUTIONS; SIGMOIDOSCOPY; PARTICIPATION; POPULATION; ADHERENCE; WOMEN; MORTALITY AB Background: Psychosocial constructs are widely used to predict colorectal cancer screening and are targeted as intermediate outcomes in behavioral intervention studies. Reliable and valid instruments for measuring general colorectal cancer screening psychosocial constructs are needed; yet, few studies have conducted psychometric analyses. This study replicated a five-factor structure for 16 theory-based, general colorectal cancer screening items measuring salience and coherence, cancer worries, perceived susceptibility, response efficacy, and social influence. In addition, we examined factorial invariance across race and sex. Methods: African American and Caucasian patients (n = 1,413) attending an urban, primary care clinic were included in this study. These individuals completed a baseline survey as part of a colorectal cancer screening intervention trial. Single and multigroup confirmatory factor analyses using maximum-likelihood estimation were done. Results: The five-factor general colorectal cancer screening model provided excellent fit and was invariant across race-sex subgroups. Conclusions: The findings of invariance across sex and race subgroups support the use of these scales to measure group differences. C1 NCI, Div Canc Control & Populat Sci, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. Univ Texas, Sch Publ Hlth, Ctr Hlth Promot & Prevent Res, Houston, TX USA. Thomas Jefferson Univ, Dept Med, Div Clin Pharmacol, Philadelphia, PA 19107 USA. Thomas Jefferson Univ, Dept Med, Div Genet & Prevent Med, Philadelphia, PA 19107 USA. RP Tiro, JA (reprint author), NCI, Div Canc Control & Populat Sci, Canc Prevent Fellowship Program, 6130 Execut Blvd,Room 4103A, Bethesda, MD 20892 USA. EM tiroj@mail.nih.gov OI Myers, Ronald E./0000-0002-8059-7390; Tiro, Jasmin/0000-0001-8300-0441 FU NCI NIH HHS [R01 CA 084140, R01 CA 097263, R01 CA 76330] NR 66 TC 47 Z9 47 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 2005 VL 14 IS 12 BP 2855 EP 2861 DI 10.1158/1055-9965.EPI-05-0217 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 994UB UT WOS:000234055600006 PM 16365000 ER PT J AU Irwin, ML McTiernan, A Bernstein, L Gilliland, FD Baumgartner, R Baumgartner, K Ballard-Barbash, R AF Irwin, ML McTiernan, A Bernstein, L Gilliland, FD Baumgartner, R Baumgartner, K Ballard-Barbash, R TI Relationship of obesity and physical activity with C-peptide, leptin, and insulin-like growth factors in breast cancer survivors SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID RANDOMIZED CLINICAL-TRIAL; FACTOR-I; POSTMENOPAUSAL WOMEN; BINDING-PROTEINS; FASTING INSULIN; WEIGHT-LOSS; FAT DISTRIBUTION; LIFE-STYLE; IGF-I; EXERCISE AB Introduction: Obese and physically inactive breast cancer patients may have poorer survival compared with lighter weight and more active women. Several obesity-related and physical activity-related hormones and peptides may explain this association, including insulin, leptin, insulin-like growth factor-I (IGF-I), and IGF-binding protein-3. Few studies have examined the associations between obesity, physical activity, and these hormones/peptides among breast cancer survivors. Purpose: To determine whether obesity and physical activity are associated with insulin, IGFs, and leptin levels in a population-based sample of 710 women diagnosed with in situ to stage IIIA breast cancer and enrolled in the Health, Eating, Activity, and Lifestyle Study. Methods: We collected a blood sample and information on physical activity among women diagnosed 2 to 3 years earlier using an interview-administered questionnaire. Trained staff measured weight. C-peptide, leptin, and IGFs were assayed by RIA. Mean hormone levels within body mass index and physical activity categories were adjusted for confounders using analysis of covariance methods. Results: We observed higher C-peptide (P for trend = 0.0001) and leptin (P for trend = 0.0001) levels and lower IGF-I levels (P for trend = 0.0001) with higher levels of body mass index. We observed lower C-peptide (P for trend = 0.001) and leptin (P for trend = 0.001) levels and higher IGF-I (P for trend = 0.0037) and IGF-binding protein-3 (P for trend = 0.055) levels with higher levels of physical activity. Conclusions: Increasing physical activity and decreasing body fat may be a reasonable intervention approach toward changing insulin and leptin, thereby potentially influencing breast cancer prognosis. C1 Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. Univ New Mexico, Albuquerque, NM 87131 USA. NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Irwin, ML (reprint author), Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, POB 208034, New Haven, CT 06520 USA. EM melinda.irwin@yale.edu FU NCI NIH HHS [N01 PC035138-22, N01 CN 05228, T32 CA 09661, N01 PC067010, N01 CN 75036-20, N01 CN005228, N01 PC 67010, T32 CA009661]; NCRR NIH HHS [M01 RR000037, M01 RR 00037]; NICHD NIH HHS [N01 HD 33175] NR 47 TC 59 Z9 60 U1 0 U2 6 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 2005 VL 14 IS 12 BP 2881 EP 2888 DI 10.1158/1055-9965.EPI-05-0185 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 994UB UT WOS:000234055600011 PM 16365005 ER PT J AU Brinton, LA Sakoda, LC Sherman, ME Frederiksen, K Kjaer, SK Graubard, BI Olsen, JH Mellemkjaer, L AF Brinton, LA Sakoda, LC Sherman, ME Frederiksen, K Kjaer, SK Graubard, BI Olsen, JH Mellemkjaer, L TI Relationship of benign gynecologic diseases to subsequent risk of ovarian and uterine tumors SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID ATYPICAL ENDOMETRIOSIS; CANCER RISK; MALIGNANT-TRANSFORMATION; GENETIC ALTERATIONS; REDUCED RISK; CLEAR-CELL; WOMEN; SARCOMA; INFERTILITY; BORDERLINE AB Objective: Although endometriosis and uterine leiomyomas are common conditions, the extent to which either is associated with certain types of malignancies remains uncertain. Methods: Using record linkage techniques, we assessed the relationships between hospital and outpatient admissions for endometriosis or leiomyomas and the development of ovarian and uterine cancers in Denmark between 1978 and 1998. Based on a population-based cohort exceeding 99,000 women, including 2,491 ovarian cancers, 860 borderline ovarian tumors, and 1,398 uterine cancers, we derived relative risks (RR) and 95% confidence intervals (95% CI) associated with overall and histology-specific tumor risks after adjustment for calendar time and reproductive characteristics. Results: Endometriosis seemed to predispose to the development of ovarian cancer, with the association restricted to endometrioid or clear cell malignancies. Five or more years after the diagnosis of endometriosis, the RRs (95% CIs) were 2.53 (1.19-5.38) for endometrioid (7 exposed cases) and 3.37 (1.24-9.14) for clear cell (4 exposed cases) malignancies. Uterine leiomyomas were associated with increases in the risk of uterine malignancies, particularly sarcomas, where the RRs (95% CIs) were 20.80 (11.32-38.22) for women with 1 to 4 years of follow-up (11 exposed cases) and 5.70 (2.27-14.32) for those with more extended follow-up (5 exposed cases). Conclusion: In combination with clinical, pathologic, and molecular data, our results support that some endometriotic lesions may predispose to clear cell and endometrioid ovarian cancers. Uterine leiomyomas also showed a strong connection with subsequent uterine sarcomas, although it was difficult to decipher whether this reflected detection bias, shared risk factors, or an etiologic relationship. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Inst Canc Epidemiol, Danish Canc Soc, Copenhagen, Denmark. RP Brinton, LA (reprint author), NCI, Div Canc Epidemiol & Genet, Room 7068,6120 Execut Blvd, Rockville, MD 20852 USA. EM brinton@nih.gov RI Brinton, Louise/G-7486-2015; OI Brinton, Louise/0000-0003-3853-8562; Olsen, Jorgen Helge/0000-0001-9633-5662; Kjaer, Susanne/0000-0002-8347-1398 FU Intramural NIH HHS NR 58 TC 67 Z9 69 U1 0 U2 6 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 2005 VL 14 IS 12 BP 2929 EP 2935 DI 10.1158/1055-9965.EPI-05-0394 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 994UB UT WOS:000234055600018 PM 16365012 ER PT J AU Lleonart, ME Kirk, GD Villar, S Lesi, OA Dasgupta, A Goedert, JJ Mendy, M Hollstein, MC Montesano, R Groopman, JD Hainaut, P Friesen, MD AF Lleonart, ME Kirk, GD Villar, S Lesi, OA Dasgupta, A Goedert, JJ Mendy, M Hollstein, MC Montesano, R Groopman, JD Hainaut, P Friesen, MD TI Quantitative analysis of plasma TP53 249(Ser)-mutated DNA by electrospray ionization mass spectrometry SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HEPATOCELLULAR-CARCINOMA PATIENTS; CELL-FREE DNA; HEPATITIS-B; P53 GENE; AFLATOXIN B-1; WEST-AFRICA; CODON-249 MUTATIONS; PROSTATE-CANCER; GAMBIA; INFECTION AB A mutation in codon 249 of the TP53 gene (249(Ser)), related to aflatoxin B, exposure, has previously been associated with hepatocellular carcinoma risk. Using a novel internal standard plasmid, plasma concentrations of 249(Ser)-mutated DNA were quantified by electrospray ionization mass spectrometry in 89 hepatocellular carcinoma cases, 42 cirrhotic patients, and 131 nonliver diseased control subjects, all from highly aflatoxin-exposed regions of The Gambia. The hepatocellular carcinoma cases had higher median plasma concentrations of 249 Se, (2,800 copies/mL; interquartile range: 500-11,000) compared with either cirrhotic (500 copies/mL; interquartile range: 500-2,600) or control subjects (500 copies/mL; interquartile range: 500-2,000; P < 0.05). About half (52%) of the hepatocellular carcinoma cases had >2,500 copies of 249(Ser)/mL plasma, corresponding to the prevalence of this mutation in liver tumors in The Gambia. In comparison, only 15% of control group and 26% of cirrhotic participants exceeded this level (P < 0.05). Further subset analysis revealed a statistically significant, quantitative relation between diagnosis of hepatocellular carcinoma and levels of 249(Ser) detected at 2,501 to 10,000 copies/mL plasma (odds ratio, 3.8; 95% confidence interval, 1.3-10.9) and at >10,000 copies/mL plasma (odds ratio, 62; 95% confidence interval, 4.7-820) when compared with control subjects and after adjusting for age, gender, recruitment site, hepatitis B and C serologic status, and total DNA concentration. Levels of >10,000 copies of 249(Ser)/mL plasma were also significantly associated with the diagnosis of hepatocellular carcinoma (odds ratio, 15; 95% confidence interval, 1.6-140) when compared with cirrhotic patients. Potential applications for the quantification of 249(Ser) DNA in plasma include estimation of long-term, cumulative aflatoxin exposure and selection of appropriate high-risk individuals for targeted intervention. C1 Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD 21205 USA. IARC, Lyon, France. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. MRC, Banjul, Gambia. German Canc Res Ctr, Dept Genet Alterat Carcinogenesis, Heidelberg, Germany. RP Friesen, MD (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, 615 N Wolfe St,Room E7032, Baltimore, MD 21205 USA. EM mfriesen@jhsph.edu RI Kirk, Gregory/A-8484-2009; Friesen, Marlin/D-7328-2012; Hainaut, Pierre /B-6018-2012 OI Hainaut, Pierre /0000-0002-1303-1610 FU NCI NIH HHS [N02 CP 40521]; NIEHS NIH HHS [P01 ES 06052] NR 36 TC 22 Z9 22 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 2005 VL 14 IS 12 BP 2956 EP 2962 DI 10.1158/1055-9965.EPI-05-0612 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 994UB UT WOS:000234055600022 PM 16365016 ER PT J AU McBride, CM Lipkus, IM Jolly, D Lyna, P AF McBride, CM Lipkus, IM Jolly, D Lyna, P TI Interest in testing for genetic susceptibility to lung cancer among black college students "At Risk" of becoming cigarette smokers SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SMOKING-CESSATION; ATTITUDES AB Receptivity to genetic testing for lung cancer susceptibility was assessed among African American college freshmen, who held attitudes favorable towards or had experimented with cigarette smoking. Students (n = 95) completed a telephone survey that assessed beliefs about genetics and lung cancer risk, interest in genetic testing, and expectations about the test outcome. Interest in being tested was moderately high (mean, 5; SD, 2.2; scale of 1-7) and highest among those who believed lung cancer was influenced by genetics (r = 0.22, P < 0.05) and those who expected to be at high risk (r = 0.27, P < 0.05). Overall, 34% thought if tested, the result would show high risk for lung cancer. In multivariate analyses, students' test result expectation was the only significant predictor of interest in testing. Those who believed the test would show them to be at higher risk were thrice more likely to be interested in testing than those who thought the test would show that they were at lower risk (odds ratio, 2.99; confidence interval, 1.03-8.64; P = 0.04). Future research is needed to understand how young adults will respond to genetic susceptibility feedback that confirms or contradicts their expectations about personal risks of smoking. C1 NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA. Duke Univ, Ctr Comprehens Canc, Durham, NC 27706 USA. N Carolina Cent Univ, Chapel Hill, NC USA. RP McBride, CM (reprint author), NHGRI, Social & Behav Res Branch, NIH, Room 4E08,Bldg 2,2 Ctr Dr, Bethesda, MD 20892 USA. EM cmcbride@mail.nih.gov FU NCI NIH HHS [CA 90716, CA 89122, P20 CA 091433] NR 22 TC 10 Z9 10 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 2005 VL 14 IS 12 BP 2978 EP 2981 DI 10.1158/1055-9965.EPI-05-0269 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 994UB UT WOS:000234055600026 PM 16365020 ER PT J AU Glasker, S Lonser, RR Tran, MGB Ikejiri, B Butman, JA Zeng, WF Maxwell, PH Zhuang, ZP Oldfield, EH Vortmeyer, AO AF Glasker, S Lonser, RR Tran, MGB Ikejiri, B Butman, JA Zeng, WF Maxwell, PH Zhuang, ZP Oldfield, EH Vortmeyer, AO TI Effects of VHL deficiency on endolymphatic duct and sac SO CANCER RESEARCH LA English DT Article ID HIPPEL-LINDAU-DISEASE; PAPILLARY CYSTADENOMA; TEMPORAL BONE; INNER-EAR; TUMORS; GENE; ADENOCARCINOMA; EPIDIDYMIS; ADENOMAS; MUTATION AB The von Hippel-Lindau (VHL) disease is caused by VHL germ line mutation. Inactivation of the wild-type copy of the VHL gene leads to up-regulation of hypoxic response and tumor formation within central nervous system (CNS), kidneys, pancreas, adrenal glands, epididymis, broad ligament, and the endolymphatic sac/petrous bone. Endolymphatic sac tumors (ELST) have been proposed to be derived from endolymphatic sac epithelium, but other possible structures of origin have been implicated. To clarify the anatomic and cellular origin of ELSTs, we did a morphologic and molecular pathologic analysis of 16 tumors. In addition, we investigated effects of VHL deficiency on "tumor-free" endolymphatic duct and sac of VHL patients. Several tumors included in this study were <1 cm in size, and their origin could be placed in the intraosseous portion of the endolymphatic duct/sac. Furthermore, by analysis of clinically uninvolved "tumor-free" endolymphatic duct and sac tissues of VHL patients, we discovered a variety of VHL-deficient microscopic abnormalities with morphologic similarities to ELSTs. We conclude that most, if not all, ELSTs arise within the intraosseous portion of the endolymphatic duct/sac, the vestibular aqueduct. In analogy to renal parenchyma and selected topographical sites within the CNS, endolymphatic duct/sac epithelia are preferentially and multi-focally targeted in VHL disease. The primary effect of VHL deficiency on human endolymphatic duct/sac epithelium seems to be the generation of multifocal sites of VHL-deficient cell proliferations from which tumorigenesis may or may not occur. Therefore, inactivation of the VHL wild-type allele seems necessary but not sufficient for the formation of tumor. C1 Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. Univ London Imperial Coll Sci Technol & Med, Renal Sect, Hammersmith Hosp, London, England. RP Vortmeyer, AO (reprint author), Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, 10 Ctr Dr,Room 5D37, Bethesda, MD 20892 USA. EM vortmeyera@ninds.nih.gov RI Maxwell, Patrick/C-5557-2008; Butman, John/A-2694-2008; OI Maxwell, Patrick/0000-0002-0338-2679; Butman, John/0000-0002-1547-9195 FU Intramural NIH HHS NR 34 TC 24 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 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 2005 VL 65 IS 23 BP 10847 EP 10853 DI 10.1158/0008-5472.CAN-05.1104 PG 7 WC Oncology SC Oncology GA 987HE UT WOS:000233508200029 PM 16322231 ER PT J AU De Roos, AJ Hartge, P Lubin, JH Colt, JS Davis, S Cerhan, JR Severson, RK Cozen, W Patterson, DG Needham, LL Rothman, N AF De Roos, AJ Hartge, P Lubin, JH Colt, JS Davis, S Cerhan, JR Severson, RK Cozen, W Patterson, DG Needham, LL Rothman, N TI Persistent organochlorine chemicals in plasma and risk of non-Hodgkin's lymphoma SO CANCER RESEARCH LA English DT Article ID ADIPOSE-TISSUE; POLYCHLORINATED-BIPHENYLS; PHENOXY HERBICIDES; MALIGNANT-DISEASE; CANCER MORTALITY; YU-CHENG; SERUM; EXPOSURE; YUSHO; 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN AB Polychlorinated biphenyls (PCB) have been suspected as possible contributors to increasing non-Hodgkin's lymphoma incidence during the latter half of the 20th century based on their toxicologic properties and provocative epidemiologic reports. We investigated PCBs and other organochlorines and risk of non-Hodgkin's lymphoma in a population-based case-control study in the United States. Congeners of PCBs (including coplanar congeners), dioxins, furans and pesticides or pesticide metabolites were measured in plasma of 100 untreated cases and 100 control subjects. We used a multiple imputation procedure to fill in missing values of levels determined to be below the detection limits. Risks of non-Hodgkin's lymphoma associated with each analyte were estimated using conditional logistic regression for the continuous measure, exposure quartiles, trend across quartile categories, and exposures above the 95th percentile. Certain PCB congeners were associated with increased risk of non-Hodgkin's lymphoma, including coplanar PCBs 156, 180, and 194, with odds ratios for the highest versus lowest quartile ranging from 2.7 to 3.5, and significant trends. Each of the furan congeners was associated with risk of non-Hodgkin's lymphoma, as were total furans, with 3.5-fold increased risk for the highest versus lowest quartile and a significant trend across quartiles (P = 0.006). The toxic equivalency quotient (TEQ), a summed metric that weights congeners by their dioxin-like potency, was associated with non-Hodgkin's lymphoma, with 35% increased risk per 10 TEQ pg/g lipid (95% confidence interval, 1.02-1.79). Our results add to existing literature, which suggests that exposure to organochlorines contributes to non-Hodgkin's lymphoma risk; these risks were most apparent for certain PCBs and furans. C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98109 USA. NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Rockville, MD USA. Mayo Clin, Coll Med, Rochester, MN USA. Univ Iowa, Iowa City, IA USA. Wayne State Univ, Dept Family Med, Detroit, MI USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA. Ctr Dis Control & Prevent, Div Sci Lab, Natl Ctr Environm Hlth, Atlanta, GA USA. RP De Roos, AJ (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,Bldg M,POB 19024, Seattle, WA 98109 USA. EM aderoos@fhcrc.org OI Cerhan, James/0000-0002-7482-178X FU Intramural NIH HHS; NCI NIH HHS [N01-PC-67009, N01-CN-67008, N01-CN-67010, N01-PC-65064, Y1-CP-8028-02] NR 44 TC 75 Z9 76 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 2005 VL 65 IS 23 BP 11214 EP 11226 DI 10.1158/0008-5472.CAN-05-1755 PG 13 WC Oncology SC Oncology GA 987HE UT WOS:000233508200070 PM 16322272 ER PT J AU Cleary, S Brouwers, FM Eisenhofer, G Pacak, K Christie, DL Lipski, J McNeil, AR Phillips, JK AF Cleary, S Brouwers, FM Eisenhofer, G Pacak, K Christie, DL Lipski, J McNeil, AR Phillips, JK TI Expression of the noradrenaline transporter and phenylethanolamine N-methyltransferase in normal human adrenal gland and phaeochromocytoma SO CELL AND TISSUE RESEARCH LA English DT Article DE immunohistochemistry; tyrosine hydroxylase; catecholamine; chromaffin cells; adrenal medulla; norepinephrine transporter; chromogranin A; human ID CATECHOLAMINE-SYNTHESIZING ENZYMES; POLYMERASE-CHAIN-REACTION; NEUROBLASTOMA CELL-LINES; CHROMAFFIN CELLS; PC12 CELLS; NOREPINEPHRINE TRANSPORTER; MESSENGER-RNA; DIFFERENTIAL EXPRESSION; GENE-EXPRESSION; CHROMOGRANIN-A AB Expression of the noradrenaline transporter (NAT) was examined in normal human adrenal medulla and phaeochromocytoma by using immunohistochemistry and confocal microscopy. The enzymes tyrosine hydroxylase (TH) and phenylethanolamine N-methyltransferase (PNMT) were used as catecholamine biosynthetic markers and chromogranin A (CGA) as a marker for secretory granules. Catecholamine content was measured by using high performance liquid chromatography (HPLC). In normal human adrenal medulla (n=5), all chromaffin cells demonstrated strong TH, PNMT and NAT immunoreactivity. NAT was co-localized with PNMT and was located within the cytoplasm with a punctate appearance. Human phaeochromocytomas demonstrated strong TH expression (n=20 samples tested) but variable NAT and PNMT expression (n=24). NAT immunoreactivity ranged from absent (n=3) to weak (n=10) and strong (n=11) and, in some cases, occupied an apparent nuclear location. Unlike the expression seen in normal human adrenal medullary tissue, NAT expression was not consistently co-localized with PNMT. PNMT also showed highly variable expression that was poorly correlated with tumour adrenaline content. Immunoreactivity for CGA was colocalized with NAT within the cytoplasm of normal human chromaffin cells (n=4). This co-localization was not consistent in phaeochromocytoma tumour cells (n=7). The altered pattern of expression for both NAT and PNMT in phaeochromocytoma indicates a significant disruption in the regulation and possibly in the function of these proteins in adrenal medullary tumours. C1 Murdoch Univ, Div Hlth Sci, Perth, WA 6150, Australia. W Australian Biomed Res Inst, Perth, WA 6845, Australia. NICHHD, NIH, Bethesda, MD 20892 USA. NINDS, NIH, Bethesda, MD 20892 USA. Univ Auckland, Sch Biol Sci, Auckland 1, New Zealand. Univ Auckland, Fac Med & Hlth Sci, Div Physiol, Auckland 1, New Zealand. Dorevitch Pathol, Heidelberg, Vic 3084, Australia. RP Phillips, JK (reprint author), Murdoch Univ, Div Hlth Sci, Perth, WA 6150, Australia. EM j.k.phillips@murdoch.edu.au RI Christie, David/C-8065-2009; Phillips, Jacqueline/G-7901-2011 OI Phillips, Jacqueline/0000-0002-4917-7734 NR 48 TC 12 Z9 12 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0302-766X J9 CELL TISSUE RES JI Cell Tissue Res. PD DEC PY 2005 VL 322 IS 3 BP 443 EP 453 DI 10.1007/s00441-005-0026-y PG 11 WC Cell Biology SC Cell Biology GA 987QO UT WOS:000233532600010 PM 16047163 ER PT J AU Hunter, K AF Hunter, K TI The intersection of inheritance and metastasis - The role and implications of germline polymorphism in tumor dissemination SO CELL CYCLE LA English DT Article DE metastasis; genetics; susceptibility; polymorphism; modifiers; QTLs ID BREAST-CANCER METASTASIS; IMPORTANT DETERMINANT; MICROARRAY PLATFORMS; SUPPRESSOR GENE; PROGRESSION; SIGNATURES; MOUSE AB Metastasis is an enormously complex process that involves both spatial and temporal barriers. Metastatic cells must not only acquire all of the characteristics of a primary tumor, but additionally must be capable of invasion, survival during transit and in the secondary site, interact productively with a novel microenvironment and proliferate to form a clinically relevant lesion.(1) Adding complexity to the process is the fact that it can be years or even decades after diagnosis of the primary tumor before the secondary tumors are apparent. A number of models have been proposed to explain the origins of metastasis. However, while all of the models can account for some aspects of the experimental observations, suggesting they may be at least in part true, none adequately explain all of the data. This implies that the existing models are likely to be too simplistic and additional factors must be considered to adequately account for existing and newly emerging data. C1 NCI, Lab Populat Genet, CCR, NIH, Bethesda, MD 20892 USA. RP Hunter, K (reprint author), NCI, Lab Populat Genet, CCR, NIH, Bldg 41,Room D702,41 Lib Dr, Bethesda, MD 20892 USA. EM hunterk@mail.nih.gov FU Intramural NIH HHS NR 23 TC 6 Z9 6 U1 0 U2 1 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD DEC PY 2005 VL 4 IS 12 BP 1719 EP 1721 DI 10.4161/cc.4.12.2258 PG 3 WC Cell Biology SC Cell Biology GA 990OG UT WOS:000233752500008 PM 16294041 ER PT J AU Pack, SD Weil, RJ Vortmeyer, AO Zeng, WF Li, J Okamoto, H Furuta, M Pak, E Lubensky, IA Oldfield, EH Zhuang, ZP AF Pack, SD Weil, RJ Vortmeyer, AO Zeng, WF Li, J Okamoto, H Furuta, M Pak, E Lubensky, IA Oldfield, EH Zhuang, ZP TI Individual adult human neurons display aneuploidy - Detection by fluorescence in situ hybridization and single neuron PCR SO CELL CYCLE LA English DT Article DE aneuploidy; neurons; Alzheimer's disease; stem cells; progenitor cells; fluorescence in situ hybridization ID CELL; MECHANISMS; DISEASE; BRAIN AB Neurons, once committed, exit the cell cycle and undergo maturation that promote specialized activity and are believed to operate upon a stable genome. We used fluorescence in situ hybridization, selective cell microdissection, and loss of heterozygosity analysis to assess degree of aneuploidy in patients with a neurodegenerative disease and in normal controls. We found that aneuploidy occurs in approximately 40% of mature, adult human neurons in health or disease and may be a physiological mechanism that maintains neuronal fate and function; it does not appear to be an unstable state. The fact that neuronal stem cells can be identified in adult humans and that somatic mosaicism may be found in neuronal precursor cells deserves further investigation before using adult neural stem cells to treat human disease. C1 Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bethesda, MD USA. NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. Cleveland Clin Fdn, Brain Tumor Inst, Cleveland, OH 44195 USA. Sun Yat Sen Univ, Zhongshan Med Coll, Dept Pathol, Guangzhou, Peoples R China. Saga Med Sch, Dept Neurosurg, Saga, Japan. RP Zhuang, ZP (reprint author), Bldg 10,Room 5D37, Bethesda, MD 20892 USA. EM zhuangp@ninds.nih.gov RI Pack, Svetlana/C-2020-2014 FU Intramural NIH HHS NR 10 TC 21 Z9 22 U1 0 U2 2 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD DEC PY 2005 VL 4 IS 12 BP 1758 EP 1760 DI 10.4161/cc.4.12.2153 PG 3 WC Cell Biology SC Cell Biology GA 990OG UT WOS:000233752500018 PM 16258289 ER PT J AU Fukui, K Yang, Q Cao, Y Takahashi, N Hatakeyama, H Wang, HY Wada, J Zhang, YL Marselli, L Nammo, T Yoneda, K Onishi, M Higashiyama, S Matsuzawa, Y Gonzalez, FJ Weir, GC Kasai, H Shimomura, L Miyagawa, J Wollheim, CB Yamagata, K AF Fukui, K Yang, Q Cao, Y Takahashi, N Hatakeyama, H Wang, HY Wada, J Zhang, YL Marselli, L Nammo, T Yoneda, K Onishi, M Higashiyama, S Matsuzawa, Y Gonzalez, FJ Weir, GC Kasai, H Shimomura, L Miyagawa, J Wollheim, CB Yamagata, K TI The HNF-1 target Collectrin controls insulin exocytosis by SNARE complex formation SO CELL METABOLISM LA English DT Article ID HEPATOCYTE NUCLEAR FACTOR-1-ALPHA; PANCREATIC BETA-CELLS; DIABETES-MELLITUS; MOLECULAR-MECHANISMS; TRANSCRIPTION FACTOR; MEMBRANE-FUSION; ALPHA-GENE; FACTOR-I; MUTATIONS; SECRETION AB Defective glucose-stimulated insulin secretion is the main cause of hyperglycemia in type 2 diabetes mellitus. Mutations in HNF-1 alpha cause a monogenic form of type 2 diabetes, maturity-onset diabetes of the young (MODY), characterized by impaired insulin secretion. Here we report that collectrin, a recently cloned kidney-specific gene of unknown function, is a target of HNF-1 alpha in pancreatic beta cells. Expression of collectrin was decreased in the islets of HNF-1 alpha (-/-) mice, but was increased in obese hyperglycemic mice. Overexpression of collectrin in rat insulinoma INS-1 cells or in the beta cells of transgenic mice enhanced glucose-stimulated insulin exocytosis, without affecting Ca2+ influx. Conversely, suppression of collectrin attenuated insulin secretion. Collectrin bound to SNARE complexes by interacting with snapin, a SNAP-25 binding protein, and facilitated SNARE complex formation. Therefore, collectrin is a regulator of SNARE complex function, which thereby controls insulin exocytosis. C1 Osaka Univ, Dept Metab Med, Grad Sch Med, Suita, Osaka 5650871, Japan. Natl Inst Physiol Sci, Dept Cell Physiol, Okazaki, Aichi 4448787, Japan. Grad Univ Adv Studies, Okazaki, Aichi 4448787, Japan. Japan Sci & Technol Agcy, Precursory Res Embryon Sci & Technol, Kawaguchi, Saitama 3320012, Japan. Univ Geneva, Med Ctr, Dept Cell Physiol & Metab, CH-1211 Geneva, Switzerland. Okayama Univ, Dept Med & Clin Sci, Grad Sch Med & Dent, Okayama 7008558, Japan. Joslin Diabet Ctr, Boston, MA 02215 USA. Ehime Univ, Div Biochem & Mol Genet, Dept Cellular & Mol Biol, Sch Med, Ehime 7910295, Japan. NCI, Lab Metab, Canc Res Ctr, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. RP Yamagata, K (reprint author), Osaka Univ, Dept Metab Med, Grad Sch Med, Suita, Osaka 5650871, Japan. EM kazu@imed2.med.osaka-u.ac.jp RI WADA, Jun/B-2023-2011; OI WADA, Jun/0000-0003-1468-5170; Kasai, Haruo/0000-0003-2327-9027 FU NCRR NIH HHS [U4Z RR 16606]; NIDDK NIH HHS [U19DK61251] NR 41 TC 88 Z9 93 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD DEC PY 2005 VL 2 IS 6 BP 373 EP 384 DI 10.1016/j.cmet.2005.11.003 PG 12 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 992NX UT WOS:000233891900009 PM 16330323 ER PT J AU Wang, RH Li, CL Xu, XL Zheng, Y Xiao, CY Zerfas, P Cooperman, S Eckhaus, M Rouault, T Mishra, L Deng, CX AF Wang, RH Li, CL Xu, XL Zheng, Y Xiao, CY Zerfas, P Cooperman, S Eckhaus, M Rouault, T Mishra, L Deng, CX TI A role of SMAD4 in iron metabolism through the positive regulation of hepicidin expression SO CELL METABOLISM LA English DT Article ID AUTOSOMAL-DOMINANT HEMOCHROMATOSIS; ANTIMICROBIAL PEPTIDE HEPCIDIN; CONDITIONAL KNOCKOUT MICE; SQUAMOUS-CELL CARCINOMA; TUMOR-SUPPRESSOR GENE; TGF-BETA; HEREDITARY HEMOCHROMATOSIS; JUVENILE HEMOCHROMATOSIS; DPC4 GENE; ABSORPTION AB Hereditary hemochromatosis, characterized by iron overload in multiple organs, is one of the most common genetic disorders among Caucasians. Hepcidin, which is synthesized in the liver, plays important roles in iron overload syndromes. Here, we show that a Cre-IoxP-mediated liver-specific disruption of SMAD4 results in markedly decreased hepcidin expression and accumulation of iron in many organs, which is most pronounced in liver, kidney, and pancreas. Transcript levels of genes involved in intestinal iron absorption, including Dcytb, DMT1, and ferroportin, are significantly elevated in the absence of hepcidin. We demonstrate that ectopic overexpression of SMAD4 activates the hepcidin promoter and is associated with epigenetic modification of histone H3 to a transcriptionally active form. Moreover, transcriptional activation of hepcidin is abrogated in SMAD4-deficient hepatocytes in response to iron overload, TGF-beta, BMP, or IL-6. Our study uncovers a novel role of TGF-beta/SMAD4 in regulating hepcidin expression and thus intestinal iron transport and iron homeostasis. C1 NIDDKD, Genet Dev & Dis Branch, Bethesda, MD 20892 USA. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Dev Biol Lab, Dept Med & Surg, Washington, DC 20007 USA. RP Deng, CX (reprint author), NIDDKD, Genet Dev & Dis Branch, 10-9N105, Bethesda, MD 20892 USA. EM chuxiad@bdg10.niddk.nih.gov RI deng, chuxia/N-6713-2016 FU Intramural NIH HHS NR 56 TC 357 Z9 375 U1 3 U2 14 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD DEC PY 2005 VL 2 IS 6 BP 399 EP 409 DI 10.1016/j.cmet.2005.10.010 PG 11 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 992NX UT WOS:000233891900011 PM 16330325 ER PT J AU Melikov, K Chernomordik, L AF Melikov, K Chernomordik, L TI Arginine-rich cell penetrating peptides: from endosomal uptake to nuclear delivery SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Review DE cell-penetrating peptide; protein transduction; arginine-rich peptide; heparan sulfate; endocytosis; TAT; penetratin ID TAT-FUSION PROTEINS; HUMAN IMMUNODEFICIENCY VIRUS; FULL-LENGTH PROTEINS; HIV-1 TAT; TRANSDUCTION DOMAINS; HEPARAN-SULFATE; LIPID-BILAYERS; MEMBRANE TRANSLOCATION; PHOSPHOLIPID-VESICLES; BASIC DOMAIN AB Delivery of macromolecules into living cells by arginine-rich cell penetrating peptides (AR-CPPs) is an important new avenue for the development of novel therapeutic strategies. However, to date the mechanism of this delivery remains elusive. Recent data implicate endocytosis in the internalization of AR-CPPs and their macromolecular cargo and also indicate limited delivery of macromolecules into the cell cytoplasm and nucleus. Different types of endocytosis-clathrin-dependent endocytosis, raft/caveolin-dependent endocytosis and macropinocytosis-are all implicated in the uptake of AR- CPPs and their cargo into different cells. Cationic AR-CPPs dramatically increase uptake of conjugated molecules through efficient binding to surface proteoglycans. Whether this increase in binding can assure delivery of a sufficient amount of functionally active macromolecules into the cytoplasm and nucleus or whether there is a specific mechanism by which AR-CPPs facilitate the escape of conjugated cargo from endosomes remains to be understood. C1 NICHD, Sect Membrane Biol, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. RP Melikov, K (reprint author), NICHD, Sect Membrane Biol, Lab Cellular & Mol Biophys, NIH, Bldg 10 Rm 10D05,10 Ctr Dr, Bethesda, MD 20892 USA. EM melikovk@mail.nih.gov RI Melikov, Kamran/A-6604-2009 FU Intramural NIH HHS NR 91 TC 102 Z9 105 U1 4 U2 36 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD DEC PY 2005 VL 62 IS 23 BP 2739 EP 2749 DI 10.1007/s00018-005-5293-y PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 992IG UT WOS:000233877000004 PM 16231085 ER PT J AU Dautry-Varsat, A Subtil, A Hackstadt, T AF Dautry-Varsat, A Subtil, A Hackstadt, T TI Recent insights into the mechanisms of Chlamydia entry SO CELLULAR MICROBIOLOGY LA English DT Review ID EPITHELIAL-CELLS; LIPID RAFTS; TYROSINE PHOSPHORYLATION; ACTIN CYTOSKELETON; RHO GTPASES; HOST-CELLS; TRACHOMATIS INCLUSIONS; TRANSLOCATED PROTEIN; SIGNAL-TRANSDUCTION; BACTERIAL INVASION AB Chlamydia are widespread bacteria that grow in human and animal cells. They enter their host cell, establish an intracellular environment favourable for their multiplication and finally exit the host cell. A combination of host cell factors and of bacterial proteins contribute to pathogen entry. Recent advances have shed new light on the entry mechanism, following attachment. Here we review recent data concerning endocytosis, host cell signalling, proteins secreted by the bacteria, the actin cytoskeleton in entry and the involvement of small GTPases. C1 Inst Pasteur, CNRS, Unite Biol Interact Cellulaires, URA 2585, F-75724 Paris, France. NIAID, Intracellular Parasites Lab, NIH, Rocky Mtn Labs, Hamilton, MT 59840 USA. RP Dautry-Varsat, A (reprint author), Inst Pasteur, CNRS, Unite Biol Interact Cellulaires, URA 2585, 25 Rue Dr Roux, F-75724 Paris, France. EM adautry@pasteur.fr RI Subtil, Agathe/C-7464-2017 OI Subtil, Agathe/0000-0002-7481-4846 NR 57 TC 71 Z9 72 U1 1 U2 10 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1462-5814 J9 CELL MICROBIOL JI Cell Microbiol. PD DEC PY 2005 VL 7 IS 12 BP 1714 EP 1722 DI 10.1111/j.1462-5822.2005.00627.x PG 9 WC Cell Biology; Microbiology SC Cell Biology; Microbiology GA 984OS UT WOS:000233314800003 PM 16309458 ER PT J AU Kim, WH Lee, JW Gao, B Jung, MH AF Kim, WH Lee, JW Gao, B Jung, MH TI Synergistic activation of JNK/SAPK induced by TNF-alpha and IFN-gamma: Apoptosis of pancreatic beta-cells via the p53 and ROS pathway SO CELLULAR SIGNALLING LA English DT Article DE islet cells; apoptosis; cytokines; JNK/SAPK; reactive oxygen species ID NECROSIS-FACTOR-ALPHA; N-TERMINAL KINASE; OXIDATIVE STRESS; MITOCHONDRIAL-MEMBRANE; INTERFERON-GAMMA; CYTOCHROME-C; INDEPENDENT APOPTOSIS; SIGNALING PATHWAYS; INSULIN-RESISTANCE; PC12 CELLS AB IFN-gamma and TNF-alpha are major proinflammatory cytokines implicated in islet beta-cell destruction, which results in type-1 diabetes; however, the underlying mechanism is not clear. Using pancreatic beta-cell line MIN6N8 cells, co-treatment with TNF-alpha and IFN-gamma, but neither cytokine alone, synergistically induced apoptosis, correlated with the activation of the JNK/SAPK, which resulted in the production of reactive oxidative species (ROS) and loss of mitochondrial transmembrane potential (Delta Psi m). Additionally, cells transfected with wild-type JNK1 became more susceptible to apoptosis induced by TNF-alpha/IFN-gamma through ROS production and loss of A m, while cascading apoptotic events were prevented in dominant-negative JNK1-transfected or JNK inhibitor SP600125-treated cells. As the antioxidant, N-acetyl-cysteine, failed to completely suppress apoptosis induced by TNF-alpha/IFN-gamma, an additional pathway was considered to be involved. The level of p53 was significantly increased through synergistic activation of JNK by TNF-alpha/AFN-gamma. Furthermore, the synergistic effect of TNF-alpha/IFN-gamma on apoptosis and ROS production was further potentiated by the overexpression of wild-type p53, but not with mutant p53. This synergistic activation of JNK/SAPK by TNF-alpha/IFN-gamma was also induced in insulin-expressing pancreatic islet cells, and increased ROS production and p53 level, which was significantly inhibited by SP600125. Collectively, these data demonstrate that TNF-alpha/IFN-gamma synergistically activates JNK/SAPK, playing an important role in promoting apoptosis of pancreatic beta-cell via activation of p53 pathway together with ROS. (c) 2005 Elsevier Inc. All rights reserved. C1 Natl Inst Hlth, Dept Biomed Sci, Div Metab Dis, Seoul 122701, South Korea. NIAAA, Lab Physiol Studies, Sect Liver Biol, NIH, Bethesda, MD 20892 USA. RP Jung, MH (reprint author), Natl Inst Hlth, Dept Biomed Sci, Div Metab Dis, 5 Nokbun Dong, Seoul 122701, South Korea. EM jung0603@nih.go.kr NR 40 TC 64 Z9 67 U1 0 U2 1 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 2005 VL 17 IS 12 BP 1516 EP 1532 DI 10.1016/j.cellsig.2005.03.020 PG 17 WC Cell Biology SC Cell Biology GA 971KA UT WOS:000232381600007 PM 15908180 ER PT J AU Choi, K Mollapour, E Shears, SB AF Choi, K Mollapour, E Shears, SB TI Signal transduction during environmental stress: InsP(8) operates within highly restricted contexts SO CELLULAR SIGNALLING LA English DT Article DE inositol phosphate; inositol pyrophosphates; heat stress; cold stress; signal transduction ID POLYPHOSPHATE KINASE-ACTIVITY; MILD HEAT-STRESS; NF-KAPPA-B; INOSITOL PYROPHOSPHATES; GENE-EXPRESSION; PROTEIN-KINASES; SHOCK; CELLS; ACTIVATION; DICTYOSTELIUM AB Genetic manipulation of diphosphoinositol polyphosphate synthesis impacts many biological processes (reviewed in S.B. Shears, Biochem. J. 377, 2004, 265-280). These observations lacked a cell-signalling context, until the recent discovery that bis-diphosphoinositol tetrakisphosphate ([PP](2)-InSP4 or "InsP(8)") accumulates rapidly in mammalian cells in response to hyperosmotic stress (X. Pesesse, K. Choi, T. Zhang, and S. B. Shears J. Biol. Chem. 279, 2004, 43378-43381). We now investigate how widely applicable is this new stress-response. [PP](2)-InSP4 did not respond to mechanical strain or oxidative stress in mammalian cells. Furthermore, despite tight conservation of many molecular stress responses across the phylogenetic spectrum, we show that cellular [PP](2)-InSP4 levels do not respond significantly to osmotic imbalance, heat stress and salt toxicity in Saccharomyces cerevisiae. In contrast, we show that [PP](2)-InSP4 is a novel sensor of mild thermal stress in mammalian cells: [PP](2)-InSP4 levels increased 3-4 fold when cells were cooled from 37 to 33 degrees C, or heated to 42 degrees C. Increases in [PP](2)-InSP4 levels following heat-shock were evident < 5 min, and reversible (t(1/2)= 7 min) once cells were returned to 37 degrees C. These responses were blocked by pharmacological inhibition of the ERK/MEK pathway. Additional control processes may lie upstream Of [PP](2)-InSP4 synthesis, which was synergistically activated when heat stress and osmotic stress were combined. Our data add to the repertoire of signaling responses following thermal challenges, a topic of current interest for its possible therapeutic value. Published by Elsevier Inc. C1 NIEHS, Inositide Signaling Grp, US Dept HHS, NIH, Res Triangle Pk, NC 27709 USA. RP Shears, SB (reprint author), NIEHS, Inositide Signaling Grp, US Dept HHS, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM shears@niehs.nih.gov NR 48 TC 24 Z9 25 U1 0 U2 3 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 2005 VL 17 IS 12 BP 1533 EP 1541 DI 10.1016/j.cellsig.2005.03.021 PG 9 WC Cell Biology SC Cell Biology GA 971KA UT WOS:000232381600008 PM 15936174 ER PT J AU Schulz, GM Varga, M Jeffires, K Ludlow, CL Braun, AR AF Schulz, GM Varga, M Jeffires, K Ludlow, CL Braun, AR TI Functional neuroanatomy of human vocalization: An (H2OPET)-O-15 study SO CEREBRAL CORTEX LA English DT Article DE PAG; self-monitoring; species-specific calls; speech production; voice ID HUMAN AUDITORY-CORTEX; POSITRON-EMISSION-TOMOGRAPHY; PERIAQUEDUCTAL GRAY; SQUIRREL-MONKEY; TEMPORAL-LOBE; BRAIN-STEM; NUCLEUS RETROAMBIGUALIS; ELECTRICAL-STIMULATION; RHESUS-MONKEY; BASAL GANGLIA AB Vocalization in lower animals is associated with a well-described visceromotor call system centered on the mesencephalic periacqueductal grey matter (PAG), which is itself regulated by paramedian cortical structures. To determine the role this phylogenetically older system plays in human phonation, we contrasted voiced and unvoiced speech using positron emission tomography and then evaluated functional connectivity of regions that significantly differentiated these conditions. Vocalization was associated with increased and highly correlated activity within the midline structures-PAG and paramedian cortices-described in lower mammalian species. Concurrent activation and connectivity of neocortical and subcortical motor regions - medial and lateral premotor structures and elements of basal ganglia thalamocortical circuitry-suggest a mechanism by which this system may have come under an increasing degree of voluntary control in humans. Additionally, areas in the temporal lobe and cerebellum were selectively activated during voiced but not unvoiced speech. These regions are functionally coupled to both visceromotor and neocortical motor areas during production of voiced speech, suggesting they may play a central role in self-monitoring and feedback regulation of human phonation. C1 George Washington Univ, Dept Speech & Hearing Sci, Washington, DC 20052 USA. NIDCD, Language Sect, Voice Speech & Language Branch, NIH, Bethesda, MD 20892 USA. NINDS, Laryngeal & Speech Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Schulz, GM (reprint author), George Washington Univ, Dept Speech & Hearing Sci, 1922 F St NW,Room 406-D, Washington, DC 20052 USA. EM schulz@egwu.edu OI Schulz, Geralyn/0000-0003-3831-8105 FU Intramural NIH HHS [Z01 NS002980-09] NR 71 TC 78 Z9 78 U1 1 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD DEC PY 2005 VL 15 IS 12 BP 1835 EP 1847 DI 10.1093/cercor/bhi061 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 983FS UT WOS:000233217300001 PM 15746003 ER PT J AU Eichler, JF Cramer, JC Kirk, KL Bann, JG AF Eichler, JF Cramer, JC Kirk, KL Bann, JG TI Biosynthetic incorporation of fluorohistidine into proteins in E-coli: A new probe of macromolecular structure SO CHEMBIOCHEM LA English DT Article DE amino acids; biosynthesis; fluorine; histidine; protein modification ID RING-FLUORINATED IMIDAZOLES; DOMAIN-DOMAIN INTERACTIONS; AMINO-ACIDS; PROTECTIVE ANTIGEN; DIAZONIUM SALTS; CHAPERONE PAPD; ANTHRAX TOXIN; F-19 NMR; IN-VIVO; HISTIDINE C1 Wichita State Univ, Dept Chem, Wichita, KS 67226 USA. NIDDKD, Bioorgan Chem Lab, Bethesda, MD 20892 USA. RP Bann, JG (reprint author), Wichita State Univ, Dept Chem, Wichita, KS 67226 USA. EM jim.bann@wichita.edu FU NIAID NIH HHS [U54 AI057160] NR 40 TC 19 Z9 19 U1 1 U2 13 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1439-4227 J9 CHEMBIOCHEM JI Chembiochem PD DEC PY 2005 VL 6 IS 12 BP 2170 EP 2173 DI 10.1002/cbic.200500249 PG 4 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 992XF UT WOS:000233916600009 PM 16261552 ER PT J AU Manimala, JC Li, ZT Jain, A VedBrat, S Gildersleeve, JC AF Manimala, JC Li, ZT Jain, A VedBrat, S Gildersleeve, JC TI Carbohydrate array analysis of anti-Tn antibodies and lectins reveals unexpected specificities: Implications for diagnostic and vaccine development SO CHEMBIOCHEM LA English DT Article DE carbohydrates; glycoconjugates; glycosylation; microarrays; Tn antigen ID POLYPEPTIDE N-ACETYLGALACTOSAMINYLTRANSFERASE; SHIGELLA-DYSENTERIAE TYPE; SIALYL-TN; THOMSEN-FRIEDENREICH; SIALOSYL-TN; NEOPLASTIC TRANSFORMATION; METASTATIC LESIONS; OVARIAN CARCINOMAS; BINDING-PROTEINS; IMMUNOREACTIVE T AB The Tn antigen is a carbohydrate antigen expressed in most carcinomas, during embryogenesis, on pathogenic parasites, and on HIV. It has been evaluated extensively as a potential diagnostic marker and several Tn-based vaccines are in clinical trials. Based on discrepancies in the literature regarding Tn expression, we began to question whether antibodies and lectins used routinely to, detect the Tn antigen were providing accurate information. To investigate this possibility, a carbohydrate microarray and a highly sensitive assay were developed and three frequently used Tn receptors (HBTn1, Bric111, and VVL-B4) were evaluated. Carbohydrate-array analysis revealed unexpected cross-reactivity with other human carbohydrate epitopes. WL-B4 bound the Tn antigen, GalNAc alpha l-6Gal, and GalNAc alpha 1-3Gal. Bric111 bound the Tn antigen, blood group A GalNAc alpha 1-6Gal, and GalNAc alpha 1-3Gal. HBTn1 showed the best selectivity but still displayed moderate binding to blood group A. Implications for the development of Tn-based diagnostics and vaccines are discussed. C1 NCI, Ctr Canc Res, Med Chem Lab, Frederick, MD 21702 USA. KamTek Inc, Gaithersburg, MD 20879 USA. RP Gildersleeve, JC (reprint author), NCI, Ctr Canc Res, Med Chem Lab, 376 Boyles St,Bldg 376,Room 109, Frederick, MD 21702 USA. EM gildersleevej@ncifcrf.gov RI Gildersleeve, Jeffrey/N-3392-2014 FU Intramural NIH HHS NR 80 TC 81 Z9 81 U1 0 U2 11 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1439-4227 J9 CHEMBIOCHEM JI Chembiochem PD DEC PY 2005 VL 6 IS 12 BP 2229 EP 2241 DI 10.1002/cbic.200500165 PG 13 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 992XF UT WOS:000233916600018 PM 16252298 ER PT J AU Parker, RJ Hartman, NR Roecklein, BA Mortko, H Kupferberg, HJ Stables, J Strong, JM AF Parker, RJ Hartman, NR Roecklein, BA Mortko, H Kupferberg, HJ Stables, J Strong, JM TI Stability and comparative metabolism of selected felbamate metabolites and postulated fluorofelbamate metabolites by postmitochondrial suspensions SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID CARBONYL REDUCTASE; MERCAPTURIC ACIDS; IN-VITRO; CARBAMATE; URINE AB Evidence has been presented suggesting that a reactive metabolite, 2-phenylpropenal (ATPAL), may be responsible for the toxicities observed during therapy with the antiepileptic drug felbamate (FBM). Formation of ATPAL from its unstable immediate precursor, 3-carbamoyl-2-phenylpropionaldedhyde (CBMA) requires the loss of the hydrogen atom at position 2 in the propane chain, and it has been postulated that substitution of this atom with fluorine would prevent the formation of ATPAL. On the basis of this hypothesis, 2-fluoro-2-phenyl-1,3-propanediol dicarbamate (F-FBM) was synthesized and is presently undergoing drug development. To test this hypothesis, we compared the metabolism by human liver post-mitochondrial suspensions (S9) in vitro of selected FBM and postulated F-FBM metabolites leading to formation of CBMA or 3-carbamoyl-2-fluoro-2-phenyl-propionaldehyde (F-CBMA). All S9 incubations included GSH as a trapping agent for any reactive metabolites formed. Our results indicated that, in phosphate buffer, pH 7.4, at 37 degrees C, the half-life for 4-hydroxy5-phenyltetrahydro-1,3-oxazin-2-one (CCMF) was 2.8 and 3.6 h in the presence or absence of GSH, respectively; compared to 4-hydroxy-5-fluoro-5-phenyl-tetrahydro-1,3-oxazin-2-one (FCCMF) which lost only 2.5% or 4.9% over 24 h under the same conditions. When incubated with S9 in the presence of the cofactor, NAD+, 2-phenyl-1,3-propanediol monocarbamate (MCF) was oxidized to CCMF which was further oxidized to 3-carbamoyl-2-phenylpropionic acid (CPPA). 2-Fluoro-2-phenyl-1,3-propanediol monocarbamate (F-MCF) under similar conditions was stable, and no metabolites were observed. When CCMF was incubated with S9 in the presence of NAD+ cofactor, oxidation to CPPA and reduction to MCF were observed. In addition, a new atropic acid GSH adduct (ATPA-GSH) was identified by mass spectrometry. When F-CCMF was incubated under the same conditions as CCMF, both reduced and oxidized metabolites, F-MCF and 3-carbamoyl-2-fluoro-2-phenylpropionic acid (F-CPPA), respectively, were formed but at significantly lower rates, and no GSH conjugates were identified. Our results support the hypothesis that F-FBM and F-CCMF are not metabolized by S9 in vitro to the known reactive FBM metabolite, ATPAL. C1 US FDA, Ctr Drug Evaluat & Res, Lab Clin Pharmacol, Silver Spring, MD 20993 USA. MedPointe Pharmceut, Somerset, NJ 08873 USA. Natl Inst Neurol Dis & Stroke, NIH, Bethesda, MD 20892 USA. RP Strong, JM (reprint author), US FDA, Ctr Drug Evaluat & Res, Lab Clin Pharmacol, 10903 New Hampshire Ave,White Oak Bldg 64, Silver Spring, MD 20993 USA. EM strongj@cder.fda.gov NR 17 TC 14 Z9 14 U1 4 U2 9 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 2005 VL 18 IS 12 BP 1842 EP 1848 DI 10.1021/tx050130r PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 004XY UT WOS:000234787200007 PM 16359174 ER PT J AU Karaczyn, AA Golebiowski, F Kasprzak, KS AF Karaczyn, AA Golebiowski, F Kasprzak, KS TI Truncation, deamidation, and oxidation of histone H2B in cells cultured with nickel(II) SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID POLYACRYLAMIDE-GEL-ELECTROPHORESIS; NITRIC-OXIDE SYNTHASE; AMINO-ACID-RESIDUES; C-TERMINAL TAIL; DNA-DAMAGE; PHYSIOLOGICAL-FUNCTION; CORE HISTONES; BINDING-SITE; PROTEINS; CALPAIN AB Molecular mechanisms of nickel-induced carcinogenesis include interactions of Ni(II) cations with histones. Previously, we demonstrated in vitro and in cells that Ni(II) cleaved off the -SHHKAKGK C-terminal motif of histone H2A. In the present study, Western blotting of histones isolated from rat and human cell lines, cultured for 3-5 days with 0.05-0.5 mM Ni(II), revealed time- and dose-dependent appearance of a new band of histone H2B. This effect was also induced by Co(II), but not by Cu(II), Cd(II), and Zn(II). Mass spectrometry and amino acid sequencing of proteins from the new band allowed for identification of two derivatives of the major variant of histone H2B. The larger protein was histone H2B lacking 16 N-terminal amino acids. The smaller one was histone H2B which, in addition to being shortened at the N-terminus, had nine amino acids deleted from its C-terminus. At both termini, the truncation occurred between lysine and alanine in the two identical -KAVTK- repeats of histone H2B. Also, the truncated H2B proteins had their Q(22) residues deamidated and M-59 and M-62 residues oxidized to sulfoxides, a signature of oxidative stress. The truncation did not concur with apoptosis. Its mechanism involved activation by Ni(II) treatment of specific nuclear proteolytic enzymes belonging to the calpain family. The terminal tails of core histones participate in structuring chromatin and regulating gene expression. Therefore, the observed truncation and other modifications of histone H2B may assist in Ni(II) carcinogenesis through epigenetic mechanisms. C1 NCI, Lab Comparat Carcinogenesis, Frederick, MD 21702 USA. RP Kasprzak, KS (reprint author), NCI, Lab Comparat Carcinogenesis, Kasprzak Bldg 538,Room 205E, Frederick, MD 21702 USA. EM kasprkaz@mail.ncifcrf.gov FU Intramural NIH HHS NR 61 TC 40 Z9 41 U1 0 U2 4 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 2005 VL 18 IS 12 BP 1934 EP 1942 DI 10.1021/tx050122a PG 9 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 004XY UT WOS:000234787200017 PM 16359184 ER PT J AU Kisker, C Truglio, JJ Rhau, B Karakas, E Croteau, DL Van Houten, B AF Kisker, C Truglio, JJ Rhau, B Karakas, E Croteau, DL Van Houten, B TI How does it cut? Insights into the incision reactions during nucleotide excision repair. 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 230th National Meeting of the ACS CY AUG 28-SEP 01, 2005 CL Washington, DC SP Amer Chem Soc, Div Chem Toxicol C1 SUNY Stony Brook, Dept Pharmacol, Stony Brook, NY 11795 USA. NIEHS, Genet Mol Lab, NIH, Res Triangle Pk, NC 27709 USA. EM kisker@pharm.stonybrook.edu 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 2005 VL 18 IS 12 MA 5 BP 1967 EP 1968 PG 2 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 004XY UT WOS:000234787200025 ER PT J AU Yang, W AF Yang, W TI Translesion DNA synthesis. 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 230th National Meeting of the ACS CY AUG 28-SEP 01, 2005 CL Washington, DC SP Amer Chem Soc, Div Chem Toxicol C1 NIH, Mol Biol Lab, Bethesda, MD 20892 USA. EM wei.yang@nih.gov 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 2005 VL 18 IS 12 MA 7 BP 1968 EP 1968 PG 1 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 004XY UT WOS:000234787200027 ER PT J AU Karp, JE Passaniti, A Gojo, I Kaufmann, S Bible, K Garimella, TS Greer, J Briel, J Smith, BD Gore, SD Tidwell, ML Ross, DD Wright, JJ Colevas, AD Bauer, KS AF Karp, JE Passaniti, A Gojo, I Kaufmann, S Bible, K Garimella, TS Greer, J Briel, J Smith, BD Gore, SD Tidwell, ML Ross, DD Wright, JJ Colevas, AD Bauer, KS TI Phase I and pharmacokinetic study of flavopiridol followed by 1-beta-D-arabinofuranosylcytosine and mitoxantrone in relapsed and refractory adult acute leukemias SO CLINICAL CANCER RESEARCH LA English DT Article ID ACUTE MYELOID-LEUKEMIA; KINASE INHIBITOR FLAVOPIRIDOL; CHRONIC LYMPHOCYTIC-LEUKEMIA; 72-HOUR CONTINUOUS-INFUSION; BREAST-CARCINOMA CELLS; HIGH-DOSE MITOXANTRONE; TIMED SEQUENTIAL THERAPY; MULTIPLE-MYELOMA; DOWN-REGULATION; TRANSCRIPTIONAL REPRESSION AB Purpose: The serine/threonine kinase inhibitor flavopiridol targets multiple cycl in-dependent kinases, induces checkpoint arrest, and interrupts transcriptional elongation. We designed a phase I clinical trial using a timed sequential therapy approach where flavopiridol was given for the dual purpose of initial cytoreduction and enhancing cell cycle progression of the remaining leukemia cell cohort followed by cycle-dependent drugs 1-beta-D-arabinofuranosylcytosine (ara-C) and mitoxantrone. Experimental Design: Flavopiriclol was given by 1-hour infusion daily for 3 days beginning day 1 followed by 2 g/m(2)/72 h ara-C beginning day 6 and 40 mg/m(2) mitoxantrone beginning day 9. In vivo correlates included pharmacokinetics, modulation of blast cycle regulators, and serum and marrow supernatant vascular endothelial growth factor levels. Results: Of 34 adults receiving induction therapy, 16 (47%) evinced direct leukemia cytotoxicity with >= 50% drop in peripheral blast counts and tumor lysis in 9 (26%). Four (12%) died during therapy (two fungal infections and two sudden death). Dose-limiting toxicity occurred at 60 mg/m(2)/d with profound neutropenia > 40 days duration, and maximal tolerated dose was 50 mg/m(2)/d. Overall response rate was 31% in 26 acute myelogenous leukemia and 12.5% in acute lymphoblastic leukemia. Pharmacokinetics showed that a linear two-compartment model with first-order elimination provided the best fit of the observed concentration versus time data. Flavopiridol down-regulated one or more target proteins in marrow blasts in vivo. Vascular endothelial growth factor was detected in sera and marrow supernatant pretreatment, and sera obtained on day 3 inhibited bovine aortic endothelial cell proliferation by a mean of 32% (range, 10-80%). Conclusions: Our data suggest that flavopiridol is cytotoxic to leukemic cells and, when followed by ara-C and mitoxantrone, exerts biological and clinical effects in patients with relapsed and refractory acute leukemias. These findings warrant continuing development of flavopiridol at 50 mg/m(2)/d x 3 days in combination with cytotoxic and biological agents for acute leukemias. C1 Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA. Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. Baltimore Vet Affairs Med Ctr, Baltimore, MD USA. Mayo Clin, Rochester, MN USA. NCI, Invest Drug Branch, Clin Trials Evaluat Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Karp, JE (reprint author), Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, 1650 Orleans St,CRB Room 289, Baltimore, MD 21231 USA. EM jkarp2@jhmi.edu NR 50 TC 50 Z9 53 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 1 PY 2005 VL 11 IS 23 BP 8403 EP 8412 DI 10.1158/1078-0432.CCR-05-1201 PG 10 WC Oncology SC Oncology GA 989VF UT WOS:000233701300026 PM 16322302 ER PT J AU Rudek, MA Zhao, M Smith, NF Robey, RW He, P Hallur, G Khan, S Hidalgo, M Jimeno, A Colevas, AD Messersmith, WA Wolff, AC Baker, SD AF Rudek, MA Zhao, M Smith, NF Robey, RW He, P Hallur, G Khan, S Hidalgo, M Jimeno, A Colevas, AD Messersmith, WA Wolff, AC Baker, SD TI In vitro and in vivo clinical pharmacology of dimethyl benzoylphenylurea, a novel oral tubulin-interactive agent SO CLINICAL CANCER RESEARCH LA English DT Article ID CANCER RESISTANCE PROTEIN; ANTITUMOR ACTIVITIES; DRUG-DELIVERY; HUMAN PLASMA; TRANSPORTERS; METABOLISM; INHIBITOR; RITONAVIR; INTESTINE; TOXICITY AB Dimethyl benzoylphenylurea (BPU) is a novel tubulin-interactive agent with poor and highly variable oral bioavailability. In a phase I clinical trial of BPU, higher plasma exposure to BPU and metabolites was observed in patients who experienced dose-limiting toxicity. The elucidation of the clinical pharmacology of BPU was sought. BPU, monomethylBPU, and aminoBPU were metabolized by human liver microsomes. Studies with cDNA-expressed human cytochrome P450 enzymes revealed that BPU was metabolized predominantly by CYP3A4 and CYP1A1 but was also a substrate for CYP2C8, CYP2D6, CYP3A5, and CYP3A7. BPU was not a substrate for the efflux transporter ABCG2. Using simultaneous high-performance liquid chromatography/ diode array and tandem mass spectrometry detection, we identified six metabolites in human liver microsomes, plasma, or urine: monomethylBPU, aminoBPU, G280, G308, G322, and G373. In patient urine, aminoBPU, G280, G308, and G322 collectively represented < 2% of the given BPU dose. G280, G308, G322, and G373 showed minimal cytotoxicity. When BPU was given p.o. to mice in the presence and absence of the CYP3A and ABCG2 inhibitor, ritonavir, there was an increase in BPU plasma exposure and decrease in metabolite exposure but no overall change in cumulative exposure to BPU and the cytotoxic metabolites. Thus, we conclude that (a) CYP3A4 and CYP1A1 are the predominant cytochrome P450 enzymes that catalyze BPU metabolism, (b) BPU is metabolized to two cytotoxic and four noncytotoxic metabolites, and (c) ritonavir inhibits BPU metabolism to improve the systemic exposure to BPU without altering cumulative exposure to BPU and the cytotoxic metabolites. C1 Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA. NCI, Canc Therapeut Branch, Bethesda, MD 20892 USA. NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Rockville, MD USA. RP Rudek, MA (reprint author), Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Bunting Blaustein Canc Res Bldg,Room 1M90,1650 Or, Baltimore, MD 21231 USA. EM mrudek2@jhmi.edu RI HIDALGO, MANUEL/I-4995-2015; OI HIDALGO, MANUEL/0000-0002-3765-3318; Wolff, Antonio/0000-0003-3734-1063 FU NCI NIH HHS [P30CA069773, U01CA70095] NR 35 TC 6 Z9 6 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 1 PY 2005 VL 11 IS 23 BP 8503 EP 8511 DI 10.1158/1078-0432.CCR-05-1037 PG 9 WC Oncology SC Oncology GA 989VF UT WOS:000233701300038 PM 16322314 ER PT J AU Huestis, MA Barnes, A Smith, ML AF Huestis, MA Barnes, A Smith, ML TI Estimating the time of last cannabis use from plasma Delta(9)-tetrahydrocannabinol and II-nor-9-carboxy-Delta(9)-tetrahydrocannabinol concentrations SO CLINICAL CHEMISTRY LA English DT Article ID BLOOD CANNABINOIDS; SMOKING MARIJUANA; PERFORMANCE; ALCOHOL; TETRAHYDROCANNABINOL; THCCOOH; THC; DELTA-9-TETRAHYDROCANNABINOL; DELTA(9)-THC; DISPOSITION AB Background: Knowing the time cannabis was last used is important for determining impairment in accident investigations and clinical evaluations. Two models for predicting time of last cannabis use from single plasma cannabinoid concentrations-model 1, using Delta(9)-tetrahydrocannabinol (THC), and model 11, using the concentration ratio of 11-nor-9-carboxy-THC (THCCOOH) to THC-were developed and validated from controlled drug administration studies. Objectives of the current study were to extend the validation by use of a large number of plasma samples collected after administration of single and multiple doses of THC and to examine the effectiveness of the models at low plasma cannabinoid concentrations. Methods: Thirty-eight cannabis users each smoked a 2.64% THC cigarette in the morning, and 30 also smoked a second cigarette in the afternoon. Blood samples (n = 717) were collected at intervals after smoking, and plasma THC and THCCOOH concentrations measured by gas chromatography-mass spectrometry. Predicted times of cannabis smoking, based on each model, were compared with actual smoking times. Results: The most accurate approach applied a combination of models I and II. For all 717 plasma samples, 99% of predicted times of last use were within the 95% confidence interval, 0.9% were overestimated, and none were underestimated. For 289 plasma samples collected after multiple doses, 97% were correct with no underestimates. All time estimates were correct for 76 plasma samples with THC concentrations between 0.5 and 2 mu g/L, a concentration range not previously examined. Conclusions: This study extends the validation of the predictive models of time of last cannabis use to include multiple exposures and low THC concentrations. The models provide an objective and validated method for assessing the contribution of cannabis to accidents or clinical symptoms. (c) 2005 American Association for Clinical Chemistry. C1 Natl Inst Drug Abuse, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Off Armed Forces Med Examiner, Div Forens Toxicol, Rockville, MD USA. RP Huestis, MA (reprint author), Natl Inst Drug Abuse, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov FU Intramural NIH HHS NR 36 TC 38 Z9 39 U1 0 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 2005 VL 51 IS 12 BP 2289 EP 2295 DI 10.1373/clinchem.2005.056838 PG 7 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 987QV UT WOS:000233533300012 PM 16223887 ER PT J AU Ruhl, CE Everhart, JE AF Ruhl, CE Everhart, JE TI Joint effects of body weight and alcohol on elevated serum alanine aminotransferase in the United States population SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID FATTY LIVER-DISEASE; GENERAL-POPULATION; HEPATIC STEATOSIS; RISK-FACTOR; PREVALENCE; OVERWEIGHT; OBESITY; STEATOHEPATITIS; CAFFEINE; DAMAGE AB Background & Aims: Both alcohol and obesity are associated with hepatic steatosis. However, little is known about whether the toxicity of alcohol to the liver is influenced by adiposity. We examined the relationship of alcohol drinking and binge drinking with abnormal serum aminotransferase activity in normal weight, overweight, and obese persons in a national, population-based study. Methods: Data were analyzed from 1.3,580 adult participants in the third US National Health and Nutrition Examination Survey, 1988-1994, after excluding participants with hepatitis B or C or iron overload. Abnormal aminotransferase levels were defined by using sex-specific cutoffs for ALT and AST. Analyses were adjusted for other liver injury risk factors. Results: The prevalence of abnormal aminotransferase activity was elevated with consumption of > 2 drinks per day or with overweight and obesity. In multivariate analysis, there was no association of alcohol intake with a higher prevalence of elevated aminotransferase levels among normal weight persons. In contrast, among overweight persons, consumption of >2 drinks per day increased the risk of elevated aminotransferase levels, and among the obese, >= 1 drink per day was associated with a higher risk. Results were similar with elevated ALT alone as the outcome. With elevated AST alone as the outcome, intake of >2 drinks per day increased the risk, even among normal weight persons. Binge drinking was associated with aminotransferase elevation among obese consumers of 1-2 drinks per day. Conclusions: In this large, national, population-based study, overweight and obesity increased the risk of alcohol-related abnormal ami notransferase activity. C1 Social & Sci Syst Inc, Silver Spring, MD 20910 USA. NIDDKD, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Ruhl, CE (reprint author), Social & Sci Syst Inc, 8757 Georgia Ave,12th Floor, Silver Spring, MD 20910 USA. EM cruhl@s-3.com FU NIDDK NIH HHS [N01-DK-1-2478] NR 30 TC 99 Z9 100 U1 1 U2 1 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 2005 VL 3 IS 12 BP 1260 EP 1268 DI 10.1016/S1542-3565(05)00743-3 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 997HN UT WOS:000234236200018 PM 16361053 ER PT J AU Perlman, DC Segal, Y Rosenkranz, S Rainey, PM Remmel, RP Salomon, N Hafner, R Peloquin, CA AF Perlman, DC Segal, Y Rosenkranz, S Rainey, PM Remmel, RP Salomon, N Hafner, R Peloquin, CA CA Aids Clinical Trials Grp 309 Team TI The clinical pharmacokinetics of rifampin and ethambutol in HIV-infected persons with tuberculosis SO CLINICAL INFECTIOUS DISEASES LA English DT Article AB Background. The pharmacokinetics of rifampin and ethambutol in HIV-infected patients with tuberculosis ( TB) are incompletely characterized. We examined the pharmacokinetics of rifampin and ethambutol in a cohort of patients with HIV-related TB who were treated in the United States. Methods. Serum drug concentrations were determined 2, 6, and 10 h after dosing in 36 HIV-infected patients with TB who were taking rifampin and in 49 who were taking ethambutol. Observed serum concentrations were compared with published normal ranges and published data. Results. With daily dosing of rifampin (600 mg), 26 (77%) of 34 patients (95% confidence interval [CI], 59%-89%]) had a low maximum concentration of rifampin (< 8 mu g/mL), and 12 (35%; 95% CI, 20%-54%) had a very low maximum concentration (< 4 mu g/mL). With intermittent rifampin dosing ( 600 mg), 13 (68%) of 19 patients (95% CI, 44%-85%) had a low maximum concentration of rifampin, and 5 (26%; 95% CI, 11%-50%) had a very low maximum concentration. With daily ethambutol dosing (20 mg/kg), 33 (69%) of 48 patients ( 95% CI, 55%-81%) had a low maximum concentration of ethambutol (< 2 mu g/mL), and 18 ( 38%; 95% CI, 24%-53%) had a very low maximum concentration (< 1 mu g/mL). With intermittent ethambutol dosing (50 mg/kg twice weekly or 30 mg/kg thrice weekly), 13 (72%) of 18 patients ( 95% CI, 47%-88%) had a low maximum concentration Conclusions. In HIV-infected patients with TB who are receiving rifampin and ethambutol, low maximum concentrations of rifampin and ethambutol were common. For patients with HIV-related TB, therapeutic monitoring of rifampin and ethambutol levels may help clinicians achieve target serum concentrations. C1 Beth Israel Med Ctr, New York, NY 10003 USA. Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA USA. Univ Washington, Seattle, WA 98195 USA. Univ Minnesota, Minneapolis, MN USA. NIAID, Bethesda, MD 20892 USA. Natl Jewish Med & Res Ctr, Denver, CO USA. RP Perlman, DC (reprint author), Beth Israel Med Ctr, 1st Ave 16th St, New York, NY 10003 USA. EM dperlman@bethisraelny.org RI Remmel, Rory/N-2453-2015 FU NCRR NIH HHS [M01 RR05096]; NIAID NIH HHS [U01 AI046370, 1U01AI46370, AI 38855]; PHS HHS [1U01A13844, A0603, A12015802, A1701, A1802, A2205, A2503, A5802, A5901, A6201, UO1A127673] NR 30 TC 44 Z9 45 U1 0 U2 2 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 2005 VL 41 IS 11 BP 1638 EP 1647 DI 10.1086/498024 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 980KY UT WOS:000233018600015 PM 16267738 ER PT J AU Miyazawa, N Arbab, AS Umeda, T Akiyama, L AF Miyazawa, N Arbab, AS Umeda, T Akiyama, L TI Perfusion CT investigation of chronic internal carotid artery occlusion: comparison with SPECT SO CLINICAL NEUROLOGY AND NEUROSURGERY LA English DT Article DE perfusion; computed tomography; cerebral ischemia; single photon emission computed tomography ID CEREBRAL-BLOOD-FLOW; XENON CT; VALIDATION; ISCHEMIA; STROKE AB This study investigated the usefulness of perfusion computed tomography (CT) for the evaluation of patients with chronic internal carotid artery (ICA) occlusion by comparing the findings with those of iodine-123 iodoamphetarnine ([I-123]IMP) single photon emission computed tomography (SPECT). Twenty five patients with chronic ICA occlusion were investigated on the same day by perfusion CT to measure the cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transient time (MTT), and [(123)]IMP SPECT to measure the regional CBF, significant correlations were observed between regional CBF measured by SPECT and CBF measured by per-fusion CT (r = 0.659, R-2 = 0.434, p < 0.001), regional CBF and CBV (r = -0.406, R-2 = 0.165, p < 0.001) and regional CBF and MT-17 (r = -0.592, R-2 = 0.350, p < 0.001). Significant correlations were also observed between CBF and CBV (r = -0.153, R-2 = 0.023, p < 0.001) CBF and MTT (r = -0.580, R-2 = 0.337, p < 0.001) and MTT and CBV (r = 0.763, R-2 = 0.582, p < 0.001). Perfusion CT is useful to evaluate the hemodynamic state of patients with chronic major cerebral artery occlusive disorders. (c) 2005 Published by Elsevier B.V. C1 Akiyama Neurosurg Clin, Dept Neurosurg, Yamanashi 4070037, Japan. NIH, Lab Diagnost Radiol Res, Bethesda, MD 20892 USA. Yamanashi Med Univ, Dept Radiol, Tamaho, Yamanashi 4093898, Japan. RP Miyazawa, N (reprint author), Akiyama Neurosurg Clin, Dept Neurosurg, 1330 Wakao Ohkusa Cho, Yamanashi 4070037, Japan. EM akinouge@crux.ocn.ne.jp NR 18 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0303-8467 J9 CLIN NEUROL NEUROSUR JI Clin. Neurol. Neurosurg. PD DEC PY 2005 VL 108 IS 1 BP 11 EP 17 DI 10.1016/j.clineuro.2004.12.024 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 996RG UT WOS:000234191400003 PM 16098657 ER PT J AU Hechtman, L Etcovitch, J Platt, R Arnold, LE Abikoff, HB Newcorn, JH Hoza, B Hinshaw, SP Kraemer, HC Wells, K Conners, K Elliott, G Greenhill, LL Jensen, PS March, JS Molina, B Pelham, WE Severe, JB Swanson, JM Vitiello, B Wigal, T AF Hechtman, L Etcovitch, J Platt, R Arnold, LE Abikoff, HB Newcorn, JH Hoza, B Hinshaw, SP Kraemer, HC Wells, K Conners, K Elliott, G Greenhill, LL Jensen, PS March, JS Molina, B Pelham, WE Severe, JB Swanson, JM Vitiello, B Wigal, T TI Does multimodal treatment of ADHD decrease other diagnoses? SO CLINICAL NEUROSCIENCE RESEARCH LA English DT Article DE ADHD; comorbidity; behavioral treatment; multimodal treatment; outcome ID ATTENTION-DEFICIT-HYPERACTIVITY; 4-YEAR FOLLOW-UP; DEFICIT/HYPERACTIVITY DISORDER; TREATMENT STRATEGIES; PSYCHIATRIC STATUS; CONDUCT DISORDER; PSYCHOSOCIAL TREATMENT; COMORBID ANXIETY; CHILDREN; METHYLPHENIDATE AB Comorbid conditions in children with attention deficit hyperactivity disorder (ADHD) are frequent and can affect treatment response and life course. From the multimodal treatment study of ADHD (MTA), we examined the persistence or development of conditions other than ADHD, e.g. oppositional defiant disorder (ODD), conduct disorder (CD), anxiety, depression, and learning disorder (LD) in 576 children, age 7-9 years, diagnosed rigorously with ADHD, who were randomly assigned to four different treatments for 14 months. The treatment groups were medication management alone (MedMgt), behavioral treatment alone (Beh), the combination (Comb), and community comparison routine care (CC). For the sample as a whole, we found significant decreases from baseline to 14 months in diagnoses of ODD, CD, and anxiety disorder but not LD or mood disorder. The CC group developed significantly more new ODD and retained more baseline ODD than the Comb or MedMgt groups. There were no significant treatment group differences for specific other conditions. Only the Comb group was significantly better than the CC group in reducing total number of disorders and impairment at 14 months in subjects with multiple conditions at baseline. Well-titrated and monitored stimulant medication can decrease ODD and possibly prevent future CD. Combined treatment may be required for the most disturbed children with ADHD who have multiple disorders and severe impairment. (c) 2005 Association for Research in, Nervous and Mental Disease. Published by Elsevier B.V. All rights reserved. C1 McGill Univ, Montreal Childrens Hosp, Div Child Psychiat, Montreal, PQ H3Z 1P2, Canada. Ohio State Univ, Sunbury, OH 43074 USA. CUNY, Mt Sinai Med Ctr, Dept Psychiat, New York, NY 10029 USA. Univ Vermont, Dept Psychol, Burlington, VT 05405 USA. Duke Univ, Child & Family Study Ctr, Durham, NC 27705 USA. Langley Porter, Childrens Ctr, San Francisco, CA 94143 USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Psychol, Pittsburgh, PA 15213 USA. Univ Calif Irvine, Child Dev Ctr, Dept Pediat, Irvine, CA 92612 USA. Columbia Univ, NY State Psychiat Inst, Ctr Advancement Childrens Mental Hlth, New York, NY 10032 USA. NIMH, Bethesda, MD 20892 USA. RP Hechtman, L (reprint author), McGill Univ, Montreal Childrens Hosp, Div Child Psychiat, 4018 St Catherine St W, Montreal, PQ H3Z 1P2, Canada. EM lhechtman@hotmail.com OI Jensen, Peter/0000-0003-2387-0650; Platt, Robert/0000-0002-5981-8443; Newcorn, Jeffrey /0000-0001-8993-9337 NR 44 TC 8 Z9 8 U1 4 U2 10 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1566-2772 J9 CLIN NEUROSCI RES JI Clin. Neurosci. Res. PD DEC PY 2005 VL 5 IS 5-6 BP 273 EP 282 DI 10.1016/j.cnr.2005.09.007 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 998YX UT WOS:000234356900008 ER PT J AU Arnold, LE Elliott, M Lindsay, RL Molina, B Cornelius, MD Vitiello, B Hechtman, L Elliott, GR Newcorn, J Epstein, JN Wigal, T Swanson, JM Wells, K AF Arnold, LE Elliott, M Lindsay, RL Molina, B Cornelius, MD Vitiello, B Hechtman, L Elliott, GR Newcorn, J Epstein, JN Wigal, T Swanson, JM Wells, K TI Gestational and postnatal tobacco smoke exposure as predictor of ADHD, comorbid ODD/CD, and treatment response in the MTA SO CLINICAL NEUROSCIENCE RESEARCH LA English DT Article DE ADHD; tobacco smoke; maternal smoking; ODD; ADHD treatment; pregnancy ID DEFICIT HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; MATERNAL SMOKING; MULTIMODAL-TREATMENT; TREATMENT STRATEGIES; CIGARETTE-SMOKING; PREGNANCY; CHILDREN; BEHAVIOR; RISK AB Objective: To examine relationships among early smoke exposure (ESE), attention-deficit/hyperactivity disorder (ADHD), oppositional-defiant or conduct disorder (ODD/CD), and whether ESE affects symptom severity, comorbidity, and later treatment response. Study design: The Multimodal Treatment Study of Children with ADHD (MTA) had 468 children with ADHD and 279 others from the same classrooms (local normative comparison group, LNCG) with smoke-exposure data. We compared ESE as 'gestational' or 'postnatal' (ambient house smoke only, without gestational) between ADHD and LNCG, and tested its association with ADHD severity, comorbid ODD/CD, methylphenidate response, and differential treatment response to four randomly assigned treatments. Results: About 1/3 more ADHD than LNCG children had ESE (both types), but association with gestational smoke attenuated from P=0.024 to 0.094 when subjects with comorbid ODD/CD were excluded, although total smoke exposure retained significance (P=0.006). In the MTA/ADHD participants, comorbid ODD/CD, and parent/teacher-rated ADHD and ODD symptom severity were not associated with gestational smoking, but severity of ODD was associated with postnatal smoke, and for boys only. ADHD severity at 14 months associated with postnatal smoke. When ODD and CD were `unbundled', CD was associated (P=0.005) with gestational smoke. Neither ESE moderated response to methylphenidate, optimal dose, 2-year growth slowing, or differential ODD symptom response to 14-months of 4 randomly assigned treatments. However, for ADHD symptoms, postnatal smoke moderated (P=0.008) the 14-month advantage of behavioral treatment (Beh) over community-treated comparison (CC): postnatally exposed boys benefited relatively more from Beh (d > 0.5). ADHD symptom improvement also showed significant interaction of sex with gestational (P=0.015) and postnatal (P=0.044) smoke moderator effect for the contrast of MTA medication algorithm vs. Beh and CC: smoke-exposed girls did not show the usual algorithm superiority. Conclusions: These findings suggest possible moderating effects of postnatal ESE on the advantage of intensive behavioral treatment and sex-differential moderating effects of ESE on the advantage of intensive medication over behavioral treatment. This exploratory result requires replication. The findings do not convincingly support the hypothesis that the association of gestational smoking with offspring ADHD is accounted for by comorbid ODD/CD. (c) 2005 Association for Research in Nervous and Mental Disease. Published by Elsevier B.V. All rights reserved. C1 Ohio State Univ, Columbus, OH 43074 USA. St Louis Univ, St Louis, MO 63103 USA. St Josephs Hosp, Childrens Hlth Ctr, Phoenix, AZ 85013 USA. Univ Pittsburgh, Pittsburgh, PA USA. NIMH, Rockville, MD 20857 USA. Montreal Childrens Hosp, Montreal, PQ H3H 1P3, Canada. Univ Calif San Francisco, San Francisco, CA 94143 USA. Mt Sinai Med Ctr, New York, NY 10029 USA. Duke Univ, Med Ctr, Durham, NC USA. Univ Calif Irvine, Irvine, CA USA. RP Arnold, LE (reprint author), Ohio State Univ, 479 S Galena Rd, Columbus, OH 43074 USA. EM arnold.6@osu.edu OI Newcorn, Jeffrey /0000-0001-8993-9337 NR 45 TC 7 Z9 7 U1 4 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1566-2772 J9 CLIN NEUROSCI RES JI Clin. Neurosci. Res. PD DEC PY 2005 VL 5 IS 5-6 BP 295 EP 306 DI 10.1016/j.cnr.2005.09.009 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 998YX UT WOS:000234356900010 ER PT J AU Santosh, PJ Taylor, E Swanson, J Wigal, T Chuang, S Davies, M Greenhill, L Newcorn, J Arnold, LE Jensen, P Vitiello, B Elliott, G Hinshaw, S Hechtman, L Abikoff, H Pelham, W Hoza, B Molina, B Wells, K Epstein, J Posner, M AF Santosh, PJ Taylor, E Swanson, J Wigal, T Chuang, S Davies, M Greenhill, L Newcorn, J Arnold, LE Jensen, P Vitiello, B Elliott, G Hinshaw, S Hechtman, L Abikoff, H Pelham, W Hoza, B Molina, B Wells, K Epstein, J Posner, M TI Refining the diagnoses of inattention and overactivity syndromes: A reanalysis of the Multimodal Treatment study of attention deficit hyperactivity disorder (ADHD) based on ICD-10 criteria for hyperkinetic disorder SO CLINICAL NEUROSCIENCE RESEARCH LA English DT Article DE attention deficit\hyperactivity disorder; hyperkinetic disorder; nosology; stimulant medication; treatment guidelines ID DEFICIT/HYPERACTIVITY DISORDER; DISRUPTIVE BEHAVIOR; CHILDREN; TRIAL AB There are large differences between nations in the diagnosis and management of children with marked impulsiveness and inattention. The differences extend to the names and definitions of disorder and the extent to which medication should be used. This paper uses data from a large randomized clinical trial of pharmacological and psychosocial treatments, conducted in North America, to clarify its implications for other parts of the world. A diagnostic algorithm was applied to 579 children, diagnosed with ADHD-Combined Type in the MTA trial, to generate the ICD-10 diagnosis of `hyperkinetic disorder' (HD); only a quarter met these more stringent criteria. HD was a moderator of treatment response. The superiority of medication to behavioral treatment was greater for children with HD. Children with ADHD but not HD also showed some improvement with medication. The results provide evidence for the validity of HD as a subgroup of those presenting ADHD; and suggest that treatment with stimulants is a high priority in children with HD. Results also suggest that some children with other forms of ADHD will respond better to medication than to psychosocial intervention, and therefore that European guidelines should extend their indications. (c) 2005 Association for Research in Nervous and Mental Disease. Published by Elsevier B.V. All rights reserved. C1 Kings Coll London, Inst Psychiat, Dept Child & Adolescent Psychiat, London SE5 8AF, England. Great Ormond St Hosp Sick Children, London WC1N 3JH, England. Univ Calif Irvine, Dept Pediat, Irvine, CA 92717 USA. Columbia Univ, New York State Psychiat Inst, New York, NY USA. Columbia Univ, Dept Psychiat, New York, NY USA. Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. Ohio State Univ, Dept Psychiat, Sunbury, OH USA. Columbia Univ, NYSPI, Dept Child Psychiat, New York, NY USA. NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. Univ Calif Berkeley, Dept Psychol, Berkeley, CA 94720 USA. McGill Univ, Montreal Childrens Hosp, Dept Psychiat, Montreal, PQ H3H 1P3, Canada. NYU, Sch Med, Ctr Child Study, New York, NY USA. SUNY Buffalo, Pittsburgh Dept Psychol, Buffalo, NY 14260 USA. Purdue Univ, MTA Dept Psychol, W Lafayette, IN 47907 USA. Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA USA. Duke Univ, Med Ctr, Dept Psychiat, Durham, NC 27710 USA. Cornell Univ, Weill Med Coll, Dept Psychiat, Sackler Inst, New York, NY 10021 USA. RP Taylor, E (reprint author), Kings Coll London, Inst Psychiat, Dept Child & Adolescent Psychiat, P046,De Crespigny Pk, London SE5 8AF, England. EM r.kelly@iop.kcl.ac.uk OI Jensen, Peter/0000-0003-2387-0650; Newcorn, Jeffrey /0000-0001-8993-9337 NR 13 TC 35 Z9 38 U1 2 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1566-2772 J9 CLIN NEUROSCI RES JI Clin. Neurosci. Res. PD DEC PY 2005 VL 5 IS 5-6 BP 307 EP 314 DI 10.1016/j.cnr.2005.09.010 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 998YX UT WOS:000234356900011 ER PT J AU Dalakas, MC AF Dalakas, MC TI Intravenous immunoglobulin in with anti-GAD anti body-associated patients neurological diseases and patients with inflammatory myopathies - Effects on clinicopathological features and immunoregulatory genes SO CLINICAL REVIEWS IN ALLERGY & IMMUNOLOGY LA English DT Review DE IVIg; anti-GAD antibodies; inflammatory myopathies; immunoregulatory proteins; genes ID GLUTAMIC-ACID DECARBOXYLASE; STIFF-MAN SYNDROME; AUTOIMMUNE NEUROMUSCULAR DISEASES; PERSON SYNDROME; CONTROLLED TRIAL; IMMUNE GLOBULIN; GAMMA-GLOBULIN; MESSENGER-RNA; DOUBLE-BLIND; MYOSITIS AB Controlled trials with intravenous immunoglobulin (IVIg) were conducted in patients with tiff erson Syndrome (SPS) and dermatomyositis (DM), two humoraly mediated neurological disorders, and in inclusion body myositis (IBM), a T-cell-mediated inflammatory myopathy. The clinical efficacy was compared with alterations on tissue expression of complement, cytokines, chemokines, adhesion molecules, and immunoregulatory genes. The following patients were randomized in three separate trials to receive IVIg or placebo A for 3 mo: (a) 16 patients with anti-GAD antibody-positive SPS; (b) 15 patients with DM resistant to therapies; and (c) 19 patients with IBM. After a washout, they crossed to the alternative therapy for another 3 mo. Efficacy was based on the difference in the respective disease scores from baseline to the second and third month of the infusions. In patients with SPS and DM, the scores changed positively and significantly from months 1 through 3, but returned to baseline when the patients crossed to placebo. In contrast, the scores in the placebo-randomized group remained constant or worsened from months I to 3, but improved significantly after crossing to IVIg. The, muscle scores of patients with IBM did not significantly change between IVIg or placebo. In SPS, the anti-GAD(65) antibody titers declined after IVIg but not after placebo. In DM, there was reduction of complement consumption, interception of membranolytic attack complex formation, downregulation of inflammation, fibrosis, cytokines, chemokines and adhesion molecules, and alterations in thousands of immunoregulatory genes. We conclude that IVIg is a safe and effective therapy for patients with SPS and DM unresponsive to other agents. In tissues, IVIg restores tissue cytoarchitecture by suppressing the inflammatory mediators at the protein, mRNA, and gene level. C1 NINDS, Neuromuscular Dis Sect, NIH, Bethesda, MD 20892 USA. RP Dalakas, MC (reprint author), NINDS, Neuromuscular Dis Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM dalakasm@ninds.nih.gov NR 55 TC 9 Z9 9 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1080-0549 J9 CLIN REV ALLERG IMMU JI Clin. Rev. Allergy Immunol. PD DEC PY 2005 VL 29 IS 3 BP 255 EP 269 DI 10.1385/CRIAI:29:3:255 PG 15 WC Allergy; Immunology SC Allergy; Immunology GA 021EV UT WOS:000235967400012 PM 16391401 ER PT J AU Abati, A Simsir, A AF Abati, A Simsir, A TI Breast fine needle aspiration biopsy: Prevailing recommendations and contemporary practices SO CLINICS IN LABORATORY MEDICINE LA English DT Article ID HORMONE-RECEPTOR STATUS; DUCTAL LAVAGE; MAMMOGRAPHIC ABNORMALITIES; PROBABILISTIC APPROACH; DIAGNOSTIC-ACCURACY; CELL-PROLIFERATION; UNIFORM APPROACH; CANCER; CYTOLOGY; ADEQUACY AB In 1996, a National Cancer Institute conference was held in Bethesda, Maryland to define parameters for the practice of breast fine needle aspiration (BFNA). Representatives of the American Society of Cytopathology, Papanicolaou Society of Cytopathology, American College of Radiology, American College of Obstetricians & Gynecologists, Society of Surgical Oncology, American Academy of Family Physicians, College of American Pathologists, National Consortium of Breast Centers, International Academy of Cytology, American Society of Clinical Pathologists, American Cancer Society, American College of Surgeons, and American Society for Cytotechnology developed and reviewed recommendations. These guidelines were referred to as "The Uniform Approach to Breast Fine Needle Aspiration Biopsy" This article reviews these recommendations and the contemporary evolution of the practice of BFNA since their original publication. C1 NCI, Cytopathol Sect, NIH, Bethesda, MD 20892 USA. NYU, Sch Med, Cytopathol Sect, Bellevue HOsp, New York, NY 10016 USA. RP Abati, A (reprint author), NCI, Cytopathol Sect, NIH, 10 Ctr Dr,Bldg 10,Room 2A19, Bethesda, MD 20892 USA. EM aa52x@nih.gov NR 57 TC 22 Z9 22 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-2712 J9 CLIN LAB MED JI Clin. Lab. Med. PD DEC PY 2005 VL 25 IS 4 BP 631 EP + DI 10.1016/j.cll.2005.08.003 PG 25 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 997IN UT WOS:000234238900002 PM 16308084 ER PT J AU Williams, AM Barefield, SJ Carter, ER Collins, WE Sullivan, JS Tate, MK AF Williams, AM Barefield, SJ Carter, ER Collins, WE Sullivan, JS Tate, MK TI Adaptation of Plasmodium vivax to growth in owl monkeys (Aotus nancymai) SO COMPARATIVE MEDICINE LA English DT Article ID BANDING-PATTERNS; NIGHT MONKEYS; CEBIDAE; TRIVIRGATUS; POPULATION; INFECTIONS; FALCIPARUM; MALARIA; PRIMATES; STRAIN AB The purpose of this study was reactivation and adaptation of a strain of Plasmodium vivax to Aotus nancymai monkeys. A need arose for malarial parasites for use in serologic and molecular studies and for teaching slides. This particular strain of parasite had been characterized previously as producing high-density parasitemia in splenectomized New World monkeys and therefore represented a good candidate for reactivation. P. vivax (Vietnam II), isolated in 1970, was reactivated after adaptation in Aotus lemurinus griseimembra monkeys nearly 33 years earlier and adapted to A. nancymai monkeys. Passage was achieved by intravenous inoculation of parasite blood stages into splenectomized A. nancymai monkeys. Parasitemia was determined by analyzing daily blood smears stained with Giemsa. Maximum parasite counts ranged from 10,630 to 94,000 parasites/mu l; the mean maximum parasite count for the four animals was 39,565 parasites/mu l. Parasite counts of > 10,000/mu l were maintained for 2 to 64 days. After only three passages of the parasite, attempts to reactive were successful. A nancymai proved a suitable animal model for the recovery of this parasite. In conclusion, successful reactivation and adaptation of this parasite offers the capability to perform a series of diagnostic, immunologic, and molecular studies as well as to provide otherwise potentially unavailable teaching materials to healthcare professionals. C1 Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Sci Resources Program, Anim Resources Branch, Atlanta, GA 30333 USA. NIAID, Off Biodef Res Affairs, Div Microbiol & Infect Dis, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Div Parasit Dis, Malaria Branch, Chamblee, GA USA. RP Williams, AM (reprint author), Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Sci Resources Program, Anim Resources Branch, Atlanta, GA 30333 USA. NR 27 TC 3 Z9 3 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1532-0820 J9 COMPARATIVE MED JI Comparative Med. PD DEC PY 2005 VL 55 IS 6 BP 528 EP 532 PG 5 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 002CR UT WOS:000234589500007 PM 16422149 ER PT J AU Yu, BB Tiwari, RC Cronin, KA McDonald, C Feuer, EJ AF Yu, BB Tiwari, RC Cronin, KA McDonald, C Feuer, EJ TI CANSURV: A Windows program for population-based cancer survival analysis SO COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE LA English DT Article DE mixture cure model; population-based survival data; relative survival; SEER program ID CURE MODELS AB Patient survival is one of the most important measures of cancer patient care (the diagnosis and treatment of cancer). The optimal method for monitoring the progress of patient care across the full spectrum of provider settings is through the population-based study of cancer patient survival, which is only possible using data collected by population -based cancer registries. The probability of cure, "statistical cure", is defined for a cohort of cancer patients as the percent of patients whose annual death rate equals the death rate of general cancer-free population. Mixture cure models have been widely used to model failure time data. The models provide simultaneous estimates of the proportion of the patients cured from cancer and the distribution of the failure times for the uncured patients (latency distribution). CANSURV (CAN-cer SURVival) is a Windows software fitting both the standard survival models and the cure models to population -based cancer survival data. CANSURV can analyze both cause-specific survival data and, especially, relative survival data, which is the standard measure of net survival in population-based cancer studies. It can also fit parametric (cure) survival models to the individual data. The program is available at http://srab.cancer.gov/cansurv. The colorectal cancer survival data from the Surveillance, Epidemiology and End Results (SEER) program [Surveillance, Epidemiology and End Results Program, The Portable Survival System/Mainframe Survival System, National Cancer Institute, Bethesda, 1999.] of the National Cancer Institute, NIH is used to demonstrate the use of CANSURV program. Published by Elsevier Ireland Ltd. C1 Informat Management Serv Inc, Silver Spring, MD 20904 USA. NCI, Stat Res & Applicat Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Yu, BB (reprint author), Informat Management Serv Inc, 12501 Prosper Dr Suite 200, Silver Spring, MD 20904 USA. NR 12 TC 15 Z9 17 U1 0 U2 0 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 2005 VL 80 IS 3 BP 195 EP 203 DI 10.1016/j.cmpb.2005.08.002 PG 9 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Engineering, Biomedical; Medical Informatics SC Computer Science; Engineering; Medical Informatics GA 991WK UT WOS:000233845000002 PM 16257080 ER PT J AU Blair, RJR AF Blair, RJR TI Responding to the emotions of others: Dissociating forms of empathy through the study of typical and psychiatric populations SO CONSCIOUSNESS AND COGNITION LA English DT Review DE empathy; psychopath; autism ID BILATERAL AMYGDALA DAMAGE; FUSIFORM FACE AREA; FRONTAL-LOBE DAMAGE; FACIAL EXPRESSIONS; PSYCHOPATHIC TENDENCIES; IMPAIRED RECOGNITION; PREFRONTAL CORTEX; ASPERGER-SYNDROME; PERSONALITY-DISORDER; CRIMINAL PSYCHOPATHS AB Empathy is a lay term that is becoming increasingly viewed as a unitary function within the field of cognitive neuroscience. In this paper, a selective review of the empathy literature is provided. It is argued from this literature that empathy is not a unitary system but rather a loose collection of partially dissociable neurocognitive systems. In particular, three main divisions can be made: cognitive empathy (or Theory of Mind), motor empathy, and emotional empathy. The two main psychiatric disorders associated with empathic dysfunction are considered autism and psychopathy. It is argued that individuals with autism show difficulties with cognitive and motor empathy but less clear difficulties with respect to emotional empathy. In contrast, individuals with psychopathy show clear difficulties with a specific form of emotional empathy but no indications of impairment with cognitive and motor empathy. Published by Elsevier Inc. C1 NIMH, Mood & Anxiety Program, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Blair, RJR (reprint author), NIMH, Mood & Anxiety Program, NIH, Dept Hlth & Human Serv, 15K N Dr,Room 206,MSC 2670, Bethesda, MD 20892 USA. EM blairj@intra.nimh.nih.gov NR 179 TC 352 Z9 358 U1 25 U2 156 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8100 J9 CONSCIOUS COGN JI Conscious. Cogn. PD DEC PY 2005 VL 14 IS 4 BP 698 EP 718 DI 10.1016/j.concog.2005.06.004 PG 21 WC Psychology, Experimental SC Psychology GA 995SL UT WOS:000234124000004 PM 16157488 ER PT J AU Wood, JN Tierney, M Bidwell, LA Grafman, J AF Wood, JN Tierney, M Bidwell, LA Grafman, J TI Neural correlates of script event knowledge: A neuropsychological study following prefrontal injury SO CORTEX LA English DT Article DE prefrontal cortex; scripts; brain lesion; event knowledge ID FRONTAL-LOBE LESIONS; WORD-FREQUENCY; MENTAL REPRESENTATION; SOCIAL COGNITION; LEXICAL ACCESS; FUNCTIONAL MRI; CORTEX; INTELLIGIBILITY; DAMAGE; BRAIN AB Scripts sequentially link information about daily activities and event knowledge. Patients have difficulty sequencing script events following lesions of the prefrontal cortex while showing intact access to selective aspects of script knowledge. It has been suggested that the sequencing impairment is due to a deficit in an inhibitory gating mechanisms that usually enables selection of an item from competing alternatives. If this is the case, then an inhibitory task should reveal script processing impairments on a script categorization task that is not normally associated with poor performance following prefrontal damage. To test this hypothesis, we administered a simple untimed classification task and a modified Go/NoGo task in which subjects classified events from social and non-social activities (e.g., read the menu, order the food) and related semantic items (e.g., menu, order) in terms of whether they belonged to a target activity. Participants were patients with lesions of the prefrontal cortex and matched controls. The results showed that damage to the right orbitofrontal cortex was associated with social item classification errors in the simple untimed classification task. In addition, the damage to the right prefrontal cortex was associated with increased response times to respond correctly to Go trials in the modified Go/NoGo task. The data demonstrate that damage to the right orbitofrontal cortex results in impairment in the accessibility of script and semantic representations of social activities. This impairment is exacerbated by an inefficient inhibitory gating mechanism. C1 NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. Cardiff Univ, Sch Psychol, Cardiff, Wales. RP Grafman, J (reprint author), NINDS, Cognit Neurosci Sect, NIH, Bldg 10,Room 5C205,10 Ctr Dr, Bethesda, MD 20892 USA. EM grafmanj@ninds.nih.gov OI Grafman, Jordan H./0000-0001-8645-4457 NR 48 TC 7 Z9 7 U1 0 U2 2 PU ELSEVIER MASSON PI MILANO PA VIA PALEOCAPA 7, 20121 MILANO, ITALY SN 0010-9452 J9 CORTEX JI Cortex PD DEC PY 2005 VL 41 IS 6 BP 796 EP 804 DI 10.1016/S0010-9452(08)70298-3 PG 9 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 992OT UT WOS:000233894200007 PM 16350660 ER PT J AU Hoehn, GT Suffredini, AF AF Hoehn, GT Suffredini, AF TI Proteomics SO CRITICAL CARE MEDICINE LA English DT Article ID ACUTE RESPIRATORY SYNDROME; PROSTATE-CANCER; SERUM; PROTEIN; IDENTIFICATION; BIOMARKERS; STRATEGIES; DIAGNOSIS; PATTERNS; WORDS C1 NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Hoehn, GT (reprint author), NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA. NR 23 TC 14 Z9 16 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2005 VL 33 IS 12 SU S BP S444 EP S448 DI 10.1097/01.CCM.0000187001.44171.5E PG 5 WC Critical Care Medicine SC General & Internal Medicine GA 000ZK UT WOS:000234501300015 PM 16340417 ER PT J AU Hensley, LE Jones, SM Feldmann, H Jahrling, PB Geisbert, TW AF Hensley, LE Jones, SM Feldmann, H Jahrling, PB Geisbert, TW TI Ebola and Marburg viruses: Pathogenesis and development of countermeasures SO CURRENT MOLECULAR MEDICINE LA English DT Review ID TUMOR-NECROSIS-FACTOR; ENDOTHELIAL-CELL MONOLAYERS; SMALL GLYCOPROTEIN SGP; HEMORRHAGIC-FEVER; NONHUMAN-PRIMATES; DENDRITIC CELLS; TISSUE FACTOR; NITRIC-OXIDE; DC-SIGN; VIRION GLYCOPROTEINS AB Ebola and Marburg viruses, family Filoviridae, are among the best known examples of emerging and re-emerging pathogens. Although outbreaks have been sporadic and geographically restricted to areas of Central Africa, the hemorrhagic fevers caused by these viruses are remarkably severe and are associated with high case fatality rates often exceeding 80 percent. In addition to humans, these viruses have decimated populations of wild apes in Central Africa. Currently, there are no vaccines or effective therapies available for human use. Progress in understanding the geneses of the pathophysiological changes that make filoviral infections of humans so destructive has been slow, primarily because these viruses require special containment for safe research. However, an increasing understanding of the molecular mechanisms of filoviral pathogenesis, facilitated by the development of new tools to elucidate critical regulatory elements in the viral life cycle, is providing new targets that can be exploited for therapeutic interventions. In addition, substantial progress has been made in developing recombinant vaccines against these viruses. C1 USA, Med Res Inst Infect Dis, Div Virol, Ft Detrick, MD 21702 USA. Publ Hlth Agcy Canada, Natl Microbiol Lab, Special Pathogens Program, Winnipeg, MB, Canada. Univ Manitoba, Dept Immunol, Winnipeg, MB R3E 0W3, Canada. Univ Manitoba, Dept Med Microbiol, Winnipeg, MB R3T 2N2, Canada. NIAID, Integrated Res Facil, NIH, Bethesda, MD 20892 USA. RP Geisbert, TW (reprint author), USA, Med Res Inst Infect Dis, Div Virol, 1425 Porter St, Ft Detrick, MD 21702 USA. EM tom.geisbert@amedd.army.mil NR 120 TC 26 Z9 26 U1 5 U2 27 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1566-5240 EI 1875-5666 J9 CURR MOL MED JI Curr. Mol. Med. PD DEC PY 2005 VL 5 IS 8 BP 761 EP 772 DI 10.2174/156652405774962344 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 992XX UT WOS:000233918400004 PM 16375711 ER PT J AU Jahrling, PB Fritz, EA Hensley, LE AF Jahrling, PB Fritz, EA Hensley, LE TI Countermeasures to the bioterrorist threat of smallpox SO CURRENT MOLECULAR MEDICINE LA English DT Review ID NF-KAPPA-B; DISSEMINATED INTRAVASCULAR COAGULATION; DEPENDENT PROTEIN-KINASE; VACCINIA VIRUS; MONKEYPOX VIRUS; VARIOLA VIRUS; LETHAL MONKEYPOX; RABBITPOX VIRUS; GENE-EXPRESSION; IMMUNE EVASION AB Variola, the agent of smallpox, is a bioterrorist threat, as is monkeypox virus, which also occurs naturally in Africa. Development of countermeasures, in the form of improved vaccines, antiviral drugs, and other therapeutic strategies are a high priority. Recent advances in molecular biology and in animal model development have provided fresh insight into the virulence determinants for smallpox and the pathophysiology of disease. The complex replication cycle for orthopoxviruses, and the pivotal role for viral-specific immunomodulatory proteins which contribute to escape from immunologic surveillance, provide many unique targets for therapeutic intervention. The "toxemia" of smallpox has been elucidated in part by variola-infected primate studies which revealed the central role of apoptosis and the evolution of a cytokine storm leading to hemorrhagic diathesis, resembling fulminent "black" smallpox. This suggests a potential role for therapeutic strategies developed for septic shock, in treatment of smallpox. Drugs licensed for other viruses which share molecular targets with orthopoxviruses (e.g. Cidofovir) or cancer drugs (e.g. Gleevec and other tyrosine kinase inhibitors) have immediate application for treatment of smallpox and monkeypox and provide leads for second generation drugs with higher therapeutic indices. Recent advances in identification of virulence determinants and immune evasion genes facilitate the design of alternative vaccines to replace live vaccinia strains that are unsuitable for a large proportion of individuals in a mass immunization campaign. C1 NIAID, NIH, Bethesda, MD 20892 USA. USA, Med Res Inst Infect Dis, Div Virol, Ft Detrick, MD 21702 USA. RP Jahrling, PB (reprint author), NIAID, NIH, 6700-B Rockledge Dr, Bethesda, MD 20892 USA. EM jahrlingp@niaid.nih.gov NR 76 TC 27 Z9 28 U1 1 U2 1 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1566-5240 J9 CURR MOL MED JI Curr. Mol. Med. PD DEC PY 2005 VL 5 IS 8 BP 817 EP 826 DI 10.2174/156652405774962326 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 992XX UT WOS:000233918400008 PM 16375715 ER PT J AU Stewart, DM Tian, L Notarangelo, LD Nelson, DL AF Stewart, DM Tian, L Notarangelo, LD Nelson, DL TI Update on X-linked hypogammaglobulinemia with isolated growth hormone deficiency SO CURRENT OPINION IN ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Review DE ets family transcription factor; growth hormone; hypogammaglobulinemia ID TRANSCRIPTION FACTOR; BTK GENE; AGAMMAGLOBULINEMIA; PATIENT; MEF AB Purpose of review To provide an update on the syndrome X-linked hypogammaglobulinemia with isolated growth hormone deficiency, focusing on the pedigree described originally. Recent findings An additional case of X-linked hypogammaglobulinemia 1 with isolated growth hormone deficiency and an unaffected male have been born to a female carrier in the family, allowing improved disease locus mapping. Unpublished research has identified a mutation in the transcription factor myeloid elf-1-like factor that may be the cause of the disease. Summary X-linked hypogammaglobulinemia with isolated growth hormone deficiency is not caused by Bruton's tyrosine kinase mutations in the family described originally, but may be due to a mutation in myeloid elf-1 -like factor. C1 NCI, Immunophysiol Sect, Metab Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. Univ Brescia, Dept Pediat, I-25121 Brescia, Italy. Univ Brescia, Angelo Nocivelli Inst Mol Med, I-25121 Brescia, Italy. RP Nelson, DL (reprint author), NCI, Immunophysiol Sect, Metab Branch, Ctr Canc Res,NIH, Rm 4N115,10 Ctr Dr, Bethesda, MD 20892 USA. EM dln@helix.nih.gov RI Notarangelo, Luigi/F-9718-2016 OI Notarangelo, Luigi/0000-0002-8335-0262 NR 14 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1528-4050 J9 CURR OPIN ALLERGY CL JI Curr. Opin. Allergy Clin. Immunol. PD DEC PY 2005 VL 5 IS 6 BP 510 EP 512 DI 10.1097/01.all.0000191235.35879.29 PG 3 WC Allergy; Immunology SC Allergy; Immunology GA 988GY UT WOS:000233582200005 PM 16264330 ER PT J AU Uzel, G AF Uzel, G TI The range of defects associated with nuclear factor kappa B essential modulator SO CURRENT OPINION IN ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Review DE ectodermal dysplasia; immunodeficiency; NEMO; NF kappa B; nonpathogenic mycobacterial infection; nuclear factor; nuclear factor kappa B essential modulator ID ANHIDROTIC ECTODERMAL DYSPLASIA; HYPER-IGM SYNDROME; X-LINKED DISORDER; INCONTINENTIA-PIGMENTI; IKK-GAMMA; IMMUNE-DEFICIENCY; NEMO/IKK-GAMMA; HUMAN-DISEASE; IMMUNODEFICIENCY; MUTATIONS AB Purpose of review Impaired ability to signal and activate specific gene transcription through nuclear factor kappa B (NF kappa B) has been directly linked to immunodeficiency. Hypomorphic mutations in the gene encoding NF kappa B essential modulator(NEMO), located on the X chromosome, impair NF kappa B function and lead to ectodermal dysplasia with immunodeficiency (END) with increased susceptibility to pyogenic bacteria, viruses and nonpathogenic mycobacterial infections. This is due to impaired, but not abolished, response to a variety of stimuli including Toll-like receptor agonists. Alternatively, loss-of-function (amorphic) mutations,in the same gene lead to incontinentia pigmenti. The purpose of this review is to explore the range of immunologic defects associated with mutations in NEMO, a key regulatory molecule in the NF kappa B pathway. Recent findings In addition to the discovery of X-linked recessive hypomorphic mutations in NEMO as the cause of anhidrotic END, autosomal-dominant hypermorphic mutations in inhibitor of NF kappa B (I kappa B) alpha have been described recently. In addition, a better understanding of genotype-phenotype correlation in END patients is evolving. Summary ED-ID is a combined, variable but profound immunodeficiency characterized by susceptibility to pyogenic bacteria and mycobacterial infection. Understanding the features of particular NEMO mutations will provide insight into the role of this gene and will help define the crucial role of the function and regulation of NF kappa B in the immune, response. C1 NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Uzel, G (reprint author), NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike,Bldg 10 CRC B3-4141 MSC 1684, Bethesda, MD 20892 USA. EM guzel@mail.nih.gov FU Intramural NIH HHS NR 33 TC 22 Z9 26 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1528-4050 J9 CURR OPIN ALLERGY CL JI Curr. Opin. Allergy Clin. Immunol. PD DEC PY 2005 VL 5 IS 6 BP 513 EP 518 DI 10.1097/01.all.0000191241.66373.74 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA 988GY UT WOS:000233582200006 PM 16264331 ER PT J AU Brody, T Odenwald, WF AF Brody, T Odenwald, WF TI Regulation of temporal identities during Drosophila neuroblast lineage development SO CURRENT OPINION IN CELL BIOLOGY LA English DT Review ID DEVELOPING NERVOUS-SYSTEM; GENE-EXPRESSION; TRANSCRIPTION FACTORS; PIONEER NEURONS; MUSHROOM BODIES; SPECIFICATION; FATE; POU; HUNCHBACK; COMPLEX AB One of the major goals of neurobiology is to describe, in molecular terms, how a neural progenitor cell can generate an ordered series of uniquely fated neurons and glia. It has become clear that many, or all, neural-subtype identities can be linked to sequentially changing regulatory programs within neural precursors. Recent studies shed light on regulatory inputs and timing mechanisms that generate temporally defined cell identities, and new contributions are beginning to establish a link between the temporal network and cell function. C1 NINDS, Neural Cell Fate Determinants Sect, NIH, Bethesda, MD 20824 USA. RP Brody, T (reprint author), NINDS, Neural Cell Fate Determinants Sect, NIH, Bethesda, MD 20824 USA. EM ward@codon.nih.gov; brodyt@ninds.nih.gov NR 38 TC 15 Z9 15 U1 0 U2 1 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 2005 VL 17 IS 6 BP 672 EP 675 DI 10.1016/j.ceb.2005.09.013 PG 4 WC Cell Biology SC Cell Biology GA 989IO UT WOS:000233666300017 PM 16243502 ER PT J AU O'Brien, SJ Fraser, CM AF O'Brien, SJ Fraser, CM TI The power of comparative genomics - Editorial overview SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Editorial Material C1 Natl Canc Inst, Lab Genom Divers, Frederick, MD 21702 USA. Inst Genom Res, Rockville, MD 20850 USA. RP O'Brien, SJ (reprint author), Natl Canc Inst, Lab Genom Divers, Frederick, MD 21702 USA. EM obrien@ncifcrf.gov; cmfraser@tigr.org NR 1 TC 4 Z9 4 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD DEC PY 2005 VL 15 IS 6 BP 569 EP 571 DI 10.1016/j.gde.2005.10.001 PG 3 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 989PM UT WOS:000233686200001 PM 16246544 ER PT J AU Roca, AL O'Brien, SJ AF Roca, AL O'Brien, SJ TI Genomic inferences from Afrotheria and the evolution of elephants SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Review ID CONTROL REGION SEQUENCES; AFRICAN ELEPHANT; MITOCHONDRIAL-DNA; ASIAN ELEPHANTS; POPULATION-STRUCTURE; NATIONAL-PARK; IVORY TRADE; NUCLEAR; PHYLOGEOGRAPHY; BEHAVIOR AB Recent genetic studies have established that African forest and savanna elephants are distinct species with dissociated cytonuclear genomic patterns, and have identified Asian elephants from Borneo and Sumatra as conservation priorities. Representative of Afrotheria, a superordinal clade encompassing six eutherian orders, the African savanna elephant was among the first mammals chosen for whole-genome sequencing to provide a comparative understanding of the human genome. Elephants have large and complex brains and display advanced levels of social structure, communication, learning and intelligence. The elephant genome sequence might prove useful for comparative genomic studies of these advanced traits, which have appeared independently in only three mammalian orders: primates, cetaceans and proboscideans. C1 SAIC Frederick, Lab Genom Divers, Basic Res Program, Frederick, MD 21702 USA. NCI, Frederick, MD 21702 USA. RP Roca, AL (reprint author), SAIC Frederick, Lab Genom Divers, Basic Res Program, Frederick, MD 21702 USA. EM roca@ncifcrf.gov FU NCI NIH HHS [N01 CO 12400] NR 51 TC 22 Z9 22 U1 2 U2 15 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD DEC PY 2005 VL 15 IS 6 BP 652 EP 659 DI 10.1016/j.gde.2005.09.014 PG 8 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 989PM UT WOS:000233686200014 PM 16226885 ER PT J AU Modi, WS Crews, D AF Modi, WS Crews, D TI Sex chromosomes and sex determination in reptiles - Commentary SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Editorial Material ID X-CHROMOSOME; DOSAGE-COMPENSATION; INACTIVATION; MECHANISMS; GENE; MORPHOLOGY; EVOLUTION; PROTEINS; BEHAVIOR; COMPLEX AB Reptiles occupy a crucial position with respect to vertebrate phylogeny, having roamed the earth for more than 300 million years and given rise to both birds and mammals. To date, this group has been largely ignored by contemporary genomics technologies, although the green anole lizard was recently recommended for whole genome sequencing. Future experiments using flow-sorted chromosome libraries and high-throughout genomic sequencing will help to discover important findings regarding sex chromosome evolution, early events in sex determination, and dosage compensation. This information should contribute extensively toward a general understanding of the genetic control of development in amniotes. C1 Natl Canc Inst, SAIC Frederick, Core Genotyping Facil, Gaithersburg, MD 20877 USA. Univ Texas, Sect Integrat Biol, Austin, TX 78712 USA. RP Modi, WS (reprint author), Natl Canc Inst, SAIC Frederick, Core Genotyping Facil, 8717 Grovement Circle, Gaithersburg, MD 20877 USA. EM modiw@mail.nih.gov FU NIMH NIH HHS [MH 41770] NR 28 TC 27 Z9 28 U1 0 U2 5 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD DEC PY 2005 VL 15 IS 6 BP 660 EP 665 DI 10.1016/j.gde.2005.09.009 PG 6 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 989PM UT WOS:000233686200015 PM 16214335 ER PT J AU Hummel, FC Cohen, LG AF Hummel, FC Cohen, LG TI Drivers of brain plasticity SO CURRENT OPINION IN NEUROLOGY LA English DT Review DE motor; plasticity; stimulation; stroke; tDCS; TMS ID TRANSCRANIAL MAGNETIC STIMULATION; HUMAN MOTOR CORTEX; USE-DEPENDENT PLASTICITY; PERIPHERAL-NERVE STIMULATION; LONG-TERM DEPRESSION; CHRONIC STROKE; LOW-FREQUENCY; CORTICAL EXCITABILITY; SENSORY CORTEX; D-AMPHETAMINE AB Purpose of review. Neural plasticity represnts a crucial mechanism of the human brain to adapt to environmental changes in the developing and adult human central nervous system contributes to learning and functional recovery from neurological diseases such as stroke. Novel interventional approaches have been proposed and are under investigation to modulate neural plasticity, enhance it when it plays an adaptive role and downregulate it when it is considered maladaptive. Recent findings. One of the purposes of research in neurorehabiltation has been to develop interventional approaches to enhance the beneficial effects of training. Procedures like cortical stimulation, administration of central nervous system active drugs and modulation of afferent input have been evaluated as drivers of neural plasticity in healthy subjects and in small groups of patients with stroke. So far, these studies have shown promising results and translation into the clinic is under investigation. Summary. Cortical stimulation and purposeful changes in afferent input that modulate neural plasticity impact on behavioral markers of performance, learning and functional recovery and represent promising tools in neurorehabilitation. C1 NINDS, Human Cortical Physiol Sect, NIH, Bethesda, MD 20817 USA. Univ Tubingen, Dept Neurol, Cort Physiol Res Grp, D-72074 Tubingen, Germany. Univ Tubingen, Hertie Inst Clin Brain Res, D-72074 Tubingen, Germany. RP Cohen, LG (reprint author), NINDS, Human Cortical Physiol Sect, NIH, Bethesda, MD 20817 USA. EM cohenl@ninds.nih.gov RI Westwood, Sam/P-7000-2015 NR 117 TC 86 Z9 94 U1 1 U2 19 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1350-7540 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD DEC PY 2005 VL 18 IS 6 BP 667 EP 674 DI 10.1097/01.wco.0000189876.37475.42 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 989MT UT WOS:000233678800008 PM 16280678 ER PT J AU Cookson, MR Xiromerisiou, G Singleton, A AF Cookson, MR Xiromerisiou, G Singleton, A TI How genetics research in Parkinson's disease is enhancing understanding of the common idiopathic forms of the disease SO CURRENT OPINION IN NEUROLOGY LA English DT Article DE DJ-1; LRRK2/dardarin; parkin; PINK1; synuclein ID EARLY-ONSET PARKINSONISM; AUTOSOMAL-DOMINANT PARKINSONISM; LRRK2 G2019S MUTATION; ALPHA-SYNUCLEIN; DOPAMINERGIC DYSFUNCTION; RECESSIVE PARKINSONISM; LOCUS TRIPLICATION; PINK1 MUTATIONS; LEWY BODIES; POLYMORPHISMS AB Purpose of review Rapid progress in genetics has meant that there are now five genes identified for 'Parkinson's disease'. The detailed phenotypes vary, but generally the dominant genes cause a Lewy body disease spectrum whereas recessive genes cause a milder parkinsonism with variable inclusion body pathology. The subject of this review is to highlight these discoveries and to discuss their relationships to idiopathic Parkinson's disease. Recent findings In January 2004, mutations in PINK1, coding for a mitochondrial kinase, were found to be causal for recessive parkinsonism. Subsequently, several studies have found additional mutations associated with early onset parkinsonism. Some cases have been described with a phenotype much closer to idiopathic Parkinson's disease, but it does not appear that PINK1 is a major risk factor for the sporadic disease. Later in the same year, the LRRK2 gene was shown to cause a dominant disease with a broader phenotype. The protein product was named dardarin and contains GTPase and kinase domains. Lewy bodies have been reported in LRRK2 cases, potentially linking this gene with sporadic Parkinson's disease. One mutation, G2019S, is found in a significant percentage of cases, including sporadic Parkinson's disease. Summary Mutations in these two genes, along with previously described Mendelian variants, are beginning to yield important information about loss of specific neuronal groups or to protein inclusion pathology. How this relates to sporadic Parkinson's disease, however, is not yet fully defined. There are clear phenotypic overlaps with genetic and sporadic Parkinson's disease, especially for the dominant genes, suggesting that common facets of pathogenesis may exist. C1 NIA, Neurogenet Lab, NIH, Bethesda, MD 20982 USA. Univ Thessly, Sch Med, Dept Neurol, Neurogenet Unit, Larisa, Greece. RP Cookson, MR (reprint author), NIA, Neurogenet Lab, NIH, Bldg 35,Room 1A116,MSC 3707,35 Convent Dr, Bethesda, MD 20982 USA. EM cookson@mail.nih.gov RI Singleton, Andrew/C-3010-2009 NR 51 TC 46 Z9 48 U1 4 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1350-7540 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD DEC PY 2005 VL 18 IS 6 BP 706 EP 711 DI 10.1097/01.wco.0000186841.43505.e6 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 989MT UT WOS:000233678800013 PM 16280683 ER PT J AU Borie, DC Starr, R Hendry, S Changelian, PS O'Shea, J AF Borie, DC Starr, R Hendry, S Changelian, PS O'Shea, J TI Janus kinase 3 inhibition for immunosuppression: getting closer to the starting line SO CURRENT OPINION IN ORGAN TRANSPLANTATION LA English DT Review DE CP-690; 550; immunosuppression; Janus kinase 3; Janus kinase/signal transducer and activator of transcription pathway; primates; transplantation ID SEVERE COMBINED IMMUNODEFICIENCY; VERSUS-HOST DISEASE; CYTOKINE SIGNAL-TRANSDUCTION; STAGE RENAL-DISEASE; JAK3 INHIBITOR; T-CELLS; HOMEOSTATIC PROLIFERATION; ALLOGRAFT SURVIVAL; NONHUMAN-PRIMATES; NATURAL-KILLER AB Purpose of review Most current immunosuppressive drugs have side effects. It is recognized that the mechanisms for such side effects are similar to that responsible for efficacy and reflects undesirable effects of the drug outside of the immune system. In this review, we will discuss recent developments that led to the introduction of a compound selectively targeting immune cells and that appears devoid of classical side effects observed with current immunosuppressive drugs. Recent findings A large number of cytokines exert their effect by binding to receptors that activate the Janus kinase/signal transducer and activator of transcription pathway, so targeting intracellular signaling pathways is a logical strategy. A selective inhibitor of Janus kinase 3 has been generated and is effective for the prevention of transplant rejection in nonhuman primates and other models. Consistent with predictions from murine studies, drug treatment results in significant reductions in numbers of natural killercells and modest reductions in effector memory CD8(+) cells. The side-effect profile appears limited to anemia observed only at high exposure. None of the dose-limiting side effects observed with other immunosuppressants that have been linked with early graft rejection and patient demise have been observed with the inhibition of Janus kinase 3. Summary A selective inhibitor of Janus kinase 3 has now been generated. It most likely represents a new class of effective immunosuppressants. Because of its particular mechanism of action - targeting a wide array of immune cells (T, B, and natural killer) - the compound may offer solutions to acute problems as well as chronic allograft rejection. C1 Stanford Univ, Sch Med, Transplantat Immunol Lab, Dept Cardiothorac Surg,Falk Cardiovasc Res Ctr, Stanford, CA 94305 USA. St Vincents Inst, Signal Transduct Lab, Fitzroy, Vic 3065, Australia. Pfizer, Ann Arbor Labs, Inflammat Mol Sci, Ann Arbor, MI USA. NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. RP Borie, DC (reprint author), Stanford Univ, Sch Med, Transplantat Immunol Lab, Dept Cardiothorac Surg,Falk Cardiovasc Res Ctr, 300 Pasteur Dr, Stanford, CA 94305 USA. EM dborie@stanford.edu NR 60 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1087-2418 J9 CURR OPIN ORGAN TRAN JI Curr. Opin. Organ Transpl. PD DEC PY 2005 VL 10 IS 4 BP 273 EP 278 DI 10.1097/01.mot.0000184017.93455.7e PG 6 WC Transplantation SC Transplantation GA 989NQ UT WOS:000233681200005 ER PT J AU Ohyama, K Ellis, P Kimura, S Placzek, M AF Ohyama, K Ellis, P Kimura, S Placzek, M TI Directed differentiation of neural cells to hypothalamic dopaminergic neurons SO DEVELOPMENT LA English DT Article DE Shh; Bmp7; chick; dopamine; hypothalamus ID EMBRYONIC STEM-CELLS; CENTRAL-NERVOUS-SYSTEM; SONIC-HEDGEHOG; FLOOR PLATE; TYROSINE-HYDROXYLASE; FOREBRAIN DEVELOPMENT; TRANSCRIPTION FACTORS; PRECHORDAL MESODERM; INDUCTIVE SIGNALS; MOTOR-NEURONS AB Hypothalamic neurons play a key role in homeostasis, yet little is known about their differentiation. Here, we demonstrate that Shh and Bmp7 from the adjacent prechordal mesoderm govern hypothalamic neural fate, their sequential action controlling hypothalamic dopaminergic neuron generation in a Six3-dependent manner. Our data suggest a temporal distinction in the requirement for the two signals. Shh acts early to specify dopaminergic neurotransmitter phenotype. Subsequently, Bmp7 acts on cells that are ventralised by Shh, establishing aspects of hypothalamic regional identity in late-differentiating/postmitotic cells. The concerted actions of Shh and Bmp7 can direct mouse embryonic stem cell-derived neural progenitor cells to a hypothalamic dopaminergic fate ex vivo. C1 Univ Sheffield, Dept Biomed Sci, Western Bank, Sheffield S10 STN, S Yorkshire, England. NCI, NIH, Bethesda, MD 20892 USA. RP Ohyama, K (reprint author), Univ Sheffield, Dept Biomed Sci, Western Bank, Firth Court, Sheffield S10 STN, S Yorkshire, England. EM k.ohyama@sheffield.ac.uk; m.placzek@sheffield.ac.uk RI Placzek, Marysia/E-6172-2010 FU Medical Research Council [G0300241] NR 47 TC 55 Z9 58 U1 1 U2 3 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD DEC PY 2005 VL 132 IS 23 BP 5185 EP 5197 DI 10.1242/dev.02094 PG 13 WC Developmental Biology SC Developmental Biology GA 999RU UT WOS:000234409000005 PM 16284116 ER PT J AU Nakaya, MA Biris, K Tsukiyama, T Jaime, S Rawls, JA Yamaguchi, TP AF Nakaya, MA Biris, K Tsukiyama, T Jaime, S Rawls, JA Yamaguchi, TP TI Wnt3a links left-right determination with segmentation and anteroposterior axis elongation SO DEVELOPMENT LA English DT Article DE mouse; Wnt3a; left-right determination ID LEFT-RIGHT ASYMMETRY; NODAL EXPRESSION; SIGNALING PATHWAY; SITUS-INVERSUS; MOUSE EMBRYO; LUNATIC FRINGE; GENE; MICE; INDUCTION; REGULATOR AB The alignment of the left-right (LR) body axis relative to the anteroposterior (AP) and dorsoventral (DV) axes is central to the organization of the vertebrate body plan and is controlled by the node/organizer. Somitogenesis plays a key role in embryo morphogenesis as a principal component of AP elongation. How morphogenesis is coupled to axis specification is not well understood. We demonstrate that Wnt3a is required for LR asymmetry. Wnt3a activates the Delta/Notch pathway to regulate perinodal expression of the left determinant Nodal, while simultaneously controlling the segmentation clock and the molecular oscillations of the Wnt/beta-catenin and Notch pathways. We provide evidence that Wnt3a, expressed in the primitive streak and dorsal posterior node, acts as a long-range signaling molecule, directly regulating target gene expression throughout the node and presomitic mesoderm. Wnt3a may also modulate the symmetry-breaking activity of mechanosensory cilia in the node. Thus, Wnt3a links the segmentation clock and AP axis elongation with key left-determining events, suggesting that Wnt3a is an integral component of the trunk organizer. C1 NCI, Canc & Dev Biol Lab, Canc Res Ctr, NIH, Ft Detrick, MD 21702 USA. Arizona State Univ, Sch Life Sci, Tempe, AZ 85287 USA. RP Yamaguchi, TP (reprint author), NCI, Canc & Dev Biol Lab, Canc Res Ctr, NIH, Ft Detrick, MD 21702 USA. EM tyamaguchi@ncifcrf.gov RI Tsukiyama, Tadasuke/D-7589-2012 FU Intramural NIH HHS; NCI NIH HHS [Z01 BC010455-04] NR 62 TC 112 Z9 116 U1 0 U2 7 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 PY 2005 VL 132 IS 24 BP 5425 EP 5436 DI 10.1242/dev.02149 PG 12 WC Developmental Biology SC Developmental Biology GA 005LM UT WOS:000234823900008 PM 16291790 ER PT J AU Ishizuya-Oka, A Shi, YB AF Ishizuya-Oka, A Shi, YB TI Molecular mechanisms for thyroid hormone-induced remodeling in the amphibian digestive tract: A model for studying organ regeneration SO DEVELOPMENT GROWTH & DIFFERENTIATION LA English DT Review DE amphibian metamorphosis; gastrointestinal remodeling; stem cell; thyroid hormone response gene; tissue interaction ID MATRIX-METALLOPROTEINASE STROMELYSIN-3; ADULT EPITHELIAL DEVELOPMENT; INTESTINAL STEM-CELL; XENOPUS-LAEVIS; CONNECTIVE-TISSUE; SONIC HEDGEHOG; FROG METAMORPHOSIS; MESENCHYMAL INTERACTIONS; LAMININ RECEPTOR; PROGENITOR CELLS AB During amphibian metamorphosis the digestive tract is extensively remodeled under the control of epithelial-connective tissue interactions. At the cellular level, larval epithelial cells undergo apoptosis, while a small number of stem cells appear, actively proliferate, and then differentiate to form adult epithelium that is analogous to its mammalian counterpart. Therefore the amphibian digestive tract is a unique model system for the study of postembryonic organ regeneration. As amphibian intestinal remodeling can be triggered by thyroid hormone (TH), the molecular mechanisms involved can be studied from the perspective of examining the expression cascade of TH response genes. A number of these genes have been isolated from the intestine of Xenopus laevis. Recent progress in the functional analysis of this cascade has shed light on key molecules in intestinal remodeling such as matrix metalloproteinase-11, sonic hedgehog, and bone morphogenetic protein-4. These genes are also thought to play key roles in organogenesis and/or homeostasis in both chick and mammalian digestive tract, suggesting the existence of conserved mechanisms underlying such events in terrestrial vertebrates. In this article, we review our recent findings in this field, focusing on the development of adult epithelium in the X. laevis intestine. C1 Nippon Med Coll, Dept Biol, Nakahara Ku, Kawasaki, Kanagawa 2110063, Japan. NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Ishizuya-Oka, A (reprint author), Nippon Med Coll, Dept Biol, Nakahara Ku, 2-297-2 Kosugi Cho, Kawasaki, Kanagawa 2110063, Japan. EM a-oka@nms.ac.jp NR 59 TC 20 Z9 21 U1 0 U2 11 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0012-1592 J9 DEV GROWTH DIFFER JI Dev. Growth Diff. PD DEC PY 2005 VL 47 IS 9 BP 601 EP 607 PG 7 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 987PJ UT WOS:000233529500003 PM 16316405 ER PT J AU Kuehn, MR AF Kuehn, MR TI Mouse Ubc9 knockout: Many path(way)s to ruin SO DEVELOPMENTAL CELL LA English DT Editorial Material ID UBIQUITIN; SUMO AB In this issue of Developmental Cell, Nacerddine et al. (2005) describe a targeted germ line mutation of the mouse SUMO-specific E2 Ubc9, which abrogates the SUMO conjugation pathway, broadly crippling nuclear function in proliferating cells of the early embryo. This study reveals the wide-ranging roles for this protein modifier in nuclear organization, chromosome segregation, and Ran-driven nucleo-cytoplasmic transport. C1 NCI, Lab Prot Dynam & Signaling, Frederick, MD 21702 USA. RP Kuehn, MR (reprint author), NCI, Lab Prot Dynam & Signaling, Frederick, MD 21702 USA. RI Kuehn, Michael/A-4573-2014 OI Kuehn, Michael/0000-0002-7703-9160 NR 7 TC 3 Z9 3 U1 0 U2 0 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 2005 VL 9 IS 6 BP 727 EP 728 DI 10.1016/j.devcel.2005.11.008 PG 2 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 993MV UT WOS:000233959100004 PM 16326385 ER PT J AU Etard, C Behra, M Ertzer, R Fischer, N Jesuthasan, S Blader, P Geisler, R Strahle, U AF Etard, C Behra, M Ertzer, R Fischer, N Jesuthasan, S Blader, P Geisler, R Strahle, U TI Mutation in the delta-subunit of the nAChR suppresses the muscle defects caused by lack of dystrophin SO DEVELOPMENTAL DYNAMICS LA English DT Article DE acetylcholine receptor; delta subunit; myopathy; dystrophin; dystroglycan ID NICOTINIC ACETYLCHOLINE-RECEPTOR; MUSCULAR-DYSTROPHY; ZEBRAFISH EMBRYO; NEUROMUSCULAR-JUNCTION; RAPSYN CLUSTERS; EPSILON-SUBUNIT; GAMMA-SUBUNIT; MOUSE MUSCLE; DYSTROGLYCAN; EXPRESSION AB Normal motility of the zebrafish embryo requires a large number of gene loci, many of which have human orthologues implicated in myasthenias and other myopathies. We have identified a mutation in the zebrafish that abolishes body motility. Embryos have narrower myofibrils and lack clusters of nicotinic acetylcholine receptors (nAChRs) on the surface of the somitic muscle. We mapped the mutation to the 6-subunit of the nAChR, showing this mutant to be a new allele of the previously named sofa potato (sop). The mutant allele carries a missense mutation in the extracellular domain altering the cysteine at position 150 to an arginine. The 6-subunit is expressed in all striated muscles in embryonic and early larval stages together with the alpha 1, beta 1, epsilon, and gamma-subunits of nAChR. In contrast to mammals that show switching from the gamma embryonic to the adult E-subunit, the two subunits are coexpressed in zebrafish embryos. We, furthermore, demonstrated that the sop/delta-nAChR mutation is a suppressor of the myopathy caused by lack of Dystrophin. The myofiber detachment phenotype of Dystroglycan-deficient embryos was not suppressed, suggesting that Dystrophin and Dystroglycan play distinct roles in muscle formation and maintenance of muscle integrity. C1 Forschungszentrum Karlsruhe, Inst Toxicol & Genet, D-76021 Karlsruhe, Germany. CU Strasbourg, Inst Genet & Biol Mol Cellulaire, Illkirch Graffenstaden, France. NHGRI, NIH, Bethesda, MD 20892 USA. Natl Univ Singapore, Temasek Life Sci Lab, Dev Neurobiol Lab, Singapore 117548, Singapore. Univ Toulouse 3, Ctr Dev Biol, F-31062 Toulouse, France. Max Planck Inst Entwicklungsbiol, D-72076 Tubingen, Germany. RP Strahle, U (reprint author), Forschungszentrum Karlsruhe, Inst Toxicol & Genet, D-76021 Karlsruhe, Germany. EM uwe.straehle@itg.fzk.de RI Straehle, Uwe/K-7054-2013; Jesuthasan, Suresh/B-7870-2016 NR 50 TC 21 Z9 21 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD DEC PY 2005 VL 234 IS 4 BP 1016 EP 1025 DI 10.1002/dvdy.20592 PG 10 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 990AL UT WOS:000233715500020 PM 16245342 ER PT J AU Obrosova, IG Drel, VR Pacher, P Ilnytska, O Wang, ZQ Stevens, MJ Yorek, MA AF Obrosova, IG Drel, VR Pacher, P Ilnytska, O Wang, ZQ Stevens, MJ Yorek, MA TI Oxidative-nitrosative stress and poly(ADP-ribose) polymerase (PARP) activation in experimental diabetic neuropathy - The relation is revisited SO DIABETES LA English DT Article ID ENDONEURIAL BLOOD-FLOW; ALPHA-LIPOIC ACID; ENDOTHELIAL DYSFUNCTION; NERVE-CONDUCTION; PERIPHERAL NEUROPATHY; TRANSCRIPTION FACTORS; SENSORY NEURONS; RATS; INHIBITION; MICE AB Poly(ADP-ribose) polymerase (PARP) activation, an important factor in the pathogenesis of diabetes complications, is considered a downstream effector of oxidative-nitrosative stress. However, some recent findings suggest that it is not necessarily the case and that PARP activation may precede and contribute to free radical and oxidant-induced injury. This study evaluated the effect of PARP inhibition on oxidative-nitrosative stress in diabetic peripheral nerve, vasa nervorum, aorta, and high glucose-exposed human Schwann cells. In vivo experiments were performed in control rats and streptozocin (STZ)-induced diabetic rats treated with and without the PARP inhibitor 3-aminobenzamide (ABA) (30 mg center dot kg(-1) center dot day(-1) i.p. for 2 weeks after 2 weeks of untreated diabetes). Human Schwann cells (HSC) (passages 7-10; ScienCell Research Labs) were cultured in 5.5 or 30 mmol/l glucose with and,without 5 mmol/l ABA. Diabetes-induced increase in peripheral nerve nitrotyrosine immunoreactivity, epineurial vessel superoxide and nitrotyrosine immunoreactivities, and aortic superoxide production was reduced by ABA. PARP-1 (Western blot analysis) was abundantly expressed in HSC, and its expression was not affected by high glucose or ABA treatment. High-glucose-induced superoxide production and overexpression of nitrosylated and poly(ADP-ribosyl)ated protein, chemically reduced amino acid-(4)hydroxynonenal adducts, and inducible nitric oxide synthase were decreased by ABA. We concluded that PARP activation contributes to superoxide anion radical and peroxynitrite formation in peripheral nerve, vasa nervorum, and aorta of STZ-induced diabetic rats and high-glucose-exposed HSC. The relations between oxidative-nitrosative stress and PARP activation in diabetes are bi-rather than unidirectional, and PARP activation cannot only result from but also lead to free radical and oxidant generation. C1 Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 90034 USA. Univ Iowa, Vet Affairs Med Ctr, Iowa City, IA USA. Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA. RP Obrosova, IG (reprint author), Louisiana State Univ, Pennington Biomed Res Ctr, 6400 Perkins Rd, Baton Rouge, LA 70808 USA. EM obrosoig@pbrc.edu RI Pacher, Pal/B-6378-2008; Drel, Viktor/G-8883-2016 OI Pacher, Pal/0000-0001-7036-8108; Drel, Viktor/0000-0003-4542-0132 FU Intramural NIH HHS [Z01 AA000375-02]; NIDDK NIH HHS [DK 058005-04, DK59809-01, K01 DK059809, R01 DK058005] NR 47 TC 127 Z9 134 U1 3 U2 5 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 2005 VL 54 IS 12 BP 3435 EP 3441 DI 10.2337/diabetes.54.12.3435 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 988HB UT WOS:000233582500012 PM 16306359 ER PT J AU Nunemaker, CS Zhang, M Wasserman, DH McGuinness, OP Powers, AC Bertram, R Sherman, A Satin, LS AF Nunemaker, CS Zhang, M Wasserman, DH McGuinness, OP Powers, AC Bertram, R Sherman, A Satin, LS TI Individual mice can be distinguished by the period of their islet calcium oscillations - Is there an intrinsic islet period that is imprinted in vivo? SO DIABETES LA English DT Article ID PANCREATIC BETA-CELLS; PULSATILE INSULIN-SECRETION; CYTOPLASMIC CA2+ OSCILLATIONS; DEPENDENT DIABETES-MELLITUS; HEPATIC GLUCOSE-PRODUCTION; ELECTRICAL-ACTIVITY; METABOLIC OSCILLATIONS; PLASMA-INSULIN; B-CELLS; LANGERHANS AB Pulsatile insulin secretion in vivo is believed to be derived, in part, from the intrinsic glucose-dependent intracellular calcium concentration ([Ca2+](i)) pulsatility of individual islets. In isolation, islets display fast, slow, or mixtures of fast and slow [Ca2+](i) oscillations. We show that the period of islet [Ca2+](i) oscillations is unique to each mouse, with the islets from an individual mouse demonstrating similar rhythms to one another. Based on their rhythmic period, mice were broadly classified as being either fast (0.65 +/- 0.1 min; n = 6 mice) or slow (4.7 +/- 0.2 min; n = 15 mice). To ensure this phenomenon was not an artifact of islet-to-islet communication, we confirmed that islets cultured in isolation (period: 2.9 +/- 0.1 min) were not statistically different from islets cultured together from the same mouse (3.1 +/- 0.1 min, P > 0.52, n = 5 mice). We also compared pulsatile insulin patterns measured in vivo with islet [Ca2+](i) patterns measured in vitro from six mice. Mice with faster insulin pulse periods corresponded to faster islet [Ca2+](i) patterns, whereas slower insulin patterns corresponded to slower [Ca2+](i) patterns, suggesting that the insulin rhythm of each mouse is preserved to some degree by its islets in vitro. We propose that individual mice have characteristic oscillatory [Ca2+](i) patterns, which are imprinted in vivo through an unknown mechanism. C1 Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. Vanderbilt Univ, Mouse Metab Phenotyping Ctr, Nashville, TN USA. Vanderbilt Univ, Dept Med, Div Diabet & Endocrinol, Nashville, TN USA. Florida State Univ, Dept Math, Tallahassee, FL 32306 USA. Florida State Univ, Inst Mol Biophys, Tallahassee, FL 32306 USA. NIH, Lab Biol Modeling, Bethesda, MD 20892 USA. RP Satin, LS (reprint author), Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, POB 980524, Richmond, VA 23298 USA. EM lsatin@hsc.vcu.edu FU NIDDK NIH HHS [DK-U24-DK-59637, F32 DK065462, F32-DK-065462, R01-DK-46409] NR 46 TC 41 Z9 42 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 2005 VL 54 IS 12 BP 3517 EP 3522 DI 10.2337/diabetes.54.12.3517 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 988HB UT WOS:000233582500023 PM 16306370 ER PT J AU Harashima, S Notkins, AL AF Harashima, S Notkins, AL TI Overexpression of IA-2 induces G2/M arrest and apoptosis SO DIABETES LA English DT Meeting Abstract CT 6th Servier-IGIS Symposium CY MAR 10-13, 2005 CL St Jean Cap Ferrat, FRANCE C1 NIH, Bethesda, MD 20892 USA. EM sharashi@mail.nih.gov NR 0 TC 0 Z9 0 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 2005 VL 54 SU 2 MA 09 BP S161 EP S161 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 990EZ UT WOS:000233727300031 ER PT J AU Kubosaki, A Nakamura, S Notkins, AL AF Kubosaki, A Nakamura, S Notkins, AL TI Dense core vesicle proteins IA-2 and IA-2 beta - Metabolic alterations in double knockout mice SO DIABETES LA English DT Article; Proceedings Paper CT 6th Servier-IGIS Symposium CY MAR 10-13, 2005 CL St Jean Cap Ferrat, FRANCE ID DEPENDENT DIABETES-MELLITUS; TYROSINE-PHOSPHATASE HOMOLOG; INSULIN-SECRETION; MEMBRANE-PROTEIN; TRANSMEMBRANE PROTEIN; TARGETED DISRUPTION; GLUCOSE-INTOLERANCE; MOLECULAR-CLONING; BETA-CELLS; NOD MICE AB IA-2 and IA-20 are members of the transmembrane protein tyrosine phosphatase family located in dense core vesicles of neuroendocrine cells, including the beta-cells of pancreatic islets. In the present study, by mating C57B/6Nci IA-2(+/-) with IA-2 beta(+/-) mice, we generated double knockout mice (IA-2(-/-)/IA-2 beta(-/-)) to study the effect of the combined deletion of these two proteins on insulin secretion and blood glucose levels. The double knockout mice appeared healthy at birth and showed normal growth and development. Histological examination and immunostaining for insulin, glucagon, somatostatin, and pancreatic polypeptide revealed no difference between the double knockout and wild-type mice. Nonfasting blood glucose and insulin levels also were within the normal range. However, compared with the wild-type mice, the double knockout mice showed glucose intolerance and an absent first-phase insulin release curve. No evidence of insulin resistance was observed nor were there alterations in fasting blood glucose, insulin, or leptin levels in the double knockout mice maintained on a high-fat diet compared with the wild-type mice maintained on the same diet. In addition, to determine whether the combined deletion of IA-2 and IA-2 beta played any role in the development of diabetes in NOD mice, we generated double knockout mice on the NOD/LtJ background. The incidence of diabetes in these mice was not significantly different than that in the wild-type mice. Taken together, our experiments show that the dense core vesicle proteins IA-2 and IA-2 beta, alone or in combination, are involved in insulin secretion, but neither alone nor in combination are they required for the development of diabetes in NOD mice. C1 Natl Inst Dent & Craniofacial Res, Expt Med Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. RP Notkins, AL (reprint author), Natl Inst Dent & Craniofacial Res, Expt Med Sect, Oral Infect & Immun Branch, NIH, Bldg 30,Room 106,30 Convent Dr,MSC 4322, Bethesda, MD 20892 USA. EM anotkins@mail.nih.gov NR 22 TC 39 Z9 41 U1 0 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 2005 VL 54 SU 2 BP S46 EP S51 DI 10.2337/diabetes.54.suppl_2.S46 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 990EZ UT WOS:000233727300008 PM 16306340 ER PT J AU Hu, YF Zhang, HL Cai, T Harashima, S Notkins, AL AF Hu, YF Zhang, HL Cai, T Harashima, S Notkins, AL TI The IA-2 interactome SO DIABETOLOGIA LA English DT Article DE autoimmunity; dense-core secretory vesicles; IA-2; insulin secretion; interactome; protein interaction; protein tyrosine phosphatase; type 1 diabetes; yeast two-hybrid ID PROTEIN-TYROSINE-PHOSPHATASE; INSULIN-SECRETION; RECEPTOR; KINASE; CELLS; MADD AB Aims/hypothesis: Islet antigen-2 (IA-2), a major autoantigen in type 1 diabetes, is an enzymatically inactive member of the transmembrane protein tyrosine phosphatase (PTP) family. IA-2 is located in dense-core secretory vesicles and is involved in the regulation of insulin secretion. The present experiments were initiated to identify those proteins that interact with IA-2 (i.e. the IA-2 interactome) as a first step towards elucidating the mechanism(s) by which IA-2 influences insulin secretion and serves as an autoantigen. Materials and methods: To determine the proteins with which IA-2 interacts, a yeast two-hybrid system was used to screen a human foetal library, and deletion mutants were used to determine the binding sites. Positive interactions were confirmed by immunoprecipitation pull-down experiments using cell lysate from transfected mammalian cell lines. Results: Six new interacting proteins were identified by this approach: mitogen-activated protein kinase-activating death domain ( MADD), the MADD isoform IG20, PTP rho, PTP sigma, sorting nexin 19 (SNX19) and cyclophilin A. Using a series of IA-2 deletion mutants, we identified the regions on the IA-2 molecule to which five of the interacting proteins bound. Amino acids 744 - 979 of IA-2 were required for the maximum binding of MADD, IG20 and SNX19, whereas amino acids 602 - 907 of IA-2 were required for the maximum binding of PTP. and PTPs. Pull-down experiments with cell lysate from transfected mammalian cells confirmed the binding of the interacting proteins to IA-2. Conclusions/interpretation: The IA-2 interactome, based on pull-down experiments, currently consists of 12 proteins. The identification of these interacting proteins provides clues as to how IA-2 exerts its biological functions. C1 NIDCR, Expt Med Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Lab Mol Signaling & Apoptosis, Ann Arbor, MI 48109 USA. RP Notkins, AL (reprint author), NIDCR, Expt Med Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. EM anotkins@mail.nih.gov FU Intramural NIH HHS NR 14 TC 13 Z9 15 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD DEC PY 2005 VL 48 IS 12 BP 2576 EP 2581 DI 10.1007/s00125-005-0037-y PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 990CU UT WOS:000233721600021 PM 16273344 ER PT J AU Westphal, H AF Westphal, H TI Restoring stemness SO DIFFERENTIATION LA English DT Review ID CELL SELF-RENEWAL; SOMATIC-CELLS; ES CELLS; NUCLEAR TRANSPLANTATION; GENE-EXPRESSION; MOUSE EMBRYOS; DIFFERENTIATION; PLURIPOTENCY; CLONING; DEDIFFERENTIATION AB This essay is focused on a specific line of research toward regenerative therapies that is based on the use of embryonic stem cells but tries to avoid cloning techniques that are the heart of current ethical debates. C1 NICHHD, Lab Mammalian Genes & Dev, PHS, HHS,NIH, Bethesda, MD 20892 USA. RP Westphal, H (reprint author), NICHHD, Lab Mammalian Genes & Dev, PHS, HHS,NIH, Bethesda, MD 20892 USA. EM westphal@mail.nih.gov NR 38 TC 6 Z9 6 U1 0 U2 13 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0301-4681 J9 DIFFERENTIATION JI Differentiation PD DEC PY 2005 VL 73 IS 9-10 BP 447 EP 451 DI 10.1111/j.1432-0436.2005.00034.x PG 5 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 991SS UT WOS:000233834600003 PM 16351688 ER PT J AU Berezovskaya, F Karev, G Snell, TW AF Berezovskaya, F Karev, G Snell, TW TI Modeling the dynamics of natural rotifer populations: Phase-parametric analysis SO ECOLOGICAL COMPLEXITY LA English DT Article DE dynamical model; rotifer populations; phase-parameter portraits; dynamics of natural populations; population persistence; extinction ID TIME-SERIES; CHAOS; INTERVAL; MAPS AB A model of the dynamics of natural rotifer populations is described as a discrete non-linear map depending on three parameters; which reflect characteristics of the population and environment. Model dynamics and their change by variation of these parameters were investigated by methods of bifurcation theory. A phase-parametric portrait of the model was constructed and domains of population persistence (stable equilibrium, periodic and a-periodic oscillations of population size) as well as population extinction were identified and investigated. The criteria for population persistence and approaches to determining critical parameter values are described. The results identify parameter values that lead to population extinction under various environmental conditions. They further illustrate that the likelihood of extinction can be substantially increased by small changes in environmental quality, which shifts Populations into new dynamical regimes. (c) 2005 Elsevier B.V. All rights reserved. C1 Howard Univ, Dept Math, Washington, DC 20059 USA. Georgia Inst Technol, Sch Biol, Atlanta, GA 30332 USA. Oak Ridge Inst Sci & Educ, NIH, Bethesda, MD 20894 USA. RP Berezovskaya, F (reprint author), Howard Univ, Dept Math, Washington, DC 20059 USA. EM fsberezo@hotmail.com NR 21 TC 6 Z9 8 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1476-945X J9 ECOL COMPLEX JI Ecol. Complex. PD DEC PY 2005 VL 2 IS 4 BP 395 EP 409 DI 10.1016/j.ecocom.2005.04.008 PG 15 WC Ecology SC Environmental Sciences & Ecology GA 987NF UT WOS:000233523900004 ER PT J AU Seki, M Gearhart, PJ Wood, RD AF Seki, M Gearhart, PJ Wood, RD TI DNA polymerases and somatic hypermutation of immunoglobulin genes SO EMBO REPORTS LA English DT Review DE AID; bypass; DNA polymerase; POLQ; somatic hypermutation; translesion ID CLASS-SWITCH RECOMBINATION; DEPENDENT IMMUNE-RESPONSE; HUMAN DINB1 GENE; TRANSLESION SYNTHESIS; EMBRYONIC LETHALITY; REV1 PROTEIN; POL-IOTA; IN-VITRO; XERODERMA-PIGMENTOSUM; NONTRANSCRIBED STRAND AB Somatic hypermutation of immunoglobulin variable genes, which increases antibody diversity, is initiated by the activation-induced cytosine deaminase (AID) protein. The current DNA-deamination model posits that AID deaminates cytosine to uracil in DNA, and that mutations are generated by DNA polymerases during replication or repair of the uracil residue. Mutations could arise as follows: by DNA replicating past the uracil; by removing the uracil with a uracil glycosylase and replicating past the resulting abasic site with a low-fidelity polymerase; or by repairing the uracil and synthesizing a DNA-repair patch downstream using a low-fidelity polymerase. In this review, we summarize the biochemical properties of specialized DNA polymerases in mammalian cells and discuss their participation in the mechanisms of hypermutation. Many recent studies have examined mice deficient in the genes that encode various DNA polymerases, and have shown that DNA polymerase H ( POLH) contributes to hypermutation, whereas POLI, POLK and several other enzymes do not have major roles. The low-fidelity enzyme POLQ has been proposed as another candidate polymerase because it can efficiently bypass abasic sites and recent evidence indicates that it might participate in hypermutation. C1 Univ Pittsburgh, Inst Canc, Hillman Canc Ctr, Pittsburgh, PA 15213 USA. NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. RP Wood, RD (reprint author), Univ Pittsburgh, Inst Canc, Hillman Canc Ctr, Suite 2-6,Res Pavil,5117 Ctr Ave, Pittsburgh, PA 15213 USA. EM rdwood@pitt.edu RI Wood, Richard/E-7855-2011 OI Wood, Richard/0000-0002-9495-6892 FU Intramural NIH HHS; NCI NIH HHS [R01 CA098675, CA098675, CA101980, R01 CA101980] NR 73 TC 49 Z9 51 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1469-221X J9 EMBO REP JI EMBO Rep. PD DEC PY 2005 VL 6 IS 12 BP 1143 EP 1148 DI 10.1038/sj.embor.7400582 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 988QP UT WOS:000233616000010 PM 16319960 ER PT J AU Lissek, S Baas, JMP Pine, DS Orme, K Dvir, S Rosenberger, E Grillon, C AF Lissek, S Baas, JMP Pine, DS Orme, K Dvir, S Rosenberger, E Grillon, C TI Sensation seeking and the aversive motivational system SO EMOTION LA English DT Article DE sensation seeking; anxiety; fear; startle; psychophysiology ID FEAR-POTENTIATED STARTLE; POSTTRAUMATIC-STRESS-DISORDER; TRAIT ANXIETY; CONDITIONED FEAR; RISK-TAKING; PERSONALITY; MODULATION; AMYGDALA; EMOTION; PREFERENCE AB Sensation seeking (SS) has traditionally been viewed as a phenomenon of the appetitive motivational system. The limited SS research exploring contributions from the aversive motivational system reveals greater anxious reactivity to dangerous activities among low sensation seekers. The present study extends this line of work by comparing levels of fear and anxiety during anticipation of predictable and unpredictable aversive stimuli across high- and low-SS groups. Low sensation seekers displayed greater fear-potentiated startle (FPS) to predictable aversive stimuli, and only those low on SS showed FPS and skin conductance response effects during experimental contexts in which aversive stimuli were delivered unpredictably. Findings implicate enhanced apprehensive anticipation among those low on SS as a potential deterrent for their participation in intense and threatening stimulus events. C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. Univ Utrecht, Dept Psychonom, Utrecht, Netherlands. RP Lissek, S (reprint author), NIMH, Mood & Anxiety Disorders Program, 15K N Dr,Bldg 15K,MSC 2670, Bethesda, MD 20892 USA. EM lisseks@intra.nimh.nih.gov RI Lissek, Shmuel/B-6577-2008; OI Baas, Johanna/0000-0001-6267-8712 FU Intramural NIH HHS NR 76 TC 28 Z9 28 U1 11 U2 25 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1528-3542 J9 EMOTION JI Emotion PD DEC PY 2005 VL 5 IS 4 BP 396 EP 407 DI 10.1037/1528-3542.5.4.396 PG 12 WC Psychology, Experimental SC Psychology GA 996DN UT WOS:000234154700002 PM 16366744 ER PT J AU Amendola, E De Luca, P Macchia, PE Terracciano, D Rosica, A Chiappetta, G Kimura, S Mansouri, A Affuso, A Arra, C Macchia, V Di Lauro, R De Felice, M AF Amendola, E De Luca, P Macchia, PE Terracciano, D Rosica, A Chiappetta, G Kimura, S Mansouri, A Affuso, A Arra, C Macchia, V Di Lauro, R De Felice, M TI A mouse model demonstrates a multigenic origin of congenital hypothyroidism SO ENDOCRINOLOGY LA English DT Article ID AUTOSOMAL-DOMINANT TRANSMISSION; STIMULATING HORMONE-RECEPTOR; OF-FUNCTION MUTATION; THYROID DYSGENESIS; MONOZYGOTIC TWINS; WILLIAMS-SYNDROME; SUBCLINICAL HYPOTHYROIDISM; PAX8 MUTATIONS; CLEFT-PALATE; HEMIAGENESIS AB Congenital hypothyroidism with thyroid dysgenesis (TD) is a frequent human condition characterized by elevated levels of TSH in response to reduced thyroid hormone levels. Congenital hypothyroidism is a genetically heterogeneous disease. In the majority of cases studied, no causative mutations have been identified and very often the disease does not show a Mendelian transmission. However, in approximately 5% of cases, it can be a consequence of mutations in genes encoding the TSH receptor or the transcription factors TITF1, FOXE1, or PAX8. We report here that in mouse models, the combination of partial deficiencies in the Titf1 and Pax8 genes results in an overt TD phenotype that is absent in either of the singly deficient, heterozygous mice. The disease is characterized by a small thyroid gland, elevated levels of TSH, reduced thyroglobulin biosynthesis, and high occurrence of hemiagenesis. The observed phenotype is strain specific, and the pattern of transmission indicates that at least two other genes, in addition to Titf1 and Pax8, are necessary to generate the condition. These results show that TD can be of multigenic origin in mice and strongly suggest that a similar pathogenic mechanism may be observed in humans. C1 CEINGE, Lab Anim Genet, Stn Zool Anton Dohrn, I-80145 Naples, Italy. Univ Naples Federico II, Dipartimento Endocrinol & Oncol Mol & Clin, Naples, Italy. Univ Naples Federico II, Dipartimento Biol & Patol Cellulare & Mol, Naples, Italy. CEINGE, Biogem, Naples, Italy. Inst Nazl Tumori Fdn Pascale, I-80131 Naples, Italy. NCI, NIH, Lab Metab, Bethesda, MD 20892 USA. Max Planck Inst Biophys Chem, Abt Mol Zellbiol, D-37077 Gottingen, Germany. RP Di Lauro, R (reprint author), CEINGE, Lab Anim Genet, Stn Zool Anton Dohrn, Via Comunale Margherita 482, I-80145 Naples, Italy. EM rdilauro@unina.it RI Di Lauro, Roberto/A-2746-2012; Amendola, Elena/P-2434-2016; OI Di Lauro, Roberto/0000-0001-9493-3036; Macchia, Paolo Emidio/0000-0001-6503-6942; De Luca, Pasquale/0000-0003-4289-6784; Arra, Claudio/0000-0003-3162-2091; , Daniela/0000-0003-4296-429X FU Telethon [GP0208Y01] NR 51 TC 54 Z9 56 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 2005 VL 146 IS 12 BP 5038 EP 5047 DI 10.1210/en.2005-0882 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 984JY UT WOS:000233301000002 PM 16150900 ER PT J AU Cheng, CM Tseng, V Wang, J Wang, D Matyakhina, L Bondy, CA AF Cheng, CM Tseng, V Wang, J Wang, D Matyakhina, L Bondy, CA TI Tau is hyperphosphorylated in the insulin-like growth factor-I null brain SO ENDOCRINOLOGY LA English DT Article ID GLYCOGEN-SYNTHASE KINASE-3-BETA; CENTRAL-NERVOUS-SYSTEM; ALZHEIMERS-DISEASE; TRANSGENIC MICE; LIFE-SPAN; OXIDATIVE STRESS; NEURODEGENERATIVE DISEASES; GLUCOSE-METABOLISM; GENE-EXPRESSION; IGF-I AB IGF action has been implicated in the promotion of oxidative stress and aging in invertebrate and murine models. However, some in vitro models suggest that IGF-I specifically prevents neuronal oxidative damage. To investigate whether IGF-I promotes or retards brain aging, we evaluated signs of oxidative stress and neuropathological aging in brains from 400-d-old Igf1-/- and wild-type (WT) mice. Lipofuscin pigment accumulation reflects oxidative stress and aging, but we found no difference in lipofuscin deposition in Igf1-/- and WT brains. Likewise, there was no apparent difference in accumulation of nitrotyrosine residues in Igf1-/- and WT brains, except for layer IV/V of the cerebral cortex, where these proteins were about 20% higher in the Igf1-/- brain (P = 0.03). We found no difference in the levels of oxidative stress-related enzymes, neuronal nitric oxide synthase, inducible nitric oxide synthase, and superoxide dismutase in Igf1-/- and WT brains. Tau is a microtubule-associated protein that causes the formation of neurofibrillary tangles and senile plaques as it becomes hyperphosphorylated in the aging brain. Tau phosphorylation was dramatically increased on two specific residues, Ser-396 and Ser-202, both glycogen synthase kinases target sites implicated in neurodegeneration. These observations indicate that IGF-I has a major role in regulating tau phosphorylation in the aging brain, whereas its role in promoting or preventing oxidative stress remains uncertain. C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Cheng, CM (reprint author), NICHHD, Dev Endocrinol Branch, NIH, Bldg 10,CRC 1-3330,10 Ctr Dr, Bethesda, MD 20892 USA. EM chengc@mail.nih.gov NR 50 TC 35 Z9 36 U1 0 U2 0 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 2005 VL 146 IS 12 BP 5086 EP 5091 DI 10.1210/en.2005-0063 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 984JY UT WOS:000233301000008 PM 16123158 ER PT J AU Wang, ZH Prins, GS Coschigano, KT Kopchick, JJ Green, JE Ray, VH Hedayat, S Christov, KT Unterman, TG Swanson, SM AF Wang, ZH Prins, GS Coschigano, KT Kopchick, JJ Green, JE Ray, VH Hedayat, S Christov, KT Unterman, TG Swanson, SM TI Disruption of growth hormone signaling retards early stages of prostate carcinogenesis in the C3(1)/T antigen mouse SO ENDOCRINOLOGY LA English DT Article ID IGF-BINDING PROTEIN-3; DEFICIENT ADULT PATIENTS; FACTOR-I; CANCER-RISK; INTRAEPITHELIAL NEOPLASIA; FACTOR (IGF)-I; KNOCKOUT MICE; SERUM-LEVELS; INSULIN; CARCINOMA AB Recent epidemiological studies suggest that elevated serum titers of IGF-I, which are, to a large degree, regulated by GH, are associated with an increase in prostate cancer risk. The purpose of the current study was to develop the first animal models to directly test the hypothesis that a normal, functional GH/IGF-I axis is required for prostate cancer progression. The GH receptor (GHR) gene-disrupted mouse (Ghr(-/-)), which has less than 10% of the plasma IGF-I found in GHR wild-type mice, was crossed with the C3(1)/T antigen (Tag) mouse, which develops prostatic intraepithelial neoplasia driven by the large Tag that progress to invasive prostate carcinoma in a manner similar to the process observed in humans. Progeny of this cross were genotyped and Tag/Ghr(+/+) and Tag/Ghr(+/+) mice were killed at 9 months of age. Seven of eight Tag/Ghr(+/+) mice harbored prostatic intraepithelial neoplasia lesions of various grades. In contrast, only one of the eight Tag/Ghr(+/+) mice exhibited atypia (P < 0.01, Fischer's exact test). Disruption of the GHR gene altered neither prostate androgen receptor expression nor serum testosterone titers. Expression of the Tag oncogene was similar in the prostates of the two mouse strains. Immunohistochemistry revealed a significant decrease in prostate epithelial cell proliferation and an increase in basal apoptotic indices. These results indicate that disruption of GH signaling significantly inhibits prostate carcinogenesis. C1 Univ Illinois, Dept Med Chem & Pharmacognosy, Chicago, IL 60612 USA. Univ Illinois, Dept Urol, Chicago, IL 60612 USA. Univ Illinois, Dept Surg Oncol, Chicago, IL 60612 USA. Univ Illinois, Dept Math Stat & Comp Sci, Chicago, IL 60612 USA. Univ Illinois, Dept Med, Chicago, IL 60612 USA. Jesse Brown Med Ctr, Dept Vet Affairs, Chicago, IL 60612 USA. Ohio Univ, Dept Biomed Sci, Athens, OH 45701 USA. Ohio Univ, Edison Biotechnol Inst, Athens, OH 45701 USA. Provident Hosp Cook Cty, Chicago, IL 60615 USA. NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. RP Swanson, SM (reprint author), Univ Illinois, Dept Med Chem & Pharmacognosy, M-C 781,833 S Wood St, Chicago, IL 60612 USA. EM swanson@uic.edu FU NIA NIH HHS [R03 AG020820] NR 42 TC 37 Z9 39 U1 1 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 2005 VL 146 IS 12 BP 5188 EP 5196 DI 10.1210/en.2005-0607 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 984JY UT WOS:000233301000019 PM 16141391 ER PT J AU Claus, M Jaeschke, H Kleinau, G Neumann, S Krause, G Paschke, R AF Claus, M Jaeschke, H Kleinau, G Neumann, S Krause, G Paschke, R TI A hydrophobic cluster in the center of the third extracellular loop is important for thyrotropin receptor signaling SO ENDOCRINOLOGY LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; LUTROPIN CHORIOGONADOTROPIN RECEPTOR; PROTEIN-COUPLED RECEPTORS; TSH RECEPTOR; EXTRACELLULAR DOMAIN; GONADOTROPIN RECEPTORS; CONSTITUTIVE ACTIVITY; RICH REPEATS; TRANSMEMBRANE DOMAIN; SOMATIC MUTATIONS AB Previous reports on the follicle-stimulating hormone receptor and choriogonadotropic/LH receptor, which belong to the glycoprotein hormone receptor family, suggest that the extracellular loop (ECL) 3 could be a key domain for ligand binding and intramolecular receptor signaling. In contrast to ECLs 1 and 2 of glycoprotein hormone receptors, the ECL3 displays high sequence homology, particularly in the central portion of the loop. Therefore, we opted to identify amino acids with functional importance within ECL3 of the TSH receptor (TSHR). Single alanine substitutions of all residues in ECL3 were generated. Functional characterization revealed the importance of five amino acids in the central portion of ECL3 and K660 at the ECL3/transmembrane helix (TMH) 7 junction for TSHR signaling. Decrease of G(s) activation and loss of G(q) activation by substitutions of K660 demonstrates a role for this position for TSHR conformation and signal transduction. By molecular modeling, we predicted potential interaction partners of K660: E409 and D410 in the N terminus of TMH1 and D573 in the ECL2. Complementary double mutants did not reconstitute G(s)/G(q)-mediated signaling, suggesting that K660 is not directly involved in a structural unit between ECL3 and the N terminus of TMH1. These results support a TSHR model in which the side chain of K660 is orientated toward the backbone of ECL2. Moreover, our findings provide evidence that a hydrophobic cluster, comprising residues 652-656 of ECL3, strongly influences intramolecular signal transduction and G protein activation of the TSHR. C1 Univ Leipzig, Dept Med, D-04103 Leipzig, Germany. Forsch Inst Mol Pharmakol, D-13125 Berlin, Germany. NIDDK, NIH, Bethesda, MD 20814 USA. RP Paschke, R (reprint author), Univ Leipzig, Dept Med, Philipp Rosenthal Str 27, D-04103 Leipzig, Germany. EM pasr@medizin.uni-leipzig.de OI Claus, Maren/0000-0001-8732-0645 NR 48 TC 30 Z9 31 U1 0 U2 2 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 2005 VL 146 IS 12 BP 5197 EP 5203 DI 10.1210/en.2005-0713 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 984JY UT WOS:000233301000020 PM 16150909 ER PT J AU Barnard, JC Williams, AJ Rabier, B Chassande, O Samarut, J Cheng, SY Bassett, JHD Williams, GR AF Barnard, JC Williams, AJ Rabier, B Chassande, O Samarut, J Cheng, SY Bassett, JHD Williams, GR TI Thyroid hormones regulate fibroblast growth factor receptor signaling during chondrogenesis SO ENDOCRINOLOGY LA English DT Article ID ATDC5 IN-VITRO; CHONDROCYTE PROLIFERATION; BONE-DEVELOPMENT; HYPERTROPHIC DIFFERENTIATION; PLATE CHONDROCYTES; GENE-EXPRESSION; INDIAN HEDGEHOG; FGF RECEPTOR; MOUSE MODEL; CARTILAGE AB Childhood hypothyroidism causes growth arrest with delayed ossification and growth-plate dysgenesis, whereas thyrotoxicosis accelerates ossification and growth. Thyroid hormone (T-3) regulates chondrocyte proliferation and is essential for hypertrophic differentiation. Fibroblast growth factors (FGFs) are also important regulators of chondrocyte proliferation and differentiation, and activating mutations of FGF receptor-3 (FGFR3) cause achondroplasia. We investigated the hypothesis that T-3 regulates chondrogenesis via FGFR3 in ATDC5 cells, which undergo a defined program of chondrogenesis. ATDC5 cells expressed two FGFR1, four FGFR2, and one FGFR3 mRNA splice variants throughout chondrogenesis, and expression of each isoform was stimulated by T-3 during the first 6-12d of culture, when T-3 inhibited proliferation by 50%. FGFR3 expression was also increased in cells treated with T-3 for 21 d, when T-3 induced an earlier onset of hypertrophic differentiation and collagen X expression. FGFR3 expression was reduced in growth plates from T-3 receptor alpha-null mice, which exhibit skeletal hypothyroidism, but was increased in T-3 receptor beta(PV/ PV) mice, which display skeletal thyrotoxicosis. These findings indicate that FGFR3 is a T-3-target gene in chondrocytes. In further experiments, T3 enhanced FGF2 and FGF18 activation of the MAPK-signaling pathway but inhibited their activation of signal transducer and activator of transcription-1. FGF9 did not activate MAPK or signal transducer and activator of transcription-1 pathways in the absence or presence of T-3. Thus, T-3 exerted differing effects on FGFR activation during chondrogenesis depending on which FGFligand stimulated the FGFR and which downstream signaling pathway was activated. These studies identify novel interactions between T-3 and FGFs that regulate chondrocyte proliferation and differentiation during chondrogenesis. C1 Univ London Imperial Coll Sci & Technol, Mol Endocrinol Grp, Div Med, London W12 0NN, England. Univ London Imperial Coll Sci & Technol, MRC, Ctr Clin Sci, London W12 0NN, England. Univ Victor Segalen Bordeaux 2, INSERM Unite 443, Bordeaux, France. Ecole Normale Super, Lab Biol Mol & Cellulaire, UMR 5665, CNRS,Inst Natl Rech Agron Lyon LA 913, Lyon, France. NCI, Gene Regulat Sect, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Williams, GR (reprint author), Hammersmith Hosp, MRC, Ctr Clin Sci, Mol Endocrinol Grp, 5th Floor Clin Res Bldg,Du Cane Rd, London W12 0NN, England. EM graham.williams@imperial.ac.uk FU Medical Research Council [G108/502] NR 57 TC 41 Z9 44 U1 0 U2 10 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 2005 VL 146 IS 12 BP 5568 EP 5580 DI 10.1210/en.2005-0762 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 984JY UT WOS:000233301000062 PM 16150908 ER PT J AU Srinivasan, S Collman, GW AF Srinivasan, S Collman, GW TI Evolving partnerships in community SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE community-based participatory research; community-university partnership; environmental exposures; health disparities; methodology ID HEALTH AB In recent years there have been a significant number of publications on the benefits and challenges of community-based participatory research (CBPR). In this introduction we give an overview of three projects presented in this mini-monograph and highlight their commonalities and differences in developing community-university partnerships. While the studies presented here were not required to use CBPR strategies in their work, they did engage community members in a participatory manner. In this mini-monograph we examine how these multifaceted research questions are addressed while simultaneously negotiating complex relationships among researchers and communities as they strive for a more equitable partnership-not only in the distribution of resources but also in power/authority, the process of research, and its outcome. The three papers in this mini-monograph offer insights into various ways of forming, working, and sustaining community-university partnerships in conducting CBPR. They illustrate both the potential benefits and some of the challenges involved with establishing partnerships between community groups and researchers committed to the mutual goal of promoting environmental health. They suggest the importance of nonprescriptive frameworks for conducting community-based participatory research that focuses on more equitable power relationships to address health disparities to help alleviate environmental health problems. C1 NIEHS, Div Extramural Res & Training, NIH, DHHS, Res Triangle Pk, NC 27709 USA. RP Collman, GW (reprint author), NIEHS, Div Extramural Res & Training, NIH, DHHS, POB 12233,MD EC-21,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM collman@niehs.nih.gov NR 5 TC 20 Z9 20 U1 1 U2 2 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 EI 1552-9924 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 2005 VL 113 IS 12 BP 1814 EP 1816 DI 10.1289//ehp.7911 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 989ZP UT WOS:000233713200059 PM 16330370 ER PT J AU Goehl, TJ AF Goehl, TJ TI Note from the editor: Good bye and thank you SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material C1 NIEHS, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. RP Goehl, TJ (reprint author), NIEHS, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. 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 2005 VL 113 IS 12 BP A795 EP A795 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 989ZP UT WOS:000233713200002 ER PT J AU Kamel, F Gladen, BC Hoppin, JA Sandler, DP Engel, LS Alavanja, MCR AF Kamel, F Gladen, BC Hoppin, JA Sandler, DP Engel, LS Alavanja, MCR TI Pesticides and neurologic symptoms - Reply SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Letter C1 NIEHS, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NCI, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Kamel, F (reprint author), NIEHS, NIH, US Dept HHS, POB 12233, Res Triangle Pk, NC 27709 USA. EM kamel@niehs.nih.gov NR 5 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 2005 VL 113 IS 12 BP A800 EP A801 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 989ZP UT WOS:000233713200005 ER PT J AU Resnik, DB Portier, C AF Resnik, DB Portier, C TI Benefits and risks of pesticide testing on humans - Reply SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Letter C1 NIEHS, Off Sci Director, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. NIEHS, Natl Toxicol Program, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. RP Resnik, DB (reprint author), NIEHS, Off Sci Director, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. EM resnikd@niehs.nih.gov RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 1 TC 0 Z9 0 U1 0 U2 1 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 2005 VL 113 IS 12 BP A805 EP A805 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 989ZP UT WOS:000233713200011 ER PT J AU Schwartz, DA AF Schwartz, DA TI Physician-scientists in environmental health SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material ID CLINICAL INVESTIGATOR C1 NIEHS, Res Triangle Pk, NC 27709 USA. NTP, Res Triangle Pk, NC USA. RP Schwartz, DA (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. EM david.schwartz@niehs.nih.gov NR 5 TC 0 Z9 0 U1 1 U2 2 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 2005 VL 113 IS 12 BP A796 EP A796 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 989ZP UT WOS:000233713200003 PM 16332545 ER PT J AU Galperin, MY AF Galperin, MY TI More cool news from marine bacteria SO ENVIRONMENTAL MICROBIOLOGY LA English DT Editorial Material ID WHOLE-GENOME SEQUENCE; VIRULENCE; REVEALS C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Galperin, MY (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, 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 18 TC 3 Z9 3 U1 0 U2 0 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 2005 VL 7 IS 12 BP 1864 EP 1867 DI 10.1111/j.1462-2920.2005.00951.x PG 4 WC Microbiology SC Microbiology GA 984OE UT WOS:000233313400002 PM 16309385 ER PT J AU Lisk, G Desai, SA AF Lisk, G Desai, SA TI The plasmodial surface anion channel is functionally conserved in divergent malaria parasites SO EUKARYOTIC CELL LA English DT Article ID RED-BLOOD-CELLS; INFECTED ERYTHROCYTES; HOST ERYTHROCYTE; FALCIPARUM; TRANSPORT; MEMBRANE; CHOLINE; PERMEABILITY; PERMEATION; PHYLOGENY AB The plasmodial surface anion channel (PSAC), a novel ion channel induced on human erythrocytes infected with Plasmodium falciparum, mediates increased permeability to nutrients and presumably supports intracellular parasite growth. Isotope flux studies indicate that other malaria parasites also increase the permeability of their host erythrocytes, but the precise mechanisms are unknown. Channels similar to PSAC or alternative mechanisms, such as the upregulation of endogenous host transporters, might fulfill parasite nutrient demands. Here we evaluated these possibilities with rhesus monkey erythrocytes infected with Plasmodium knowlesi, a parasite phylogenetically distant from P. falciparum. Tracer flux and osmotic fragility studies revealed dramatically increased permeabilities paralleling changes seen after P. falciparum infection. Patchclamp of P. knowlesi-infected rhesus erythrocytes revealed an anion channel with striking similarities to PSAC: its conductance, voltage-dependent gating, pharmacology, selectivity, and copy number per infected cell were nearly identical. Our findings implicate a family of unusual anion channels highly conserved on erythrocytes infected with various malaria parasites. Together with PSAC's exposed location on the host cell surface and its central role in transport changes after infection, this conservation supports development of antimalarial drugs against the PSAC family. C1 NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. RP Desai, SA (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Room 3W-01,12735 Twinbrook Pkwy, Rockville, MD 20852 USA. EM sdesai@niaid.nih.gov RI Desai, Sanjay/B-7110-2009 FU Intramural NIH HHS [Z01 AI000882-07] NR 40 TC 24 Z9 24 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1535-9778 J9 EUKARYOT CELL JI Eukaryot. Cell PD DEC PY 2005 VL 4 IS 12 BP 2153 EP 2159 DI 10.1128/EC.4.12.2153-2159.2005 PG 7 WC Microbiology; Mycology SC Microbiology; Mycology GA 994LC UT WOS:000234032300019 PM 16339732 ER PT J AU Fiorentino, S Chopin, M Dastot, H Boissel, N Reboul, M Legres, L Janin, A Aplan, P Sigaux, F Regnault, A AF Fiorentino, S Chopin, M Dastot, H Boissel, N Reboul, M Legres, L Janin, A Aplan, P Sigaux, F Regnault, A TI Disruption of T cell regulatory pathways is necessary for immunotherapeutic cure of T cell acute lymphoblastic leukemia in mice SO EUROPEAN CYTOKINE NETWORK LA English DT Article DE immunotherapy; leukemia; dendritic cells; T-ALL; regulatory T cells ID HUMAN DENDRITIC CELLS; TUMOR-NECROSIS-FACTOR; ANTIGEN-4 BLOCKADE; MONOCLONAL-ANTIBODY; CYTOKINE PRODUCTION; PEPTIDE COMPLEXES; CANCER REGRESSION; CTLA-4 BLOCKADE; TRANSGENIC MICE; WT1 PEPTIDE AB Acute lymphoblastic leukemia (ALL) is the most common cancer in children. In recent years, the outcome has been globally improved by current therapies, but it remains poor in patients with high, persistent residual disease following the first course of chemotherapy, prompting evaluation of the possible beneficial effects of immunotherapy protocols. In this study, we hypothesized that the disruption of two immunoregulatory pathways controlling the auto-reactive T cell response might synergize with dendritic cell-based immunotherapy of the disease, which is considered to be poorly immunogenic. In this study, we used TAL1xLMO1 leukemia cells adoptively transferred in mice, to generate murine leukemia with poorly immunogenic cells as a model for human T-ALL. Subsequently, these animals were treated with several different immunotherapeutic protocols. We compared the efficiency of a classical, dendritic cell-based immunotherapy (injection of dendritic cells loaded with tumor-derived antigenic products), to a combined treatment associating injection of antigen-loaded dendritic cells and disruption of the two immunoregulatory pathways: CD25+ suppressive T cells and cytotoxic T lymphocyte-associated antigens (CTLA-4). We show that this combined treatment resulted in cure, concomitantly with in vivo generation of immune memory, and TNF-alpha secretion. This study demonstrates that the disruption of these two immunoregulatory pathways synergized with immunostimulation by dendritic cells loaded with tumor-derived antigens, and paves the way for the testing of this combination in clinical trials. C1 Univ Paris 07, Hop St Louis, Unite U728, INSERM Lab Pathol,Inst Univ Hematol, F-75475 Paris 10, France. Inst Univ Hematol, Hop St Louis, Unite INSERM U396, Paris, France. NCI, NIH, Genet Branch, Bethesda, MD 20889 USA. RP Regnault, A (reprint author), Univ Paris 07, Hop St Louis, Unite U728, INSERM Lab Pathol,Inst Univ Hematol, 1 Ave Claude Vellefaux, F-75475 Paris 10, France. EM regnault@chu-stlouis.fr RI LEGRES, Luc/A-7650-2012; REGNAULT, Armelle/G-4142-2011; Aplan, Peter/K-9064-2016; OI REGNAULT, Armelle/0000-0001-7286-9491; FIORENTINO, SUSANA/0000-0002-4664-0682 NR 50 TC 5 Z9 5 U1 0 U2 1 PU JOHN LIBBEY EUROTEXT LTD PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1148-5493 J9 EUR CYTOKINE NETW JI Eur. Cytokine Netw. PD DEC PY 2005 VL 16 IS 4 BP 300 EP 308 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 014KQ UT WOS:000235479400008 PM 16464745 ER PT J AU Manini, TM Clark, BC Tracy, BL Burke, J Ploutz-Snyder, L AF Manini, TM Clark, BC Tracy, BL Burke, J Ploutz-Snyder, L TI Resistance and functional training reduces knee extensor position fluctuations in functionally limited older adults SO EUROPEAN JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE steadiness; aging; elderly; motor control; motor output variability ID MOTOR UNIT DISCHARGE; FORCE FLUCTUATIONS; QUADRICEPS FEMORIS; ISOMETRIC CONTRACTIONS; HAND MUSCLE; STRENGTH; STEADINESS; IMPROVES; WOMEN; ACCELERATION AB The purpose of this study was to determine the effect of task-specificity on knee extensor steadiness adaptations in functionally limited older adults. Twenty-four functionally limited older adults (74.6 +/- 7.6 years: 22 women, 2 men) completed a 10-week control period followed by 10 weeks (2 days/week) of resistance (RT), functional (FT) (practicing everyday tasks, i.e., chair rises) or functional + resistance (FRT) training, which featured both shortening and lengthening movements. During testing, subjects performed a steady isometric [10, 25, 50% of maximal voluntary contraction (MVC)] and shortening/lengthening (5, 30, 65% of MVC) knee extensor contractions. There were no steadiness (isometric, shortening or lengthening contractions) changes in the control period and no adaptations in isometric steadiness due to training. RT induced a 37% reduction in shortening fluctuations at 5% of MVC and 35% reduction in lengthening fluctuations at both 30% and 65% of MVC. FRT induced a 60% reduction in shortening fluctuations at 30% of MVC. No adaptations in dynamic steadiness were observed in the FT group. Further analysis indicated that those who were the least steady at baseline showed the greatest training effects during isometric (RT: R-2 = 0.25, FRT: R-2 = 0.49, FT: R-2 = 0.38), shortening (RT: R-2 = 0.36, FT: R-2 = 0.35) and lengthening (RT: r(2) = 0.29, FRT: r(2) = 0.44) contractions. In conclusion, steadiness improvements in groups performing resistance exercise, without a concomitant improvement in the FT group, supports a role for task-specificity in explaining steadiness adaptations, particularly for unsteady older adults. C1 Syracuse Univ, Musculoskeletal Res Lab, Syracuse, NY 13244 USA. Colorado State Univ, Dept Hlth & Exercise Sci, Ft Collins, CO 80523 USA. New York Chiropract Coll, Res Dept, Seneca Fall, NY 13148 USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. Syracuse Univ, Dept Exercise Sci, Syracuse, NY 13224 USA. RP Manini, TM (reprint author), Syracuse Univ, Musculoskeletal Res Lab, Syracuse, NY 13244 USA. EM maninit@mail.nih.gov NR 39 TC 19 Z9 19 U1 0 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1439-6319 J9 EUR J APPL PHYSIOL JI Eur. J. Appl. Physiol. PD DEC PY 2005 VL 95 IS 5-6 BP 436 EP 446 DI 10.1007/s00421-005-0048-x PG 11 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 986RT UT WOS:000233468100007 PM 16193338 ER PT J AU Dodeller, F Skapenko, A Kalden, JR Lipsky, PE Schulze-Koops, H AF Dodeller, F Skapenko, A Kalden, JR Lipsky, PE Schulze-Koops, H TI The p38 mitogen-activated protein kinase regulates effector functions of primary human CD4 T cells SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE allergy; human; protein kinases; signal transduction; Th1/Th2 cells ID HELPER TYPE-2 DIFFERENTIATION; IL-4 GENE-EXPRESSION; MAP-KINASE; IFN-GAMMA; NUCLEAR FACTOR; MESSENGER-RNA; SIGNALING PATHWAYS; TCR LIGATION; IN-VIVO; CD28 AB The role of p38 mitogen-activated protein kinase in primary human T cells is incompletely understood. We analyzed in detail the role of p38 in the regulation of effector functions and differentiation of human CD4 T cells by using a p38-specific inhibitor and a dominant-negative mutant of p38. p38 was found to mediate expression of IL-10 and the Th2 cytokines IL-4, IL-5, and IL-13 in both, primary naive and memory T cells. In contrast, inhibition of p38 activity did not affect expression of the Th1 cytokines IFN-gamma and TNF induced by TCR-stimulation, but decreased IL-12-mediated IFN-gamma expression. Cytokine expression from established Th2 effector cells was also regulated by p38, however, the role of p38 was less pronounced compared to primary CD4 T cells. p38 MAPK regulated cytokine gene expression at both, the transcriptional level by activating gene transcription and the post-transcriptional level by stabilizing cytokine mRNA. As a result of the effect of p38 on IL-4 expression, p38 activity modulated differentiation of naive precursor T cells by inducing a shift of the Th1/Th2. balance toward the immuno-modulatory Th2 direction. Together, the data suggest that p38 plays a key role in human Th2 cell immune responses. C1 Univ Erlangen Nurnberg, Clin Res Grp 3, Nikolaus Fiebiger Ctr Mol Med, D-91054 Erlangen, Germany. Univ Erlangen Nurnberg, Dept Internal Med 3, Erlangen, Germany. Univ Erlangen Nurnberg, Inst Clin Immunol, Erlangen, Germany. NIAMSD, NIH, Bethesda, MD 20892 USA. RP Schulze-Koops, H (reprint author), Univ Erlangen Nurnberg, Clin Res Grp 3, Nikolaus Fiebiger Ctr Mol Med, Glueckstr 6, D-91054 Erlangen, Germany. EM Schulze-Koops@med3.imed.uni-erlangen.de NR 49 TC 26 Z9 31 U1 0 U2 2 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 2005 VL 35 IS 12 BP 3631 EP 3642 DI 10.1002/eji.200535029 PG 12 WC Immunology SC Immunology GA 996VN UT WOS:000234203400026 PM 16259005 ER PT J AU Goldstein, MS Brown, ER Ballard-Barbash, R Morgenstern, H Bastani, R Lee, J Gatto, N Ambs, A AF Goldstein, MS Brown, ER Ballard-Barbash, R Morgenstern, H Bastani, R Lee, J Gatto, N Ambs, A TI The use of complementary and alternative medicine among California adults with and without cancer SO EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE LA English DT Article DE CAM; cancer; chronic illness ID UNITED-STATES; HEALTH-CARE; THERAPIES; TRENDS; PREVALENCE; PREDICTORS; ARTHRITIS; SURVIVORS; BREAST AB This article examines the extent and correlates of complementary and alternative medicine (CAM) use among a population-based sample of California adults that is highly diverse in terms of sociodemographic characteristics and health status. As a follow-up to a state-wide health survey of 55 428 people, 9187 respondents were interviewed by phone regarding their use of I I different types of CAM providers, special diets, dietary supplements, mind-body interventions, self-prayer and support groups. The sample included all participants in the initial survey who reported a diagnosis of cancer, all the non-white respondents, as well as a random sample of all the white respondents. The relation of CAM use to the respondents' demographic characteristics and health status is assessed. CAM use among Californians is generally high, and the demographic factors associated with high rates of CAM use are the same in California as have been found in other studies. Those reporting a diagnosis of cancer and those who report other chronic health problems indicate a similar level of visits to CAM providers. However, those with cancer are less likely to report using special diets, and more likely to report using support groups and prayer. Health status, gender, ethnicity and education have an independent impact upon CAM use among those who are healthy as well as those who report suffering from chronic health problems, although the precise relation varies by the type of CAM used. C1 Univ Calif Los Angeles, Sch Publ Hlth, Dept Community Hlth Sci, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Community Hlth Sci, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Ctr Hlth Policy Res, Los Angeles, CA USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA USA. Univ So Calif, Sch Med, Dept Prevent Med, Los Angeles, CA 90089 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Goldstein, MS (reprint author), Univ Calif Los Angeles, Sch Publ Hlth, Dept Community Hlth Sci, Los Angeles, CA 90095 USA. EM msgoldst@ucla.edu RI Lee, Jennifer/C-2698-2008 NR 28 TC 70 Z9 71 U1 3 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1741-427X J9 EVID-BASED COMPL ALT JI Evid.-based Complement Altern. Med. PD DEC PY 2005 VL 2 IS 4 BP 557 EP 565 DI 10.1093/ecam/neh138 PG 9 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 988XT UT WOS:000233638200017 PM 16322814 ER PT J AU Wu, JM Zelinski, MB Ingram, DK Ottinger, MA AF Wu, JM Zelinski, MB Ingram, DK Ottinger, MA TI Ovarian aging and menopause: Current theories, hypotheses, and research models SO EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Review DE ovarian aging; perimenopause; ovarian steroid hormones; animal models; ovulatory cycles; inhibin ID FOLLICLE-STIMULATING-HORMONE; HUMAN MENSTRUAL-CYCLE; BCL-2 GENE FAMILY; 4-VINYLCYCLOHEXENE DIEPOXIDE; CELL-DEATH; ESTROUS CYCLICITY; DIMERIC INHIBIN; C57BL/6J MICE; RAT OVARY; REPRODUCTIVE SENESCENCE AB Aging of the reproductive system has been studied in numerous vertebrate species. Although there are wide variations in reproductive strategies and hormone cycle components, many of the fundamental changes that occur during aging are similar. Evolutionary hypotheses attempt to explain why menopause occurs, whereas cellular hypotheses attempt to explain how it occurs. It is commonly believed that a disruption in the hypothalamic-pituitary-gonadal axis is responsible for the onset of menopause. Data exist to demonstrate that the first signs of menopause occur at the level of the brain or the ovary. Thus, finding an appropriate and representative animal model is especially important for the advancement of menopause research. In primates, there is a gradual decline in the function of the hypothalamic-pituitary-gonadal (HPG) axis ultimately resulting in irregularities in menstrual cycles and increasingly sporadic incidence of ovulation. Rodents a so exhibit a progressive deterioration in HPG axis function; however, they also experience a period of constant estrus accompanied by intermittent ovulations, reduced progesterone levels, and elevated circulating estradiol levels. It is remarkable to observe that females of other classes also demonstrate deterioration in HPG axis function and ovarian failure. Comparisons of aging in various taxa provide insight into fundamental biological mechanisms of aging that could underlie reproductive decline. C1 Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20742 USA. Oregon Hlth Sci Univ, Oregon Natl Primate Res Ctr, Div Reprod Sci, Beaverton, OR 97006 USA. NIA, Lab Expt Gerontol, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Ottinger, MA (reprint author), Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20742 USA. EM maotting@umd.edu FU Intramural NIH HHS; NIA NIH HHS [U01-AG21380-03] NR 100 TC 60 Z9 65 U1 1 U2 21 PU SOC EXPERIMENTAL BIOLOGY MEDICINE PI MAYWOOD PA 195 WEST SPRING VALLEY AVE, MAYWOOD, NJ 07607-1727 USA SN 1535-3702 J9 EXP BIOL MED JI Exp. Biol. Med. PD DEC PY 2005 VL 230 IS 11 BP 818 EP 828 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 992CU UT WOS:000233862800006 PM 16339746 ER PT J AU Salem, N Loewke, J Catalan, JN Majchrzak, S Moriguchi, T AF Salem, N Loewke, J Catalan, JN Majchrzak, S Moriguchi, T TI Incomplete replacement of docosahexaenoic acid by n-6 docosapentaenoic acid in the rat retina after an n-3 fatty acid deficient diet SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE docosahexaenoic acid; docosapentaenoic acid; arachidonic acid; docosatetraenoic acid; n-3 fatty acid deficiency; retina; reciprocal replacement ID ALPHA-LINOLENIC ACID; ARACHIDONIC-ACID; PRETERM INFANTS; VISUAL-ACUITY; RANDOMIZED TRIAL; RHESUS-MONKEYS; TERM INFANTS; BRAIN LIPIDS; LIVER; DHA AB When sources of n-3 fatty acids are not present in the diet, nervous system docosahexaenoic acid (22:6n3) is replaced by docosapentaenoic acid (22:5n6). Dams were fed either an n-3 deficient diet or one containing alpha-linolenic acid (18:3n3) and 22:6n3 throughout pregnancy and lactation. Their male offspring at weaning also received either the n-3 deficient or n-3 adequate diets and were sacrificed at 5, 10, 20, 50 and 91 days of age. Retinal lipids were extracted and analysed by gas chromatography for fatty acyl content. The percentage of retinal 22:60 increased continuously over the 13 week course of the experiment but reached its maximal concentration around day 20. Non-reciprocal replacement of 22:60 by 22:5n6 was observed at postnatal day 20 and 50 but not at other time points. Complete replacement of 22:60 was apparent if elevations in both 22:5n6 and docosatetraenoic acid (22:4n6) were considered. These data indicate that during the rapid period of accretion of retinal 22:60 around postnatal day 20, the supply of 22:5n6 to the retina was inadequate to completely replace 22:60 in n-3 deficient rats. Published by Elsevier Ltd. C1 NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA. RP Salem, N (reprint author), 5625 Fishers Lane,Room 3N-07,MSC 9410, Bethesda, MD 20892 USA. EM nsalem@niaaa.nih.gov FU Intramural NIH HHS NR 57 TC 7 Z9 7 U1 2 U2 2 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD DEC PY 2005 VL 81 IS 6 BP 655 EP 663 DI 10.1016/j.exer.2005.04.003 PG 9 WC Ophthalmology SC Ophthalmology GA 998QA UT WOS:000234332700005 PM 15967432 ER PT J AU Curcio, CA Presley, JB Malek, G Medeiros, NE Avery, DV Kruth, HS AF Curcio, CA Presley, JB Malek, G Medeiros, NE Avery, DV Kruth, HS TI Esterified and unesterified cholesterol in drusen and basal deposits of eyes with age-related maculopathy SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE cholesterol; drusen; basal deposits; lipoproteins; Bruch's membrane; age-related maculopathy ID PHOTORECEPTOR OUTER SEGMENTS; RETINAL-PIGMENT EPITHELIUM; MACULAR DEGENERATION; BRUCHS MEMBRANE; ATHEROSCLEROTIC LESIONS; GEOGRAPHIC ATROPHY; VITRONECTIN GENE; TRANSFER PROTEIN; LIPID PARTICLES; IN-VITRO AB To address the potential for an outer segment (OS) contribution to the sub-retinal pigment epithelium (RPE) lesions of age-related maculopathy (ARM), we quantified esterified and unesterified cholesterol (EC, UC) with the sterol-specific fluorescent probe filipin in cryosections of ARM eyes. Twenty six eyes from 20 donors were preserved < 5 hr after death in 4% paraformaldehyde (n = 16) or 2.5% glutaraldehyde/1% paraformaldehyde (n = 10). Eyes had exudative late ARM (n = 6), geographic atrophy (n = 15), and drusen ! 125 Pm (n = 11). Sections were stained with filipin for UC or were extracted and hydrolysed with cholesterol esterase before filipin staining for EC. Drusen varied in cholesterol content, with a rough correlation between EC and UC. Dome-shaped drusen contained distinctive, loosely packed UC-rich loops. In basal deposits, EC and UC were more prominent near Bruch's membrane than near the RPE. A UC-rich material was localized within the subretinal space (n=4). Maximum filipin fluorescence due to UC was quantified in 47 lesions (19 drusen, 24 basal deposits, and 4 sub-retinal) from 12 ARM eyes and compared to OS and inner plexiform layer (IPL) of uninvolved retina in the same sections. Relative to IPL, UC fluorescence was higher in lesions (mean +/- S.D: 1.63 +/- 0.69) and lower in OS (0.64 +/- 0.18). If only the packing of membranes explained fluorescence intensity, then one would expect much higher intensities in membrane-rich OS than in lesions. Because the converse is true, the membranous material in lesions must be more highly enriched in cholesterol on a per unit area basis. UC in sub-RPE deposits cannot be derived directly from OS without considerable intracellular processing within RPE, additional cholesterol sources, or both. (c) 2005 Elsevier Ltd. All rights reserved. C1 Univ Alabama, Callahan Eye Fdn Hosp, Sch Med, Dept Ophthalmol, Birmingham, AL 35294 USA. Retina Specialists N Alabama, Huntsville, AL USA. NHLBI, Sect Expt Atherosclerosis, Bethesda, MD 20892 USA. RP Curcio, CA (reprint author), Univ Alabama, Callahan Eye Fdn Hosp, Sch Med, Dept Ophthalmol, 700 S 18th St,Room H020, Birmingham, AL 35294 USA. EM curcio@uab.edu FU NEI NIH HHS [EY06109] NR 55 TC 106 Z9 107 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD DEC PY 2005 VL 81 IS 6 BP 731 EP 741 DI 10.1016/j.exer.2005.04.012 PG 11 WC Ophthalmology SC Ophthalmology GA 998QA UT WOS:000234332700014 PM 16005869 ER PT J AU Leng, SX Xue, QL Huang, Y Ferrucci, L Fried, LP Walston, JD AF Leng, SX Xue, QL Huang, Y Ferrucci, L Fried, LP Walston, JD TI Baseline total and specific differential white blood cell counts and 5-year all-cause mortality in community-dwelling older women SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE total WBC count; neutrophils; lymphocytes; predictive value; all-cause mortality; older women ID CORONARY HEART-DISEASE; CARDIOVASCULAR-DISEASE; LEUKOCYTE COUNT; LUNG-FUNCTION; ELDERLY MEN; INTERLEUKIN-6; ASSOCIATIONS; PREDICTOR; RISK; HEALTH AB Increasing evidence demonstrates that inflammation is associated with many pathophysiologic processes and mortality in older adults. Increase in total white blood cell (WBC) counts is recognized as an important cellular marker of systemic inflammation. However, relationships of total WBC and individual differential counts with mortality in older adults, particularly in older women, have not been adequately evaluated. To address this important question, we obtained baseline total WBC and differential counts and 5-year all-cause mortality of 624 community-dwelling women age 65-101 in the Women's Health and Aging Study cohort, excluding those with WBC counts above the normal range. Using Kaplan-Meier survival and Cox proportional hazard regression analyses, and adjusting for age, race, body mass index, smoking, and education, we identified that baseline higher total WBC, higher neutrophil, or lower lymphocyte counts were independently associated with increased mortality. No significant associations of eosinophil, monocyte, or basophil counts with mortality were observed. These results suggest that beyond acute bacterial infection, changes in counts of baseline total WBC and its specific subpopulations predict increased mortality in older women. They provide a basis for further investigation into the role of leukocytes in age-related inflammation and its associated adverse outcomes in older adults. (c) 2005 Elsevier Inc. All rights reserved. C1 Johns Hopkins Asthma & Allergy Ctr, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Div Geriatr Med & Gerontol, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Ctr Aging & Hlth, Baltimore, MD USA. NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD USA. RP Walston, JD (reprint author), Johns Hopkins Asthma & Allergy Ctr, Rm 5A-24,5501 Hopkins Bayview Circle, Baltimore, MD 21224 USA. EM jwalston@jhmi.edu NR 27 TC 20 Z9 21 U1 1 U2 4 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 2005 VL 40 IS 12 BP 982 EP 987 DI 10.1016/j.exger.2005.08.006 PG 6 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 994LO UT WOS:000234033500009 PM 16183235 ER PT J AU Watanapokasin, Y Chuncharunee, S Sanmund, D Kongnium, W Winichagoon, P Rodgers, GP Fucharoen, S AF Watanapokasin, Y Chuncharunee, S Sanmund, D Kongnium, W Winichagoon, P Rodgers, GP Fucharoen, S TI In vivo and in vitro studies of fetal hemoglobin induction by hydroxyurea in beta-thalassemia/hemoglobin E patients SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID SICKLE-CELL-ANEMIA; ADULT ERYTHROID-CELLS; BURST-FORMING UNITS; GLOBIN; REACTIVATION; HBF; RNA; ERYTHROPOIETIN; EXPRESSION; INTERMEDIA AB Objective. Some, but not all, beta-thalassemia/hemoglobin E (beta-thal/HbE) patients respond to hydroxyurea treatment. It would be helpful if patient responses to hydroxyurea could be screened in vitro to identify responders and nonresponders before beginning in vivo treatment. Materials and Methods. Thirteen beta-Thal/HbE patients were treated with hydroxyurea orally for 2 years at a starting dose of 5 mg/kg/day for 5 days/week with escalation to a maximum of 10 mg/kg/day. For comparison, erythroid cells obtained from peripheral blood of the same patients 1 year after they had stopped hydroxyurea treatment were treated with hydroxyurea in vitro. The gamma-globin mRNA was measured by real-time reverse-transcription polymerase chain reaction, fetal hemoglobin (HbF) by high-performance liquid chromatography, (G)gamma- and (A)gamma-globin chains by Triton X-100 acid urea polyacrylamide gel electrophoresis. Results. Treatment of cells in primary culture with 30 mu M hydroxyurea for 96 hours significantly increased the fractional HbF content in beta-Thal/HbE patients. The (G)gamma:(A)gamma-globin mRNA was induced 0.30- to 8-fold in vitro and 0.30- to 6-fold in vivo (r(2) = 0.51, p = 0.16 by paired t-test); the fractional HbF content was induced 0.50- to 19-fold in vitro and 0.30- to 12-fold in vivo (r(2) = 0.61, p = 0.20) and the (G)gamma:(A)gamma-globin chain ratio was increased 0.80- to 1.40-fold in vitro and 1- to 1.20-fold in vivo (r(2) = 0.62, p = 0.13). Conclusion. The correlation of in vivo and in vitro results of HbF synthesis and globin mRNA suggest that in vitro testing may predict the in vivo response. (c) 2005 International Society for Experimental Hematology. Published by Elsevier Inc. C1 Srinakharinwirot Univ, Fac Med, Dept Biochem, Bangkok 10110, Thailand. Mahidol Univ, Ramathibodi Hosp, Fac Med, Dept Med,Div Hematol, Bangkok 10700, Thailand. Mahidol Univ, Inst Sci & Technol Res & Dev, Bangkok 10700, Thailand. NIDDKD, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Watanapokasin, Y (reprint author), Srinakharinwirot Univ, Fac Med, Dept Biochem, Sukhumvit 23, Bangkok 10110, Thailand. EM ywwatana@yahoo.com NR 29 TC 13 Z9 13 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD DEC PY 2005 VL 33 IS 12 BP 1486 EP 1492 DI 10.1016/j.exphem.2005.09.006 PG 7 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 999MK UT WOS:000234393400007 PM 16338491 ER PT J AU Bibbiani, F Oh, JD Kielaite, A Collins, MA Smith, C Chase, TN AF Bibbiani, F Oh, JD Kielaite, A Collins, MA Smith, C Chase, TN TI Combined blockade of AMPA and NMDA glutamate receptors reduces levodopa-induced motor complications in animal models of PD SO EXPERIMENTAL NEUROLOGY LA English DT Article DE AMPA; NMDA; Parkinson's; dyskinesias; levodopa ID PARKINSONS-DISEASE; INDUCED DYSKINESIAS; RESPONSE ALTERATIONS; TYROSINE PHOSPHORYLATION; DOPAMINE; FLUCTUATIONS; ANTAGONISTS; AMANTADINE; PREVENTS; MONKEYS AB AMPA and NMDA receptors, abundantly expressed on striatal medium spiny neurons, have been implicated in the regulation of corticostriatal synaptic efficacy. To evaluate the contribution of both glutamate receptor types to the pathogenesis of motor response alterations associated with dopaminergic treatment, we studied the ability of the selective AMPA receptor antagonist GYKI-47261 and the selective NMDA receptor antagonists, MK-801 and amantadine, to mitigate these syndromes in rodent and primate models of Parkinson's disease. The effects of GYKI-47261 and amantadine (or MK-801), alone and in combination, were compared for their ability to modify dyskinesias induced by levodopa. In rats, simultaneous administration of subthreshold doses of AMPA and NMDA receptor antagonists completely normalized the wearing-off response to acute levodopa challenge produced by chronic levodopa treatment (P < 0.05). In primates, the glutamate antagonists GYKI-47261 and amantadine, co-administered at low doses (failing to alter dyskinesia scores), reduced levodopa-induced dyskinesias by 5 1% (P < 0.05). The simultaneous AMPA and NMDA receptor blockade acts to provide a substantially greater reduction in the response alterations induced by levodopa than inhibition of either of these receptors alone. The results suggest that mechanisms mediated by both ionotropic glutamate receptors make an independent contribution to the pathogenesis of these motor response changes and further that a combination of both drug types may provide relief from these disabling complications at lower and thus safer and more tolerable doses than required when either drug is used alone. Published by Elsevier Inc. C1 NINDS, ETB, NIH, Bethesda, MD 20892 USA. Cent Michigan Univ, Dept Psychol, Mt Pleasant, MI 48859 USA. RP Chase, TN (reprint author), Hamilton Pharmaceut Inc, Suite 707,1825 K St NW, Sydney, NSW 2006, Australia. EM tchase@hamiltonpharma.com NR 46 TC 78 Z9 84 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 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD DEC PY 2005 VL 196 IS 2 BP 422 EP 429 DI 10.1016/j.expneurol.2005.08.017 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 987WG UT WOS:000233547700023 PM 16203001 ER PT J AU Shears, SB AF Shears, SB TI Can intervention in inositol phosphate signalling pathways improve therapy for cystic fibrosis? SO EXPERT OPINION ON THERAPEUTIC TARGETS LA English DT Review DE Ca2+-activated Cl- channel (CaCC); cystic fibrosis; inositol phosphate ID TRANSMEMBRANE CONDUCTANCE REGULATOR; ACTIVATED CHLORIDE CONDUCTANCE; INTRACELLULAR CL-CONCENTRATION; DEPENDENT PROTEIN-KINASE; AIRWAY EPITHELIAL-CELLS; ION-TRANSPORT; LUNG-DISEASE; LINE T-84; CALCIUM; CHANNELS AB Airway epithelial cells from cystic fibrosis (CF) individuals cannot secrete adequate Cl- through cystic fibrosis transmembrane regulator, and their Na+ channel (ENaC) activity is increased so that excessive Na+ and water is absorbed from the lumen. These aberrant transport activities can, at least partly, be compensated by pharmacologically increasing the activities of Ca2+-activated Cl-channels (CaCCs). The therapeutic value of this approach is currently being examined in clinical trials of candidate CF drugs such as INS-37217 (Inspire Pharmaceuticals) and Moli1901 (Lantibio, Inc.). This review argues that these drug development programmes will be helped if one can fully understand how the CaCCs are inhibited by inositol 3,4,5,6-tetrakisphosphate (Ins(3,4,5,6)P-4), so that there can be pharmacological intervention in this process. Furthermore, genes that encode enzymes controlling Ins(3,4,5,6)P-4 metabolism should be viewed as impacting upon CaCC activity; this, in turn, may influence the severity of the CF condition. Expression profiling of genes that regulate inositol phosphate metabolism may also illuminate variability in patient response to treatment regimens that target CaCCs. Compounds have been developed that can activate CaCCs by antagonising their inhibition by Ins(3,4,5,6)P4. One member of this drug family (INO-4995; Inologic) was recently shown to inhibit ENaC, thereby reducing fluid absorbtion by airway epithelial cells. C1 NIEHS, US Dept HHS, NIH, Inositol Phosphate Signaling Grp, Res Triangle Pk, NC 27709 USA. RP Shears, SB (reprint author), NIEHS, US Dept HHS, NIH, Inositol Phosphate Signaling Grp, Res Triangle Pk, NC 27709 USA. NR 63 TC 4 Z9 4 U1 0 U2 1 PU ASHLEY PUBLICATIONS LTD PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1472-8222 J9 EXPERT OPIN THER TAR JI Expert Opin. Ther. Targets PD DEC PY 2005 VL 9 IS 6 BP 1307 EP 1317 DI 10.1517/14728222.9.6.1307 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 992BW UT WOS:000233860200014 PM 16300477 ER PT J AU Perez, KM Titus-Ernstoff, L Hatch, EE Troisi, R Wactawski-Wende, J Palmer, JR Noller, K Hoover, RN AF Perez, KM Titus-Ernstoff, L Hatch, EE Troisi, R Wactawski-Wende, J Palmer, JR Noller, K Hoover, RN CA Natl Canc Inst DES Follow-up Study TI Reproductive outcomes in men with prenatal exposure to diethylstilbestrol SO FERTILITY AND STERILITY LA English DT Article DE DES; male infertility; reproductive outcomes ID TESTICULAR GENE-EXPRESSION; GENITAL-TRACT; LONG-TERM; FOLLOW-UP; PREGNANCY; INUTERO; ABNORMALITIES; WOMEN; METABOLISM; FERTILITY AB Objective: To examine prenatal diethylstilbestrol (DES) exposure in relation to male reproductive outcomes. Design: Prospective observational study: Setting: Participants were identified through record review, clinical trial participation, or an obstetrics clinic. Patient(s): A total of 1,085 DES-exposed and 1,047 unexposed men. Intervention(s): Participants were exposed prenatally to DES through the mother's obstetrics care or clinical trial participation. Main Outcome Measure(s): Infertility; never fathering a pregnancy or live birth; number of pregnancies or live births fathered. Result(s): We found little evidence that prenatal DES exposure affects the likelihood of never fathering a pregnancy or live birth, or influences the mean number of fathered pregnancies or live births. Our data suggest that DES-exposed men are slightly more likely to experience infertility (relative risk [RR] = 1.3, 95% confidence interval [CI] = 1.0-1.6). The DES dose and gestational timing did not influence infertility or the number of pregnancies or live births fathered, but: results were inconsistent for dose effects on the likelihood of never fathering a pregnancy or a live birth: Conclusion(s): Prenatal DES exposure may be associated with a slightly increased risk of having an infertility experience, but does not increase the likelihood of never fathering a pregnancy or a live birth, or the number of pregnancies or live births fathered. C1 Dartmouth Hitchcock Med Ctr, Lebanon, NH 03756 USA. SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA 02215 USA. NCI, Div Epidemiol & Genet, Bethesda, MD 20892 USA. SUNY Buffalo, Dept Obstet Gynecol, Buffalo, NY 14260 USA. Boston Univ, Sch Publ Hlth, Slone Epidemiol Unit, Boston, MA 02215 USA. Tufts Univ New England Med Ctr, Dept Obstet & Gynecol, Boston, MA 02111 USA. RP Titus-Ernstoff, L (reprint author), Dartmouth Hitchcock Med Ctr, 1 Med Ctr Dr, Lebanon, NH 03756 USA. EM Linda.Titus-Ernstoff@Dartmouth.edu OI Palmer, Julie/0000-0002-6534-335X; Hatch, Elizabeth/0000-0001-7901-3928 FU NCI NIH HHS [CP-50531, N01-CP-01012] NR 32 TC 10 Z9 10 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD DEC PY 2005 VL 84 IS 6 BP 1649 EP 1656 DI 10.1016/j.fertnstert.2005.05.062 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 996OT UT WOS:000234184200016 PM 16359959 ER PT J AU Murabito, JM Yang, Q Fox, CS Cupples, LA AF Murabito, JM Yang, Q Fox, CS Cupples, LA TI Genome-wide linkage analysis to age at natural menopause in a community-based sample: the Framingham Heart Study SO FERTILITY AND STERILITY LA English DT Article DE menopause; genetics; linkage analysis ID VARIANCE-COMPONENTS; PEDIGREES; REPRODUCIBILITY; HERITABILITY; VALIDITY; WOMEN AB Objective: To identify chromosomal regions linked to age at natural menopause. Design: Two-generation families studied with a 10-centimorgan (cM) genome-wide scan. Setting: The Framingham Study, a community-based epidemiologic study: Patient(s): A total of 861 women in 291 families reporting a natural menopause (mean age at menopause, 49 years). Intervention(s): None: Main Outcome Measure(s): Multipoint variance components linkage analysis was performed with Genehunter software (Whitehead Institute, Massachusetts Institute of Technology, Boston, MA) forage at natural menopause. Result(s): In the crude variance components analysis, 11 chromosomes had a log odds ratio (LOD) score of >= 1.0. Two chromosomal regions revealed suggestive linkage: chromosome 8 at 26 cM (LOD 2.6; nearest marker GATA23D06) and chromosome 16 at 11 cM (LOD 2.4; nearest marker ATA41E04). In the analysis adjusted for generation, smoking, and body mass index, chromosome 11 revealed suggestive linkage at 113 cM (LOD 2.1; nearest marker GATA23E06). Conclusion(s): We have identified novel loci suggestive for linkage to age at natural menopause. Further research is needed to identify genes involved in the onset of menopause, which might provide insights into loss of fertility. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Boston Univ, Gen Internal Med Sect, Sch Med, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Dept Neurol, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Biostat, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NHLBI, Bethesda, MD 20892 USA. RP Murabito, JM (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM Murabito@bu.edu RI Yang, Qiong/G-5438-2014; OI Murabito, Joanne/0000-0002-0192-7516; Cupples, L. Adrienne/0000-0003-0273-7965 FU NHLBI NIH HHS [N01-HC-25195] NR 24 TC 26 Z9 28 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD DEC PY 2005 VL 84 IS 6 BP 1674 EP 1679 DI 10.1016/j.fertnstert.2005.05.046 PG 6 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 996OT UT WOS:000234184200020 PM 16359963 ER PT J AU Hewett, SJ Espey, MG Uliasz, TF Wink, DA AF Hewett, SJ Espey, MG Uliasz, TF Wink, DA TI Neurotoxicity of nitroxyl: Insights into HNO and NO biochemical imbalance SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE protein nitration; neurotoxicity; excitotoxicity; nitroxyl; nitric oxide; cell death; free radicals ID NITRIC-OXIDE SYNTHASE; PEROXYNITRITE DECOMPOSITION CATALYSTS; CORTICAL CELL-CULTURE; SUPEROXIDE-DISMUTASE; ANGELIS SALT; NEUROTRANSMITTER RELEASE; CYTOCHROME-C; GLUTATHIONE METABOLISM; SODIUM TRIOXODINITRATE; GLUTAMATE-RECEPTOR AB Nitroxyl anion (NO-), and/or its conjugate acid, HNO, may be formed in the cellular milieu by several routes under both physiological and pathophysiological conditions. Since experimental evidence suggests that certain reactive nitrogen oxide species can contribute significantly to cerebral ischemic injury, we investigated the neurotoxic potential of HNO/NO- using Angeli's salt (AS), a spontaneous HNO/ NO--generating compound. Exposure to AS resulted in a time- and concentration-dependent increase in neural cell death that progressed markedly following the initial exposure. Coadministration of the donor with Tempol (1 mM), a one-electron oxidant that converts NO- to NO, prevented its toxic effect, as did the concomitant addition of Fe(III)TPPS. Media containing various chelators, catalase, Cu/Zn superoxide dismutase, or carboxy-PTIO did not ameliorate AS-mediated neurotoxicity, ruling out the involvement of transition metal complexes, H2O2, O-2(-), and NO, respectively. A concentration-dependent increase in supernatant protein 3-nitrotyrosine immunoreactivity was observed when cultures were exposed to AS under aerobic conditions, an effect lost in the absence of oxygen. A bell-shaped curve for augmented AS-mediated nitration was observed with increasing Fe(III)TPPS concentration, which contrasted with its linear effect on abating cytotoxicity. Finally, addition of glutamate receptor antagonists, MK-801 (10 mu M) and CNQX (30 mu M) to the cultures abrogated toxicity when given during, but not following, AS exposure; as did pretreatment with the exocytosis inhibitor, tetanus toxin (300 ng/ml). Taken together, our data suggest that under aerobic conditions, AS toxicity is initiated via HNO/NO- but progresses via secondary excitotoxicity. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Connecticut, Sch Med, Dept Neurosci, Farmington, CT 06030 USA. NCI, Tumor Biol Sect, Radiat Biol Branch, Bethesda, MD 20892 USA. RP Hewett, SJ (reprint author), Univ Connecticut, Sch Med, Dept Neurosci, Farmington, CT 06030 USA. EM shewett@neuron.uchc.edu; SP@nih.gov OI Hewett, Sandra/0000-0002-2987-3791 FU NINDS NIH HHS [R01 NS036812] NR 74 TC 23 Z9 23 U1 0 U2 1 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 2005 VL 39 IS 11 BP 1478 EP 1488 DI 10.1016/j.freeradbiomed.2005.07.007 PG 11 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 987ZJ UT WOS:000233556200008 PM 16274883 ER PT J AU Nadif, R Mintz, M Jedlicka, A Bertrand, JP Kleeberger, SR Kauffmann, F AF Nadif, R Mintz, M Jedlicka, A Bertrand, JP Kleeberger, SR Kauffmann, F TI Association of CAT polymorphisms with catalase activity and exposure to environmental oxidative stimuli SO FREE RADICAL RESEARCH LA English DT Article DE catalase; polymorphism; coal dust; lymphotoxin; tumor necrosis factor; catalase by environment interaction ID SUPEROXIDE DISMUTASES; GENE-TRANSCRIPTION; HUMAN ERYTHROCYTES; HYDROGEN-PEROXIDE; PROMOTER REGION; LUNG-DISEASES; COAL-MINERS; STRESS; SUSCEPTIBILITY; INFLAMMATION AB We tested the hypotheses that catalase activity is modified by CAT single nucleotide polymorphisms (SNPs) (-262;-844), and by their interactions with oxidant exposures (coal dusts, smoking), lymphotoxin alpha (LTA , Nco I) and tumor necrosis factor (TNF , -308) in 196 miners. Erythrocyte catalase, superoxide dismutase, and glutathione peroxidase activities were measured. The CAT -262 SNP was related to lower catalase activity (104, 87 and 72 k/g hemoglobin for CC, CT and TT, respectively, p < 0.0001). Regardless of CAT SNPs, the LTA Nco I but not the TNF-308 SNP was associated with catalase activity (p = 0.04 and p = 0.8). CAT - 262 T carriers were less frequent in highly exposed miners (OR = 0.39 [0.20-0.78], p = 0.007). In CAT- 262 T carriers only, catalase activity decreased with high dust exposure (p = 0.01). Haplotype analyses (combined CAT SNPs) confirm these results. Results show that CAT- 262 and LTA Nco I SNPs, and interaction with coal dust exposure, influenced catalase activity. C1 INSERM, U472 Epidemiol & Biostat, IFR69, F-94807 Villejuif, France. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. HBL, Lorraine Coal Mine Basin, Dept Med, Freyming Merlebach, France. NIEHS, Lab Resp Biol, Res Triangle Pk, NC 27709 USA. RP Nadif, R (reprint author), INSERM, U472 Epidemiol & Biostat, IFR69, 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, P01 ES009606] NR 34 TC 55 Z9 60 U1 0 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1071-5762 J9 FREE RADICAL RES JI Free Radic. Res. PD DEC PY 2005 VL 39 IS 12 BP 1345 EP 1350 DI 10.1080/10715760500306711 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 986DO UT WOS:000233430100008 PM 16298864 ER PT J AU Summers, RM Yao, JH Pickhardt, PJ Franaszek, M Bitter, I Brickman, D Krishna, V Choi, JR AF Summers, RM Yao, JH Pickhardt, PJ Franaszek, M Bitter, I Brickman, D Krishna, V Choi, JR TI Computed tomographic virtual colonoscopy computer-aided polyp detection in a screening population SO GASTROENTEROLOGY LA English DT Article ID CONTRAST BARIUM ENEMA; CT COLONOGRAPHY; COLORECTAL NEOPLASIA; COLONIC POLYPS; DIAGNOSIS SCHEME; PERFORMANCE; FEASIBILITY; EXPERIENCE AB Background & Aims: The sensitivity of computed tomographic (CT) virtual colonoscopy (CT colonography) for detecting polyps varies widely in recently reported large clinical trials. Our objective was to determine whether a computer program is as sensitive as optical colonoscopy for the detection of adenomatous colonic polyps on CT virtual colonoscopy. Methods: The data set was a cohort of 1186 screening patients at 3 medical centers. All patients underwent same-day virtual and optical colonoscopy. Our enhanced gold standard combined segmental unblinded optical colonoscopy and retrospective identification of precise polyp locations. The data were randomized into separate training (n = 394) and test (n = 792) sets for analysis by a computer-aided polyp detection (CAD) program. Results: For the test set, per-polyp and per-patient sensitivities for CAD were both 89.3% (25/28; 95% confidence interval, 71.8%-97.7%) for detecting retrospectively identifiable adenomatous polyps at least 1 cm in size. The false-positive rate was 2.1 (95% confidence interval, 2.0-2.2) false polyps per patient. Both carcinomas were detected by CAD at a false-positive rate of 0.7 per patient; only :1 of 2 was detected by optical colonoscopy before segmental unblinding. At both 8-mm and 10-mm adenoma size thresholds, the per-patient sensitivities of CAD were not significantly different from those of optical colonoscopy before segmental unblinding. Conclusions: The per-patient sensitivity of CT virtual colonoscopy CAD in an asymptomatic screening population is comparable to that of optical colonoscopy for adenomas 8 mm and is generalizable to new CT virtual colonoscopy data. C1 NIH, Dept Diagnost Radiol, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Natl Naval Med Ctr, Bethesda, MD USA. Walter Reed Army Med Ctr, Washington, DC 20307 USA. RP Summers, RM (reprint author), NIH, Dept Diagnost Radiol, Warren Grant Magnuson Clin Ctr, Bldg 10,Room 1C660,10 Ctr Dr MSC 1182, Bethesda, MD 20892 USA. EM rms@nih.gov FU CLC NIH HHS [Z01 CL040003-03]; Intramural NIH HHS NR 54 TC 179 Z9 183 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD DEC PY 2005 VL 129 IS 6 BP 1832 EP 1844 DI 10.1053/j.gastro.2005.08.054 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 995DE UT WOS:000234079300005 PM 16344052 ER PT J AU Ruhl, CE Everhart, JE AF Ruhl, CE Everhart, JE TI Coffee and tea consumption are associated with a lower incidence of chronic liver disease in the United States SO GASTROENTEROLOGY LA English DT Article ID GAMMA-GLUTAMYL-TRANSFERASE; AGED JAPANESE MEN; SELF-DEFENSE OFFICIALS; HEPATOCELLULAR-CARCINOMA; POPULATION DETERMINANTS; CAFFEINE CONSUMPTION; ALCOHOL-CONSUMPTION; LIFE-STYLE; RISK; CIRRHOSIS AB Background & Aims: Coffee drinking has been suggested to protect against liver injury, but it is uncertain whether this is of clinical significance. We examined the relationship of coffee and tea consumption with the incidence of hospitalization or death from chronic liver disease (CLD). Method : Participants in the population-based, first National Health and Nutrition Examination Survey, 1971 - 1975, were asked about coffee and tea consumption, which was categorized as < 1 cup (mean, 0.2 cups), 1 to 2 cups, and > 2 cups per day (mean, 4.0 cups). A second analysis included persons who, in 1982 - 1984, were asked more detailed questions on coffee and tea drinking. Participants were followed through 1992 - 1993 for a hospital or death certificate diagnosis of CLD or cirrhosis (ICD-9-CM 571). Hazard rate ratios for CLD according to coffee and tea intake were calculated using Cox proportional hazards analysis. Results: Among 9849 persons followed for a median of 19.0 years (range, 0.02 - 22.1), the cumulative incidence of CLD was 1.4%. In multivariate analysis, participants who drank > 2 cups per day had less than half the rate of CLD as those who drank < 1 cup per day (hazard ratio, 0.43, 95% confidence interval: 0.24 - 0.78). Protection by coffee and tea was limited to persons at higher risk for liver diseases from heavier alcohol intake, overweight, diabetes, or high iron saturation. Among 9650 participants who provided detailed drink information in 1982 - 1984, intake of regular ground coffee and of caffeine was associated with lower incidence of CLD. Conclusions: Coffee and tea drinking decreases the risk of clinically significant CLD. C1 Social & Sci Syst Inc, Silver Spring, MD 20910 USA. NIDDK, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. RP Ruhl, CE (reprint author), Social & Sci Syst Inc, 8757 Georgia Ave,12th Floor, Silver Spring, MD 20910 USA. EM cruhl@s-3.com FU NIDDK NIH HHS [N01-DK-1-2478] NR 44 TC 118 Z9 121 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD DEC PY 2005 VL 129 IS 6 BP 1928 EP 1936 DI 10.1053/j.gast.2005.08.056 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 995DE UT WOS:000234079300014 PM 16344061 ER PT J AU Pineda-Salgado, L Craig, EJ Blank, RB Kessler, DS AF Pineda-Salgado, L Craig, EJ Blank, RB Kessler, DS TI Expression of Panza, an alpha 2-macroglobulin, in a restricted dorsal domain of the primitive gut in Xenopus laevis SO GENE EXPRESSION PATTERNS LA English DT Article DE Xenopus laevis; alpha 2-macroglobulin; endoderm; gut; digestive tract; liver ID BETA-AMYLOID PEPTIDE; GROWTH-FACTOR-BETA; ALZHEIMERS-DISEASE; HUMAN ALPHA(2)-MACROGLOBULIN; FIBRIL FORMATION; GENE-EXPRESSION; BINDING-PROTEIN; CELL; RECEPTOR; ALPHA AB alpha 2-Macroglobulin is a major serum protein with diverse functions, including inhibition of protease activity and binding of growth factors, cytokines, and disease factors. We have cloned and characterized Panza, a new Xenopus laevis alpha 2-macroglobulin. Panza has 56-60% amino acid similarity with previously identified Xenopus, mouse, rat and human alpha 2-macroglobulins, indicating that Panza is a new member of the alpha 2-macroglobulin family. Panza mRNA is first detected at the beginning of neurulation in the dorsal endoderm lining the primitive gut (archenteron roof). At the completion of neurulation and continuing through the late tadpole stage, Panza is restricted to a dorsal domain of the gut endoderm adjacent to the notochord and extending along the entire anterior-posterior axis. With outgrowth of the tailbud, Panza expression persists in the chordaneural hinge at the posterior end of the differentiating notochord and extends into the floor plate of the posterior neural tube. As gut coiling commences, Panza expression is initiated in the liver, and the dorsal domain of Panza expression becomes limited to the midgut and hindgut. With further gut coiling, strong Panza expression persists in the liver, but is lost from other regions of the gut. The expression of Panza in endodermal cells adjacent to the notochord points to a potential role for Panza in signal modulation and/or morphogenesis of the primitive gut. (c) 2005 Elsevier B.V. All rights reserved. C1 Univ Penn, Sch Med, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA. Dartmouth Coll, Dept Sci Biol, Hanover, NH 03755 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Kessler, DS (reprint author), Univ Penn, Sch Med, Dept Cell & Dev Biol, 421 Curie Blvd,Room 1110, Philadelphia, PA 19104 USA. EM kesslerd@mail.med.upenn.edu FU NICHD NIH HHS [HD35159, R01 HD035159] NR 38 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-133X J9 GENE EXPR PATTERNS JI Gene Expr. Patterns PD DEC PY 2005 VL 6 IS 1 BP 3 EP 10 DI 10.1016/j.modgep.2005.09.001 PG 8 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 994RB UT WOS:000234047800001 PM 16275122 ER PT J AU Jiang, Q Li, WQ Aiello, FB Klarmann, K Keller, JR Durum, SK AF Jiang, Q Li, WQ Aiello, FB Klarmann, K Keller, JR Durum, SK TI Retroviral transduction of IL-7R alpha into IL-7R alpha(-/-) bone marrow progenitors: correction of lymphoid deficiency and induction of neutrophilia SO GENE THERAPY LA English DT Article DE IL-7; IL-7R; severe combined immunodeficiency; neutrophilia ID SEVERE COMBINED IMMUNODEFICIENCY; RECOMBINANT HUMAN INTERLEUKIN-7; T-CELL DEVELOPMENT; G-CSF RECEPTOR; IN-VIVO; HEMATOPOIETIC PROGENITORS; TRANSGENIC MICE; GENE-THERAPY; EXPRESSION; DIFFERENTIATION AB Defects in the gene for the IL-7 receptor (R) a chain are one cause of severe combined immunodeficiency disease (SCID) based on a strict requirement for IL-7 in T lymphoid development and survival. We tested the feasibility and potentially undesirable consequences of IL- 7R alpha gene transfer as a therapy for this genetic defect. The murine IL- 7Ra gene was introduced into IL- 7R alpha (/) one marrow progenitors using retrovirus and transplanted into Rag (/) recipient mice. Both alpha beta and gamma delta T cells were reconstituted in thymus and spleen showing proof of principle. B-cell development was also restored in some mice, but their numbers were much lower than in the T-cell compartment. Splenomegaly was observed due to an increase in neutrophils. We showed that hematopoeitic progenitors, after transfection with IL- 7R alpha, could respond to IL-7 in vitro by a striking production of neutrophils and other myeloid cells. These data indicate that although IL7 is a critical lymphopoietin, ectopic expression of its receptor on multipotential progenitors can also induce production of myeloid cells, presumably through survival and proliferation signals that are not restricted to lymphoid cells. This supports the stochastic model of progenitor differentiation, in which cytokines give permissive and not instructive signals. C1 NCI, FCRDC, Lab Mol Regulat, NIH, Frederick, MD 21702 USA. SAIC, Frederick, MD USA. RP Durum, SK (reprint author), NCI, FCRDC, Lab Mol Regulat, NIH, Bldg 560,Rm 31-71, Frederick, MD 21702 USA. NR 39 TC 9 Z9 9 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD DEC PY 2005 VL 12 IS 24 BP 1761 EP 1768 DI 10.1038/sj.gt.3302558 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 990MS UT WOS:000233748400004 PM 16208423 ER PT J AU Modi, WS Scott, K Goedert, JJ Vlahov, D Buchbinder, S Detels, R Donfield, S O'Brien, SJ Winkler, C AF Modi, WS Scott, K Goedert, JJ Vlahov, D Buchbinder, S Detels, R Donfield, S O'Brien, SJ Winkler, C TI Haplotype analysis of the SDF-1 (CXCL12) gene in a longitudinal HIV-1/AIDS cohort study SO GENES AND IMMUNITY LA English DT Article DE SDF-1 chemokine; epidemiology; haplotypes; HIV-1; AIDS ID CELL-DERIVED FACTOR; CHEMOKINE RECEPTOR CXCR4; VIRUS TYPE-1 INFECTION; DISEASE PROGRESSION; FACTOR-I; NEURONAL APOPTOSIS; HIV-INFECTION; AIDS COHORT; EXPRESSION; PROTEIN AB The stromal-derived factor-1 (SDF-1) chemokine gene encodes the only natural ligand for CXCR4, the coreceptor for the pathogenic X4 HIV-1 strains. A single-nucleotide polymorphism ( SNP) in the 30 untranslated region (SDF1-30A = rs1801157) of SDF-1 was reported to be protective against infection and progression in some, but not other, epidemiological studies. To identify additional alleles that may influence HIV-1 infection and progression to AIDS, nine SNPs ( including rs1801157) spanning 20.2 kb in and around the SDF-1 gene were genotyped in over 3000 African American ( AA) and European American ( EA) participants enrolled in five longitudinal HIV-1/AIDS natural cohort studies. Six or five haplotypes were present at frequencies greater than 5% in AA or EA, respectively. Six of the nine SNPs occur on only one common haplotype (45%), while the remaining three SNPs were found on multiple haplotypes, suggesting a complex history of recombination. Among EA, rs754618 was associated with an increased risk of infection (OR = 1.50, P = 0.03), while rs1801157 (SDF1-30A) was associated with protection against infection (OR = 0.63, P = 0.01). In the MACS cohort, rs1801157 was associated with AIDS-87 (RH = 0.31, P = 0.02) and with death (RH = 0.18, P = 0.02). Significant associations to a single disease outcome were found for two SNPs and one haplotype in AA. C1 NCI, SAIC Frederick, Frederick, MD 21702 USA. NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. San Francisco Dept Publ Hlth, San Francisco, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. Rho Inc, Chapel Hill, NC USA. NCI, Lab Genom Divers, Frederick, MD 21701 USA. RP Winkler, C (reprint author), NCI, SAIC Frederick, Frederick, MD 21702 USA. EM winkler@ncifcrf.gov FU NCI NIH HHS [N01 CO 56000] NR 55 TC 17 Z9 18 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 J9 GENES IMMUN JI Genes Immun. PD DEC PY 2005 VL 6 IS 8 BP 691 EP 698 DI 10.1038/sj.gene.6364258 PG 8 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 989EX UT WOS:000233656800007 PM 16177829 ER PT J AU Roth, MJ Hu, N Johnson, LL Quon-Hang, W Ahnen, DJ Iwamoto, M Dawsey, SM Taylor, PR Huppi, K AF Roth, MJ Hu, N Johnson, LL Quon-Hang, W Ahnen, DJ Iwamoto, M Dawsey, SM Taylor, PR Huppi, K TI beta-catenin splice variants and downstream targets as markers for neoplastic progression of esophageal cancer SO GENES CHROMOSOMES & CANCER LA English DT Article ID SQUAMOUS-CELL CARCINOMA; HIGH-RISK POPULATION; C-MYC; TRANSLATIONAL CONTROL; GENE-EXPRESSION; CHINA; ADENOCARCINOMA; AMPLIFICATION; FREQUENT; BCL-2 AB This study characterizes the frequency of exon 3 CTNNBI mutations and compares the expression of CTNNBI transcript variants and downstream targets MYC and WAFI (p21) across the neoplastic progression of esophageal squamous cell carcinomas (ESCCs). Mutational analysis was performed on 56 tumors and corresponding germline DNA, using primers to exon 3 of CTNNBI and SSCP DNA sequencing gels. Quantitative Real Time RT-PCR was performed on 45 foci representing the histological spectrum from normal to invasive cancer, using specific primer sets for alternative splice variants that differ by the presence (16A) or absence (16B) of a 159-by noncoding segment of exon 16 of CTNNBI, in conjunction with downstream targets MYC and WAFT. Two unique mutations were identified, S37F in the SxxxS repeat region, and a germline polymorphism, T59A. Thus, mutation of CTNNBI exon 3 is a rare event in this population. RTPCR analysis successfully confirmed the presence of both (beta-catenin splice variants in histologically normal and preneoplastic squamous epithelium, and invasive tumors of the esophagus, and identified a significant reduction in the 16Al16B ratio (P = 0.014) and an accompanying significant increase in the MYCIWAFI expression ratio (P = 0.001) with progression from normal mucosa to dysplasia. This represents the first identification of two CTNNBI transcripts in histologically "normal" esophageal squamous cells, squamous dysplasia, and invasive ESCC. These results show an increase in the minor mRNA (16B) isoform and changes in the expression of downstream markers consistent with increased transcription during the histological progression from normal to squamous dysplasia. Published 2005 Wiley-Liss, Inc.(dagger) C1 NCI, Nutrit Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD USA. Natl Ctr Complementary & Alternat Med, NIH, Bethesda, MD USA. Shanxi Canc Hosp, Taoyuan, Shanxi, Taiwan. Dept Vet Affairs Med Ctr, Denver, CO USA. NCI, Gene Silencing Sect, Ctr Adv Technol, NIH, Bethesda, MD USA. RP Roth, MJ (reprint author), NCI, Nutrit Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Suite 705,MSC 8314, Bethesda, MD 20892 USA. EM mr166i@nih.gov FU Intramural NIH HHS NR 26 TC 7 Z9 8 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD DEC PY 2005 VL 44 IS 4 BP 423 EP 428 DI 10.1002/gcc.20251 PG 6 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 972BN UT WOS:000232428900009 PM 16114033 ER PT J AU Atanassov, BS Barrett, JC Davis, BJ AF Atanassov, BS Barrett, JC Davis, BJ TI Homozygous germ line mutation in exon 27 of murine Brca2 disrupts the Fancd2-Brca2 pathway in the homologous recombination-mediated DNA interstrand cross-links' repair but does not affect meiosis SO GENES CHROMOSOMES & CANCER LA English DT Article ID FANCONI-ANEMIA PROTEIN; DOUBLE-STRAND BREAKS; NUCLEAR-COMPLEX; DIRECTED REPAIR; CANCER; DAMAGE; RAD51; MICE; HYPERSENSITIVITY; INSTABILITY AB The role of the region encoded by exon 27 of the Brca2 gene in DNA repair was studied in cells and tissues from Brca2(Delta 27/27) mice. The COOH-terminal truncated Brca2 localized to the nucleus in primary mouse embryo fibroblasts from Brca2(Delta 27/Delta 27) mice. Fluorescence-activated cell sorting (FACS) analysis demonstrated that these fibroblasts were hypersensitive to mitomycin C-induced cross-links, but not to double-strand breaks (DSBs) induced by irradiation. The gamma H2AX appearance kinetics and comet assay showed that DSBs were repaired through non-homologous end joining pathways, while interstrand cross-links were not repaired due to deficient homologous recombination pathways. Immunoprecipitation experiments showed that Fancd2 did not coprecipitate with the mutated Brca2. There were also no detectable Rad51-positive foci formed in these cells after damage. On the other hand, we did not find any difference during gametogenesis in mice harboring exon 27 truncating mutation of the Brca2 gene and control mice, and in both cases, Rad51 localized to the recombination foci. Our results suggest that exon 27 of murine Brca2 is crucial for the interaction of Brca2 and Fancd2 in Rad51-mediated recombination in response to DNA damage, but that this interaction is not taking place in the homologous recombination during meiosis. Published 2005 Wiley-Liss, Inc.(dagger) C1 NIEHS, Lab Womens Hlth, NIH, Res Triangle Pk, NC USA. NCI, Lab Biosyst & Canc, Canc Res Ctr, NIH, Bethesda, MD USA. RP Davis, BJ (reprint author), AstraZeneca R&D Boston, US Safety Assessment, 35 Gatehouse Pk, Waltham, MA 02415 USA. EM Barbara.Davis@astrazeneca.com NR 30 TC 16 Z9 16 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD DEC PY 2005 VL 44 IS 4 BP 429 EP 437 DI 10.1002/gcc.20255 PG 9 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 972BN UT WOS:000232428900010 PM 16127665 ER PT J AU Yamashita, T Allende, ML Kalkofen, DN Werth, N Sandhoff, K Proia, RL AF Yamashita, T Allende, ML Kalkofen, DN Werth, N Sandhoff, K Proia, RL TI Conditional LoxP-flanked glucosylceramide synthase allele controlling glycosphingolipid synthesis SO GENESIS LA English DT Article DE mouse; Ugcg; cre recombinase; glucosylceramide; sphingolipid ID CENTRAL-NERVOUS-SYSTEM; COMPLEX GANGLIOSIDES; KNOCKOUT MICE; GENE; GM3; DISRUPTION; DISEASE; DEGENERATION; EXPRESSION; DEFECTS AB Glycosphingolipids are organizational building blocks of plasma membranes that participate in key cellular functions, such as signaling and cell-to-cell interactions. Glucosylceramide synthase-encoded by the Ugcg gene-controls the first committed step in the major pathway of glycosphingolipid synthesis. Global disruption of the Ugcg gene in mice is lethal during gastrulation. We have now established a Ugcg allele flanked by IoxP sites (floxed). When cre recombinase was expressed in the nervous system under control of the nestin promoter, the floxed gene underwent recombination, resulting in a substantial reduction of Ugcg expression and of glycosphingolipid ganglio-series levels. The mice deficient in Ugcg expression in the nervous system show a striking loss of Purkinje cells and abnormal neurologic behavior. The floxed Ugcg allele will facilitate analysis of the function of glycosphingolipids in development, physiology, and in diseases such as diabetes and cancer. C1 NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. Univ Bonn, Kekule Inst Organ Chem & Biochem, D-5300 Bonn, Germany. RP Proia, RL (reprint author), NIDDKD, Genet Dev & Dis Branch, NIH, Bldg10,10 Ctr DR MSC 1821, Bethesda, MD 20892 USA. EM proia@nih.gov RI Proia, Richard/A-7908-2012 FU Intramural NIH HHS NR 25 TC 20 Z9 22 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 2005 VL 43 IS 4 BP 175 EP 180 DI 10.1002/gene.20167 PG 6 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 000WF UT WOS:000234492400003 PM 16283624 ER PT J AU Platts, AE Moldenhauer, JS Fayz, B Wang, DW Borgaonkar, DS Krawetz, SA AF Platts, AE Moldenhauer, JS Fayz, B Wang, DW Borgaonkar, DS Krawetz, SA TI LARaLink 2.0: A comprehensive aid to basic and clinical cytogenetic research SO GENETIC TESTING LA English DT Article ID LINKAGE; TOOLS; NCBI; WEB AB LARaLink 2.0 (Loci Analysis for Rearrangement Link) is an enabling web technology that permits the rapid retrieval of clinical cytogenetic and molecular data. New data mining capabilities have been incorporated into version 2.0, building upon LARaLink 1.0, to extend the utility of the system for applications in both the clinical and basic sciences. These include access to the Chromosomal Variation in Man database and the GEO database. Together these new resources enhance the user's ability to associate genotype with phenotype to identify potential gene candidates. Unlimited access for researchers exploring disease- gene relationships and for clinicians extending practice in patient care is available at LARaLink. bioinformatics.wayne.edu: 8080/unigene. C1 Wayne State Univ, Sch Med, Dept Obstet & Gynecol,Ctr Excellence, Ctr Mol Med & Genet,Inst Sci Comp,WSU Bioinformat, Detroit, MI 48201 USA. Wayne State Univ, Appl Genom Technol Ctr, Detroit, MI 48201 USA. NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. Wayne State Univ, Ctr Mol Med & Genet, Inst Comp Sci, Detroit, MI 48201 USA. RP Krawetz, SA (reprint author), Wayne State Univ, Sch Med, Dept Obstet & Gynecol,Ctr Excellence, Ctr Mol Med & Genet,Inst Sci Comp,WSU Bioinformat, 275 E Hancock, Detroit, MI 48201 USA. EM steve@compbio.med.wayne.edu RI Platts, Adrian/H-5633-2013 OI Platts, Adrian/0000-0001-9238-9647 NR 7 TC 2 Z9 2 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1090-6576 J9 GENET TEST JI Genet. Test. PD DEC PY 2005 VL 9 IS 4 BP 334 EP 341 DI 10.1089/gte.2005.9.334 PG 8 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 000YH UT WOS:000234497900010 PM 16379548 ER PT J AU Thon, G Hansen, KR Altes, SP Sidhu, D Singh, G Verhein-Hansen, J Bonaduce, MJ Klart, AJS AF Thon, G Hansen, KR Altes, SP Sidhu, D Singh, G Verhein-Hansen, J Bonaduce, MJ Klart, AJS TI The Clr7 and Clr8 directionality factors and the Pcu4 cullin mediate heterochromatin formation in the fission yeast Schizosaccharomyces pombe SO GENETICS LA English DT Article ID MATING-TYPE REGION; POSITION EFFECT VARIEGATION; HISTONE H3 METHYLATION; DNA-BINDING PROTEIN; RNA INTERFERENCE; CHROMODOMAIN PROTEIN; SACCHAROMYCES-CEREVISIAE; REPRESS TRANSCRIPTION; LYSINE-9 METHYLATION; NUCLEAR MORPHOLOGY AB Fission yeast heterochromatin is formed at centromeres, telomeres, and in the mating-type region where it mediates the transcriptional silencing of the mat2-P and mat3-M donor loci and the directionality of mating-type switching. We conducted a genetic screen for directionality mutants. This screen revealed the essential role of two previously uncharacterized factors, Clr7 and Clr8, in heterochromatin formation. Clr7 and Clr8 are required for localization of the Swi6 chromodomain protein and for histone H3 lysine 9 methylation, thereby influencing not only mating-type switching but also transcriptional silencing in all previously characterized heterochromatic regions, chromosome segregation, and meiotic recombination in the mating-type region. We present evidence for physical interactions between Clr7 and the mating-type region and between Ch-7 and the S. pombe cullin Pcu4, indicating that a complex containing these proteins mediates an early step in heterochromatin formation and implying a role for ubiquitination at this early stage prior to the action of the Clr4 histone methyl-transferase. Like Clr7 and Clr8, Pcu4 is required for histone H3 lysine 9 methylation, and bidirectional centromeric transcripts that are normally processed into siRNA by the RNAi machinery in wild-type cells are easily detected in cells lacking Clr7, Clr8, or Pcu4. Another physical interaction, between the nucleoporin Nup189 and Clr8, suggests that Clr8 might be involved in tethering heterochromatic regions to the nuclear envelope by association with the nuclear-pore complex. C1 Univ Copenhagen, Inst Mol Biol & Physiol, Dept Genet, DK-1353 Copenhagen K, Denmark. NCI, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA. RP Thon, G (reprint author), Univ Copenhagen, Inst Mol Biol & Physiol, Dept Genet, Oster Farimasgade 2A, DK-1353 Copenhagen K, Denmark. EM gen@my.molbio.ku.dk RI Thon, Genevieve/L-9497-2014 OI Thon, Genevieve/0000-0001-8550-5945 FU Intramural NIH HHS NR 70 TC 61 Z9 67 U1 0 U2 2 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD DEC PY 2005 VL 171 IS 4 BP 1583 EP 1595 DI 10.1534/genetics.105.048298 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 999RB UT WOS:000234407100014 PM 16157682 ER PT J AU Biessmann, H Prasad, S Semeshin, VE Andreyeva, EN Nguyen, Q Walter, MF Mason, JM AF Biessmann, H Prasad, S Semeshin, VE Andreyeva, EN Nguyen, Q Walter, MF Mason, JM TI Two distinct domains in Drosophila melanogaster telomeres SO GENETICS LA English DT Article ID POSITION EFFECT VARIEGATION; HET-A; POLYTENE CHROMOSOMES; CHROMATIN-STRUCTURE; DNA-SEQUENCES; P-ELEMENT; HETEROCHROMATIN PROTEIN-1; SACCHAROMYCES TELOMERES; TRANSPOSABLE ELEMENT; DIFFERENT MECHANISMS AB Telomeres are generally considered heterochromatic. On the basis of DNA composition, the telomeric region of Drosophila melanogaster contains two distinct subdomains: a subtelomeric region of repetitive DNA, termed TAS, and a terminal array of retrotransposons, which perform the elongation function instead of telomerase. We have identified several P-element insertions into this retrotransposon array and compared expression levels of transgenes with similar integrations into TAS and euchromatic regions. In contrast to insertions in TAS, which are silenced, reporter genes in the terminal HeT-A, TAHRL, or TART retroelements did not exhibit repressed expression in comparison with the same transgene construct in euchromatin. These data, in combination with cytological studies, provide evidence that the subtelomeric TAS region exhibits features resembling heterochromatin, while the terminal retrotransposon array exhibits euchromatic characteristics. C1 Natl Inst Environm Hlth Sci, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. Univ Calif Irvine, Ctr Dev Biol, Irvine, CA 92697 USA. Russian Acad Sci, Lab Mol Cytogenet, Inst Cytol & Genet, Novosibirsk 630090, Russia. Univ Calif Irvine, Dept Biol Chem, Irvine, CA 92697 USA. RP Mason, JM (reprint author), Natl Inst Environm Hlth Sci, Mol Genet Lab, 111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM masonj@niehs.nih.gov RI Andreyeva, Evgeniya/N-2733-2015 FU Intramural NIH HHS; NIEHS NIH HHS [Z01 ES021054-12]; NIGMS NIH HHS [GM 56729, R01 GM056729-04, R01 GM056729] NR 58 TC 21 Z9 22 U1 0 U2 3 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD DEC PY 2005 VL 171 IS 4 BP 1767 EP 1777 DI 10.1534/genetics.105.048827 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 999RB UT WOS:000234407100029 PM 16143601 ER PT J AU Yampolsky, LY Allen, C Shabalina, SA Kondrashov, AS AF Yampolsky, LY Allen, C Shabalina, SA Kondrashov, AS TI Persistence time of loss-of-function mutations at nonessential loci affecting eye color in Drosophila melanogaster SO GENETICS LA English DT Article ID DELETERIOUS-MUTATION; NATURAL-POPULATIONS; VIABILITY; GENES; SELECTION; EVOLUTION; RATES AB Persistence time of a mutant allele, the expected number of generations before its elimination from the population, can be estimated as the ratio of the number of segregating mutations per individual over the mutation rate per generation. We screened two natural populations of Drosophila melanogaster for mutations causing clear-cut eye phenotypes and detected 25 mutant alleles, falling into 19 complementation groups, in 1164 haploid genomes, which implies 0.021 eye mutations/genome. The de novo haploid mutation rate for the same set of loci was estimated as 2 x 10(-4) in a 10-generation mutation-accumulation experiment. Thus, the average persistence time of all mutations causing clear-cut eye phenotypes is similar to 100 generations (95% confidence interval: 61-219). This estimate shows that the strength of selection against phenotypically drastic alleles of nonessential loci is close to that against recessive lethals. In both cases, deleterious alleles are apparently eliminated by selection against heterozygous individuals, which show no visible phenotypic differences from wild type. C1 E Tennessee State Univ, Dept Biol Sci, Johnson City, TN 37614 USA. NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. RP Yampolsky, LY (reprint author), E Tennessee State Univ, Dept Biol Sci, Johnson City, TN 37614 USA. EM yampolsk@etsu.edu RI Shabalina, Svetlana/N-8939-2013 OI Shabalina, Svetlana/0000-0003-2272-7473 NR 34 TC 2 Z9 2 U1 2 U2 7 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD DEC PY 2005 VL 171 IS 4 BP 2133 EP 2138 DI 10.1534/genetics.105.046094 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 999RB UT WOS:000234407100060 PM 16118190 ER PT J AU Ostrander, EA Wayne, RK AF Ostrander, EA Wayne, RK TI The canine genome SO GENOME RESEARCH LA English DT Review ID RADIATION HYBRID MAP; DOMESTIC DOG; LINKAGE DISEQUILIBRIUM; GENE-THERAPY; MOLECULAR-GENETICS; MITOCHONDRIAL-DNA; WILD CANIDS; COAT COLOR; CHROMOSOME ASSIGNMENT; POPULATION-STRUCTURE AB The dog has emerged as a premier species for the study of morphology, behavior, and disease. The recent availability of a high-quality draft sequence lifts the dog system to a new threshold. We provide a primer to use the dog genome by first focusing on its evolutionary history. We overview the relationship of dogs to wild canids and discuss their origin and domestication. Dogs clearly originated from a substantial number of gray wolves and dog breeds define distinct genetic units that can be divided into at least four hierarchical groupings. We review evidence showing that dogs have high levels of linkage disequilibrium. Consequently, given that dog breeds express specific phenotypic traits and vary in behavior and the incidence of genetic disease, genomic-wide scans for linkage disequilibrium may allow the discovery of genes influencing breed-specific characteristics. Finally, we review studies that have utilized the dog to understand the genetic underpinning of several traits, and we summarize genomic resources that can be used to advance such studies. We suggest that given these resources and the unique characteristics of breeds, that the dog is a uniquely valuable resource for studying the genetic basis of complex traits. C1 NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA. RP Ostrander, EA (reprint author), NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. EM eostrand@mail.nih.gov OI Ostrander, Elaine/0000-0001-6075-9738 NR 107 TC 111 Z9 114 U1 8 U2 76 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 2005 VL 15 IS 12 BP 1706 EP 1716 DI 10.1101/gr.3736605 PG 11 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 992ZG UT WOS:000233921900014 PM 16339369 ER PT J AU Chase, K Carrier, DR Adler, FR Ostrander, EA Lark, KG AF Chase, K Carrier, DR Adler, FR Ostrander, EA Lark, KG TI Interaction between the X chromosome and an autosome regulates size sexual dimorphism in Portuguese Water Dogs SO GENOME RESEARCH LA English DT Article ID QUANTITATIVE TRAIT LOCI; BODY SIZE; GENE-EXPRESSION; MATING SYSTEM; RENSCHS-RULE; LINKED GENES; GROWTH; SELECTION; MAP; INACTIVATION AB Size sexual dimorphism occurs in almost all mammals. In Portuguese Water Dogs, much of the difference in skeletal size between females and males is due to the interaction between a Quantitative Trait Locus (QTL) on the X-chromosome and a QTL linked to Insulin-like Growth Factor 1 (IGF-1) on the CFA 15 autosome. In females, the haplotype of CFA 15 resulting in small size is dominant. In males, the haplotype for large size is dominant. Females homozygous at the CHM marker on the X chromosome and homozygous for the large size CFA 15 haplotype are, on average, as large as large males. However, all females that are heterozygous at the CHM marker are small, regardless of their CFA 15 genotype. This interaction suggests a genetic mechanism that in turn leads to a scenario for the evolution of size sexual dimorphism consistent with a proposal of Lande that sexual dimorphism can evolve because females secondarily become smaller than males as a consequence of natural selection for optimal size. Our results also can explain Rensch's Rule, which states that size is often positively correlated with the level of size sexual dimorphism. C1 Univ Utah, Dept Biol, Salt Lake City, UT 84112 USA. NHGRI, Comparat Genet Sect, NIH, Bethesda, MD 20892 USA. RP Univ Utah, Dept Biol, Salt Lake City, UT 84112 USA. EM lark@bioscience.utah.edu OI Ostrander, Elaine/0000-0001-6075-9738 FU NIGMS NIH HHS [R01 GM063056, R01 GM063056-04]; PHS HHS [63056] NR 38 TC 28 Z9 29 U1 0 U2 4 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 EI 1549-5469 J9 GENOME RES JI Genome Res. PD DEC PY 2005 VL 15 IS 12 BP 1820 EP 1824 DI 10.1101/gr.3712705 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 992ZG UT WOS:000233921900025 PM 16339380 ER PT J AU Thomas, R Scott, A Langford, CF Fosmire, SP Jubala, CM Lorentzen, TD Hitte, C Karlsson, EK Kirkness, E Ostrander, EA Galibert, F Lindblad-Toh, K Modiano, JF Breen, M AF Thomas, R Scott, A Langford, CF Fosmire, SP Jubala, CM Lorentzen, TD Hitte, C Karlsson, EK Kirkness, E Ostrander, EA Galibert, F Lindblad-Toh, K Modiano, JF Breen, M TI Construction of a 2-Mb resolution BAC microarray for CGH analysis of canine tumors SO GENOME RESEARCH LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; COPY NUMBER CHANGES; DOG; ABERRATIONS; KARYOTYPE; CLONES AB Recognition of the domestic dog as a model for the comparative Study of human genetic traits has led to major advances in canine genomics. The pathophysiological similarities shared between many human and dog diseases extend to a range of cancers. Human tumors frequently display recurrent chromosome aberrations, many of which are hallmarks of particular tumor subtypes. Using a range of molecular cytogenetic techniques we have generated evidence indicating that this is also true of canine tumors. Detailed knowledge of these genomic abnormalities has the potential to aid diagnosis, prognosis, and the selection of appropriate therapy in both species. We recently improved the efficiency and resolution of canine cancer cytogenetics studies by developing a small-scale genomic microarray comprising a panel of canine BAC clones representing subgenomic regions of particular interest. We have now extended these studies to generate a comprehensive canine comparative genomic hybridization (CGH) array that comprises 1158 canine BAC clones ordered throughout the genome with an average interval of 2 ME. Most of the clones (84.3%) have been assigned to a precise cytogenetic location by fluorescence in situ hybridization (FISH), and 98.5% are also directly anchored within the Current canine genome assembly, permitting direct translation from cytogenetic aberration to DNA sequence. We are now using this resource routinely for high-throughput array CGH and single-locus probe analysis of a range of canine cancers. Here we provide examples of the varied applications of this resource to tumor cytogenetics, in combination with other molecular cytogenetic techniques. C1 N Carolina State Univ, Coll Vet Med, Dept Mol Biomed Sci, Raleigh, NC 27606 USA. Wellcome Trust Sanger Inst, Microarray Facil, Cambridge CB10 1SA, England. Univ Colorado, Intregrated Dept Immunol, Colorado Springs, CO 80214 USA. Univ Colorado, AMC Canc Ctr, Colorado Springs, CO 80214 USA. Fred Hutchinson Canc Res Ctr, Clin Res & Human Biol Div, Seattle, WA 98109 USA. CNRS, UMR 6061, Fac Med, F-35043 Rennes, France. Harvard Univ, Broad Inst, Cambridge, MA 02141 USA. MIT, Cambridge, MA 02141 USA. Boston Univ, Bioinformat Program, Boston, MA 02215 USA. Inst Gen Res, Rockville, MD 20850 USA. NHGRI, NIH, Bethesda, MD 20892 USA. Univ Colorado, Ctr Canc, Denver, CO 80214 USA. RP Breen, M (reprint author), N Carolina State Univ, Coll Vet Med, Dept Mol Biomed Sci, 4700 Hillsborough St, Raleigh, NC 27606 USA. EM Matthew_Breen@ncsu.edu OI Karlsson, Elinor/0000-0002-4343-3776; Modiano, Jaime/0000-0001-6398-7648; Ostrander, Elaine/0000-0001-6075-9738 FU Wellcome Trust NR 25 TC 37 Z9 39 U1 0 U2 1 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 2005 VL 15 IS 12 BP 1831 EP 1837 DI 10.1101/gr.3825705 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 992ZG UT WOS:000233921900027 PM 16339382 ER PT J AU Nilsen, TIL Romundstad, PR Troisi, R Potischman, N Vatten, LJ AF Nilsen, TIL Romundstad, PR Troisi, R Potischman, N Vatten, LJ TI Birth size and colorectal cancer risk: a prospective population based study SO GUT LA English DT Article ID ISCHEMIC-HEART-DISEASE; IGF-BINDING-PROTEINS; ABERRANT CRYPT FOCI; BREAST-CANCER; CHILDHOOD GROWTH; DIABETES-MELLITUS; TESTICULAR CANCER; PROSTATE-CANCER; SUBSEQUENT RISK; FETAL-GROWTH AB Objective: To study whether birth size influences colorectal cancer risk in adulthood. Design: A cohort of Norwegian men and women identified from midwives' birth records with long term cancer follow up through the Norwegian Cancer Registry. Setting: St Olav's University Hospital, Trondheim, Norway. Participants: 16 016 women and 19 681 men born between 1920 and 1958 and alive in 1960. Outcome measures: Incidence rate ratios (RRs) for colorectal cancer with 95% confidence intervals (CIs) and two sided p values for trend across categories of birth dimensions. Results: Men whose birth length was less than 51 cm had a nearly twofold higher risk of colorectal cancer (RR 1.9 (95% CI 1.0-3.7)) compared with men who were 53 cm or more, after adjustment for birth cohort, maternal age at childbearing, length of gestation, gestational hypertension or pre-eclampsia, birth order, maternal height, and indicators of maternal socioeconomic status. The association displayed a linear trend across categories of birth length (p(trend) = 0.03). Among men, similar associations were found for birth weight and head circumference, but for women there was no association between any of these birth dimensions and risk of colorectal cancer. Conclusion: The results suggest that among men, but not women, being relatively short at birth is associated with increased risk of colorectal cancer in adulthood, indicating that intrauterine growth could be important for colorectal carcinogenesis. C1 Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, Fac Med, NO-7489 Trondheim, Norway. NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. RP Vatten, LJ (reprint author), Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, Fac Med, NO-7489 Trondheim, Norway. EM lars.vatten@medisin.ntnu.no OI Romundstad, Pal Richard/0000-0003-2061-4336 NR 34 TC 19 Z9 19 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD DEC PY 2005 VL 54 IS 12 BP 1728 EP 1732 DI 10.1136/gut.2004.060475 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 983ND UT WOS:000233238300015 PM 15843419 ER PT J AU Bierl, C Karem, K Poon, AC Swan, D Tortolero-Luna, G Follen, M Wideroff, L Unger, ER Reeves, WC AF Bierl, C Karem, K Poon, AC Swan, D Tortolero-Luna, G Follen, M Wideroff, L Unger, ER Reeves, WC TI Correlates of cervical mucosal antibodies to human papillomavirus 16: Results from a case control study SO GYNECOLOGIC ONCOLOGY LA English DT Article; Proceedings Paper CT 4th International Cancer Conference CY MAY 18-22, 2005 CL Houston, TX SP Johns Hopkins Med Inst, Natl Canc Inst, Ctr Dis Control, M D Anderson Canc Ctr, European Inst Oncol, Univ Turin, Med Sch, Mirano Med Ctr ID HUMAN-PAPILLOMAVIRUS TYPE-16; VIRUS-LIKE PARTICLES; IMMUNE-RESPONSES; IGA RESPONSES; INFECTION; HPV-16; WOMEN; DNA; NEOPLASIA; PROTEINS AB Background While the cervical mucosal immune response to human papillomavirus (HPV) infection is believed to be central to viral clearance, it is not well characterized. We performed this analysis to determine correlates of HPV-16-specific mucosal antibody response in women at high risk for infection with HPV. Methods. Cervical mucosal and serum samples were obtained from participants in a case control study that measured demographic risk factors of cervical disease and HPV infection. An HPV-16 L1-virus-like particle ELISA was used to detect HPV-16-specific IgA and IgG. Antibody results were correlated to demographic characteristics, sexual history, cervical disease, and HPV detection. Results. Cervical anti-HPV-16 IgA and IgG inversely correlated with HPV DNA, HPV-16 DNA, and cervical disease. Conclusions. These findings suggest that mucosal antibodies may protect against HPV infection and cervical disease. However additional longitudinal studies evaluating serum and mucosal antibody correlates of incident, persistent, and clearing HPV infection are needed. In addition, standardization of mucosal sample collection and testing methods are required. C1 Ctr Dis Control & Prevent, Viral Exanthems & Herpesvirus Branch, Div Viral & Rickettsial Dis, Atlanta, GA 30333 USA. Univ Texas, MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA. Univ Texas, Sch Publ Hlth, Houston, TX 77030 USA. NCI, Appl Res Branch, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. RP Unger, ER (reprint author), Ctr Dis Control & Prevent, Viral Exanthems & Herpesvirus Branch, Div Viral & Rickettsial Dis, Atlanta, GA 30333 USA. EM cbie2606@ginp.usyd.edu.au; kdk6@cdc.gov; alysia@gcorgiapoon.net; dcsl@cdc.gov; gtortole@mdanderson.org; mfollen@mdanderson.org; widerofl@mail.nih.gov; eru0@cdc.gov; wcr1@cdc.gov RI Hernandez, Jessica/G-6527-2011; OI Unger, Elizabeth/0000-0002-2925-5635 FU NCI NIH HHS [Y1-CN-0101-01] NR 17 TC 12 Z9 13 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD DEC PY 2005 VL 99 IS 3 SU 1 BP S262 EP S268 DI 10.1016/j.ygyno.2005.07.100 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 000ZV UT WOS:000234502500070 PM 16229879 ER PT J AU Solomon, D AF Solomon, D TI Update on cervical screening SO GYNECOLOGIC ONCOLOGY LA English DT Editorial Material C1 NCI, Div Canc Prevent, NIH, Rockville, MD 20852 USA. RP Solomon, D (reprint author), NCI, Div Canc Prevent, NIH, 6130 Execut Blvd,EPN 2130, Rockville, MD 20852 USA. EM ds87v@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD DEC PY 2005 VL 99 IS 3 SU 1 BP S13 EP S13 DI 10.1016/j.ygyno.2005.07.035 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 000ZV UT WOS:000234502500005 PM 16419183 ER PT J AU Trimble, EL AF Trimble, EL TI Grants, clinical trials, and building research teams SO GYNECOLOGIC ONCOLOGY LA English DT Editorial Material C1 NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Trimble, EL (reprint author), NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. EM tt6m@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD DEC PY 2005 VL 99 IS 3 SU 1 BP S6 EP S6 DI 10.1016/j.ygyno.2005.07.032 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 000ZV UT WOS:000234502500002 PM 16419182 ER PT J AU Trimble, T AF Trimble, T TI Global strategies for cervical cancer control in the 21st century SO GYNECOLOGIC ONCOLOGY LA English DT Editorial Material C1 NCI, Bethesda, MD 20892 USA. RP Trimble, T (reprint author), NCI, 6130 Execut Blvd,Suite 741,MSC 7436, Bethesda, MD 20892 USA. EM Tt6m@nih.gov NR 0 TC 0 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD DEC PY 2005 VL 99 IS 3 SU 1 BP S245 EP S245 DI 10.1016/j.ygyno.2005.07.096 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 000ZV UT WOS:000234502500066 PM 16419215 ER PT J AU Ahmet, I Lakatta, EG Talan, MI AF Ahmet, I Lakatta, EG Talan, MI TI Pharmacological stimulation of beta(2)-adrenergic receptors (beta(2)AR) enhances therapeutic effectiveness of beta(1)AR blockade in rodent dilated ischemic cardiomyopathy SO HEART FAILURE REVIEWS LA English DT Article DE beta-adrenergic receptor subtypes; chronic heart failure; rat; myocardial infarction; left ventricular remodeling ID CARDIAC MYOCYTE APOPTOSIS; HEART-FAILURE; MYOCARDIAL-INFARCTION; BETA(2) AGONISTS; CARVEDILOL; METOPROLOL; MORTALITY AB Background. We have reported that beta(2) adrenoreceptor (beta(2)AR) stimulation is anti-apoptotic, and has strong beneficial effect on cardiac remodeling in an experimental model of post myocardial infarction chronic heart failure (CHF) in rats. Here we investigate whether the addition of chronic pharmacological beta(2)AR stimulation enhances the therapeutic effects of beta(1)AR blockade on cardiac remodeling in the same model. Methods and Results. Metoprolol, a beta(1)AR blocker, given alone (beta(1)) or in combination with beta(2)AR agonist, fenoterol (beta(1)beta(2)) were administered to rats via drinking water for 6 weeks, beginning 2 weeks following permanent coronary ligation. Progressive left ventricular (LV) remodeling of untreated animals, assessed by repeated echocardiography, occurred during the observation time, i.e., 42% and 25% increases in end-systolic and end-diastolic LV volumes respectively, 27% fall in ejection fraction, and 35% infarct expansion. Pressure-volume loop analyses at 2d and 8th post infarction weeks showed continuous deterioration of systolic and diastolic functions and arterio-ventricular mismatch. Histological evaluation at the end of 8 weeks revealed the MI expansion and hypertrophy of cardiomyocytes. beta(1)beta(2) prevented LV remodeling, MI expansion and cardiomyocytes hypertrophy to a greater degree than beta(1), due, in large part, to a vasodilatory effect of beta(2)AR stimulation and thus improvement of arterio-ventricular mismatch. The abnormal diastolic performance improved only in beta(1)beta(2). beta(1)beta(2) treatment reduced myocardial apoptosis throughout myocardium, but beta(1) reduced apoptopsis only in the areas remote from MI. Conclusion. The therapeutic effects of chronic beta(1)AR blockade on cardiac remodeling of heart failure are enhanced and extended when supplemented with beta(2)AR stimulation. C1 NIA, Cardiovasc Sci Lab, Intramural Res Program, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Talan, MI (reprint author), NIA, Cardiovasc Sci Lab, Intramural Res Program, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM talanm@grc.nia.nih.gov FU Intramural NIH HHS NR 19 TC 42 Z9 44 U1 1 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1382-4147 J9 HEART FAIL REV JI Heart Fail. Rev. PD DEC PY 2005 VL 10 IS 4 BP 289 EP 296 DI 10.1007/s10741-005-7543-3 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 028TR UT WOS:000236512200005 PM 16583177 ER PT J AU Hassan, R Alexander, R AF Hassan, R Alexander, R TI Nonpleural mesothelioma: Mesothelioma of the peritoneum, tunica vaginalis, and pericardium SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Review ID BENIGN CYSTIC MESOTHELIOMA; DIFFERENTIATED PAPILLARY MESOTHELIOMA; SERUM CA-125 LEVELS; OF-THE-LITERATURE; MALIGNANT MESOTHELIOMA; INTRAPERITONEAL CHEMOTHERAPY; CYTOREDUCTIVE SURGERY; MULTICYSTIC MESOTHELIOMA; ABDOMINAL RADIATION; UNITED-STATES AB Mesotheliomas are tumors that arise from the mesothelial cells of the pleura, peritoneum, pericardium, or tunica vaginalis. Although the number of new mesothelioma cases diagnosed each year in the United States seems to be leveling off or decreasing, several other countries are projected to have continued increased incidence of mesothelioma over the next several years. Of the approximately 2500 new cases of mesothelioma in the United States each year, most are pleural mesotheliomas. The peritoneum is the second most common site of mesothelioma development and accounts for approximately 10% to 20% of all mesotheliomas. Mesotheliomas that involve die pericardium or originate from the tunica vaginalis are rare tumors. Given the rarity of these tumors, it is difficult to obtain precise information regarding their 'incidence, natural history, and optimal management. C1 NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Hassan, R (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Room 5116, Bethesda, MD 20892 USA. EM hassanr@mail.nih.gov NR 105 TC 23 Z9 25 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD DEC PY 2005 VL 19 IS 6 BP 1067 EP + DI 10.1016/j.hoc.2005.09.005 PG 22 WC Oncology; Hematology SC Oncology; Hematology GA 998PZ UT WOS:000234332600006 PM 16325124 ER PT J AU Hoofnagle, JH AF Hoofnagle, JH TI AASLD 2005 distinguished service award to Dr. Leonard B. Seeff SO HEPATOLOGY LA English DT Biographical-Item C1 NIDDKD, Liver Dis Res Branch, NIH, Bethesda, MD 20892 USA. RP Hoofnagle, JH (reprint author), NIDDKD, Liver Dis Res Branch, NIH, 31 Ctr Dr,Bldg 31,Room 9A27, Bethesda, MD 20892 USA. EM hoofnaglej@extra.niddk.nih.gov NR 0 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD DEC PY 2005 VL 42 IS 6 BP 1246 EP 1247 DI 10.1002/hep.20986 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 989TS UT WOS:000233697400002 PM 16317697 ER PT J AU Heller, T Seeff, LB AF Heller, T Seeff, LB TI Viral load as a predictor of progression of chronic hepatitis C? SO HEPATOLOGY LA English DT Editorial Material ID POLYMERASE CHAIN-REACTION; LIVER FIBROSIS PROGRESSION; VIRUS-RNA LEVELS; NATURAL-HISTORY; HISTOLOGICAL FEATURES; UNITED-STATES; INFECTION; DISEASE; SERUM; GENOTYPE C1 NIDDKD, NIH, Bethesda, MD 20892 USA. RP Seeff, LB (reprint author), NIDDKD, NIH, 31 Ctr Dr Blvd,31A,Rm 9A-27, Bethesda, MD 20892 USA. EM seeffl@extra.niddk.nih.gov NR 36 TC 3 Z9 3 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD DEC PY 2005 VL 42 IS 6 BP 1261 EP 1263 DI 10.1002/hep.20982 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 989TS UT WOS:000233697400007 PM 16317702 ER PT J AU Pascale, RM Simile, MM Calvisi, DF Frau, M Muroni, MR Seddaiu, MA Daino, L Muntoni, MD De Miglio, MR Thorgeirsson, SS Feo, F AF Pascale, RM Simile, MM Calvisi, DF Frau, M Muroni, MR Seddaiu, MA Daino, L Muntoni, MD De Miglio, MR Thorgeirsson, SS Feo, F TI Role of HSP90, CDC37, and CRM1 as modulators of P16(INK4A) activity in rat liver carcinogenesis and human liver cancer SO HEPATOLOGY LA English DT Article ID HEPATOCELLULAR-CARCINOMA; C-MYC; GENETIC PREDISPOSITION; CELL-PROLIFERATION; KINASE CHAPERONE; DOWN-REGULATION; PROTEIN; LESIONS; HEPATOCARCINOGENESIS; P16 AB Current evidence indicates that neoplastic nodules induced in liver of Brown Norway (BN) rats genetically resistant to hepatocarcinogenesis are not prone to evolve into hepatocellular carcinoma. We show that BN rats subjected to diethylnitrosamine/2-acetylaininofluorene/partial hepatectomy treatment with a "resistant hepatocyte" protocol displayed higher number of glutathione-S-transferase 7-7(+) hepatocytes when compared with susceptible Fisher 344 (F344) rats, both during and at the end of 2-acetylaminofluorene treatment. However, DNA synthesis declined in BN but not F344 rats after completion of reparative growth. Upregulation of p16(INK4A), Hsp90, and Cdc37 genes; an increase in Cdc37-Cdk4 complexes; and a decrease in p16(INK4A)-Cdk4 complexes occurred in preneoplastic liver, nodules, and hepatocellular carcinoma of F344 rats. These parameters did not change significantly in BN rats. E2f4 was equally expressed in the lesions of both strains, but Crm1 expression and levels of E2f4-Crm1 complex were higher in F344 rats. Marked upregulation of P16(INK4A) was associated with moderate overexpression of HSP90, CDC37, E2F4, and CRMI in human hepatocellular carcinomas with a better prognosis. In contrast, strong induction of HSP90, CDC37, and E2F4 was paralleled by P16(INK4A) downregulation and high levels of HSP90-CDK4 and CDC37-CDK4 complexes in hepatocellular carcinomas with poorer prognosis. CDC37 downregulation by small interfering RNA inhibited in vitro growth of HepG2 cells. In conclusion, our findings underline the role of Hsp90/Cdc37 and E2f4/Crm1 systems in the acquisition of a susceptible or resistant carcinogenic phenotype. The results also suggest that protection by CDC37 and CRM1 against growth restraint by P16(INK4A) influences the prognosis of human hepatocellular carcinoma. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270-9139/suppmatlindex.html). C1 Univ Sassari, Dipartimento Sci Biomed, Sez Patol Sperimentale & Oncol, Div Expt Pathol & Oncol, I-07100 Sassari, Italy. NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Feo, F (reprint author), Univ Sassari, Dipartimento Sci Biomed, Sez Patol Sperimentale & Oncol, Div Expt Pathol & Oncol, Via P Manzella 4, I-07100 Sassari, Italy. EM feo@uniss.it OI DAINO, Lucia Maria Elisa/0000-0002-4021-2994 NR 45 TC 59 Z9 61 U1 2 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD DEC PY 2005 VL 42 IS 6 BP 1310 EP 1319 DI 10.1002/hep.20962 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 989TS UT WOS:000233697400013 PM 16317707 ER PT J AU Osawa, Y Hannun, YA Proia, RL Brenner, DA AF Osawa, Y Hannun, YA Proia, RL Brenner, DA TI Roles of AKT and sphingosine kinase in the antiapoptotic effects of bile duct ligation in mouse liver SO HEPATOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; INDUCED HEPATOCYTE APOPTOSIS; HUMAN HEPATIC MYOFIBROBLASTS; FAS-MEDIATED APOPTOSIS; FACTOR-ALPHA; GENE-TRANSFER; 1-PHOSPHATE; ACTIVATION; PATHWAY AB Tumor necrosis factor (TNF) receptor- and Fas-mediated apoptosis are major death processes of hepatocytes in liver disease. Although antiapoptotic effects in the injured liver promote chronic hepatitis and carcinogenesis, scant information is known about these mechanisms. To explore this issue, we compared acute liver injury after TNF-alpha or anti-Fas antibody (Jo2) between livers from sham-operated mice and chronic injured liver via bile duct ligation (BDL). BDL inhibited hepatocyte apoptosis induced by TNF-a but not by Jo2. On the other hand, BDL inhibited the massive hemorrhage seen in livers treated with either TNF-a or Jo2. Inactivation of AKT blocked the antiapoptotic effect of BDL. Sphingosine kinase knockout mice also lost the antihemorrhagic effect of BDL and attenuated the antiapoptotic effects of BDL. In bile duct-ligated livers, hepatic stellate cells (HSCs) were activated and produced tissue inhibitor of metalloproteinase I in a sphingosine kinase (SphK-)-1-dependent mechanism. In conclusion, BDL exerts antiapoptotic effects that appear to require activation of AKT in hepatocytes and SphK in HSCs. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html). C1 Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY 10032 USA. Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. NIDDKD, Genet Dis & Dev Branch, NIH, Bethesda, MD 20892 USA. RP Columbia Univ, Coll Phys & Surg, Dept Med, 622 W 168th St,PH 8E-105J, New York, NY 10032 USA. EM dab2106@columbia.edu RI Proia, Richard/A-7908-2012 FU Intramural NIH HHS; NIAAA NIH HHS [R01 AA15055]; NIDDK NIH HHS [DK59340]; NIGMS NIH HHS [R01 GM041804] NR 29 TC 26 Z9 28 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD DEC PY 2005 VL 42 IS 6 BP 1320 EP 1328 DI 10.1002/hep.20967 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 989TS UT WOS:000233697400014 PM 16317686 ER PT J AU Hisada, M Chatterjee, N Kalaylioglu, Z Battjes, RJ Goedert, JJ AF Hisada, M Chatterjee, N Kalaylioglu, Z Battjes, RJ Goedert, JJ TI Hepatitis C virus load and survival among injection drug users in the United States SO HEPATOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; STAGE LIVER-DISEASE; CLASS-II GENOTYPE; NATURAL-HISTORY; ANTIRETROVIRAL THERAPY; DECOMPENSATION RISK; VIRAL LOAD; HTLV-II; INFECTION; HIV AB Persons chronically infected with hepatitis C virus (HCV), some of whom may be coinfected with HIV and human T-lymphotropic virus type H (HTLV-11), are at high risk for end-stage liver disease (ESLD). We evaluated whether ESLD death was associated with premorbid HCV RNA level or specific HCV protein antibodies among persons with or without HIV/HTLV-11 coinfection in a cohort of 6,570 injection drug users who enrolled in 9 US cities between 1987 and 1991. We compared 84 ESLD descendents and 305 randomly selected cohort participants with detectable HCV RNA, stratified by sex, race, HIV, and HTLV-11 strata. Relative hazard (RH) of ESLD death was derived from the proportional hazard model. Risk of ESLD death was unrelated to the intensity of antibodies against the HCV c-22(p), c-33(p), c-100(p), and NS5 proteins, individually or combined, but it increased with HCV RNA level (RHadj = 2.26 per log(10) IU/mL, 95% CI: 1.45-5.92). The association between HCV RNA level and ESLD death remained significant after adjustment for alcohol consumption (RHadj = 2.57 per log(10) IU/mL, 95% Cl: 1.50-8-10). Deaths from AIDS (n = 45) and other causes (n = 43) were unrelated to HCV RNA (RHadj = 1.14 and 1.29 per log(10) IU/mL, respectively). HIV infection was not associated with ESLD risk in multivariate analyses adjusted for HCV RNA. Men had an increased risk of ESLD death in unadjusted analyses (RH = 1.92, 95% Cl: 1.15-3.56) but not in multivariate analysis (RHadj = 0.98, 95% Cl: 0.48-2.88). Non-black patients were at increased risk for ESLD death (RHadj = 2.76, 95% Cl: 1.49-10.09). In conclusion, HCV RNA level is a predictor of ESLD death among persons with chronic HCV infection. C1 NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. Informat Management Serv Inc, Rockville, MD USA. Friends Res Inst, Baltimore, MD USA. RP Hisada, M (reprint author), NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 8008, Rockville, MD 20852 USA. EM hisadam@exchange.nih.gov FU Intramural NIH HHS NR 39 TC 23 Z9 24 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD DEC PY 2005 VL 42 IS 6 BP 1446 EP 1452 DI 10.1002/hep.20938 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 989TS UT WOS:000233697400029 PM 16317675 ER PT J AU Hashemi, M Alavian, SM Ghavami, S de Serres, FJ Salehi, M Doroudi, T Fard, AHM Mehrabifar, H Milani, B Shahri, SJS AF Hashemi, M Alavian, SM Ghavami, S de Serres, FJ Salehi, M Doroudi, T Fard, AHM Mehrabifar, H Milani, B Shahri, SJS TI High prevalence of alpha 1 antitrypsin phenotypes in viral hepatitis B infected patients in Iran SO HEPATOLOGY RESEARCH LA English DT Article DE alpha 1 antitrypsin; viral hepatitis B; chronic active hepatitis; cirrhosis ID CHRONIC LIVER-DISEASE; ALPHA-1 ANTI-TRYPSIN; ALPHA(1)-ANTITRYPSIN DEFICIENCY; HEPATOCELLULAR-CARCINOMA; CYTO-TOXICITY; CIRRHOSIS; ALPHA1-ANTITRYPSIN; EPIDEMIOLOGY; SERUM; PREVENTION AB Objective: Hepatitis B virus (HBV) infection is a major global public health problem. Approximately 2 billion people are infected worldwide and more than 350 million of these individuals are chronic carriers of HBV. Approximately 15-40% of infected patients will develop cirrhosis, liver failure, or hepatocellular carcinoma (HCC). Alpha I antitrypsin (AAT) deficiency is one of many factors that may be involved in abnormalities such as liver and lung disease, inflammatory joint diseases, and inflammatory eye diseases. In the present study, the role played by AAT in HBV infected individuals is analyzed. Methods: AAT phenotyping and trypsin inhibitory capacity (TIC) experiments were performed on 281 HBV infected patients who were referred to Tehran and Zahedan Hepatitis Center for a period of 3 years from June 2001 to September 2003. The same tests were performed on 257 individuals who did not suffer from any systemic diseases (control group). The case group was subdivided into three groups: carrier (36.7%), chronic (50.5%), and cirrhotic (12.8%). Results: The results showed that AAT phenotypes, MS, MZ, M(I)Z, and MIS, were significantly higher in the HBV group (p < 0.01). In addition, there was a significant difference in AAT phenotypes (MS, MZ, and MIZ) among inactive carriers and individuals in the chronic and cirrhotic group (p < 0.001). Conclusions: There is a high prevalence of moderate AAT (MS, MIS, and MV) and severely deficient (MZ and M(I)Z) phenotypes in Iranian HBV individuals. In addition, AAT deficiency might be a risk factor for infected HBV individuals progressing from the carrier stage to chronic and cirrhotic stages. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Zahedan Univ Med Sci, Sch Med, Dept Clin Biochem, Zahedan, Iran. Baghyat Allah Med Univ, Sch Med, Dept Internal Med, Tehran, Iran. Ctr Evaluat Risks Human Reprod, Environm Toxicol Program, Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. Zahedan Univ Med Sci, Sch Med, Dept Infect Dis, Zahedan, Iran. Zahedan Univ Med Sci, Sch Med, Dept Virol, Zahedan, Iran. Zahedan Univ Med Sci, Sch Med, Dept Internal Med, Zahedan, Iran. Tehran Hepatitis Ctr, Tehran, Iran. Gargan Azad Univ, Dept Lab Med, Gorgan, Iran. RP Ghavami, S (reprint author), Manitoba Inst Cell Biol, 675 McDermot Ave,Rm 0N6008, Winnipeg, MB R3E 0V9, Canada. EM ghavami@cc.umanitoba.ca RI Hashemi, Mohammad/H-2446-2016; Ghavami, Saeid/Q-8918-2016; OI Hashemi, Mohammad/0000-0002-6074-7101; Alavian., Seyed Moayed/0000-0002-4443-6602 NR 40 TC 13 Z9 16 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1386-6346 J9 HEPATOL RES JI Hepatol. Res. PD DEC PY 2005 VL 33 IS 4 BP 292 EP 297 DI 10.1016/j.hepres.2005.09.035 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 996IH UT WOS:000234167100007 PM 16260177 ER PT J AU Ilias, I Pacak, K AF Ilias, I Pacak, K TI Diagnosis and management of tumors of the adrenal medulla SO HORMONE AND METABOLIC RESEARCH LA English DT Review DE pheochromocytoma; paraganglioma; neuroblastoma; metanephrines; radionuclide imaging; surgery; laparoscopy ID HEREDITARY PHEOCHROMOCYTOMA; BIOCHEMICAL-DIAGNOSIS; EXTRAADRENAL PHEOCHROMOCYTOMA; PARAGANGLIOMAS; LOCALIZATION; SURGERY; NEUROBLASTOMA; RECURRENCE; NECK; HEAD AB The adrenal medulla consists of chromaffin cells, the site of catecholamine biosynthesis. Pheochromocytomas are chromaffin-cell tumors; 80-85% arise from the adrenal medulla and 15-20% arise from extra-adrenal chromaffin tissues (paragangliomas). Neuroblastomas are primitive tumors that derive from the same blastic precursor as in pheochromocytomas, and are distributed along the sympathetic nervous system. Pheochromocytomas account for 6.5% of incidentally discovered adrenal tumors; they are found in 50% of patients with multiple endocrine neoplasia 2A (MEN 2A) and 5-25% of patients with von Hippel-Lindau (VHL) syndrome. Neuroblastomas are the most common solid extra-cranial tumors in children, and account for 7-10% of all tumors. The diagnosis of pheochromocytoma should first be established biochemically by measuring plasma free metanephrines (the measurement of urinary fractionated metanephrines is the second choice). Measurements of homovanillic acid (HVA), norepinephrine and vanilmandelic acid (VMA) in urine are a necessity in patients with suspected neuroblastoma. Anatomical (radiological) imaging with computed tomography (CT) or magnetic resonance imaging (MRI) is necessary for both pheochromocytomas and neuroblastomas. Functional (nuclear medicine) methods are useful for both tumors. Scintigraphy with [I-123]-metaiodobenzylguanidine is the specific functional imaging test of first choice; if this is not available, scintigraphy with [I-131]-MIBG is the second choice. Other newer specific modalities that have been used for evaluating pheochromocytomas include positron emission tomography (PET) with [F-18]-F-fluorodopamine (F-DA) and [F-18]-F-dihydroxyphenylalanine (DOPA). These should be used when MIBG scintigraphy is negative. Primary treatment for both types of tumor is surgical; chemotherapy is used for inoperable disease. After successful surgery, survival of patients with benign, sporadic pheochromocytomas is believed to be equal to that of the general population. Depending on the extent of disease and age, patients with neuroblastomas have cure rates of 15-90 %. C1 Univ Patras, Dept Pharmacol, Sch Med, GR-26504 Rion Patras, Greece. NIH, Reprod Biol & Med Branch, Bethesda, MD USA. RP Ilias, I (reprint author), Univ Patras, Dept Pharmacol, Sch Med, GR-26504 Rion Patras, Greece. EM iliasi@upatras.gr NR 39 TC 40 Z9 50 U1 0 U2 1 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD DEC PY 2005 VL 37 IS 12 BP 717 EP 721 DI 10.1055/s-2005-921091 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 998QL UT WOS:000234334000001 PM 16372223 ER PT J AU Zhang, QJ Zulfiqar, F Xiao, XS Riazuddin, SA Ayyagari, R Sabar, F Caruso, R Sieving, PA Riazuddin, S Hejtmancik, JF AF Zhang, QJ Zulfiqar, F Xiao, XS Riazuddin, SA Ayyagari, R Sabar, F Caruso, R Sieving, PA Riazuddin, S Hejtmancik, JF TI Severe autosomal recessive retinitis pigmentosa maps to chromosome 1p13.3-p21.2 between D1S2896 and D1S457 but outside ABCA4 SO HUMAN GENETICS LA English DT Article ID CONE-ROD DYSTROPHY; TRANSPORTER GENE ABCR; CGMP-GATED CHANNEL; STARGARDT-DISEASE; RETINAL DYSTROPHY; ALPHA-SUBUNIT; MACULAR DEGENERATION; OCULAR PHENOTYPE; BETA-SUBUNIT; MUTATIONS AB A severe form of autosomal recessive retinitis pigmentosa (arRP) was identified in a large Pakistani family ascertained in the Punjab province of Pakistan. All affected individuals in the family had night blindness in early childhood, early complete loss of useful vision, and typical RP fundus changes plus macular degeneration. After exclusion of known arRP loci, a genomewide scan was performed using microsatellite markers at about 10 cM intervals and calculating two-point lod scores. PCR cycle dideoxymicleotide sequencing was used to sequence candidate genes inside the linked region for mutations. RP in this family shows linkage to markers in a 10.5 cM (8.9 Mbp) region of chromosome 1p13.3-p21.2 between DIS2896 and DIS457. DIS485 yields the highest lod score of 6.54 at theta=0. Sequencing the exons and intron-exon boundaries of five candidate genes and six ESTs in this region, OLFM3, GNAI3, LOC126987, FLJ25070, DKFZp586GO123, AV729694, BU662869, BU656110, BU171991, BQ953690, and CA397743, did not identify any causative mutations. This novel locus lies approximately 4.9 cM (7.1 Mbp) from ABCA4, which is excluded from the linked region. Identification and study of this gene may help to elucidate the phenotypic diversity of arRP mapping to this region. C1 NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore, Pakistan. Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, Guangzhou 510060, Peoples R China. Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48105 USA. RP Hejtmancik, JF (reprint author), NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bldg 10,Room 10B10,10 Ctr Dr,MSC 1860, Bethesda, MD 20892 USA. EM f3h@helix.nih.gov RI SHEIKH, RIAZUDDIN/L-2406-2015 NR 57 TC 15 Z9 15 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD DEC PY 2005 VL 118 IS 3-4 BP 356 EP 365 DI 10.1007/s00439-005-0054-4 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 001NF UT WOS:000234542900006 PM 16189710 ER PT J AU Bernig, T Breunis, W Brouwer, N Hutchinson, A Welch, R Roos, D Kuijpers, T Chanock, S AF Bernig, T Breunis, W Brouwer, N Hutchinson, A Welch, R Roos, D Kuijpers, T Chanock, S TI An analysis of genetic variation across the MBL2 locus in Dutch Caucasians indicates that 3 ' haplotypes could modify circulating levels of mannose-binding lectin SO HUMAN GENETICS LA English DT Article DE mannose-binding lectin; innate immunity; genetic association; haplotype association; haplotype-trait interaction ID LINKAGE DISEQUILIBRIUM; GENOTYPE DATA; ACTIVATES COMPLEMENT; HUMAN GENOME; PROTEIN; SERUM; DISEASE; TESTS; RECONSTRUCTION; SUSCEPTIBILITY AB Mannose-binding protein (MBL) is a critical component of innate immunity and provides first-line protection against pathogens. Both circulating MBL serum levels and functional activity have been correlated with common genetic variants in the MBL2 gene. Associations between MBL deficiency and severe infections have been reported in immuno-incompetent patients and for autoimmune disorders; however, measured MBL serum levels do not fully correlate with the 'secretor haplotypes'. Previously, the MBL2 locus was resequenced and determined that a recombination hotspot divides MBL2 into two haplotype blocks. It was sought to investigate whether additional variants, in either block structure could associate with MBL serum levels. Therefore, 31 common variants were analysed across the locus in 212 DNA samples of healthy Caucasian individuals with known MBL serum concentrations. The additional 5' variants were in strong linkage to the elements of the 'secretor haplotypes'; functional alleles B, C and D also lie on restricted haplotypes. Four variants in the 3' block (Ex4-1483T > C, Ex4-1067G > A, Ex4-901G > A and Ex4-710G > A) are components of a distinct haplotype block. The results of this study suggest that additional 5' variants as well as markers of distinct 3' haplotype blocks in MBL2 may contribute to circulating protein levels, but further studies are required to confirm these observations. Last, there could be a selective advantage for diversification of the 3' region of the gene. C1 NCI, Sect Genom Variat, Pediat Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. Univ Amsterdam, Acad Med Ctr, Emma Childrens Hosp, Amsterdam, Netherlands. Univ Amsterdam, Cent Lab Blood Transfus Serv, Sanquin Res Inst, Amsterdam, Netherlands. NCI, Ctr Adv Technol, Core Genotyping Facil, NIH, Bethesda, MD 20892 USA. RP Chanock, S (reprint author), NCI, Sect Genom Variat, Pediat Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. EM sc83a@nih.gov NR 50 TC 22 Z9 22 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD DEC PY 2005 VL 118 IS 3-4 BP 404 EP 415 DI 10.1007/s00439-005-0053-5 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 001NF UT WOS:000234542900011 PM 16208516 ER PT J AU Goldstein, DS Eldadah, BA Holmes, C Pechnik, S Moak, J Saleem, A Sharabi, Y AF Goldstein, DS Eldadah, BA Holmes, C Pechnik, S Moak, J Saleem, A Sharabi, Y TI Neurocirculatory abnormalities in Parkinson disease with orthostatic hypotension - Independence from levodopa treatment SO HYPERTENSION LA English DT Article DE hypotension; sympathetic nervous system; norepinephrine; baroreflex ID CARDIAC SYMPATHETIC DENERVATION; MULTIPLE SYSTEM ATROPHY; BAROREFLEX SENSITIVITY; AUTONOMIC FAILURE; PLASMA-CATECHOLAMINES; BLOOD-PRESSURE; LEWY BODIES; HUMAN-HEART; NOREPINEPHRINE; NEURONS AB Patients with Parkinson disease often have orthostatic hypotension. Neurocirculatory abnormalities underlying orthostatic hypotension might reflect levodopa treatment. Sixty-six Parkinson disease patients (36 with orthostatic hypotension, 15 off and 21 on levodopa; 30 without orthostatic hypotension) had tests of reflexive cardiovagal gain (decrease in interbeat interval per unit decrease in systolic pressure during the Valsalva maneuver; orthostatic increase in heart rate per unit decrease in pressure); reflexive sympathoneural function (decrease in pressure during the Valsalva maneuver; orthostatic increment in plasma norepinephrine); and cardiac and extracardiac noradrenergic innervation (septal myocardial 6-[F-18]fluorodopamine-derived radioactivity; supine plasma norepinephrine). Severity of orthostatic hypotension did not differ between the levodopa-untreated and levodopa-treated groups with Parkinson disease and orthostatic hypotension (-52 +/- 6 [SEM] versus -49 +/- 5 mm Hg systolic). The 2 groups had similarly low reflexive cardiovagal gain (0.84 +/- 0.23 versus 1.33 +/- 0.35 ms/mm Hg during Valsalva; 0.43 +/- 0.09 versus 0.27 +/- 0.06 bpm/mm Hg during orthostasis); and had similarly attenuated reflexive sympathoneural responses (97 +/- 29 versus 71 +/- 23 pg/mL during orthostasis; -82 +/- 10 versus -73 +/- 8 mm Hg during Valsalva). In patients off levodopa, plasma norepinephrine was lower in those with (193 +/- 19 pg/mL) than without (348 +/- 46 pg/mL) orthostatic hypotension. Low values for reflexive cardiovagal gain, sympathoneural responses, and noradrenergic innervation were strongly related to orthostatic hypotension. Parkinson disease with orthostatic hypotension features reflexive cardiovagal and sympathoneural failure and cardiac and partial extracardiac sympathetic denervation, independent of levodopa treatment. C1 NINDS, NIH, Clin Neurocardiol Sect, Bethesda, MD 20892 USA. RP Goldstein, DS (reprint author), NINDS, NIH, Clin Neurocardiol Sect, 10 Ctr Dr MSC-1620,bldg 10,Rm 6N252, Bethesda, MD 20892 USA. EM goldsteind@ninds.nih.gov FU Intramural NIH HHS NR 58 TC 56 Z9 58 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD DEC PY 2005 VL 46 IS 6 BP 1333 EP 1339 DI 10.1161/01.HYP.0000188052.69549.e4 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 987ZX UT WOS:000233557700021 PM 16216982 ER PT J AU Kingston, DGI Newman, DJ AF Kingston, DGI Newman, DJ TI Natural products as drug leads: An old process or the new hope for drug discovery? SO IDRUGS LA English DT Article DE drug discovery; microbial involvement; natural products ID ANTITUMOR; GENOMICS; TARGETS AB Although the use of natural products as leads to drugs waned in the early 1980s with the rise of combinatorial chemistry as a putative discovery tool, inspection of the chemical literature shows that research in natural products, in one guise or another, is alive and active and the 'chemical inspiration' from these privileged structures is leading to novel approaches in drug design and discovery. In this short article, we propose why we consider natural products are poised for a renaissance as tools for drug discovery. C1 Virginia Polytech Inst & State Univ, Dept Chem, Blacksburg, VA 24061 USA. NCI, Nat Prod Branch, Dev Therapeut Program, Frederick, MD 21702 USA. RP Kingston, DGI (reprint author), Virginia Polytech Inst & State Univ, Dept Chem, MC 0212, Blacksburg, VA 24061 USA. EM DKingston@vt.edu; dn22a@nih.gov OI Kingston, David/0000-0001-8944-246X NR 13 TC 24 Z9 24 U1 0 U2 5 PU CURRENT DRUGS LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1P 6LB, ENGLAND SN 1369-7056 J9 IDRUGS JI IDrugs PD DEC PY 2005 VL 8 IS 12 BP 990 EP 992 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 992KH UT WOS:000233882300013 PM 16320131 ER PT J AU Hughes, AL Packer, B Welch, R Chanock, SJ Yeager, M AF Hughes, AL Packer, B Welch, R Chanock, SJ Yeager, M TI High level of functional polymorphism indicates a unique role of natural selection at human immune system loci SO IMMUNOGENETICS LA English DT Article DE gene diversity; interleukin; natural selection; single nucleotide polymorphism ID NUCLEOTIDE SUBSTITUTION; OVERDOMINANT SELECTION; GENETIC-VARIATION; CANDIDATE GENES; EVOLUTION; POPULATION AB Several studies have shown that immune system proteins have on average a higher rate of amino acid evolution between different species of mammals than do most other proteins. To test whether immune-system-expressed loci show a correspondingly elevated rate of within-species nonsynonymous (amino acid altering) polymorphism, we examined gene diversity (heterozygosity) at 4,911 single nucleotide polymorphism (SNP) sites at 481 protein-coding loci. At loci with nonimmune functions, gene diversity at nonsynonymous SNP sites was typically lower than that at silent SNP sites (those not altering the amino acid sequence) in the same gene, a pattern that is an evidence of purifying selection acting to eliminate slightly deleterious variants. However, this pattern was not seen at nonsynonymous SNPs causing conservative amino acid replacements in immune system proteins, indicating that the latter are subject to a reduced level of functional constraint. Similarly, immune system genes showed higher gene diversities in their 5' noncoding regions than did other proteins. These results identified certain immune system loci that are likely to be subject to balancing selection that acts to maintain polymorphism in either coding or regulatory regions. C1 Univ S Carolina, Dept Biol Sci, Columbia, SC 29208 USA. NCI, Frederick Canc Res & Dev Ctr, Intramural Res Support Program, SAIC Frederick, Frederick, MD 21702 USA. NCI, Core Genotyping Facil, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. NCI, Sect Genom Variat, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Hughes, AL (reprint author), Univ S Carolina, Dept Biol Sci, Coker Life Sci Bldg,700 Sumter St, Columbia, SC 29208 USA. EM austin@biol.sc.edu FU NCI NIH HHS [N01-CO-12400]; NIGMS NIH HHS [GM43940] NR 21 TC 25 Z9 26 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD DEC PY 2005 VL 57 IS 11 BP 821 EP 827 DI 10.1007/s00251-005-0052-7 PG 7 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 995PB UT WOS:000234115200004 PM 16261383 ER PT J AU Kullberg, MC Jankovic, D Gorelick, PL Cheever, AW Sher, A AF Kullberg, MC Jankovic, D Gorelick, PL Cheever, AW Sher, A TI Colitis-protective T regulatory cells develop rapidly after Helicobacter hepaticus infection through an IL-10-independent mechanism that is partially controlled by MyD88 SO IMMUNOLOGY LA English DT Meeting Abstract C1 Univ York, Dept Biol, Immunol & Infect Unit, York YO10 5YW, N Yorkshire, England. Hull York Med Sch, York YO10 5YW, N Yorkshire, England. NIAID, Immunobiol Sect, LPD, NIH, Bethesda, MD 20892 USA. NCI, Anim Hlth Diagnost Lab, Frederick, MD 21702 USA. Biomed Res Inst, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD DEC PY 2005 VL 116 SU 1 BP 20 EP 20 PG 1 WC Immunology SC Immunology GA 987QC UT WOS:000233531400086 ER PT J AU Harker, J Tregoning, JS Bukreyev, A Yamaguchi, Y Mihm, D Collins, P Openshaw, PJM AF Harker, J Tregoning, JS Bukreyev, A Yamaguchi, Y Mihm, D Collins, P Openshaw, PJM TI Contrasting effects of virally expressed IFN-gamma and IL-4 in neonatal and adult mice SO IMMUNOLOGY LA English DT Meeting Abstract C1 St Marys Hosp, Imperial Coll London, NHLI, Dept Resp Med, London W2 1PG, England. NIAID, Infect Dis Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD DEC PY 2005 VL 116 SU 1 BP 25 EP 25 PG 1 WC Immunology SC Immunology GA 987QC UT WOS:000233531400106 ER PT J AU Fear, DJ McCloskey, N Lee, TH Felsenfeld, G Gould, H AF Fear, DJ McCloskey, N Lee, TH Felsenfeld, G Gould, H TI Immunoglobulin class switch recombination to IgE is not regulated by DNA methylation SO IMMUNOLOGY LA English DT Meeting Abstract C1 Kings Coll London, Randall Div, London SE1 1UL, England. Kings Coll London, London SE1 9RT, England. NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD DEC PY 2005 VL 116 SU 1 BP 31 EP 31 PG 1 WC Immunology SC Immunology GA 987QC UT WOS:000233531400134 ER PT J AU Schwartz, RH Singh, NJ Chen, C Chiodetti, L AF Schwartz, RH Singh, NJ Chen, C Chiodetti, L TI The impact of adaptive tolerance (in vivo anergy) in a mouse model of autoimmune arthritis SO IMMUNOLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD DEC PY 2005 VL 116 SU 1 BP 43 EP 43 PG 1 WC Immunology SC Immunology GA 987QC UT WOS:000233531400187 ER PT J AU Sarkar, K Kruhlak, MJ Erlandsen, SL Shaw, S AF Sarkar, K Kruhlak, MJ Erlandsen, SL Shaw, S TI Selective inhibition by rottlerin of macropinocytosis in monocyte-derived dendritic cells SO IMMUNOLOGY LA English DT Article DE antigen presentation; dendritic cells; fluid-phase endocytosis; GM-CSF; IL-4; monocytes; T lymphocytes ID PROTEIN-KINASE-C; EXOGENOUS SOLUBLE-ANTIGEN; CONSTITUTIVE MACROPINOCYTOSIS; ACTIN POLYMERIZATION; RESPIRATORY BURST; IL-4 PRODUCTION; DOWN-REGULATION; MAST-CELLS; A431 CELLS; RECEPTOR AB We present here the analysis of fluid-phase endocytosis (FPE) in human blood monocytes and monocyte-derived dendritic cells (MDDC) facilitated by our serendipitous identification of rottlerin as an efficient inhibitor of dendritic cell FPE (IC50 of 0.4 mu M). Rottlerin was found to be an excellent tool for FPE analysis: rapid-acting, irreversible and selective for FPE (as opposed to receptor-mediated endocytosis) at concentrations of 3 mu M and below. The inhibitory effect was not due to toxicity or visible change in membrane ruffles, but affects on cytoskeletal reorganization were evident in MDDC treated with relevant rottlerin concentrations during adhesion. A marked increase in FPE was observed in 1 hr interleukin (IL)-4 and granulocyte macrophage-colony stimulating factor (GM-CSF)-stimulated monocytes. Moreover, rottlerin inhibited the augmented FPE of 1-day cytokine treated monocytes and their augmented ability to induce T cell proliferative responses to tetanus toxoid. We conclude that rottlerin is a useful tool for investigating FPE and its functional importance. C1 NCI, Human Immunol Sect, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN USA. RP Shaw, S (reprint author), NCI, Human Immunol Sect, Expt Immunol Branch, NIH, Bldg 10,Room 4B36,10 Ctr Dr,MSC 1360, Bethesda, MD 20892 USA. EM sshaw@nih.gov FU Intramural NIH HHS NR 46 TC 52 Z9 52 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD DEC PY 2005 VL 116 IS 4 BP 513 EP 524 DI 10.1111/j.1365-2567.2005.02253.x PG 12 WC Immunology SC Immunology GA 984OC UT WOS:000233313200011 PM 16313365 ER PT J AU Jin, ZG Bohach, GA Shiloach, J Norris, SE Freedberg, DI Deobald, C Coxon, B Robbins, JB Schneerson, R AF Jin, ZG Bohach, GA Shiloach, J Norris, SE Freedberg, DI Deobald, C Coxon, B Robbins, JB Schneerson, R TI Conjugates of group A and W135 capsular polysaccharides of Neisseria meningitidis bound to recombinant Staphylococcus aureus enterotoxin C1: Preparation, physicochemical characterization, and immunological properties in mice SO INFECTION AND IMMUNITY LA English DT Article ID MOLECULAR-SIZE ANALYSIS; INFLUENZAE TYPE-B; CAPSULAR POLYSACCHARIDE; O-ACETYLATION; MENINGOCOCCAL MENINGITIS; ESCHERICHIA-COLI; BURKINA-FASO; IMMUNOGENICITY; SEROGROUP; VACCINE AB Neisseria meningitidis groups A (GAM) and W135 capsular polysaccharides (CPs) were bound to recombinant Staphylococcus aureus enterotoxin C1 (rSEC)The CPs were activated with 1-cyano-4-dimethylaminopyridinium tetrafluoroborate and then bound to adipic acid dihydrazide derivatives of rSEC. Syntheses were conducted with native GAM CP (GAMP), W135 CP (W135P), and ultrasonicated or hydrazine-treated W135P at various concentrations of reactants, pHs, and ionic strengths. The conjugates were characterized by compositional and serologic analyses, high-performance size-exclusion chromatography with multi-angle laser light scattering detection, and immunogenicity in 5- to 6-week-old mice. Conjugates injected subcutaneously in phosphate-buffered saline elicited immunoglobulin G (IgG) responses against their respective CPs and rSEC, whereas GAMP and W135P alone did not induce detectable CP antibodies. The O-acetyl content of W135P was low, and its removal had no adverse effect upon the conjugate's immunogenicity. Reduction of the molecular size of W135P by treatment with hydrazine improved the immunogenicity of W135P-rSEC. IgG anti-CP elicited by the conjugates showed complement-dependent bactericidal activity against their respective organisms, and IgG anti-rSEC neutralized the T-cell proliferative activity of native SEC. A bivalent formulation of GAMP-rSEC and W135P-rSEC elicited IgG anti-CP at comparable levels to those induced by the conjugates administered separately. C1 NICHHD, NIH, Bethesda, MD 20892 USA. NIDDK, NIH, Bethesda, MD 20892 USA. Univ Idaho, Dept Microbiol Mol Biol & Biochem, Moscow, ID 83844 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Jin, ZG (reprint author), NICHHD, NIH, Bethesda, MD 20892 USA. EM jinz@mail.nih.gov FU NCRR NIH HHS [P20 RR015587, P20-RR15587]; NIAID NIH HHS [U54AI57141, U54 AI057141] NR 42 TC 5 Z9 8 U1 0 U2 4 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 2005 VL 73 IS 12 BP 7887 EP 7893 DI 10.1128/IAI.73.12.7887-7893.2005 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 986WK UT WOS:000233480200012 PM 16299279 ER PT J AU Koya, V Moayeri, M Leppla, SH Daniell, H AF Koya, V Moayeri, M Leppla, SH Daniell, H TI Plant-based vaccine: Mice immunized with chloroplast-derived anthrax protective antigen survive anthrax lethal toxin challenge\ SO INFECTION AND IMMUNITY LA English DT Article ID BACILLUS-ANTHRACIS; TRANSGENIC CHLOROPLASTS; EXPRESSION; TOBACCO; GENE; PURIFICATION; STRATEGIES; EFFICACY AB The currently available human vaccine for anthrax, derived from the culture supernatant of Bacillus anthracis, contains the protective antigen (PA) and traces of the lethal and edema factors, which may contribute to adverse side effects associated with this vaccine. Therefore, an effective expression system that can provide a clean, safe, and edicacious vaccine is required. In an effort to produce anthrax vaccine in large quantities and free of extraneous bacterial contaminants, PA was expressed in transgenic tobacco chloroplasts by inserting the pagA gene into the chloroplast genome. Chloroplast integration of the pagA gene was confirmed by PCR and Southern analysis. Mature leaves grown under continuous illumination contained PA as up to 14.2% of the total soluble protein. Cytotoxicity measurements in macrophage lysis assays showed that chloroplast-derived PA was equal in potency to PA produced in B. anthracis. Subcutaneous immunization of mice with partially purified chloroplast-derived or B. anthracis-derived PA with adjuvant yielded immunoglobulin G titers up to 1:320,000, and both groups of mice survived (100%) challenge with lethal doses of toxin. An average yield of about 150 mg of PA per plant should produce 360 million doses of a purified vaccine free of bacterial toxins edema factor and lethal factor from 1 acre of land. Such high expression levels without using fermenters and the immunoprotection offered by the chloroplast-derived PA should facilitate development of a cleaner and safer anthrax vaccine at a lower production cost. These results demonstrate the immunogenic and immunoprotective properties of plant-derived anthrax vaccine antigen. C1 Univ Cent Florida, Dept Mol Biol & Microbiol, Orlando, FL 32816 USA. NIAID, Microbial Pathogenesis Sect, NIH, Bethesda, MD 20892 USA. RP Daniell, H (reprint author), Univ Cent Florida, Dept Mol Biol & Microbiol, Biomol Sci Bldg 20,Room 336,Cent Florida Blvd, Orlando, FL 32816 USA. EM daniell@mail.ucf.edu OI Daniell, Henry/0000-0003-4485-1176 FU NIGMS NIH HHS [R01GM 63879, R01 GM063879] NR 32 TC 120 Z9 138 U1 0 U2 5 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 2005 VL 73 IS 12 BP 8266 EP 8274 DI 10.1128/IAI.73.12.8266-8274.2005 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 986WK UT WOS:000233480200056 PM 16299323 ER PT J AU Talreja, J Dileepan, K Puri, S Kabir, MH Segal, DM Stechschulte, DJ Dileepan, KN AF Talreja, Jaya Dileepan, Kavitha Puri, Sanjeev Kabir, Mohammad H. Segal, David M. Stechschulte, Daniel J. Dileepan, Kottarappat N. TI Human conjunctival epithelial cells lack lipopolysaccharide responsiveness due to deficient expression of MD2 but respond after interferon-gamma priming or soluble MD2 supplementation SO INFLAMMATION LA English DT Article DE conjunctival epithelial cells; lipopolysaccharide; TLR2; TLR4; MD2; interferon-gamma ID TOLL-LIKE RECEPTORS; INNATE IMMUNE-RESPONSE; NITRIC-OXIDE PRODUCTION; ENDOTHELIAL-CELLS; WALL COMPONENTS; MD-2; ENDOTOXIN; TLR4; ACTIVATION; INDUCTION AB Inflammatory responses to Gram-positive and Gram-negative bacterial cell wall components are initiated by Toll-like receptor 2 (TLR2) and TLR4, respectively. Therefore, the existence of functionally active TLR2 and TLR4 in human conjunctival epithelial cells (HCEC) are critical for the effective host defense against bacterial infections in the eye. We examined the ability of HCEC to respond to TLR4 ligand, lipopolysaccharide (LPS), or TLR2 ligands, lipoteichoic acid (LTA) and peptidoglycan (PGN) using the Chang conjunctival epithelial cell line and the primary conjunctival epithelial cell line (IOBA-NHC) as in vitro models. Incubation of Chang cells with LPS (1 to 1,000 ng/ ml) failed to stimulate IL-6 production where as stimulation with LTA or PGN resulted in marked increases in IL-6 production. Semi-quantitative RT-PCR and immunofluorescence analyses showed that Chang cells express TLR2 and TLR4 mRNA and proteins. However, these cells expressed little or no mRNA encoding MD2, an accessory molecule required for TLR4 signaling. Incubation of Chang epithelial cells with interferon-gamma (IFN gamma), but not TNF-alpha, stimulated MD2 mRNA expression and restored LPS responsiveness. In addition, when Chang cell cultures were supplemented with soluble MD2, LPS was able to stimulate IL-6 production. The lack of LPS response, deficient expression of MD2, and induction of MD2 expression and LPS response after IFN gamma priming, were also evident in IOBA-NHC cells. These results demonstrate that HCEC lack LPS responsiveness due to deficient expression of MD2 and that the response can be restored by IFN-gamma priming or MD2 supplementation. C1 Univ Kansas, Med Ctr, Dept Med, Div Allergy Clin Immunol & Rheumatol, Kansas City, KS 66160 USA. Univ Kansas, Med Ctr, Dept Biochem & Mol Biol, Kansas City, KS 66160 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Dileepan, KN (reprint author), Univ Kansas, Med Ctr, Dept Med, Div Allergy Clin Immunol & Rheumatol, 3901 Rainbow Blvd,Mail Stop 2026, Kansas City, KS 66160 USA. EM kdileepan@kumc.edu NR 38 TC 17 Z9 18 U1 0 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0360-3997 J9 INFLAMMATION JI Inflammation PD DEC PY 2005 VL 29 IS 4-6 BP 170 EP 181 DI 10.1007/s10753-006-9014-y PG 12 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 111EN UT WOS:000242434300007 PM 17093906 ER PT J AU Ramalho-Ortigao, JM Kamhawi, S Joshi, MB Reynoso, D Lawyer, PG Dwyer, DM Sacks, DL Valenzuela, JG AF Ramalho-Ortigao, JM Kamhawi, S Joshi, MB Reynoso, D Lawyer, PG Dwyer, DM Sacks, DL Valenzuela, JG TI Characterization of a blood activated chitinolytic system in the midgut of the sand fly vectors Lutzomyia longipalpis and Phlebotomus papatasi SO INSECT MOLECULAR BIOLOGY LA English DT Article DE sand fly; peritrophic matrix; chitinolytic activity; Leishmania ID PERITROPHIC MATRIX; AEDES-AEGYPTI; CHITINASE CDNA; LEISHMANIA; PSYCHODIDAE; INFECTION; DIGESTION; INSECTS; DIPTERA; CLONING AB We characterized a cDNA from Phlebotomus papatasi, PpChit1, which encodes a midgut specific chitinase and show the presence of a functional, blood-induced chitinolytic system in sand flies. PpChit1 is detected only in the midgut and is regulated by blood feeding. A recombinant protein (rPpChit1) produced in HEK 293-F cells exhibited a similar activity profile to that found in the native protein against several specific substrates, including an oligomeric glycol chitin and synthetic 4-methyl-umbelliferone labelled substrates. Western blotting showed that the native protein is recognized by mouse polyclonal antibodies against rPpChit1. Additionally, the rPpChit1 and the native chitinase displayed similar retention times in a HPLC size fractionation column. When added to rPpChit1 or to midgut lysates, PpChit1 sera reduced chitinolytic activity by 65-70%. C1 NIAID, Vector Mol Biol Unit, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. NIAID, Intracellular Parasite Biol Sect, NIH, Rockville, MD 20852 USA. NIAID, Cell Biol Sect, Parasit Dis Lab, NIH, Rockville, MD 20852 USA. RP Ramalho-Ortigao, JM (reprint author), NIAID, Vector Mol Biol Unit, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy,Room 2E-22, Rockville, MD 20852 USA. EM m_ortigao@nd.edu RI Ramalho-Ortigao, Marcelo/E-8225-2011 NR 21 TC 27 Z9 29 U1 0 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0962-1075 J9 INSECT MOL BIOL JI Insect Mol. Biol. PD DEC PY 2005 VL 14 IS 6 BP 703 EP 712 DI 10.1111/j.1365-2583.2005.00601.x PG 10 WC Biochemistry & Molecular Biology; Entomology SC Biochemistry & Molecular Biology; Entomology GA 985WF UT WOS:000233408700014 PM 16313571 ER PT J AU Buchholz, DR Paul, BP Shi, YB AF Buchholz, DR Paul, BP Shi, YB TI Gene-specific changes in promoter occupancy by thyroid hormone receptor during frog metamorphosis: Implications for developmental gene regulation SO INTEGRATIVE AND COMPARATIVE BIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Integrative-and-Comparative-Biology CY JAN 04-08, 2006 CL Orlando, FL C1 NICHHD, Lab Gene Regulat, Bethesda, MD 20892 USA. EM dbuchholz@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1540-7063 J9 INTEGR COMP BIOL JI Integr. Comp. Biol. PD DEC PY 2005 VL 45 IS 6 BP 971 EP 971 PG 1 WC Zoology SC Zoology GA 012KH UT WOS:000235337600068 ER PT J AU Mazza, ME Ryan, JF Mullikin, JC Rokshar, DS Finnerty, JR AF Mazza, ME Ryan, JF Mullikin, JC Rokshar, DS Finnerty, JR TI Evolutionarily conserved and derived homeobox clusters in the starlet sea anemone Nematostella vectensis SO INTEGRATIVE AND COMPARATIVE BIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Integrative-and-Comparative-Biology CY JAN 04-08, 2006 CL Orlando, FL C1 Boston Univ, Boston, MA 02215 USA. NHGRI, Bethesda, MD 20892 USA. EM tmmazza@bu.edu RI Finnerty, John/B-6564-2011 NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1540-7063 J9 INTEGR COMP BIOL JI Integr. Comp. Biol. PD DEC PY 2005 VL 45 IS 6 BP 1164 EP 1164 PG 1 WC Zoology SC Zoology GA 012KH UT WOS:000235337601317 ER PT J AU Le, YY Yu, XJ Ruan, LF Wang, OM Qi, DF Zhu, JJ Lu, XF Kong, Y Cai, K Pang, SS Shi, XL Wang, JM AF Le, YY Yu, XJ Ruan, LF Wang, OM Qi, DF Zhu, JJ Lu, XF Kong, Y Cai, K Pang, SS Shi, XL Wang, JM TI The immunopharmacological properties of transforming growth factor beta SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Review DE transforming growth factor beta; inflammation; Alzheimer's disease ID AMYLOID PRECURSOR PROTEIN; REGULATORY T-CELLS; RECEPTOR-TYPE-II; MURINE MICROGLIAL CELLS; TGF-BETA; ALZHEIMERS-DISEASE; TRANSGENIC MICE; TARGETED DISRUPTION; IN-VIVO; SYNOVIAL FIBROBLASTS AB Transforming growth factor-beta (TGF-beta) family members are multifunctional molecules, which play pivotal roles in regulating cell proliferation, differentiation, migration, development, tissue remodeling and repair. These events are closely associated with host immune responses and inflammation. Despite some controversies on their function in controlling dendritic and T regulatory cell development and activity, the importance of TGF-beta s in the progress of autoimmunity and inflammatory diseases has been well appreciated and new aspects of their contribution continue to be recognized. Since one of the major biological properties of TGF-beta s is its capacity to potently suppress immune responses, they are considered as candidates for the development of therapeutic agents to fend off undesirable damage associated with immune and inflammatory conditions. (c) 2005 Elsevier B.V. All rights reserved. C1 Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Lab Immunol & Inflammatory Dis, Shanghai 200031, Peoples R China. Chinese Acad Sci, Grad Sch, Shanghai 200031, Peoples R China. NCI, Mol Immunoregulat Lab, Canc Res Ctr, Frederick, MD 21702 USA. RP Le, YY (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Lab Immunol & Inflammatory Dis, Shanghai 200031, Peoples R China. EM yyle@sibs.ac.cn RI Shi, Xianglin/B-8588-2012; Qi, Dongfei/L-9548-2015; wang, oumei/P-5528-2015; Qi, Dongfei/M-1050-2015 OI Qi, Dongfei/0000-0001-9104-978X; Qi, Dongfei/0000-0001-9104-978X NR 101 TC 8 Z9 10 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-5769 J9 INT IMMUNOPHARMACOL JI Int. Immunopharmacol. PD DEC PY 2005 VL 5 IS 13-14 BP 1771 EP 1782 DI 10.1016/j.intimp.2005.07.006 PG 12 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA 989PQ UT WOS:000233686600002 PM 16275614 ER PT J AU Papakostas, GI Petersen, T Lebowitz, BD Mischoulon, D Ryan, JL Nierenberg, AA Bottiglieri, T Alpert, JE Rosenbaum, JF Fava, M AF Papakostas, GI Petersen, T Lebowitz, BD Mischoulon, D Ryan, JL Nierenberg, AA Bottiglieri, T Alpert, JE Rosenbaum, JF Fava, M TI The relationship between serum folate, vitamin B12, and homocysteine levels in major depressive disorder and the timing of improvement with fluoxetine SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Article DE fluoxetine; folate; homocysteine; onset; response; vitamin B12 ID ADENOSYL-L-METHIONINE; FOLIC-ACID; ANTIDEPRESSANT; ONSET; DEFICIENCY; PLASMA AB The objective of the present study was to examine the relationship between serum folate, vitamin B12, and homocysteine levels and the timing of clinical improvement to fluoxetine in major depressive disorder (MDD) patients. A total of 110 outpatients with MDD who responded to an 8-wk trial of fluoxetine had serum folate, B12, and homocysteine measurements at baseline (prior to fluoxetine initiation). Onset of clinical improvement was defined as a 30% decrease in Hamilton Depression Scale scores that led to a 50% decrease by week S. Patients with low folate levels (<= 2.5 ng/ml) were more likely to experience a later onset of clinical improvement than eufolatemic patients (p=0.0028). B12 and homocysteine level status did not predict time to clinical improvement (p > 0.05). In conclusion, low serum folate levels were found to be associated with a delayed onset of clinical improvement during treatment with fluoxetine in MDD by, on average, 1.5 wk. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Depress Clin & Res Program, Boston, MA 02114 USA. NIMH, Adult & Geriatr Treatment & Prevent Intervent Res, Bethesda, MD 20892 USA. Baylor Univ, Sch Med, Inst Metab Dis, Waco, TX 76798 USA. RP Papakostas, GI (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Depress Clin & Res Program, 15 Parkman St,WACC 812, Boston, MA 02114 USA. EM gpapakostas@partners.org RI Papakostas, George/I-6905-2013; OI Papakostas, George/0000-0002-2465-5103; Alpert, Jonathan/0000-0002-4332-908X FU NIMH NIH HHS [K23-MH069629-1, R01-MH-48-483-05] NR 26 TC 44 Z9 47 U1 0 U2 6 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD DEC PY 2005 VL 8 IS 4 BP 523 EP 528 DI 10.1017/S1461145705005195 PG 6 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986VB UT WOS:000233476700005 PM 15877935 ER PT J AU Uhmann, A Ferch, U Bauer, R Tauber, S Arziman, Z Chen, C Hemmerlein, B Wojnowski, L Hahn, H AF Uhmann, A Ferch, U Bauer, R Tauber, S Arziman, Z Chen, C Hemmerlein, B Wojnowski, L Hahn, H TI A model for PTCH1/Ptch1-associated tumors comprising mutational inactivation and gene silencing SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE patched; rhabdomyosarcoma; epigenetic silencing ID BASAL-CELL CARCINOMAS; HYPOMETHYLATING AGENT; SOMATIC MUTATIONS; PATCHED MUTANTS; HUMAN HOMOLOG; 1ST EXONS; MEDULLOBLASTOMA; HEDGEHOG; PROTEIN; MURINE AB Mutations of the Sonic hedgehog (SHH) receptor, Patched I (PITCH I), have been identified in a variety of tumors. PTCH1 is usually considered to be a tumor suppressor gene. However, one normal allele is retained in many tumors. We investigated the mechanism of tumorigenesis in murine heterozygous Ptch1 knock-out mice. Here we show that Ptch1 transcripts, which are consistently overexpressed in tumors in these mice, are derived predominantly from the mutated allele. These transcripts give rise to a mutant protein incapable of pathway inhibition. In contrast, the expression of wild-type transcripts in the tumor is reduced. The transcriptional activity of a Ptch1 promoter is sensitive to methylation. Based on these results, we propose a model, in which tumorigenesis begins with the transcriptional silencing of one PTCH1/Ptch1 allele. This alone has no functional consequences. Upon mutational inactivation of the other allele, the resulting loss of PTCH1/Ptch1 function activates PTCH1/Ptch1 transcription from the non-silenced, i.e. the mutant, allele. These events can occur in an opposite order. This model is consistent with the expression of PTCH1/Ptch1-derived transcripts and proteins found in tumors, with the sensitivity of the murine Ptch1 promoter to methylation, and with the recently reported effect of demethylating agents on Ptch1 expression. These latter agents could be effective in treatment of, at least, some tumors associated with loss of PTCH1 function. C1 Univ Gottingen, Inst Human Genet, D-37099 Gottingen, Germany. Univ Gottingen, Dept Pathol, D-37099 Gottingen, Germany. NIMH, Genet Lab, NCI, Bethesda, MD 20892 USA. Univ Mainz, Dept Pharmacol, D-6500 Mainz, Germany. RP Hahn, H (reprint author), Univ Gottingen, Inst Human Genet, Heinrich Duker Weg 12, D-37099 Gottingen, Germany. EM hhahn@gwdg.de NR 22 TC 20 Z9 24 U1 0 U2 2 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD DEC PY 2005 VL 27 IS 6 BP 1567 EP 1575 PG 9 WC Oncology SC Oncology GA 988ET UT WOS:000233575100014 PM 16273213 ER PT J AU Nishikawa, T Hayashi, T Nishioka, S Matsumoto, T AF Nishikawa, T Hayashi, T Nishioka, S Matsumoto, T TI Two cases of neuroleptic-induced prolonged extrapyramidal symptoms SO INTERNATIONAL JOURNAL OF PSYCHIATRY IN CLINICAL PRACTICE LA English DT Article DE neuroleptics; extrapyramidal symptoms; late onset; long-lasting severe rigidity and dyskinesia; reversible ID DRUG-INDUCED PARKINSONISM; TARDIVE-DYSKINESIA; MALIGNANT SYNDROME; PERSISTENT; SULPIRIDE; WITHDRAWAL; DISEASE AB Neuroleptic-induced extrapyramidal symptoms (EPS) are generally categorized as acute, withdrawal and tardive EPS. Here, we report two cases of a unique late-onset, long-lasting EPS (e.g., prolonged EPS); in those cases, EPS appeared a few months following initiation of haloperidol and lasted for a few months after significant reduction or complete withdrawal of neuroleptics. Case 1, a 41-year-old female, began to exhibit EPS such as bradykinesia, rigidity and parkinsonian gait 4 months after the haloperidol treatment. Her rigidity was ameliorated by a reduction of haloperidol; however, reduction of neuroleptics made it difficult for her to maintain a seated posture because of an imbalance of muscle tonus. Her EPS continued for 9 months even after haloperidol was switched to very low doses of thioridazine (10 mg/day). Case 2 is a 42-year-old female. She exhibited EPS including dysphagia and a difficulty in opening her mouth 3 months after the haloperidol treatment began. Her EPS lasted for 45 days, even after complete withdrawal of neuroleptics. The EPS observed in these two cases occurred even after prolactin levels became normal. "Prolonged EPS" is a unique subclass of neuroleptic-induced reversible EPS that might involve the coexistence of hypo- and hyper-dopaminergic transmission, especially in patients who show very low tolerance to neuroleptics. C1 Seiwakai Nishikawa Hosp, Hamada 6970052, Japan. NIDA, NIH, DHHS, Baltimore, MD USA. RP Nishikawa, T (reprint author), Seiwakai Nishikawa Hosp, Hamada 6970052, Japan. EM mnishikawa@s7.dion.ne.jp RI Hayashi, Teruo/A-9690-2008 NR 25 TC 0 Z9 0 U1 1 U2 1 PU TAYLOR & FRANCIS AS PI OSLO PA PO BOX 12 POSTHUSET, NO-0051 OSLO, NORWAY SN 1365-1501 J9 INT J PSYCHIAT CLIN JI Int. J. Psychiat. Clin. PD DEC PY 2005 VL 9 IS 4 BP 284 EP 288 DI 10.1080/13651500500327998 PG 5 WC Psychiatry SC Psychiatry GA 977KB UT WOS:000232801200010 PM 24930927 ER PT J AU Van Waes, C Chang, AA Lebowitz, PF Druzgal, CH Chen, Z Elsayed, YA Sunwoo, JB Rudy, SF Morris, JC Mitchell, JB Camphausen, K Gius, D Adams, J Sausville, EA Conley, BA AF Van Waes, C Chang, AA Lebowitz, PF Druzgal, CH Chen, Z Elsayed, YA Sunwoo, JB Rudy, SF Morris, JC Mitchell, JB Camphausen, K Gius, D Adams, J Sausville, EA Conley, BA TI Inhibition of nuclear factor-kappa B and target genes during combined therapy with proteasome inhibitor bortezomib and reirradiation in patients with recurrent head-and-neck squamous cell carcinoma SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE proteasome; bortezomib; nuclear factor-kappa B; radiotherapy; head-and-neck squamous cell carcinoma ID PROINFLAMMATORY CYTOKINE EXPRESSION; CONSTITUTIVE ACTIVATION; MULTIPLE-MYELOMA; TRANSCRIPTIONAL REGULATION; UNRESECTABLE HEAD; TUMOR-GROWTH; PHASE-I; CANCER; PS-341; RADIATION AB Purpose: To examine the effects the proteasome inhibitor bortezomib (VELCADE) on transcription factor nuclear factor-kappa B (NF-kappa B) and target genes and the feasibility of combination therapy with reirradiation in patients with recurrent head-and-neck squamous cell carcinoma (HNSCC). Methods and Materials: The tolerability and response to bortezomib 0.6 mg/m(2) and 0.9 mg/m(2) given twice weekly concurrent with daily reirradiation to 50-70 Gy was explored. Blood proteasome inhibition and NF-kappa B modulated cytokines and factors were measured. Proteasome inhibition, nuclear localization of NF-kappa B phospho-p65, apoptosis, and expression of NF-kappa B-modulated mRNAs were compared in serial biopsies from accessible tumors. Results: The maximally tolerated dose was exceeded, and study was limited to 7 and 2 patients, respectively, given bortezomib 0.6 mg/m(2) and 0.9 mg/m(2)/dose with reirradiation. Grade 3 hypotension and hyponatremia were dose limiting. Mucositis was Grade 3 or less and was delayed. The mean blood proteasome inhibition at 1, 24, and 48 It after 0.6 mg/m(2) was 32%, 16%, and 7% and after 0.9 mg/m(2) was 56%, 26%, and 14%, respectively. Differences in proteasome and NF-kappa B activity, apoptosis, and expression of NF-kappa B-modulated cell cycle, apoptosis, and angiogenesis factor mRNAs were detected in 2 patients with minor tumor reductions and in serum NF-kappa B-modulated cytokines in 1 patient with a major tumor reduction. Conclusions: In combination with reirradiation, the maximally tolerated dose of bortezomib was exceeded at a dose of 0.6 mg/m(2) and the threshold of proteasome inhibition. Although this regimen with reirradiation is not feasible, bortezomib induced detectable differences in NF-kappa B localization, apoptosis, and NF-kappa B-modulated genes and cytokines in tumor and serum in association with tumor reduction, indicating that other schedules of bortezomib combined with primary radiotherapy or reirradiation may merit future investigation. (c) 2005 Elsevier Inc. C1 NIDCD, Head & Neck Surg Branch, CRC, Bethesda, MD 20892 USA. NCI, Med Oncol Clin Res Unit, Bethesda, MD 20892 USA. NCI, Metab Branch, Bethesda, MD 20892 USA. NCI, Radiat Oncol Sci Program, Bethesda, MD 20892 USA. Millennium Pharmaceut, Cambridge, MA USA. RP Van Waes, C (reprint author), NIDCD, Head & Neck Surg Branch, CRC, Bldg 10,Rm 4-2732,10 Ctr Dr, Bethesda, MD 20892 USA. EM vanwaesc@nidcd.nih.gov FU Intramural NIH HHS; NIDCD NIH HHS [Z01-DC-00016] NR 42 TC 92 Z9 92 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD DEC 1 PY 2005 VL 63 IS 5 BP 1400 EP 1412 DI 10.1016/j.ijrobp.2005.05.007 PG 13 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 986VH UT WOS:000233477300018 PM 16005577 ER PT J AU Dowlati, A Chapman, R Subbiah, S Fu, PF Ness, A Cortas, T Patrick, L Reynolds, S Xu, N Levitan, N Ivy, P Remick, SC AF Dowlati, A Chapman, R Subbiah, S Fu, PF Ness, A Cortas, T Patrick, L Reynolds, S Xu, N Levitan, N Ivy, P Remick, SC TI Randomized phase II trial of different schedules of administration of rebeccamycin analogue as second line therapy in non-small cell lung cancer SO INVESTIGATIONAL NEW DRUGS LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 31-JUN 03, 2003 CL CHICAGO, IL SP Amer Soc Clin Oncol DE non-small cell lung cancer; rebeccamycin; phase II clinical trial ID CHEMOTHERAPY; NSC-655649; DOCETAXEL; STATISTICS AB Rebeccamcyin analogue (RA) is an antitumor antibiotic that results in DNA intercalation and topoisomerase I and II inhibition. Phase I trials of the daily x 5 schedule and once every 3 week schedule have been completed. Antitumor activity was observed during the phase I trials. The purpose of this study is to primarily determine the response rate of 2 different schedules of administration of RA in patients with advanced non-small cell lung cancer (NSCLC) who had progressed on one prior chemotherapy regimen. Secondary endpoints were median and 1-year survival rates. A two-stage Simon design was employed for both arms of the study. Patients were randomly assigned to either of two RA treatment schedules of 500 mg/m(2) as a 1 hr infusion repeated every 3 weeks (Arm A) or 140 mg/m(2)/day x 5 days repeated every 3 weeks (Arm B). Forty-two patients were randomized. No confirmed objective responses were seen. Stable disease was seen in 52% of patients on arm A and 37% on arm B. Median survival and I year survival rates were 5.6 months and 33.3% for arm A, 9.7 months and 42.1% for arm B respectively. Cox regression model demonstrated increased risk of death in patients younger than the age of 61 and for patients treated on arm A. RA failed to demonstrate a significant response rate in this disease setting, although the proportion of patients with stable disease and 1-year survival were encouraging and similar to other published studies of approved single agents for second-line therapy of NSCLC. C1 Univ Hosp Cleveland, Cleveland, OH 44106 USA. Case Western Reserve Univ, CASE Comprehens Canc Ctr, Dev Therapeut Program, Cleveland, OH 44106 USA. Case Western Reserve Univ, Div Hematol Oncol, Cleveland, OH 44106 USA. Henry Ford Hosp, Josephine Canc Ctr, Detroit, MI 48202 USA. NCI, Bethesda, MD 20892 USA. RP Dowlati, A (reprint author), Univ Hosp Cleveland, 11100 Euclid Ave, Cleveland, OH 44106 USA. EM afshin.dowlati@case.edu FU NCI NIH HHS [U01 CA62502]; NCRR NIH HHS [M01-RR-00080] NR 22 TC 3 Z9 4 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6997 J9 INVEST NEW DRUG JI Invest. New Drugs PD DEC PY 2005 VL 23 IS 6 BP 563 EP 567 DI 10.1007/s10637-005-0754-6 PG 5 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 995EB UT WOS:000234082500008 PM 16034518 ER PT J AU Amaral, J Fariss, RN Campos, MM Robison, WG Kim, H Lutz, R Becerra, SP AF Amaral, J Fariss, RN Campos, MM Robison, WG Kim, H Lutz, R Becerra, SP TI Transscleral-RPE permeability of PEDF and ovalbumin proteins: Implications for subconjunctival protein delivery SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID EPITHELIUM-DERIVED FACTOR; RETINAL-PIGMENT EPITHELIUM; ENDOTHELIAL GROWTH-FACTOR; CEREBELLAR GRANULE CELLS; INHIBITS CHOROIDAL NEOVASCULARIZATION; HUMAN SCLERAL PERMEABILITY; BLOOD-OCULAR BARRIERS; DIABETIC-RETINOPATHY; DRUG-DELIVERY; AQUEOUS-HUMOR AB PURPOSE. To investigate the in vitro, ex vivo, and in vivo transscleral-retinal pigment epithelium (RPE) permeability of PEDF and structurally related proteins for the exploration of novel routes of protein delivery to the retina. METHODS. Monkey RPE cells were cultured on permeable supports to separate apical and basal compartments. Porcine scleral tissue was placed in Ussing chambers to separate uveal and orbital compartments. Transepithelial resistance and voltage were measured by an electrical resistance system, and paracellular tracer flux was evaluated with trypan blue. Subconjunctival administration in rat eyes was by injections of soluble protein or by implantation of polyvinyl alcohol devices containing protein. Fluorescein-conjugated (Fl-) PEDF and ovalbumin were determined by spectrofluorometry, laser scanning, immunoblotting, epifluorescence, and confocal microscopy. Permeability was assessed by fluoresceinated-protein flux. RESULTS. Transepithelial resistance, impermeability to trypan blue, and confocal microscopy confirmed functional and structural tight junction formation of RPE cells cultured on permeable supports. Full-length Fl- PEDF and Fl-ovalbumin proteins diffused through RPE cell monolayers from either the apical or basal side. Fl-ovalbumin diffused through scleral tissues at constant rates. Subconjunctival Fl-PEDF or Fl-ovalbumin administration in vivo revealed movement of full-length protein into the choroid and retina as early as 1 hour. CONCLUSIONS. The sclera and RPE were permeable in vitro, ex vivo, and in vivo to PEDF and ovalbumin proteins. These large proteins can traverse through the sclera-RPE to reach the retina. In addition, these data prompt the proposal that subconjunctival protein delivery may represent a feasible and minimally invasive route for PEDF administration in the clinic. C1 NEI, Sect Prot Struct & Funct, LRCMB, NIH, Bethesda, MD 20892 USA. NEI, Biol Imaging Core, NIH, Bethesda, MD 20892 USA. NIH, Div Bioengn & Phys Sci, Res Off Sci, Off Director ORS OD, Bethesda, MD 20892 USA. RP Becerra, SP (reprint author), NEI, Sect Prot Struct & Funct, LRCMB, NIH, Bldg 7,Room 304,7 Mem Dr MSC 0706, Bethesda, MD 20892 USA. EM becerrap@nei.nih.gov FU Intramural NIH HHS NR 66 TC 29 Z9 31 U1 0 U2 7 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 2005 VL 46 IS 12 BP 4383 EP 4392 DI 10.1167/iovs.05-0492 PG 10 WC Ophthalmology SC Ophthalmology GA 988FV UT WOS:000233578600006 PM 16303924 ER PT J AU Fleisher, TA Oliveira, JB AF Fleisher, TA Oliveira, JB TI Autoimmune lymphoproliferative syndrome SO ISRAEL MEDICAL ASSOCIATION JOURNAL LA English DT Article DE apoptosis; immune homeostasis; autoimmunity; lymphoma ID FAS GENE-MUTATIONS; DEFECTIVE LYMPHOCYTE; APOPTOSIS; DOMINANT; DISEASE; FAMILIES; DISORDER; LIGAND C1 NIH, Dept Lab Med, Ctr Clin, DHHS,Immunol Serv, Bethesda, MD 20892 USA. RP Fleisher, TA (reprint author), NIH, Dept Lab Med, Ctr Clin, DHHS,Immunol Serv, 10 Ctr Dr,MSC 1508, Bethesda, MD 20892 USA. EM tfleishe@mail.nih.gov OI Oliveira, Joao/0000-0001-9388-8173 FU Intramural NIH HHS NR 21 TC 3 Z9 3 U1 0 U2 0 PU ISRAEL MEDICAL ASSOC JOURNAL PI RAMAT GAN PA 2 TWIN TOWERS, 11TH FL, 35 JABOTINSKY ST, PO BOX 3604, RAMAT GAN 52136, ISRAEL SN 1565-1088 J9 ISRAEL MED ASSOC J JI Isr. Med. Assoc. J. PD DEC PY 2005 VL 7 IS 12 BP 758 EP 761 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 995DL UT WOS:000234080000003 PM 16382694 ER PT J AU Imamichi, T Conrads, TP Zhou, M Liu, YX Adelsberger, JW Veenstra, TD Lane, HC AF Imamichi, T Conrads, TP Zhou, M Liu, YX Adelsberger, JW Veenstra, TD Lane, HC TI A transcription inhibitor, Actinomycin D, enhances HIV-1 replication through an interleukin-6-dependent pathway SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE transcription inhibitor; cytokines; HIV-1 activation; conditioned medium ID HUMAN-IMMUNODEFICIENCY-VIRUS; NECROSIS FACTOR-ALPHA; TYPE-1 TAX PROTEIN; T-CELL CLONE; HTLV-I; REVERSE-TRANSCRIPTASE; STRAND TRANSFER; EXPRESSION; TUMOR; INFECTION AB We previously demonstrated that Actinomycin D (ActD) enhanced HIV-1 replication in the MT-2 cell, a human T-cell leukemia virus type-1-infected cell line. The MT-2 cell is known to produce multiple cytokines spontaneously. In this study, we investigated the impact of ActD on the cytokine production from MT-2 cells and HIV-1 replication in a latently infected cell line, U1. MT-2 cells were pulse-treated with 0 or 200 nM of ActD, and culture supernatants were collected 3 days after incubation. Supernatants from untreated cells (Sup0) induced HIV-1 replication by 150-fold in U1 cells. Culture supernatants from ActD-treated cells (Sup200) enhanced HIV-1 replication by 1200-fold. A combination of a sequential chromatographic approach and mass spectrometric analysis identified that the HIV-inducing factors in Sup200 were interleukin (IL)-6 and tumor necrosis factor (TNF)-beta. Quantitative analysis revealed that ActD treatment increased the concentration of IL-6 in Sup200 by 600% compared with that in Sup0 but decreased the amount of TNF beta in Sup200 by 85%. Northern blot analysis showed that ActD treatment increased IL-6 transcripts; however, no change was seen in TNF beta transcripts. These results suggest that ActD induces replication of HIV-1 through modulation of cytokine production. C1 NIAID, Lab Human Retrovirol, Appl & Dev Res Program, SAIC Frederick, Frederick, MD 21702 USA. SAIC Frederick, Lab Proteom & Analyt Technol, Frederick, MD USA. SAIC Frederick, AIDS Monitoring Lab, Frederick, MD USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Imamichi, T (reprint author), NIAID, Lab Human Retrovirol, Appl & Dev Res Program, SAIC Frederick, Bldg 550,Room 126, Frederick, MD 21702 USA. EM timamichi@niaid.nih.gov FU NCI NIH HHS [N01-CO-56000] NR 47 TC 6 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD DEC 1 PY 2005 VL 40 IS 4 BP 388 EP 397 DI 10.1097/01.qai.0000179466.25700.2f PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 986UE UT WOS:000233474400002 PM 16280692 ER PT J AU Costa, PT Bagby, RM Herbst, JH McCrae, RR AF Costa, PT Bagby, RM Herbst, JH McCrae, RR TI Personality self-reports are concurrently reliable and valid during acute depressive episodes SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE depression; state artifact; personality assessment; validity ID MAJOR DEPRESSION; 5-FACTOR MODEL; PREMORBID PERSONALITY; CHARACTER INVENTORY; PANIC PATIENTS; LIFE-SPAN; TEMPERAMENT; DISORDERS; TRAITS; STABILITY AB Background: It is alleged that depression distorts the assessment of general personality traits. To test that hypothesis, we examined scores on the Revised NEO Personality Inventory (NEO-PI-R) administered to acutely depressed patients at baseline and 14 to 26 weeks after treatment with antidepressant medication. Method: Two hundred and fifty patients completed the NEO-PI-R at baseline, 109 patients after 14 to 26 weeks of antidepressant pharmacotherapy. 48 patients (49.5%) were identified as responders while 49 (50.5%) were identified as nonresponders. The remaining 12 patients were excluded because they met HRSD response criteria but not the SCID-I MDD criteria at treatment completion. Results: At baseline, NEO-PI-R scales showed high internal consistency and replicated the normative factor structure, suggesting that psychometric properties were preserved. Among non-responders, retest correlations were uniformly high (rs=.50 to .88) and mean levels showed little change, providing evidence for the consistency of personality self-reports during an acute depressive episode. NEO-PI-R scales showed construct validity in the concurrent prediction of a number of clinical criteria. Effective treatment bad significant effects on the mean levels of neuroticism, which decreased, and extraversion, openness, and conscientiousness, which increased. Limitations: The participants were from a clinical database and were not randomly assigned for the treatment. Conclusions: The results suggest that the effect of acute depression is to amplify somewhat the personality profile of people prone to depression. Rather than regard these depression-caused changes in assessed personality trait levels as a distortion, we interpret them as accurate reflections of the current condition of the individual. Personality traits have biological bases, and when they are changed (by disease or therapeutic interventions) trait levels change. (c) 2005 Elsevier B.V. All rights reserved. C1 NIA, DHHS, Gerontol Res Ctr, Lab Personal & Cognit,NIH, Baltimore, MD 21224 USA. Univ Toronto, Ctr Addit & Mental Hlth, Mood Disorder Program, Toronto, ON, Canada. CDC, NCHSTP, Div HIV AIDS Prevent, Prevent Res Branch,Synth & Analyt Support Team, Atlanta, GA 30333 USA. RP Costa, PT (reprint author), NIA, DHHS, Gerontol Res Ctr, Lab Personal & Cognit,NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM costap@mail.nih.gov OI Costa, Paul/0000-0003-4375-1712 NR 58 TC 110 Z9 111 U1 5 U2 18 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD DEC PY 2005 VL 89 IS 1-3 BP 45 EP 55 DI 10.1016/j.jad.2005.06.010 PG 11 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 998YJ UT WOS:000234355500005 PM 16203041 ER PT J AU Valerio, CR Murray, P Arlian, LG Slater, JE AF Valerio, CR Murray, P Arlian, LG Slater, JE TI Bacterial 16S ribosomal DNA in house dust mite cultures SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE allergen extracts; house dust mites; endotoxin; lipopolysaccharide; bacteria; allergen immunotherapy ID BARTONELLA-QUINTANA; LIPOPOLYSACCHARIDE; AMPLIFICATION; HENSELAE; DISEASE; PCR AB Background: Allergen extracts prepared from Dermatophagoides farinae contain significantly more endotoxin than Dermatophagoides pteronyssinus extracts, and extracts from both mite extracts contain more endotoxin than pollen extracts. Attempts to culture bacteria from mite cultures have failed to establish the sources of the endotoxin. Objective: To determine the bacterial sources of endotoxin in mite extracts. Methods: Live mites of both species were obtained from 2 sources, DNA was extracted from the mites, and DNA encoding bacterial 16S ribosomal RNA was amplified by using specific primers. The amount of bacterial DNA in each mite DNA sample was determined by quantitative PCR using an internal standard, and sequence homologies were determined from amplifications performed by using a high-fidelity DNA polymerase. Results: DNA from D farinae appeared to contain between 11-fold and 24-fold more 16S ribosomal gene copies than the genomic DNA from D pteronyssinus (P <= .003). Sequence analysis indicated the dominant presence of at least 3 phylogenetic clusters of Bartonella species (henselae, quintana, vinsonii, and grahamii), as well as uncharacterized alpha-proteobacteria, from both D farinae and D pteronyssinus. In a few clones, sequences from Escherichia coli, Pseudomonas species, and Acinetobacter species were also identified. Conclusion: House dust mite DNA contains evidence of Bartonella and other Gram-negative species. These Gram-negative species are likely to be the sources of the endotoxin found in mite allergenic extracts. C1 Ctr Biol Evaluat & Res, US FDA, Rockville, MD 20852 USA. Natl Inst Hlth, Bethesda, MD USA. Wright State Univ, Dayton, OH 45435 USA. RP Slater, JE (reprint author), Ctr Biol Evaluat & Res, US FDA, HFM 422,1401 Rockville Pike, Rockville, MD 20852 USA. EM slaterj@cber.fda.gov NR 23 TC 46 Z9 47 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD DEC PY 2005 VL 116 IS 6 BP 1296 EP 1300 DI 10.1016/j.jaci.2005.09.046 PG 5 WC Allergy; Immunology SC Allergy; Immunology GA 017IJ UT WOS:000235687000021 PM 16337462 ER PT J AU Tcheslavskaia, K Brewster, C Thorpe, K Sharov, A Leonard, D Roberts, A AF Tcheslavskaia, K Brewster, C Thorpe, K Sharov, A Leonard, D Roberts, A TI Effects of intentional gaps in spray coverage on the efficacy of gypsy moth mating disruption SO JOURNAL OF APPLIED ENTOMOLOGY LA English DT Article DE Lymantria dispar; disparlure; pheromone; plastic flakes; spray coverage; swath width ID SEX ATTRACTANT; PHEROMONE; LYMANTRIIDAE; LEPIDOPTERA; SUCCESS AB The study was conducted during 2001 and 2002 in forested areas in Virginia, US to examine the effects of gaps in coverage of pheromone on gypsy moth, Lymantria dispar (L.) (Lep., Lymantriidae), mating disruption. Gypsy moth male moth catches in pheromone-baited traps were significantly reduced in plots treated with the gypsy moth sex pheromone, disparlure, at an overall application rate of 37.5 g of active ingredient (AI)/ha but with untreated gaps of 30 or 90 m between 30-m wide treated swaths. In one of the two plots with 90 m gaps, significantly more males were captured in traps in the untreated areas compared with the treated areas within the plot. However, in another plot, significant differences in trap catches between treated and untreated areas were not observed. No difference in male moth catches in the pheromone-baited traps was observed between treated and untreated areas within the plots treated with 30 m gaps. Female mating success did not differ significantly between treated and untreated areas within the one plot in which it was measured. These results suggest that it may be possible to lower costs associated with gypsy moth mating disruption applications by alternating treated and untreated swaths, which would reduce flight time and fuel costs, without a reduction in efficacy. C1 Virginia Tech, Dept Entomol, Blacksburg, VA 24061 USA. ARS, USDA, Beltsville, MD USA. NIA, Baltimore, MD 21224 USA. US Forest Serv, USDA, Asheville, NC USA. RP Tcheslavskaia, K (reprint author), Virginia Tech, Dept Entomol, 202 Price Hall, Blacksburg, VA 24061 USA. EM ktchesla@vt.edu RI Onufrieva, Ksenia/A-4609-2008 OI Onufrieva, Ksenia/0000-0002-8424-850X NR 23 TC 10 Z9 11 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0931-2048 J9 J APPL ENTOMOL JI J. Appl. Entomol. PD DEC PY 2005 VL 129 IS 9-10 BP 475 EP 480 DI 10.1111/j.1439-0418.2005.00997 PG 6 WC Entomology SC Entomology GA 982GR UT WOS:000233146600002 ER PT J AU Lord, C Wagner, A Rogers, S Szatmari, P Aman, M Charman, T Dawson, G Durand, VM Grossman, L Guthrie, D Harris, S Kasari, C Marcus, L Murphy, S Odom, S Pickles, A Scahill, L Shaw, E Siegel, B Sigman, M Stone, W Smith, T Yoder, P AF Lord, C Wagner, A Rogers, S Szatmari, P Aman, M Charman, T Dawson, G Durand, VM Grossman, L Guthrie, D Harris, S Kasari, C Marcus, L Murphy, S Odom, S Pickles, A Scahill, L Shaw, E Siegel, B Sigman, M Stone, W Smith, T Yoder, P TI Challenges in evaluating psychosocial interventions for autistic spectrum disorders SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article ID INTENSIVE BEHAVIORAL TREATMENT; YOUNG-CHILDREN; CLINICAL-TRIALS; DEVELOPMENTAL DISORDER; PRESCHOOL-CHILDREN; PROGRAM; ISSUES; RISPERIDONE; MULTISITE; OUTCOMES AB In 2002, the National Institutes of Health sponsored a meeting concerning methodological challenges of research in psychosocial interventions in Autism Spectrum Disorders. This paper provides a summary of the presentations and the discussions that occurred during this meeting. Recommendations to federal and private agencies included the need for randomized clinical trials of comprehensive interventions for autism as the highest, but not the sole priority. Ongoing working groups were proposed to address psychosocial interventions with a focus on relevant statistics, standardized documentation and methods of diagnosis, development of outcome measures, establishment of standards in research; and the need for innovative treatment designs, including application of designs from other research areas to the study of interventions in ASD. C1 Univ Michigan, Autism & Commun Disorder Ctr, Ann Arbor, MI 48109 USA. NIMH, Child & Adolescent Psychosocial Intervent Program, Bethesda, MD 20892 USA. Univ Calif Davis, Tulare, CA USA. McMaster Univ, Hamilton, ON, Canada. Ohio State Univ, Columbus, OH 43210 USA. UCL, Inst Child Hlth, London, England. Univ Washington, Seattle, WA 98195 USA. Univ S Florida, St Petersburg, FL 33701 USA. Autism Soc Amer, Bethesda, MD USA. Univ Calif Los Angeles, Los Angeles, CA USA. Rutgers State Univ, New Brunswick, NJ 08903 USA. Univ N Carolina, NECTAS, Chapel Hill, NC USA. Indiana Univ, Indianapolis, IN 46204 USA. Univ Manchester, Manchester, Lancs, England. Yale Univ, New Haven, CT USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Vanderbilt Univ, Kennedy Ctr, Nashville, TN USA. Univ Rochester, Rochester, NY 14627 USA. RP Lord, C (reprint author), Univ Michigan, Autism & Commun Disorder Ctr, 1111 E Catherine St, Ann Arbor, MI 48109 USA. EM celord@umich.edu RI Durand, V Mark/G-6157-2010; Pickles, Andrew/A-9625-2011; Charman, Tony/A-2085-2014; OI Pickles, Andrew/0000-0003-1283-0346; Charman, Tony/0000-0003-1993-6549; Scahill, Lawrence/0000-0001-5073-1707 NR 63 TC 166 Z9 166 U1 3 U2 24 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD DEC PY 2005 VL 35 IS 6 BP 695 EP 708 DI 10.1007/s10803-005-0017-6 PG 14 WC Psychology, Developmental SC Psychology GA 003AG UT WOS:000234653400002 PM 16496206 ER PT J AU Gornick, MC Addington, AM Sporn, A Gogtay, N Greenstein, D Lenane, M Gochman, P Ordonez, A Balkissoon, R Vakkalanka, R Weinberger, DR Rapoport, JL Straub, RE AF Gornick, MC Addington, AM Sporn, A Gogtay, N Greenstein, D Lenane, M Gochman, P Ordonez, A Balkissoon, R Vakkalanka, R Weinberger, DR Rapoport, JL Straub, RE TI Dysbindin (DTNBP1, 6p22.3) is associated with childhood-onset psychosis and endophenotypes measured by the premorbid adjustment scale (PAS) SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE candidate gene; genetic association; transmission disequilibrium test; quantitative TDT; schizophrenia; DTNBP1; childhood onset ID GENE DTNBP1; QUANTITATIVE TRAITS; RISK-FACTORS; SCHIZOPHRENIA; FAMILY; DISORDERS; DISEASE; ILLNESS; DISEQUILIBRIUM; ANTECEDENTS AB Straub et al. (2002) recently identified the 6p22.3 gene dysbindin (DTNBP1) through positional cloning as a schizophrenia susceptibility gene. We studied a rare cohort of 102 children with onset of psychosis before age 13. Standardized ratings of early development, medication response, neuropsychological and cognitive performance, premorbid dysfunction and clinical follow-up were obtained. Fourteen SNPs were genotyped in the gene DTNBP1. Family-based pairwise and haplotype transmission disequilibrium test (TDT) analysis with the clinical phenotype, and quantitative transmission disequilibrium test (QTDT) explored endophenotype relationships. One SNP was associated with diagnosis (TDT p = .01). The QTDT analyses showed several significant relationships. Four adjacent SNPs were associated (p values = .0009 - .003) with poor premorbid functioning. These findings support the hypothesis that this and other schizophrenia susceptibility genes contribute to early neurodevelopmental impairment. C1 NIMH, Child Psychiat Branch, IRP, NIH, Bethesda, MD 20892 USA. NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Rapoport, JL (reprint author), NIMH, Child Psychiat Branch, IRP, NIH, 10 Ctr Dr,Bldg 10,Room 3N-202, Bethesda, MD 20892 USA. EM rapoport@helix.nih.gov RI Gogtay, Nitin/A-3035-2008 NR 38 TC 53 Z9 53 U1 3 U2 5 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD DEC PY 2005 VL 35 IS 6 BP 831 EP 838 DI 10.1007/s10803-005-0028-3 PG 8 WC Psychology, Developmental SC Psychology GA 003AG UT WOS:000234653400013 PM 16283082 ER PT J AU Scholl, D Merril, C AF Scholl, D Merril, C TI The genome of bacteriophage K1F, a T7-like phage that has acquired the ability to replicate on K1 strains of Escherichia coli SO JOURNAL OF BACTERIOLOGY LA English DT Article ID COMPLETE NUCLEOTIDE-SEQUENCE; DNA-REPLICATION; DEOXYRIBONUCLEIC-ACID; PSEUDOMONAS-PUTIDA; TAILSPIKE PROTEIN; PURIFIED PROTEINS; PRIMARY ORIGIN; START SITE; T7; GENE AB Bacteriophage K1F specifically infects Escherichia coli strains that produce the K1 polysaccharide capsule. Like several other K1 capsule-specific phages, K1F encodes an endo-neuraminidase (endosialidase) that is part of the tail structure which allows the phage to recognize and degrade the polysaccharide capsule. The complete nucleotide sequence of the K1F genome reveals that it is closely related to bacteriophage T7 in both genome organization and sequence similarity. The most striking difference between the two phages is that KIF encodes the endosialidase in the analogous position to the T7 tail fiber gene. This is in contrast with bacteriophage K1-5, another K1-specific phage, which encodes a very similar endosialidase which is part of a tail gene "module" at the end of the phage genome. It appears that diverse phages have acquired endosialidase genes by horizontal gene transfer and that these genes or gene products have adapted to different genome and virion architectures. C1 NIMH, NIH, Bethesda, MD 20892 USA. RP Scholl, D (reprint author), NIMH, NIH, Bldg 49,Room B1B20,9000 Rockville Pike, Bethesda, MD 20892 USA. EM dscholl@usa.net FU Intramural NIH HHS NR 55 TC 40 Z9 42 U1 0 U2 3 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 2005 VL 187 IS 24 BP 8499 EP 8503 DI 10.1128/JB.187.24.8499-8503.2005 PG 5 WC Microbiology SC Microbiology GA 992JK UT WOS:000233880000033 PM 16321955 ER PT J AU Matsson, L Parsegian, A AF Matsson, L Parsegian, A TI Completing our first decade of biological physics conferences SO JOURNAL OF BIOLOGICAL PHYSICS LA English DT Editorial Material C1 Chalmers Univ Technol, Dept Appl Phys, SE-41296 Gothenburg, Sweden. Univ Gothenburg, SE-41296 Gothenburg, Sweden. NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. RP Matsson, L (reprint author), Chalmers Univ Technol, Dept Appl Phys, SE-41296 Gothenburg, Sweden. EM leif.matsson@fy.chalmers.se NR 2 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0092-0606 J9 J BIOL PHYS JI J. Biol. Phys. PD DEC PY 2005 VL 31 IS 3-4 BP 235 EP 239 DI 10.1007/s10867-005-7138-1 PG 5 WC Biophysics SC Biophysics GA 991CN UT WOS:000233790000002 PM 23345894 ER PT J AU Al Sarraj, J Vinson, C Han, JH Thiel, G AF Al Sarraj, J Vinson, C Han, JH Thiel, G TI Regulation of GTP cyclohydrolase I gene transcription by basic region leucine zipper transcription factors SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE ATF2; CREB; c-Jun; MEKK1; p38 protein kinase; Egr-1 promoter; TNF alpha promoter ID NECROSIS-FACTOR-ALPHA; BINDING-PROTEIN-ALPHA; RENAL MESANGIAL CELLS; ACTIVATING TRANSCRIPTION; NITRIC-OXIDE; DNA-BINDING; EXPRESSION; CAMP; INDUCTION; PROMOTER AB Tetrahydrobiopterin is an essential cofactor for the phenylalanine, tyrosine and tryptophan hydroxylases, and the family of nitric oxide synthases. The initial and rate-limiting enzyme in the biosynthesis of tetrahydrobiopterin is GTP cyclohydrolase 1. The proximal promoter of the human GTP cyclohydrolase I gene contains the sequence motif 5'-TGACGCGA-3', resembling a cAMP response element (CRE). The objective of this study was to analyze the regulation of GTP cyclohydrolase I gene transcription by basic region leucine zipper (bZIP) transcription factors. A constitutively active mutant of the cAMP response element binding (CREB) protein strongly stimulated GTP cyclohydrolase I promoter activity, indicating that the CRE in the context of the GTP cyclohydrolase I gene is functional. Likewise, GTP cyclohydrolase I promoter/luciferase gene transcription was stimulated following nuclear expression of the catalytic subunit of cAMP-dependent protein kinase. Constitutively active mutants of activating transcription factor 2 (ATF2) and c-Jun additionally stimulated GTP cyclohydrolase I promoter activity, but to a lesser extent than the constitutively active CREB mutant. The fact that stress-activated protein kinases target the GTP cyclohydrolase I gene was corroborated by expression experiments involving p38 and MEKK1 protein kinases. We conclude that signaling pathways involving either the cAMP-dependent protein kinase or stress-activated protein kinases converge to the GTP cyclohydrolase I gene. Hence, enzymatic reactions that require tetrahydrobiopterin as cofactor are therefore indirectly controlled by signaling cascades involving the signal-responsive transcription factors CREB, c-Jun, and ATF2. C1 Univ Saarland, Med Ctr, Dept Med Biochem & Mol Biol, D-66421 Homburg, Germany. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. Scripps Res Inst, Dept Immunol, La Jolla, CA USA. RP Thiel, G (reprint author), Univ Saarland, Med Ctr, Dept Med Biochem & Mol Biol, Bldg 44, D-66421 Homburg, Germany. EM gerald.thiel@uniklinik-saarland.de RI Han, J/G-4671-2010 NR 42 TC 20 Z9 20 U1 0 U2 2 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 2005 VL 96 IS 5 BP 1003 EP 1020 DI 10.1002/jcb.20580 PG 18 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 985SY UT WOS:000233400000013 PM 16149046 ER PT J AU Surazynski, A Liu, YM Miltyk, W Phang, JM AF Surazynski, A Liu, YM Miltyk, W Phang, JM TI Nitric oxide regulates prolidase activity by serine/threonine phosphorylation SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE prolidase; nitric oxide; cGMP; serine/threonine phosphorylation ID COLORECTAL-CANCER CELLS; PROLINE OXIDASE; IN-VITRO; MATRIX; IMINODIPEPTIDURIA; FIBROBLASTS; INHIBITION; DEFICIENCY; INDUCTION; APOPTOSIS AB Prolidase [E.C. 3.4.13.9], a member of the matrix metalloproteinase (MMP) family, is a manganese-dependent cytosolic exopeptidase that cleaves imidodipeptides containing C-terminal proline or hydroxyproline. It plays an important role in collagen metabolism, matrix remodeling and cell growth. Nitric oxide (NO), a versatile signaling molecule, regulates many processes including collagen synthesis and matrix remodeling and, thereby, may modulate angiogenesis, tumor invasiveness, and metastasis. Thus, we considered that prolidase may be an important target of NO regulation. In our study, SIN I and DETA/NO were used as NO donors. Both donors increased prolidase activity in a time-dependent and dose-dependent manner. Prolidase activity increased not only with NO donors but also with endogenous NO in cells transfected with iNOS. The effect of iNOS was abolished by treatment with S-methylisothiourea (SMT), a selective inhibitor of iNOS. However, with either exogenous or endogenous sources of NO, the increase in prolidase activity was not accompanied by increased prolidase expression. Therefore, we suspected phosphorylation of prolidase as a potential mechanism regulating enzyme activation. We observed increased serine/threonine phosphorylation on prolidase protein in cells treated with NO donors and in cells transfected with iNOS. To determinate the pathways that may mediate prolidase induction by NO, we first used 8-Br-cGMP, a cGMP agonist, and found that 8-Br-cGMP strongly and rapidly stimulated prolidase activity accompanied by increased phosphorylation. Rp-8-Br-pCPT-cGMP, an inhibitor of cGMP, reduced NO donor-stimulated prolidase activity to control levels. To test wheher the MAPK pathway is involved in this NO-dependent activation, we used an ERK1/2 inhibitor and found that it had no effect on prolidase activity increased by NO donors. These results demonstrate that NO stimulates prolidase activity by increasing serine/threonine phosphorylation through PKG-cGMP pathway, but independent of MAPK and suggest an interaction between inflammatory signaling pathways and regulation of the terminal step of matrix degradation. C1 NCI, Frederick Canc Res & Dev Ctr, Comparat Carcinogenesis Lab, Metab & Canc Susceptibil Sect, Frederick, MD 21702 USA. RP Phang, JM (reprint author), NCI, Frederick Canc Res & Dev Ctr, Comparat Carcinogenesis Lab, Metab & Canc Susceptibil Sect, Bldg 538,Room 115, Frederick, MD 21702 USA. EM phang@mail.ncifcrf.gov FU Intramural NIH HHS NR 35 TC 27 Z9 27 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 2005 VL 96 IS 5 BP 1086 EP 1094 DI 10.1002/jcb.20631 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 985SY UT WOS:000233400000019 PM 16167338 ER PT J AU Aman, MG Arnold, LE McDougle, CJ Vitiello, B Scahill, L Davies, M McCracken, JT Tierney, E Nash, PL Posey, DJ Chuang, S Martin, A Shah, B Gonzalez, NM Swiezy, NB Ritz, L Koenig, K McGough, J Ghuman, JK Lindsay, RL AF Aman, MG Arnold, LE McDougle, CJ Vitiello, B Scahill, L Davies, M McCracken, JT Tierney, E Nash, PL Posey, DJ Chuang, S Martin, A Shah, B Gonzalez, NM Swiezy, NB Ritz, L Koenig, K McGough, J Ghuman, JK Lindsay, RL TI Acute and long-term safety and tolerability of risperidone in children with autism SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID DISRUPTIVE BEHAVIOR DISORDERS; PSYCHOACTIVE MEDICINES; INDIVIDUALS; PATTERNS; PSYCHOPHARMACOLOGY; DISCONTINUATION; PREVALENCE; SOCIETY; TRIALS; WEIGHT AB Treatment-emergent adverse events (AEs) were monitored during an 8-week, double-blind, placebo-controlled trial of risperidone (0.5-3.5 mg/day) in 101 children and adolescents with a lifetime diagnosis of autistic disorder. In addition, 37 placebo nonresponders received open-label risperidone for another 8 weeks. Of all the risperidone responders (n = 65), 63 entered an open extension of another 16 weeks (6 months total risperidone exposure), and 32 of them were rerandomized to either continued risperidone therapy (11 = 16) or gradual replacement with placebo (n = 16) over 8 weeks. We collected the following measures of safety and tolerability: (1) laboratory blood assessments (CBC with differential, electrolytes, and liver function tests) and urinalyses, (2) vital signs, (3) Side Effects Review of AEs thought to be associated with risperidone, (4) sleep records, (5) Simpson Angus Neurological Rating Scale (SARS), (6) Abnormal Involuntary Movement Scale (AIMS), and (7) height and weight. No clinically significant changes were found on the lab tests. During the 8-week acute trial, the most common AEs on the Side Effects Review, scored as moderate or higher, were as follows (placebo and risperidone, respectively): Somnolence (12% and 37%), enuresis (29% and 33%), excessive appetite (10% and 33%), rhinitis (8% and 16%), difficulty waking (8% and 12%), and constipation (12% and 10%). "Difficulty falling asleep" and anxiety actually favored the risperidone condition at statistically significant levels. The same AEs tended to recur through 6 months of treatment, although often at reduced levels. Using Centers for Disease Control (CDC) standardized scores, both weight and body mass index (BMI) increased with risperidone during the acute trial (0.5 and 0.6 SDs, respectively, for risperidone; 0.0 and 0.1 SDs, respectively, for placebo) and into open-label extension (0.19 and 0.16 SDs, respectively), although the amount of gain decelerated with time. Extrapyramidal symptoms, as assessed by the SARS, were no more common for drug than placebo, although drooling was reported more often in the risperidone group. There were no differences between groups on the AIMS. Two subjects had seizures (one taking placebo), but these were considered unrelated to active drug. Most AEs were mild to moderate and failed to interfere with therapeutic changes; there were no unanticipated AEs. The side effects of most concern were somnolence and weight gain. C1 Ohio State Univ, Nisonger Ctr, Columbus, OH 43210 USA. Indiana Univ, Indianapolis, IN 46204 USA. NIMH, Bethesda, MD 20892 USA. Yale Univ, New Haven, CT USA. Columbia Univ, New York, NY USA. Univ Calif Los Angeles, Los Angeles, CA USA. Kennedy Krieger Inst, Baltimore, MD USA. Childrens Hosp, Columbus, OH 43205 USA. Arizona Child Study Ctr, Phoenix, AZ USA. RP Aman, MG (reprint author), Ohio State Univ, Nisonger Ctr, 1581 Dodd Dr, Columbus, OH 43210 USA. EM aman.1@osu.edu OI Scahill, Lawrence/0000-0001-5073-1707 FU NCRR NIH HHS [M01 RR00034, M01RR00052, M01 RR00750, M01 RR06022]; NIMH NIH HHS [K23 MH001883-02, N01MH80011, N01MH70010, MH01805, N01MH70001, N01MH70009] NR 25 TC 73 Z9 74 U1 1 U2 7 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD DEC PY 2005 VL 15 IS 6 BP 869 EP 884 DI 10.1089/cap.2005.15.869 PG 16 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 000EC UT WOS:000234442700037 PM 16379507 ER PT J AU Kalantaridou, SN Calis, KA Mazer, NA Godoy, H Nelson, LM AF Kalantaridou, SN Calis, KA Mazer, NA Godoy, H Nelson, LM TI A pilot study of an investigational testosterone transdermal patch system in young women with spontaneous premature ovarian failure SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID POSTMENOPAUSAL WOMEN; ANDROGEN; OOPHORECTOMY; ESTROGENS; ESTRADIOL; DENSITY AB Context: Evidence suggests that young women with spontaneous premature ovarian failure (sPOF) have significantly lower androgen levels than age-matched regularly menstruating women. Objective: The objective of the study was to evaluate an investigational testosterone transdermal patch (TTP) designed to deliver the normal ovarian production rate of testosterone. Design: This was an open-label study (2-month baseline period followed by 2- month treatment period). Patients: Nine women with sPOF and a history of regular bleeding patterns on standard estrogen/progestogen cyclic treatment participated in the study. One subject with abnormal baseline levels was excluded. Intervention: Four consecutive 28-d cycles of transdermal estradiol (E(2); 0.1 mg/d) and sequential oral medroxyprogesterone acetate (MPA; 10 mg/d for the last 12 d of each cycle). During cycles 3 and 4, an investigational TTP (nominal delivery 150 mu g/d) was applied twice weekly to the abdomen. Main Outcome Measures: Steady-state pharmacokinetic profiles of free and total testosterone and scheduled vaginal bleeding patterns were studied. Results: The mean (95% confidence interval) of the time-average free testosterone levels during TTP treatment was 7.5 (4.9-9.9) mu g/ml; 26.0 (17.2-34.6) pmol/liter (with E(2)), and 6.9 (4.9-8.8) mu g/ml; 23.9 (17.2-30.5) pmol/liter (with E(2) and MPA). The confidence intervals of the means include the upper limit of normal for premenopausal women, i.e. 6.8 mu g/ml (23.5 pmol/liter), although the mean values are slightly above this. Conclusions: The addition of TTP to cyclic E(2)/MPA therapy in women with sPOF produced mean free testosterone levels that approximate the upper limit of normal. A 3-yr study to assess safety and effectiveness in this population is in progress. C1 NIH, Ctr Clin, Dept Pharm, Bethesda, MD 20892 USA. NICHHD, Dev Endocrinol Branch, Bethesda, MD 20892 USA. Univ Utah, Dept Pharmaceut, Salt Lake City, UT 84112 USA. RP Calis, KA (reprint author), NIH, Ctr Clin, Dept Pharm, Bldg 10,Room 1S-259,10 Ctr Dr MSC 1196, Bethesda, MD 20892 USA. EM kcalis@nih.gov FU Intramural NIH HHS NR 18 TC 12 Z9 12 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 2005 VL 90 IS 12 BP 6549 EP 6552 DI 10.1210/jc.2005-0692 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 990OV UT WOS:000233754000032 PM 16174721 ER PT J AU Kim, BJ Carlson, OD Jang, HJ Elahi, D Berry, C Egan, JM AF Kim, BJ Carlson, OD Jang, HJ Elahi, D Berry, C Egan, JM TI Peptide YY is secreted after oral glucose administration in a gender-specific manner SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID AMYLOID POLYPEPTIDE IAPP; GLUCAGON-LIKE PEPTIDE-1; BETA-CELL FUNCTION; BODY-MASS INDEX; FOOD-INTAKE; EXOCRINE PANCREAS; SERUM LEPTIN; RAT; PYY; INSULIN AB Context: Previous studies with small numbers of subjects showed a negative correlation between plasma peptide YY ( PYY) levels and obesity. If correct, this would imply that low PYY levels might be involved in the pathogenesis of obesity. Objective: Our objective was to investigate whether plasma PYY levels were correlated with sex and body mass index ( BMI). Design, Setting, and Patients: We conducted a cross-sectional study of 151 normal volunteers ( 19-90 yr of age) in the Baltimore Longitudinal Study of Aging. Interventions: All subjects had an oral glucose tolerance test ( 75 g) performed. Main Outcome Measures: Immunostaining of human duodenum, BMI, hemoglobin A(1c), plasma glucose, insulin, PYY, glucagon like peptide-1 (GLP-1), ghrelin, and leptin were the main outcome measures. Results: PYY and GLP-1 colocalized in the same cells in human duodenum. Both hormones reached peak plasma levels by 20 min and had similar secretory patterns. The incremental increases in PYY and GLP-1 during that first 20 min were significantly correlated ( r(2) = 0.388; P < 0.0001). The areas under the curve from 0-120 min for PYY and GLP-1 were similar in both obese and lean participants. Female participants across the range of BMI had significantly higher PYY area under the curve ( 17,464 +/- 1,240 vs. 14,120 +/- 806 pmol/ liter center dot min, female vs. male; P < 0.05) compared with male participants. Conclusions: Our findings show that PYY and GLP-1 are colocalized and cosecreted from L cells and that total secretion of PYY is higher in females than in males, but fasting PYY levels and PYY secretion in response to oral glucose were not in any way correlated with BMI. C1 NIA, Diabet Sect, NIH, Baltimore, MD 21224 USA. Univ Massachusetts, Dept Surg, Worcester, MA 01655 USA. RP Kim, BJ (reprint author), NIA, Diabet Sect, NIH, Baltimore, MD 21224 USA. RI jang, hyeung jin/C-8022-2013 FU Intramural NIH HHS NR 42 TC 70 Z9 71 U1 0 U2 6 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 2005 VL 90 IS 12 BP 6665 EP 6671 DI 10.1210/jc.2005-0409 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 990OV UT WOS:000233754000049 PM 16174724 ER PT J AU Miller, FG Moreno, JD AF Miller, FG Moreno, JD TI The state of research ethics: A tribute to John C. Fletcher SO JOURNAL OF CLINICAL ETHICS LA English DT Article ID CLINICAL-RESEARCH; CONTROLLED-TRIALS; SHAM SURGERY; INFORMED-CONSENT; EQUIPOISE C1 NIH, Unit Clin Res, Dept Clin Bioeth, Ctr Clin, Bethesda, MD 20892 USA. Univ Virginia, Ctr Biomed Eth, Charlottesville, VA 22903 USA. RP Miller, FG (reprint author), NIH, Unit Clin Res, Dept Clin Bioeth, Ctr Clin, Bethesda, MD 20892 USA. EM fmiller@cc.nih.gov NR 26 TC 1 Z9 1 U1 0 U2 1 PU UNIV PUBLISHING GROUP PI HAGERSTOWN PA 138 W WASHINGTON ST, STE 403-405, HAGERSTOWN, MD 21740 USA SN 1046-7890 J9 J CLIN ETHIC JI J. Clin. Ethics PD WIN PY 2005 VL 16 IS 4 BP 355 EP 364 PG 10 WC Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Biomedical Social Sciences GA 006OV UT WOS:000234907700010 PM 16447523 ER PT J AU Miller, FG Moreno, JD AF Miller, FG Moreno, JD TI Informed consent and the ethics of clinical research: Reply to commentaries SO JOURNAL OF CLINICAL ETHICS LA English DT Editorial Material ID PLACEBO-CONTROLLED TRIALS C1 NIH, Unit Clin Res, Dept Clin Bioeth, Ctr Clin, Bethesda, MD 20892 USA. Univ Virginia, Ctr Biomed Eth, Charlottesville, VA 22903 USA. RP Miller, FG (reprint author), NIH, Unit Clin Res, Dept Clin Bioeth, Ctr Clin, Bethesda, MD 20892 USA. EM fmiller@cc.nih.gov NR 11 TC 0 Z9 0 U1 1 U2 2 PU UNIV PUBLISHING GROUP PI HAGERSTOWN PA 138 W WASHINGTON ST, STE 403-405, HAGERSTOWN, MD 21740 USA SN 1046-7890 J9 J CLIN ETHIC JI J. Clin. Ethics PD WIN PY 2005 VL 16 IS 4 BP 376 EP 379 PG 4 WC Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Biomedical Social Sciences GA 006OV UT WOS:000234907700014 ER PT J AU Minneci, PC Deans, KJ Zhi, H Yuen, PST Star, RA Banks, SM Schechter, AN Natanson, C Gladwin, MT Solomon, SB AF Minneci, PC Deans, KJ Zhi, H Yuen, PST Star, RA Banks, SM Schechter, AN Natanson, C Gladwin, MT Solomon, SB TI Hemolysis-associated endothelial dysfunction mediated by accelerated NO inactivation by decompartmentalized oxyhemoglobin SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID CROSS-LINKED HEMOGLOBIN; CELL-FREE HEMOGLOBIN; NITRIC-OXIDE BIOAVAILABILITY; BETA-THALASSEMIA MAJOR; PULMONARY-HYPERTENSION; RELAXING FACTOR; CARDIOPULMONARY BYPASS; DEPENDENT RELAXATION; BIOLOGICAL-ACTIVITY; BLOOD SUBSTITUTES AB During intravascular hemolysis in human disease, vasomotor tone and organ perfusion may be impaired by the increased reactivity of cell-free plasma hemoglobin (Hb) with NO. We experimentally produced acute intravascular hemolysis in a canine model. in order to test the hypothesis that low levels of decompartmentalized or cell-free plasma Hb will severely reduce NO bioavailability and produce vasomotor instability. Importantly, in this model the total intravascular Hb level is unchanged; only the compartmentalization of Hb within the erythrocyte membrane is disrupted. Using a full-factorial design, we demonstrate that free water-induced intravascular hemolysis produces dose-dependent systemic vasoconstriction and impairs renal function. We find that these physiologic changes are secondary to the stoichiometric oxidation of endogenous NO by cell-free plasma oxyhemoglobin. In this model, 80 ppm of inhaled NO gas oxidized 85-90% of plasma oxyhemoglobin to methemoglobin, thereby inhibiting endogenous NO scavenging by cell-free Hb. As a result, the vasoconstriction caused by acute hemolysis was attenuated and the responsiveness to systemically infused NO donors was restored. These observations confirm that the acute toxicity of intravascular hemolysis occurs secondarily to the accelerated dioxygenation reaction of plasma oxyhemoglobin with endothelium-derived NO to form bioinactive nitrate. These biochemical and physiological studies demonstrate a major role for the intact erythrocyte in NO homeostasis and provide mechanistic support for the existence of a human syndrome of hemolysis-associated NO dysregulation, which may contribute to the vasculopathy of hereditary, acquired, and iatrogenic hemolytic states. C1 NHLBI, Vasc Med Branch, Crit Med Dept, Clin Ctr,NIH,Clin Res Ctr, Bethesda, MD 20892 USA. NIDDK, Mol Med Branch, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NIDDK, Renal Diagnost & Therapeut Unit, NIH, Bethesda, MD USA. RP Gladwin, MT (reprint author), NHLBI, Vasc Med Branch, Crit Med Dept, Clin Ctr,NIH,Clin Res Ctr, Bldg 10 CRC,Room 5-5140, Bethesda, MD 20892 USA. EM mgladwin@nih.gov RI Yuen, Peter/B-1954-2008; OI Yuen, Peter/0000-0001-9557-3909; Schechter, Alan N/0000-0002-5235-9408 FU Intramural NIH HHS NR 56 TC 151 Z9 152 U1 0 U2 4 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 2005 VL 115 IS 12 BP 3409 EP 3417 DI 10.1172/JCI25040 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 990SL UT WOS:000233763400019 PM 16294219 ER PT J AU Jennings, C Fiscus, SA Crowe, SM Danilovic, AD Morack, RJ Scianna, S Cachafeiro, A Brambilla, DJ Schupbach, J Stevens, W Respess, R Varnier, OE Corrigan, GE Gronowitz, JS Ussery, MA Bremer, JW AF Jennings, C Fiscus, SA Crowe, SM Danilovic, AD Morack, RJ Scianna, S Cachafeiro, A Brambilla, DJ Schupbach, J Stevens, W Respess, R Varnier, OE Corrigan, GE Gronowitz, JS Ussery, MA Bremer, JW TI Comparison of two human immunodeficiency virus (HIV) RNA surrogate assays to the standard HIV RNA assay SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID REVERSE-TRANSCRIPTASE ACTIVITY; P24 ANTIGEN-ASSAY; RESOURCE-LIMITED SETTINGS; HEAT-DENATURED PLASMA; VIRAL LOAD; ANTIRETROVIRAL THERAPY; TYPE-1 RNA; SIGNAL-AMPLIFICATION; CLINICAL-TRIALS; INFECTION AB Human immunodeficiency virus (HIV) RNA testing is the gold standard for monitoring antiretroviral therapy in HIV-infected patients. However, equipment and reagent costs preclude widespread use of the assay in resource-limited settings. The Perkin-Elmer Ultrasensitive p24 assay and the Cavidi Exavir Load assay both offer potentially simpler, less costly technologies for monitoring viral load. These assays were compared to the Roche Amplicor HIV-1 Monitor Test, v1.5, using panels of clinical samples (subtype B) from HIV-positive subjects and HIV-spiked samples (subtypes A, C, D, CRF_01AE, CRF_02AG, and F). The Ultrasensitive p24 assay detected 100% of the spiked samples with virus loads of > 250,000copies/ml and 61% of the clinical samples with virus loads of 219 to 288,850 copies/ml. Detection rates were improved substantially if an external lysis buffer was added to the procedure. The Cavidi assay detected 54 to 100% of spiked samples with virus loads > 10,000 copies/ml and 68% of the clinical samples. These detection rates were also greatly improved with a newly implemented version of this kit. Coefficients of variation demonstrate good reproducibility for each of these kits. The results from the Cavidi v1.0, Cavidi v2.0, and Perkin-Elmer, and the Perkin-Elmer Plus external buffers all correlated well with the results from the Roche Monitor Test (r = 0.83 to 0.96, r = 0.84 to 0.99, r = 0.58 to 0.67, and r = 0.59 to 0.95, respectively). Thus, the use of these two assays for monitoring patients, together with less-frequent confirmation testing, offers a feasible alternative to frequent HIV RNA testing in resource-limited settings. C1 Rush Med Coll, Dept Immunol Microbiol, Chicago, IL 60612 USA. Univ N Carolina, Chapel Hill, NC USA. Macfarlane Burnet Inst Med Res & Publ Hlth, Melbourne, Vic, Australia. New England Res Inst, Watertown, MA 02172 USA. Univ Zurich, Zurich, Switzerland. Natl Hlth Lab Serv, Parktown, South Africa. Univ Witwatersrand, ZA-2050 Wits, South Africa. Ctr Dis Control & Prevent, Atlanta, GA USA. Univ Genoa, Sch Med, Inst Microbiol, Genoa, Italy. Karolinska Inst, SMI, MTC, Stockholm, Sweden. Uppsala Univ, Uppsala, Sweden. NIAID, NIH, Bethesda, MD 20892 USA. RP Jennings, C (reprint author), Rush Med Coll, Dept Immunol Microbiol, 1653 W Congress Pkwy, Chicago, IL 60612 USA. EM cjenning@rush.edu FU NIAID NIH HHS [N01AI85354, N01 AI 85354] NR 38 TC 36 Z9 37 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD DEC PY 2005 VL 43 IS 12 BP 5950 EP 5956 DI 10.1128/JCM.43.12.5950-5956.2005 PG 7 WC Microbiology SC Microbiology GA 994TZ UT WOS:000234055400018 PM 16333081 ER PT J AU Kramer, JL Velazquez, IA Chen, BSE Rosenberg, PS Struewing, JP Greene, MH AF Kramer, JL Velazquez, IA Chen, BSE Rosenberg, PS Struewing, JP Greene, MH TI Prophylactic oophorectomy reduces breast cancer penetrance during prospective, long-term follow-up of BRCA1 mutation carriers SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ASHKENAZI JEWISH WOMEN; OVARIAN-CANCER; GENETIC-HETEROGENEITY; MENSTRUAL FACTORS; CUMULATIVE RISK; FAMILY-HISTORY; PREVALENCE; SURGERY; SERIES; CLINICS AB Purpose Breast cancer penetrance estimates in BRCA1 mutation carriers have varied from 40% to 85%; this heterogeneity has been attributed to variations in risk among different study populations. No study has taken oophorectomy status into account in estimating penetrance. Because prophylactic oophorectomy reduces breast cancer risk by approximately 50%, we hypothesized that population differences in oophorectomy prevalence might significantly influence breast cancer penetrance estimates. Methods Females from multiple-case breast/ovarian cancer families that segregate deleterious BRCA1 mutations were observed prospectively for breast cancer incidence and oophorectomy. Results Within this cohort, 33 cases of breast cancer developed in 98 women with deleterious BRCA1 mutations during follow-up, yielding an estimated cumulative lifetime breast cancer risk of 80%. This estimate increased to 94% when the study participants were censored at the time of oophorectomy. Six of the 33 mutation-positive women who underwent oophorectomy during follow-up developed breast cancer, compared with 27 of 65 mutation carriers with intact ovaries (hazard ratio = 0.38-1 95% CI, 0.15 to 0.97). Estimates of absolute breast cancer risk demonstrated that the protective effect of oophorectomy was strongest among women who were premenopausal at the time of surgery. When surgical status was ignored, the strong protective effect of oophorectomy, coupled with the high prevalence of the procedure in these families, led to a significantly lower estimate of the breast cancer penetrance in BRCA1 mutation carriers. Conclusion Differing rates of oophorectomy likely represent an underappreciated basis for a portion of the heterogeneity in estimated breast cancer penetrance described in BRCA mutation carriers, particularly mutation carriers from extensively affected, multiple-case families. C1 NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA. NCI, Lab Populat Genet, Canc Res Ctr, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA. RP Kramer, JL (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,Room 7016,MSC 7231, Rockville, MD 20852 USA. EM kramerj@mail.nih.gov RI Struewing, Jeffery/C-3221-2008; Struewing, Jeffery/I-7502-2013 OI Struewing, Jeffery/0000-0002-4848-3334 FU Intramural NIH HHS NR 45 TC 79 Z9 82 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 1 PY 2005 VL 23 IS 34 BP 8629 EP 8635 DI 10.1200/JCO.200502.9199 PG 7 WC Oncology SC Oncology GA 989RA UT WOS:000233690200014 PM 16314625 ER PT J AU Hussain, M Tangen, CM Lara, PN Vaishampayan, UN Petrylak, DP Colevas, AD Sakr, WA Crawford, ED AF Hussain, M Tangen, CM Lara, PN Vaishampayan, UN Petrylak, DP Colevas, AD Sakr, WA Crawford, ED TI Ixabepilone (epothilone B analogue BMS-247550) is active in chemotherapy-naive patients with hormone-refractory prostate cancer: A southwest oncology group trial S0111 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol ID MICROTUBULE-STABILIZING AGENTS; PHASE-II TRIAL; ESTRAMUSTINE PHOSPHATE; PACLITAXEL; DOCETAXEL; MITOXANTRONE; PREDNISONE; MECHANISM; EFFICACY AB Purpose The epothilones are a new class of tubulin-polymerizing agents with activity in taxane-sensitive and resistant tumor models. We evaluated ixabepilone (BMS-247550) in patients with metastatic hormone-refractory prostate cancer (HBPC). Methods Eligible patients had chemotherapy-naive metastatic HRPC, a Zubrod performance status of 0 to 2, and adequate organ function. All patients received BMS-247550 at 40 mg/m(2) over 3 hours every 3 weeks. The primary end point was proportion of patients achieving a prostate-specific antigen (PSA) response. Results Forty-eight patients with metastatic HRPC were registered. Forty-two patients were eligible, with a median age of 73 years and a median PSA level of 111 ng/mL; 78% had bone-only or bone and soft tissue metastases, and 88% had objective radiologic disease progression at registration. Grade 3 and 4 adverse events (AEs) occurred in 16 and three patients, respectively. All grade 4 toxicities were neutropenia or leukopenia. The most frequent grade 3 AEs were neuropathy (eight patients), hematologic toxicity (seven patients), flu-like symptoms, and infection (five patients each). There were no grade 3/4 thrombocytopenia or grade 5 AEs. There were 14 confirmed PSA responses (33%; 95% CI, 20% to 50%); 72% of PSA responders had declines greater than 80%, and two patients achieved an undetectable PSA. The estimated median progression-free survival is 6 months (95% CI, 4 to 8 months), and the median survival is 18 months (95% CI, 13 to 24 months). Conclusion Ixabepilone has demonstrated activity in patients with chemotherapy-naive metastatic HRPC. Major toxicities were neutropenia and neuropathy. Further testing to define its activity relative to standard therapy is warranted. C1 Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. SW Oncol Grp, Ctr Stat, Seattle, WA USA. Univ Calif Davis, Ctr Canc, Sacramento, CA 95817 USA. Columbia Univ, New York, NY USA. Natl Canc Inst, Bethesda, MD USA. Univ Colorado, Denver, CO 80202 USA. RP Hussain, M (reprint author), Operat Off, SW Oncol Grp SWOG S0111, 14980 Omicron Dr, San Antonio, TX 78245 USA. EM mahahuss@med.umich.edu FU NCI NIH HHS [CA32102, CA35178, CA38926, CA45450, CA45560, CA58861, CA63845, CA67663, CA68183, CA74647, CA46441, CA42777, CA27057, CA20319, CA14028, CA12644] NR 19 TC 114 Z9 115 U1 0 U2 1 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 2005 VL 23 IS 34 BP 8724 EP 8729 DI 10.1200/JCO.2005.02.4448 PG 6 WC Oncology SC Oncology GA 989RA UT WOS:000233690200026 PM 16314632 ER PT J AU Bellizzi, KM Rowland, JH Jeffery, DD McNeel, T AF Bellizzi, KM Rowland, JH Jeffery, DD McNeel, T TI Health behaviors of cancer survivors: Examining opportunities for cancer control intervention SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID LONG-TERM SURVIVORS; PHYSICAL-ACTIVITY; BREAST-CANCER; NONCANCER CONTROLS; CIGARETTE-SMOKING; INFORMED CHOICES; LIFE; PREVALENCE; PREDICTORS; PREVENTION AB Purpose A population-based investigation was conducted to examine the prevalence of health behaviors (smoking, alcohol use, physical activity, and cancer screening) of cancer survivors by age, time since diagnosis, and cancer site. Understanding health behaviors of survivors is imperative, as many survivors are living longer and are at risk for cancer recurrence, second cancers, and complications from treatment. Methods Using the National Health Interview Survey, this study examined the prevalence of smoking and alcohol use as well as whether cancer survivors (n = 7,384) are meeting current recommendations for physical activity and cancer screening compared with noncancer controls (n = 121,347). Results Cancer survivors are similar to controls with respect to smoking status and alcohol consumption after adjusting for group differences. However, younger survivors (18 to 40 years) are at greater risk for continued smoking than controls. Survivors are 9% more likely to meet physical activity recommendations compared with controls. chi(2) tests indicate no significant differences in smoking, alcohol consumption, and physical activity by time since diagnosis, but differences by cancer site exist. Female cancer survivors are 34% and 36% more likely to meet mammogram and Papanicolaou smear screening recommendations, respectively, compared with controls. Similar screening patterns were found for prostate-specific antigen screening in men. Conclusion This study provides benchmark approximations of the prevalence of risky health behaviors of survivors by time since diagnosis and cancer site. As part of the collective effort to reduce late effects of cancer treatment, oncologists may be in the best position to offer initial guidance for promoting healthy lifestyle behaviors among cancer survivors. C1 NCI, Off Canc Survivorship, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Informat Management Serv Inc, Silver Spring, MD USA. RP Bellizzi, KM (reprint author), NCI, Off Canc Survivorship, Div Canc Control & Populat Sci, 6116 Execut Blvd,Suite 404, Bethesda, MD 20892 USA. EM bellizzk@mail.nih.gov NR 47 TC 267 Z9 268 U1 0 U2 14 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 2005 VL 23 IS 34 BP 8884 EP 8893 DI 10.1200/JCO.2005.02.2343 PG 10 WC Oncology SC Oncology GA 989RA UT WOS:000233690200045 PM 16314649 ER PT J AU Voon, V Lang, AE AF Voon, V Lang, AE TI Antidepressant treatment outcomes of psychogenic movement disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID CONTROLLED CLINICAL-TRIAL; CONVERSION DISORDER; MOTOR TYPE; DEPRESSION; SYMPTOMS; VENLAFAXINE; HYPNOSIS AB Background: Psychogenic movement disorder (PMD) is a subtype of conversion disorder. We describe the outcomes of a series of PMD patients following antidepressant treatment. Method: Twenty-three outpatients with chronic PMD, diagnosed using Fahn and Williams' criteria, underwent psychiatric assessment. The patients were referred for assessment and management from January 2003 to July 2004. Fifteen agreed to be treated with antidepressants. Patients received citalopram or paroxetine; those who did not respond after 4 weeks of taking an optimal dose were switched to venlafaxine. Concurrently, 3 had supportive psychotherapy, and I had family intervention. Assessments included the DSM-IV-based Mini-International Neuropsychiatric Interview and scales measuring depression, anxiety, and motor and global severity. Results: Eighteen patients (78%) had at least I Axis I diagnosis in addition to the somatoform diagnosis, and 3 (13%) had somatization disorder. Five (22%) had previous psychiatric contact. Nine (39%) had previously been treated with antidepressants, but only 4 (17%) had adequate trials. No significant differences existed in patient characteristics between treated and untreated groups. Among treated patients, Montgoinery-Asberg Depression Rating Scale scores improved from baseline (p < .01). Two treated subgroups were identified: 10 patients (67%) had primary conversion disorder, of whom 8 had marked motor and global improvements with 7 complete remissions, and 5 (33%) had primary hypochondriasis, somatization disorder, or probable factitious disorder/malingering, of whom none improved. All of the patients with primary conversion disorder had a current or previous depressive or anxiety disorder compared with 40% (N = 2) of the patients with additional somatoform diagnoses. Discussion: Our preliminary findings suggest that chronic PMD with primary conversion symptoms and with recent or current depression or anxiety may respond to antidepressants. Further well-designed studies, now under way, are required to confirm these findings. C1 Natl Inst Neurol Disorders & Stroke, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. Toronto Western Hosp, Dept Med, Div Neurol, Toronto, ON, Canada. Toronto Western Hosp, Dept Psychiat, Toronto, ON, Canada. RP Voon, V (reprint author), Natl Inst Neurol Disorders & Stroke, Human Motor Control Sect, NIH, 10 Ctr Dr MSC 1428,Bldg 10 Rm 5S213, Bethesda, MD 20892 USA. EM voonv@ninds.nih.gov; Valerie.voon@uhn.on.ca NR 27 TC 61 Z9 62 U1 2 U2 5 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 2005 VL 66 IS 12 BP 1529 EP 1534 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 999UL UT WOS:000234415900005 PM 16401153 ER PT J AU Vitiello, B Davies, M Arnold, LE McDougle, CJ Aman, M McCracken, JT Scahill, L Tierney, E Posey, DJ Swiezy, NB Koenig, K AF Vitiello, B Davies, M Arnold, LE McDougle, CJ Aman, M McCracken, JT Scahill, L Tierney, E Posey, DJ Swiezy, NB Koenig, K TI Assessment of the integrity of study blindness in a pediatric clinical trial of risperidone SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID TREATMENT ASSIGNMENT; PLACEBO; CHILDREN; MEDICATION; IMIPRAMINE; PATIENT; GUESSES AB Objective: Controlled clinical trials in pediatric psychopharmacology rely on blinded parents and clinical evaluators for outcome data, but little is known about the success of the masking procedures. The blindness of clinical evaluators and parents was examined in a clinical trial of risperidone in autism. Methods: Clinical evaluators and parents were asked to guess individual treatment assignments at the end of an 8-week placebo-controlled trial of risperidone in children (aged 5-17 years) with autism. Clinical evaluators did not have access to adverse event data. Results: The rates of correctly guessing individual treatment assignment (risperidone or placebo) were significantly greater than chance for both clinical evaluators and parents (P < 0.001). Clinical evaluators associated improvement with attribution to risperidone, and lack of improvement with attribution to placebo, in both the risperidone and placebo treatment arms. Parents associated improvement with attribution to risperidone only in the placebo treatment arm. Parents reported that adverse events influenced their guesses, but presence of adverse events was not associated with correctness of guess. Conclusion: Improvement was associated with attribution to active treatment regardless of actual treatment assignment, and adverse events did not appear to be a threat to study blindness. C1 NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. Columbia Univ, New York State Psychiat Inst, New York, NY USA. Ohio State Univ, Nisonger Ctr, Columbus, OH 43210 USA. Indiana Univ, Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA. Univ Calif Los Angeles, Inst Neuropsychiat, Los Angeles, CA 90024 USA. Yale Univ, Ctr Child Study, New Haven, CT 06520 USA. Kennedy Krieger Inst, Baltimore, MD USA. RP Vitiello, B (reprint author), NIMH, Div Serv & Intervent Res, Room 7147,6001 Execut Blvd,MSC 9633, Bethesda, MD 20892 USA. EM bvitiell@mail.nih.gov OI Scahill, Lawrence/0000-0001-5073-1707 FU NIMH NIH HHS [N01MH80011, N01MH70010, N01MH70001, N01MH70009] NR 15 TC 3 Z9 3 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD DEC PY 2005 VL 25 IS 6 BP 565 EP 569 DI 10.1097/01.jcp.0000185426.08268.92 PG 5 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 988VC UT WOS:000233628200011 PM 16282839 ER PT J AU Wheatley, T Weisberg, J Beauchamp, MS Martin, A AF Wheatley, T Weisberg, J Beauchamp, MS Martin, A TI Automatic priming of semantically-related words reduces activity in the fusiform gyrus SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID INFERIOR PREFRONTAL CORTEX; LEXICAL DECISION TASK; EVENT-RELATED FMRI; FUNCTIONAL MRI; MANIPULATABLE OBJECTS; CONCEPTUAL KNOWLEDGE; DEPENDENT MODULATION; TEMPORAL CORTEX; EPISODIC MEMORY; NEURAL SYSTEMS AB We used rapid, event-related fMRI to identify, the neural systems underlying object semantics. During scanning, Subjects silently read rapidly presented word pairs (150 msec, SOA = 250 msec) that were either unrelated in meaning (ankle-carrot), semantically related (fork-cup), or identical (crow-crow). Activity in the left posterior region of the fusiform gyrus and left inferior frontal cortex was modulated by word-pair relationship. Semantically related pairs yielded less activity than unrelated pairs, but greater activity than identical pairs, mirroring the pattern of behavioral facilitation as measured by word reading times. These findings provide strong support for the involvement of these areas in the automatic processing of object meaning. In addition, words referring to animate objects produced greater activity in the lateral region of the fusiform gyri, right superior temporal sulcus, and medial region of the occipital lobe relative to manmade, manipulable objects, whereas words referring to manmade, manipulable objects produced greater activity in the left ventral premotor, left anterior cingulate, and bilateral parietal cortices relative to animate objects. These findings are consistent with the dissociation between these areas based on sensory- and motor-related object properties, providing further evidence that conceptual object knowledge is housed, in part, in the same neural systems that subserve perception and action. C1 NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. RP Wheatley, T (reprint author), NIMH, Lab Brain & Cognit, NIH, 10 Ctr Dr MSC 1366, Bethesda, MD 20892 USA. EM wheatley@nih.gov RI martin, alex/B-6176-2009; OI Beauchamp, Michael/0000-0002-7599-9934 NR 88 TC 106 Z9 107 U1 4 U2 8 PU M I T PRESS PI CAMBRIDGE PA 238 MAIN STREET, STE 500, CAMBRIDGE, MA 02142-1046 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD DEC PY 2005 VL 17 IS 12 BP 1871 EP 1885 DI 10.1162/089892905775008689 PG 15 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 993WW UT WOS:000233988600005 PM 16356325 ER PT J AU Bocharov, G Brunner, H Grossman, Z AF Bocharov, G Brunner, H Grossman, Z TI Special Issue on Mathematics Applied to Immunology - Preface SO JOURNAL OF COMPUTATIONAL AND APPLIED MATHEMATICS LA English DT Editorial Material C1 Russian Acad Sci, Inst Numer Math, Moscow, Russia. Univ Coll Chester, Dept Math, Chester, Cheshire, England. Mem Univ Newfoundland, Dept Math & Stat, St John, NF A1C 5S7, Canada. Tel Aviv Univ, Sackler Fac Med, Dept Physiol & Pharmacol, IL-69978 Tel Aviv, Israel. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Bocharov, G (reprint author), Russian Acad Sci, Inst Numer Math, Moscow, Russia. 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 0377-0427 J9 J COMPUT APPL MATH JI J. Comput. Appl. Math. PD DEC 1 PY 2005 VL 184 IS 1 BP 1 EP 3 DI 10.1016/j.cam.2005.02.006 PG 3 WC Mathematics, Applied SC Mathematics GA 959UH UT WOS:000231544300001 ER PT J AU Kasabov, N Sidorov, IA Dimitrov, DS AF Kasabov, N Sidorov, IA Dimitrov, DS TI Computational intelligence, bioinformatics and computational biology: A brief overview of methods, problems and perspectives SO JOURNAL OF COMPUTATIONAL AND THEORETICAL NANOSCIENCE LA English DT Review DE computational intelligence; neural networks; bioinformatics; computational biology; genomics; proteomics; system biology; gene expression profiling; gene regulatory networks ID PROTEIN SECONDARY STRUCTURE; GENETIC REGULATORY SYSTEMS; NEURAL-NETWORKS; GEL-ELECTROPHORESIS; BACTERIAL CHEMOTAXIS; NUCLEOTIDE-SEQUENCES; STRUCTURE PREDICTION; EXPRESSION PATTERNS; COMPUTER-ANALYSIS; DRUG DISCOVERY AB The paper is an overview of methods of computational intelligence (CI) used in the area of Bioinformatics (BI) for the purpose of advancing the area Computational Biology (CB) and facilitating discoveries from biological data. Cl is the area of developing generic intelligent information processing methods and systems with wider applications, one of them being Bioinformatics. Cl adopts many principles from Biology, thus offering suitable methods and tools for BI. While CB aims at understanding the biology principles through their computational modeling, BI is aiming at the use and the development of new information methods and systems to enhance the storage, the analysis, modeling, and discovery from biological data. The synergism between the three disciplines, their methodologies, problems, and some current solutions are review in the paper. Some new methods and experimental results are introduced, such as feature and model optimization with genetic algorithms applied on gene expression data. C1 Auckland Univ Technol, Knowledge Engn & Discovery Res Inst, Auckland 1020, New Zealand. Auckland Univ Technol, Sch Comp & Informat Sci, Auckland 1020, New Zealand. NCI, CCR, Nanobiol Program, NIH, Frederick, MD 21702 USA. Univ Otago, Ctr Innovat, Pacific Edge Biotechnol Ltd, Dunedin, New Zealand. RP Auckland Univ Technol, Knowledge Engn & Discovery Res Inst, Auckland 1020, New Zealand. NR 120 TC 2 Z9 2 U1 0 U2 6 PU AMER SCIENTIFIC PUBLISHERS PI VALENCIA PA 26650 THE OLD RD, STE 208, VALENCIA, CA 91381-0751 USA SN 1546-1955 EI 1546-1963 J9 J COMPUT THEOR NANOS JI J. Comput. Theor. Nanosci. PD DEC PY 2005 VL 2 IS 4 BP 473 EP 491 DI 10.1166/jctn.2005.002 PG 19 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA 992XG UT WOS:000233916700002 ER PT J AU Case, DA Cheatham, TE Darden, T Gohlke, H Luo, R Merz, KM Onufriev, A Simmerling, C Wang, B Woods, RJ AF Case, DA Cheatham, TE Darden, T Gohlke, H Luo, R Merz, KM Onufriev, A Simmerling, C Wang, B Woods, RJ TI The Amber biomolecular simulation programs SO JOURNAL OF COMPUTATIONAL CHEMISTRY LA English DT Review DE Amber; biomolecular simulation programs ID MOLECULAR-DYNAMICS SIMULATIONS; PARTICLE-MESH EWALD; GENERALIZED BORN MODEL; REPLICA-EXCHANGE SIMULATIONS; NMR-RELAXATION PARAMETERS; FREE-ENERGY CALCULATIONS; FORCE-FIELD; ORBITAL CALCULATIONS; SOLVENT MODELS; NUCLEIC-ACIDS AB We describe the development, current features, and some directions for future development of the Amber package of computer programs. This package evolved from a program that was constructed in the late 1970s to do Assisted Model Building with Energy Refinement, and now contains a group of programs embodying a number of powerful tools of modern computational chemistry, focused on molecular dynamics and free energy calculations of proteins, nucleic acids, and carbohydrates. (c) 2005 Wiley Periodicals, Inc. C1 Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. Univ Utah, Dept Med Chem, Salt Lake City, UT 84112 USA. Univ Utah, Dept Pharmaceut & Pharmaceut Chem, Salt Lake City, UT 84112 USA. Univ Utah, Dept Bioengn, Salt Lake City, UT 84112 USA. NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. Univ Frankfurt, Fachbereich Biol & Informat, D-60439 Frankfurt, Germany. Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92697 USA. Penn State Univ, Dept Chem, University Pk, PA 16802 USA. Virginia Tech, Dept Comp Sci, Blacksburg, VA 24061 USA. SUNY Stony Brook, Dept Chem, Stony Brook, NY 11794 USA. Univ Georgia, Complex Carbohydrate Res Ctr, Athens, GA 30602 USA. RP Case, DA (reprint author), Scripps Res Inst, Dept Mol Biol, 10550 N Torrey Pines Rd,TPC15, La Jolla, CA 92037 USA. EM case@scripps.edu RI Luo, Ray/I-6928-2012 OI Luo, Ray/0000-0002-6346-8271 FU NCRR NIH HHS [RR12255]; NIGMS NIH HHS [R01 GM055230, R01 GM061678, R01 GM061678-06A1, R01 GM076121] NR 144 TC 3428 Z9 3482 U1 51 U2 425 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0192-8651 J9 J COMPUT CHEM JI J. Comput. Chem. PD DEC PY 2005 VL 26 IS 16 BP 1668 EP 1688 DI 10.1002/jcc.20290 PG 21 WC Chemistry, Multidisciplinary SC Chemistry GA 980MA UT WOS:000233021400002 PM 16200636 ER PT J AU Thierry, KL Lamb, ME Orbach, Y Pipe, ME AF Thierry, KL Lamb, ME Orbach, Y Pipe, ME TI Developmental differences in the function and use of anatomical dolls during interviews with alleged sexual abuse victims SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article DE anatomical dolls; sexual abuse; child abuse; forensic interviews; memory ID DETAILED DOLLS; FORENSIC INTERVIEWS/; CHILD WITNESSES; YOUNG-CHILDREN; CONTRADICTIONS; PRESCHOOLERS; QUESTION; MEMORY; EVENT AB The impact of anatomical dolls on reports provided by 3- to 12-year-old alleged sexual abuse victims (N = 178) was examined. Children produced as many details in response to open-ended invitations with and without the dolls. In response to directive questions, the 3- to 6-year-olds were more likely to reenact behaviorally than to report verbally, whereas the 7- to 12-year-olds produced more verbal details than enactments when using the dolls. With the dolls, the younger children were more likely than the older children to play suggestively and to contradict details provided without the dolls, whereas the older children were more likely to provide details that were consistent. Children in both age groups produced proportionally more fantastic details with the dolls than without the dolls. C1 Univ Cambridge, Dept Social & Dev Psychol, Fac Social & Polit Sci, Cambridge CB2 3RQ, England. Rutgers State Univ, Dept Psychol, Piscataway, NJ 08855 USA. NICHHD, Sect Social & Emot Dev, Bethesda, MD 20892 USA. RP Lamb, ME (reprint author), Univ Cambridge, Dept Social & Dev Psychol, Fac Social & Polit Sci, Free Sch Lane, Cambridge CB2 3RQ, England. EM MEL37@cam.ac.uk NR 28 TC 13 Z9 13 U1 2 U2 13 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD DEC PY 2005 VL 73 IS 6 BP 1125 EP 1134 DI 10.1037/0022-006X.73.6.1125 PG 10 WC Psychology, Clinical SC Psychology GA 001XS UT WOS:000234576600014 PM 16392985 ER PT J AU Janket, SJ Wightman, A Baird, AE Van Dyke, TE Jones, JA AF Janket, SJ Wightman, A Baird, AE Van Dyke, TE Jones, JA TI Does periodontal treatment improve glycemic control in diabetic patients? A meta-analysis of intervention studies SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE meta-analysis; inflammatory mediators; hemoglobin A1c; non-surgical periodontal treatment; antibiotics treatment ID GLYCATED HEMOGLOBIN; MELLITUS; THERAPY; DISEASE; TRIALS; HEALTH AB Previous analyses regarding effects of periodontal treatment on glycemic control included studies where causal association might not be assumed, or the results were reported non- quantitatively. We initiated this meta- analysis of 10 intervention studies to quantify the effects of periodontal treatment on HbA1c level among diabetic patients, to explore possible causes for the discrepant reports, and to make recommendations for future studies. Data sources were MEDLINE ( January, 1980, to January, 2005), the EBMR, Cochrane Register, and bibliographies of the published articles. Three investigators extracted data regarding intervention, outcomes, and effect size. A total of 456 patients was included in this analysis, with periodontal treatment as predictor and the actual change in hemoglobin A1c level as the outcome. The weighted average decrease in actual HbA1c level was 0.38% for all studies, 0.66% when restricted to type 2 diabetic patients, and 0.71% if antibiotics were given to them. However, none was statistically significant. C1 Boston Univ, Goldman Sch Dent Med, Dept Gen Dent, Boston, MA 02118 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, San Antonio, TX USA. USAF, San Antonio, TX USA. NINDS, Stroke Neurosci Unit, NIH, Bethesda, MD 20892 USA. Boston Univ, Goldman Sch Dent Med, Clin Res Ctr, Boston, MA USA. VA Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. RP Janket, SJ (reprint author), Boston Univ, Goldman Sch Dent Med, Dept Gen Dent, 100 E Newton St, Boston, MA 02118 USA. EM sjanket@post.harvard.edu FU NCRR NIH HHS [M01 RR000533]; NIDCR NIH HHS [P01 DE013191, DE13191] NR 25 TC 143 Z9 152 U1 0 U2 5 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD DEC PY 2005 VL 84 IS 12 BP 1154 EP 1159 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 986LX UT WOS:000233452200014 PM 16304446 ER PT J AU Nguyen, RHN Wilcox, AJ AF Nguyen, RHN Wilcox, AJ TI Terms in reproductive and perinatal epidemiology: 2. Perinatal terms SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH LA English DT Article ID BIRTH-WEIGHT; PRETERM; DEATH AB This is the second of a two part glossary of terms used in reproductive and perinatal epidemiology. The purpose is to provide a reference for terms that are widely (if not always consistently) used in this field. While a glossary cannot resolve all these problems, it provides a point of reference for understanding them. Part 1 covered terms relevant mostly to events and conditions before birth. Part 2 emphasises terms used during the time around and after birth. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP Nguyen, RHN (reprint author), NIEHS, Epidemiol Branch, 111 TW Alexander Dr,Mail Drop A3-05, Res Triangle Pk, NC 27709 USA. EM nguyen5@niehs.nih.gov OI Wilcox, Allen/0000-0002-3376-1311 FU Intramural NIH HHS NR 19 TC 31 Z9 32 U1 0 U2 3 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0143-005X J9 J EPIDEMIOL COMMUN H JI J. Epidemiol. Community Health PD DEC PY 2005 VL 59 IS 12 BP 1019 EP 1021 DI 10.1136/jech.2004.023465 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 983ZP UT WOS:000233271200004 PM 16286486 ER PT J AU Feerick, MM Snow, KL AF Feerick, MM Snow, KL TI The relationships between childhood sexual abuse, social anxiety, and symptoms of posttraumatic stress disorder in women SO JOURNAL OF FAMILY VIOLENCE LA English DT Article DE childhood sexual abuse; long-term effects; social anxiety; PTSD ID YOUNG-ADULT WOMEN; PHYSICAL ABUSE; SELF-ESTEEM; CHILDREN; TRAUMA; ADJUSTMENT; COMMUNITY; SURVIVORS; IMPACT; INCEST AB The relationships between childhood sexual abuse, social anxiety, and symptoms of posttraumatic stress disorder were examined in a sample of 313 undergraduate women. Thirty-one percent of the women reported some form of sexual abuse in childhood. Women with a history of sexual abuse reported more symptoms of anxiety, distress in social situations, and posttraumatic stress disorder than other women. Women who experienced attempted or actual intercourse reported more avoidance than women with no history of abuse and women with exposure only, and more PTSD symptoms than all other groups of women. Women who experienced fondling reported more PTSD symptoms than women with no history of abuse. Pressure, age of onset of abuse, abuse by a family friend, and abuse by other perpetrators were all significant abuse characteristics in predicting adult social anxiety. Implications of these results for research and interventions are discussed. C1 Cornell Univ, Dept Human Dev, Ithaca, NY 14853 USA. RP Feerick, MM (reprint author), NICHHD, Child Dev & Behav Branch, NIH, 6100 Execut Blvd,Room 4B05,MSC 7510, Bethesda, MD 20892 USA. EM feerickm@mail.nih.gov NR 81 TC 20 Z9 21 U1 4 U2 13 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-7482 J9 J FAM VIOLENCE JI J. Fam. Violence PD DEC PY 2005 VL 20 IS 6 BP 409 EP 419 DI 10.1007/s10896-005-7802-z PG 11 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA 998ID UT WOS:000234311000006 ER PT J AU Farma, JM Pingpank, JF Libutti, SK Bartlett, DL Ohl, S Beresneva, T Alexander, HR AF Farma, JM Pingpank, JF Libutti, SK Bartlett, DL Ohl, S Beresneva, T Alexander, HR TI Limited survival in patients with carcinomatosis from foregut malignancies after cytoreduction and continuous hyperthermic peritoneal perfusion SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article; Proceedings Paper CT 46th Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract CY MAY 14-18, 2005 CL Chicago, IL SP Soc Surg Alimentary Tract DE regional therapy; peritoneal carcinomatosis; peritoneal perfusion; gastric cancer; duodenal cancer; pancreatic cancer ID SYSTEMIC THIOSULFATE PROTECTION; GASTRIC-CANCER; INTRAPERITONEAL CHEMOTHERAPY; SURGERY; DISSEMINATION; MESOTHELIOMA; RECURRENCE; CISPLATIN; TRIAL AB Peritoneal carcinomatosis is a frequent mode of metastasis in patients with gastric, duodenal, or pancreatic cancer. Survival in this setting is short and therapeutic options are limited. This analysis examines the outcomes of 18 patients treated with operative cytoreduction and continuous hyperthermic peritoneal perfusion. Eighteen patients (6 males and 12 females) with gastric (n = 9), pancreatic (n = 7), or duodenal (n = 2) cancer were treated on protocol. Patients under-went optimal cytoreduction (complete gross resection, 11; minimal residual disease, 7) and a 90-minute perfusion with cisplatin. Clinical parameters and tumor and treatment characteristics were analyzed. Survival curves were estimated using the Kaplan-Meier method. Procedures included gastrectomy (n = 8), pancreaticoduodenectomy (n = 3), and hemicolectomy (n = 2). After cytoreduction, patients had no evidence of residual disease (n = 11), fewer than 100 implants less than 5 mm (n = 1), more than 100 implants between 5-10 mm (n = 3), or multiple implants with greater than I cm (n 3). Five patients received a postoperative intraperitoneal dwell with 5-fluorouracil and paclitaxel. There was one perioperative mortality, and complications occurred in 10 patients. The median progression-free survival was 8 months (mean, 10 months; range, 1-47 months) with a median overall survival of 8 months (mean, 18 months; range, 1-74 months). In this cohort, peritoneal perfusion with cisplatin used to treat foregut malignancies has a high incidence of complications and does not significantly alter the natural history of the disease. Investigation of novel therapeutic approaches should be considered. C1 NCI, Surg Metab Sect, Surg Branch, NIH,CRC, Bethesda, MD 20892 USA. Univ Pittsburgh, Ctr Canc, Dept Surg, Pittsburgh, PA USA. RP Alexander, HR (reprint author), NCI, Surg Metab Sect, Surg Branch, NIH,CRC, Room 4W-5952,10 Ctr Dr,MSC 1201, Bethesda, MD 20892 USA. EM Richard_Alexander@nih.gov NR 20 TC 18 Z9 18 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD DEC PY 2005 VL 9 IS 9 BP 1346 EP 1353 DI 10.1016/j.gassur.2005.06.016 PG 8 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 998RF UT WOS:000234336100030 PM 16332493 ER PT J AU Balasubramanian, A Munshi, N Koziel, MJ Hu, ZY Liang, TJ Groopman, JE Ganju, RK AF Balasubramanian, A Munshi, N Koziel, MJ Hu, ZY Liang, TJ Groopman, JE Ganju, RK TI Structural proteins of Hepatitis C virus induce interleukin 8 production and apoptosis in human endothelial cells SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID MESSENGER-RNA EXPRESSION; T-CELLS; CORE PROTEIN; DC-SIGN; CHEMOTACTIC CYTOKINES; ADHESION MOLECULES; LEUKOCYTE ADHESION; LIVER INFLAMMATION; VIRAL-HEPATITIS; HIV-1 INFECTION AB Hepatitis C virus (HCV) infection is associated with inflammation of liver endothelium, which contributes to the pathogenesis of chronic hepatitis. The mechanism of this endothelitis is not understood, since the virus does not appear to infect endothelial cells productively. Here, an 'innocent bystander' mechanism related to HCV proteins was hypothesized and it was investigated whether the binding of HCV particles to human endothelium induced functional changes in the cells. Exposure of human umbilical vein endothelial cells (HUVECs) to HCV-Iike particles (HCV-LPs) resulted in increased interleukin 8 (IL8) production and induction of apoptosis. The IL8 supernatants collected after stimulation of HUVECs with HCV-LPs, BV-GUS (control baculovirus containing beta-glucuronidase) and appropriate controls were used to assay the transendothelial migration of neutrophils. This assay confirmed that HCV-LP-induced IL8 was functionally active. Using specific NF-kappa B inhibitors, it was also shown that HCV-LP-induced NF-kappa B activity mediated IL8 production in HUVECs. Apoptosis appeared to be mediated by the Fas/Fas-L pathway, as neutralizing antibodies for Fas and Fas-L significantly protected HUVECs against HCV-LP-induced apoptosis. Treatment of HUVECs with HCV-LPs also enhanced cellular Fas-L expression and augmented caspase-3 activation. This was confirmed by using a specific caspase-3 inhibitor, Z-Asp-Glu-Val-Asp-fluoromethyl ketone. As shown by blocking of specific chemokine receptors for IL8 on HUVECs, the induction of IL8 did not appear to contribute to HCV-LP-induced apoptosis. These results suggest that HCV proteins can trigger the release of inflammatory chemokines such as IL8 and cause endothelial apoptosis, thereby facilitating endothelitis. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Expt Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02115 USA. NIDDK, Liver Dis Sect, NIH, Bethesda, MD 20892 USA. RP Ganju, RK (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Expt Med, 4 Blackfan Circle,3rd Floor, Boston, MA 02115 USA. EM jgroopma@bidmc.harvard.edu; rganju@bidmc.harvard.edu FU NIAID NIH HHS [AI49140]; NIDA NIH HHS [DA15008] NR 65 TC 25 Z9 26 U1 0 U2 2 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD DEC PY 2005 VL 86 BP 3291 EP 3301 DI 10.1099/vir.0.81056-0 PN 12 PG 11 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 988VE UT WOS:000233628400012 PM 16298974 ER PT J AU Kraft, ARM Arndt, T Hasenkrug, KJ Dittmer, U AF Kraft, ARM Arndt, T Hasenkrug, KJ Dittmer, U TI Effective treatment of retrovirus-induced suppression of antibody responses with CpG oligodeoxynucleotides SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID T-CELLS; GAMMA-INTERFERON; HIV REPLICATION; RHESUS MACAQUES; MICE; DNA; ACTIVATION; INFECTION; LEUKEMIA; IMMUNITY AB Most retroviruses induce severe immunosuppression during acute infection. We have used the Friend retrovirus mouse model to demonstrate that immunostimulatory B-type CpG oligodeoxynucleotides (ODN) have a protective effect against retrovirus-induced suppression of antibody responses to potent B-cell antigens. CD8(+) T cells were critical for effective treatment with CpG-ODN, since in vivo depletion of these cells from treated mice impaired protection from retrovirus-induced immunosuppression. Protection also required IFN-gamma, as neutralization of this cytokine abolished the therapeutic effect of CpG-ODN. These findings may have implications for the treatment of immunosuppressive virus infections. C1 Univ Klinikum Essen, Inst Virol, D-45122 Essen, Germany. NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT USA. RP Dittmer, U (reprint author), Univ Klinikum Essen, Inst Virol, Hufelandstr 55, D-45122 Essen, Germany. EM ulf.dittmer@uni-essen.de NR 20 TC 6 Z9 6 U1 0 U2 1 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD DEC PY 2005 VL 86 BP 3365 EP 3368 DI 10.1099/vir.0.81115-0 PN 12 PG 4 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 988VE UT WOS:000233628400021 PM 16298983 ER PT J AU Zonderman, AB AF Zonderman, AB TI Predicting Alzheimer's disease in the Baltimore Longitudinal Study of Aging SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article; Proceedings Paper CT Workshop on Children of Alzheimer Parent CY MAR 06-07, 2005 CL San Diego, CA SP Natl Inst Hlth DE Alzheimer's disease; dementia; prospective study; longitudinal follow-up study; aging; risk factors ID MILD COGNITIVE IMPAIRMENT; HEALTH INITIATIVE MEMORY; POSTMENOPAUSAL WOMEN; RISK; DIAGNOSIS; DEMENTIA AB Longitudinal studies offer opportunities for studying children whose parents have Alzheimer's disease. The Baltimore Longitudinal Study of Aging (BLSA) has examined adult cognitive performance but has not systematically recruited participants' children. We initiated studies of dementia in the 1980s. This work suggested that hormone replacement and use of nonsteroidal anti-inflammatory drugs reduced the risk of Alzheimer's disease and that risk for Alzheimer's disease could be predicted from cognitive performance as many as 20 years prior to its onset. More recently, we showed that premorbid levels of free testosterone were lower in men who developed Alzheimer's disease and premorbid depressive symptomatology was a risk for Alzheimer's disease in men but not women as many as 6 years before the onset of dementia. Participants in the BLSA include family members with a variety of degrees of relationship, but there is no systematic effort to collect data from relatives of participants. C1 NIA, Lab Personal & Cognit, Cognit Sect, Baltimore, MD 21224 USA. RP Zonderman, AB (reprint author), NIA, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM zonderman@nih.gov OI Zonderman, Alan B/0000-0002-6523-4778 FU Intramural NIH HHS; NIA NIH HHS [Z01 AG000185-16] NR 18 TC 9 Z9 10 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0891-9887 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD DEC PY 2005 VL 18 IS 4 BP 192 EP 195 DI 10.1177/0891988705281863 PG 4 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 986EO UT WOS:000233433100003 PM 16306238 ER PT J AU Gu, J Li, H Li, M Vuong, C Otto, M Wen, Y Gao, Q AF Gu, J Li, H Li, M Vuong, C Otto, M Wen, Y Gao, Q TI Bacterial insertion sequence IS256 as a potential molecular marker to discriminate invasive strains from commensal strains of Staphylococcus epidermidis SO JOURNAL OF HOSPITAL INFECTION LA English DT Article DE Staphylococcus epidermidis; molecular marker; IS256; polysaccharide intercellular adhesin ID POLYSACCHARIDE INTERCELLULAR ADHESIN; COAGULASE-NEGATIVE STAPHYLOCOCCI; SLIME-PRODUCING STRAINS; BIOFILM FORMATION; ELEMENT IS256; PHASE VARIATION; ICA LOCUS; INFECTIONS; EXPRESSION; VIRULENCE AB The skin commensal, Staphylococcus epidermidis has become one of the most important causative agents of nosocomial. infections associated with medical. devices. Differentiation between invasive S. epidermidis and its commensal counterpart is crucial for clinical decision making. The ica gene locus, which codes for production of polysaccharide intercellular adhesion (PIA), represents a frequently suggested molecular marker for infectivity. Our data demonstrated that production of PIA was not significantly increased among clinical. strains, which may explain the controversial, results obtained previously on the correlation of ica presence with origin from infection. Therefore, in this study, we attempted to identify novel genes discriminating between invasive and commensal strains based on the comparison of genome sequences. Our results indicated that the bacterial, insertion sequence element IS256 occurred significantly more frequently in strains of clinical origin. Importantly, IS256 might thus constitute a molecular marker to discriminate invasive strains from commensal, strains of S. epidermidis. (C) 2005 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved. C1 Fudan Univ, Shanghai Med Coll, Key Lab Med Mol Virol, Shanghai 200032, Peoples R China. Fudan Univ, HuaShan Hosp, Ctr Lab Med, Shanghai 200040, Peoples R China. NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Gao, Q (reprint author), Fudan Univ, Shanghai Med Coll, Key Lab Med Mol Virol, Shanghai 200032, Peoples R China. EM qiangao@shmu.edu.cn RI gu, jiafeng/E-5704-2010; OI Otto, Michael/0000-0002-2222-4115 NR 27 TC 48 Z9 53 U1 0 U2 2 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0195-6701 J9 J HOSP INFECT JI J. Hosp. Infect. PD DEC PY 2005 VL 61 IS 4 BP 342 EP 348 DI 10.1016/j.jhin.2005.04.017 PG 7 WC Infectious Diseases SC Infectious Diseases GA 995LB UT WOS:000234100700009 PM 16242209 ER PT J AU Peter, I Shearman, AM Zucker, DR Schmid, CH Demissie, S Cupples, LA Larson, MG Vasan, RS D'Agostino, RB Karas, RH Mendelsohn, ME Housman, DE Levy, D AF Peter, I Shearman, AM Zucker, DR Schmid, CH Demissie, S Cupples, LA Larson, MG Vasan, RS D'Agostino, RB Karas, RH Mendelsohn, ME Housman, DE Levy, D TI Variation in estrogen-related genes and cross-sectional and longitudinal blood pressure in the Framingham Heart Study SO JOURNAL OF HYPERTENSION LA English DT Article DE polymorphism (genetics); receptors; estrogen; hypertension; blood pressure; association; epidemiology ID STEROID-RECEPTOR COACTIVATOR-1; HORMONE REPLACEMENT THERAPY; PULSE PRESSURE; POSTMENOPAUSAL WOMEN; HYPERTENSION; DISEASE; SEX; ASSOCIATION; FAMILIES; LINKAGE AB Objective To examine the association between variation in estrogen-related genes and cross-sectional and longitudinal blood pressure in men and women. Design In 1780 unrelated members of the community-based Framingham Heart Study offspring cohort, systolic blood pressure and diastolic blood pressure were measured over a total of six examination cycles encompassing 24 years of follow-up. Multivariate regression analyses were used to assess the relation between untreated cross-sectional and longitudinal blood pressure and polymorphisms at the estrogen receptor-a (ESR1), estrogen receptor-beta (ESR2), aromatase (CYP19A1), and nuclear receptor coactivator 1 (NCOA1) genes after adjustment for common risk factors. Results In men, systolic blood pressure and pulse pressure (systolic blood pressure minus diastolic blood pressure) were associated with two polymorphisms in ESR1, while pulse pressure was also associated with variations in NCOA1 and CYP19A1. Polymorphisms in ESR1, CYP19A1, and NCOA1 were associated with diastolic blood pressure in women. Conclusions Although the underlying relations between genes involved in estrogen action and hypertension remain to be completely understood, our findings provide suggestive evidence of gender-specific contributions of estrogen-related genes to blood pressure variation. As no correction for multiple testing was performed in the analyses, we view these results as suggestive and not definitive. Further studies are warranted to confirm these results using a comprehensive set of polymorphisms in order to shed more light on the involvement of estrogen in blood pressure regulation. C1 Tufts Univ, New England Med Ctr, Dept Med, Mol Cardiol Res Inst, Boston, MA 02111 USA. MIT, Biostat Res Ctr, Inst Clin Res & Hlth Policy Studies, Cambridge, MA 02139 USA. MIT, Ctr Canc Res, Cambridge, MA 02139 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. NHLBI, Framingham, MA USA. RP Peter, I (reprint author), Tufts Univ, New England Med Ctr, Dept Med, Mol Cardiol Res Inst, 750 Washington St,POB 63, Boston, MA 02111 USA. EM ipeter@tufts-nemc.org OI Ramachandran, Vasan/0000-0001-7357-5970; Schmid, Christopher/0000-0002-0855-5313 FU NHLBI NIH HHS [N01-HC25195, N01-HC38038, P01-HL077378, P50-HL63494] NR 40 TC 56 Z9 61 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD DEC PY 2005 VL 23 IS 12 BP 2193 EP 2200 DI 10.1097/01.hjh.0000188728.66183.92 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 987TA UT WOS:000233539000012 PM 16269961 ER PT J AU Huang, NN Han, SB Hwang, IY Kehrl, JH AF Huang, NN Han, SB Hwang, IY Kehrl, JH TI B cells productively engage soluble antigen-pulsed dendritic cells: Visualization of live-cell dynamics of B cell dendritic cell interactions SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PANCREATIC BETA-CELLS; T-CELL; IMMUNOLOGICAL SYNAPSE; IN-VIVO; LYMPHOCYTE LOCOMOTION; EXTRACELLULAR-MATRIX; CUTTING EDGE; 3-D COLLAGEN; ACTIVATION; CYTOSKELETON AB Interactions between B lymphocytes and Ag-bearing dendritic cells (DC) likely occur at inflammatory sites and within lymphoid organs. To better understand these interactions we imaged B cells (TgB) from hen egg lysozyme (HEL) transgenic mice and DC pulsed with HEL (DC-HEL) in collagen matrices. Analysis of live-cell dynamics revealed autonomous movements and repeated encounters between TgB cells and DC-HEL that are best described by a "kiss-run and engage" model, whereas control B cells had only short-lived interactions. Ag localized at contact sites between TgB cells and DC-HEL, and both cell types rearranged their actin cytoskeletons toward the contact zone. The interaction of a TgB cell with a HEL-bearing DC triggered strong Ca2+ transients in the B cells. Thus, B cells can productively interact with DC displaying their cognate Ag. C1 NIAID, Cell Mol Immunol Sect B, Immunoregulat Lab, Bethesda, MD 20892 USA. RP Kehrl, JH (reprint author), NIAID, Cell Mol Immunol Sect B, Immunoregulat Lab, 31 Ctr Dr, Bethesda, MD 20892 USA. EM jkehrl@niaid.nih.gov OI Kehrl, John/0000-0002-6526-159X FU Intramural NIH HHS NR 35 TC 35 Z9 35 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 2005 VL 175 IS 11 BP 7125 EP 7134 PG 10 WC Immunology SC Immunology GA 987UZ UT WOS:000233544200009 PM 16301615 ER PT J AU DiPaolo, RJ Glass, DD Bijwaard, KE Shevach, EM AF DiPaolo, RJ Glass, DD Bijwaard, KE Shevach, EM TI CD4(+)CD25(+) T cells prevent the development of organ-specific autoimmune disease by inhibiting the differentiation of autoreactive effector T cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNOLOGICAL SELF-TOLERANCE; CUTTING EDGE; IN-VIVO; TRANSCRIPTION FACTOR; PERNICIOUS-ANEMIA; DENDRITIC CELLS; ANTIGEN; GASTRITIS; MICE; INDUCTION AB Thymic-derived, naturally occurring, CD4(+)CD25(+) regulatory T cells (nTreg) are potent suppressors of immune responses. A detailed understanding of which components of the development and activation of pathogenic effector T cells are inhibited by nTreg during the course of T cell-mediated, organ-specific autoimmunity is as yet unknown. We have analyzed the effects of polyclonal nTreg on the development of autoimmune gastritis. The nTreg inhibited the development of disease, but failed to inhibit the migration of effector cells into the gastric lymph node or stomach. Notably, nTreg did not inhibit the expansion of autoreactive T cells in the gastric lymph node. The primary effect of nTreg appeared to be inhibition of differentiation of autoantigen-specific T cells to Th1 effector cells, as reflected by a decrease in Ag-stimulated IFN-gamma production and a reduction in T-bet expression. C1 NIH, Cellular Immunol Sect, Immunol Lab, Bethesda, MD 20892 USA. RP Shevach, EM (reprint author), NIH, Cellular Immunol Sect, Immunol Lab, Bldg 10 11N315, Bethesda, MD 20892 USA. EM eshevach@niaid.nih.gov NR 44 TC 83 Z9 87 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 2005 VL 175 IS 11 BP 7135 EP 7142 PG 8 WC Immunology SC Immunology GA 987UZ UT WOS:000233544200010 PM 16301616 ER PT J AU Hsu, C Hughes, MS Zheng, ZL Bray, RB Rosenberg, SA Morgan, RA AF Hsu, C Hughes, MS Zheng, ZL Bray, RB Rosenberg, SA Morgan, RA TI Primary human T lymphocytes engineered with a codon-optimized IL-15 gene resist cytokine withdrawal-induced apoptosis and persist long-term in the absence of exogenous cytokine SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SECONDARY STRUCTURE; PROTEIN EXPRESSION; ESCHERICHIA-COLI; TRANSGENIC MICE; NATURAL-KILLER; GROWTH-FACTOR; CUTTING EDGE; IN-VITRO; CELL; INTERLEUKIN-15 AB IL-15 is a common gamma-chain cytokine that has been shown to be more active than IL-2 in several murine cancer immunotherapy models. Although T lymphocytes do not produce IL-15, murine lymphocytes carrying an IL-15 transgene demonstrated superior antitumor activity in the immunotherapy of B16 melanoma. Thus, we sought to investigate the biological impact of constitutive IL-15 expression by human lymphocytes. In this report we describe the generation of a retroviral vector encoding a codon-optimized IL-15 gene. Alternate codon usage significantly enhanced the translational efficiency of this tightly regulated gene in retroviral vector-transduced cells. Activated human CD4(+) and CD8(+) human lymphocytes expressed IL-15R alpha and produced high levels of cytokine upon retroviral transduction with the IL-15 vector. IL-15-transduced lymphocytes remained viable for up to 180 days in the absence of exogenous cytokine. IL-15 vector-transduced T cells showed continued proliferation after cytokine withdrawal and resistance to apoptosis while retaining specific Ag recognition. In the setting of adoptive cell transfer, IL-15-transduced lymphocytes may prolong lymphocyte survival in vivo and could potentially enhance antitumor activity. C1 NCI, Surg Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Morgan, RA (reprint author), NCI, Surg Branch, Canc Res Ctr, NIH, 10 Ctr Dr,Bldg 10,Room 3-3940, Bethesda, MD 20892 USA. EM rmorgan@mail.nih.gov FU NCI NIH HHS [Z01 SC003811-31] NR 51 TC 47 Z9 49 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 2005 VL 175 IS 11 BP 7226 EP 7234 PG 9 WC Immunology SC Immunology GA 987UZ UT WOS:000233544200021 PM 16301627 ER PT J AU Brinster, C Shevach, EM AF Brinster, C Shevach, EM TI Bone marrow-derived dendritic cells reverse the anergic state of CD4(+)CD25(+) T cells without reversing their suppressive function SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IN-VIVO; CUTTING EDGE; AUTOIMMUNE-DISEASE; GENE-EXPRESSION; IL-2 PRODUCTION; LYMPH-NODES; ACTIVATION; TOLERANCE; VITRO; MICE AB Dendritic cells (DC) are potent inducers of immunity to foreign Ags, but also contribute to self-tolerance by induction of regulatory T cells or deletion/anergy of self-reactive T cells. In this study, we have studied the capacity of DC to activate naturally occurring CD4(+)CD25(+) regulatory T cells as well as the ability of CD4(+)CD25(+) T cells to suppress the DC-mediated activation of CD4(+)CD25(-) T cells. Mature bone marrow-derived dendritic cells, but not splenic DC, were able to induce the proliferation of CD4(+)CD25(+) T cells in the presence of a polyclonal stimulus and in the absence of exogenous IL-2. The DC-induced proliferative response of the CD4(+)CD25(+) T cells was partially dependent on IL-2 produced by a small number of contaminating CD25(+) effector cells. Because bone marrow-derived dendritic cells induce proliferation of both CD4(+)CD25(+) and CD4(+)CD25(-) T cells in vitro, it was impossible to assay the suppressive function of the CD4(+)CD25(+) T cells using [H-3]TdR uptake or CFSE dilution. We therefore measured IL-2 production in cocultures of CD4(+)CD25(+) and CD4+CD25- T cells using the IL-2 secretion assay. Surprisingly, CD4(+)CD25(+) T cells markedly suppressed IL-2 secretion by the CD4(+)CD25(-) T cells without inhibiting their proliferation. Collectively, these results suggest that Ag presentation by DC can induce the expansion of CD4(+)CD25(+) T cells while simultaneously activating their ability to suppress cytokine secretion by effector T cells. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Shevach, EM (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Room 1IN315,10 Ctr Dr,MSC 1892, Bethesda, MD 20892 USA. EM eshevach@niaid.nih.gov NR 29 TC 46 Z9 52 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 2005 VL 175 IS 11 BP 7332 EP 7340 PG 9 WC Immunology SC Immunology GA 987UZ UT WOS:000233544200033 PM 16301639 ER PT J AU Souto-Carneiro, MM Sims, GP Girschik, H Lee, JS Lipsky, PE AF Souto-Carneiro, MM Sims, GP Girschik, H Lee, JS Lipsky, PE TI Developmental changes in the human heavy chain CDR3 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TERMINAL DEOXYNUCLEOTIDYL TRANSFERASE; COMPLEMENTARITY-DETERMINING REGIONS; BLOOD ANTIBODY REPERTOIRE; B-CELL PRECURSORS; VH GENE SEGMENTS; JUNCTIONAL DIVERSITY; PREFERENTIAL UTILIZATION; AUTOANTIBODY PRODUCTION; SOMATIC HYPERMUTATION; CDR-H3 REPERTOIRE AB The CDR3 of the Ig H chain (CDR3(H)) is significantly different in fetal and adult repertoires. To understand the mechanisms involved in the developmental changes in the CDR3(H) of Ig H chains, sets of nonproductive V(H)DJ(H) rearrangements obtained from fetal, full-term neonates and adult single B cells were analyzed and compared with the corresponding productive repertoires. Analysis of the nonproductive repertoires was particularly informative in assessing developmental changes in the molecular mechanisms of V(H)DJ(H) recombination because these rearrangements did not encode a protein and therefore their distribution was not affected by selection. Although a number of differences were noted, the major reasons that fetal B cells expressed Ig H chains with shorter CDR3(H) were both diminished TdT activity in the DJ(H) junction and the preferential use of the short J(H) proximal D segment D7-27. The enhanced usage of D7-27 by fetal B cells appeared to relate to its position in the locus rather than its short length. The CDR3, progressively acquired a more adult phenotype during ontogeny. In fetal B cells, there was decreased recurrent DJ(H) rearrangements before V-H-DJ(H) rearrangement and increased usage of junctional microhomologies both of which also converted to the adult pattern during ontogeny. Overall, these results indicate that the decreased length and complexity of the CDR3(H) of fetal B cells primarily reflect limited enzymatic modifications of the joins as well as a tendency to use proximal D and J(H) segments during DJ(H) rearrangements. C1 NIAMSD, NIH, Repertoire Anal Grp, Autoimmun Branch, Bethesda, MD 20892 USA. Inst Gulbenkian Ciencias, Oeiras, Portugal. Univ Wurzburg, Div Rheumatol, Childrens Clin, Fac Med, Wurzburg, Germany. Ewha Womans Univ, Div Rheumatol, Dept Internal Med, Coll Med, Seoul, South Korea. RP Lipsky, PE (reprint author), NIAMSD, NIH, Repertoire Anal Grp, Autoimmun Branch, 9000 Rockville Pike,Bldg 10,Room 6D47C, Bethesda, MD 20892 USA. EM LipskyP@mail.nih.gov RI Souto-Carneiro, Margarida/C-4386-2016 OI Souto-Carneiro, Margarida/0000-0001-6923-0590 NR 51 TC 27 Z9 28 U1 0 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 2005 VL 175 IS 11 BP 7425 EP 7436 PG 12 WC Immunology SC Immunology GA 987UZ UT WOS:000233544200044 PM 16301650 ER PT J AU Gomez, G Gonzalez-Espinosa, C Odom, S Baez, G Cid, ME Ryan, JJ Rivera, J AF Gomez, G Gonzalez-Espinosa, C Odom, S Baez, G Cid, ME Ryan, JJ Rivera, J TI Impaired Fc epsilon RI-dependent gene expression and defective eicosanoid and cytokine production as a consequence of fyn deficiency in mast cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CYTOSOLIC PHOSPHOLIPASE A(2); NF-KAPPA-B; SRC-FAMILY KINASES; HIGH-AFFINITY RECEPTOR; C-JUN; ARACHIDONIC-ACID; TNF-ALPHA; TYROSINE PHOSPHORYLATION; ALLERGIC RESPONSE; PROTEIN-KINASES AB Fyn kinase is a key contributor in coupling Fc epsilon RI to mast cell degranulation. A limited macroarray analysis of Fc epsilon RI-induced gene expression suggested potential defects in lipid metabolism, eicosanoid and glutathione metabolism, and cytokine production. Biochemical analysis of these responses revealed that Fyn-deficient mast cells failed to secrete the inflammatory eicosanoid products leukotrienes B-4 and C-4, the cytokines IL-6 and TNF, and chemokines CCL2 (MCP-1) and CCL4 (MIP-1 beta). Fc epsilon RI-induced generation of arachidonic acid and normal induction of cytokine mRNA were defective. Defects in JNK and p38 MAPK activation were observed, whereas ERK1/2 and cytosolic phospholipase A(2) (S505) phosphorylation was normal. Pharmacological studies revealed that JNK activity was associated with generation of arachidonic acid. Fc epsilon RI-mediated activation of I kappa B kinase 13 and 1 kappa B alpha phosphorylation and degradation was defective resulting in a marked decrease of the nuclear NF-kappa B DNA binding activity that drives IL-6 and TNF production in mast cells. However, not all cytokine were affected, as IL-13 production and secretion was enhanced. These studies reveal a major positive role for Fyn kinase in multiple mast cell inflammatory responses and demonstrate a selective negative regulatory role for certain cytokines. C1 NIAMSD, Mol Inflammat Sect, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. Ctr Invest & Estudios Avanzados Zona Sur, Pharmacobiol Dept, Mexico City, DF, Mexico. Virginia Commonwealth Univ, Dept Biol, Richmond, VA 23284 USA. RP Rivera, J (reprint author), NIAMSD, Mol Inflammat Sect, Mol Immunol & Inflammat Branch, NIH, Bldg 10,Room 9N228,10 Ctr Dr,MSC 1820, Bethesda, MD 20892 USA. EM juan_rivera@nih.gov FU NCI NIH HHS [1R01CA91839]; NIAID NIH HHS [1R01AI43433] NR 66 TC 78 Z9 81 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 2005 VL 175 IS 11 BP 7602 EP 7610 PG 9 WC Immunology SC Immunology GA 987UZ UT WOS:000233544200064 PM 16301670 ER PT J AU Viau, M Longo, NS Lipsky, PE Zouali, M AF Viau, M Longo, NS Lipsky, PE Zouali, M TI Staphylococcal protein A deletes B-1a and marginal zone B lymphocytes expressing human immunoglobulins: An immune evasion mechanism SO JOURNAL OF IMMUNOLOGY LA English DT Article ID YEAST ARTIFICIAL CHROMOSOMES; IN-VIVO DELETION; CELL-DEVELOPMENT; HEAVY-CHAIN; MICE; SUPERANTIGEN; RECEPTOR; ANTIBODIES; BINDING; REPERTOIRE AB Protein A (SpA) of Staphylococcus aureus is endowed with the capacity to interact with the H chain variable region (VH) of human Abs and to target > 40% of B lymphocytes. To investigate whether this property represents a virulence factor and to determine the in vivo consequences of the confrontation of SpA with B lymphocytes, we used transgenic mice expressing fully human Abs. We found that administration of soluble SpA reduces B-la lymphocytes of the peritoneal cavity and marginal zone B lymphocytes of the spleen, resulting in a markedly deficient type 2 Immoral response. Single-cell PCR analysis and sequencing of the Ab VH gene repertoire revealed a significant reduction of V(H)3(+) marginal zone B cells. Since the two B lymphocyte subsets targeted are involved in innate immune functions, our data suggest that crippling of humoral immunity by S. aureus represents an immune evasion mechanism that may aggravate recurrent infections. C1 Inst Natl Sante & Rech Med, Paris, France. NIAMSD, Bethesda, MD 20892 USA. RP Zouali, M (reprint author), Hop Lariboisiere, Inst Natl Sante & Rech Med, Ctr Viggo Petersen, Unite 606,2, Rue Ambroise Pare, F-75475 Paris, France. EM moncef.zouali@wanadoo.fr NR 51 TC 22 Z9 24 U1 0 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 2005 VL 175 IS 11 BP 7719 EP 7727 PG 9 WC Immunology SC Immunology GA 987UZ UT WOS:000233544200076 PM 16301682 ER PT J AU Maker, AV Attia, P Rosenberg, SA AF Maker, AV Attia, P Rosenberg, SA TI Analysis of the cellular mechanism of antitumor responses and autoimmunity in patients treated with CTLA-4 blockade SO JOURNAL OF IMMUNOLOGY LA English DT Article ID REGULATORY T-CELLS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; TRANSCRIPTION FACTOR FOXP3; ANTIGEN 4 CTLA-4; IN-VITRO; CTLA-4-MEDIATED INHIBITION; IMMUNE DYSREGULATION; METASTATIC MELANOMA; TUMOR-IMMUNOTHERAPY; ACTIVATION AB We have demonstrated previously that the administration of CTLA-4 blockade has mediated objective cancer regression and autoimmunity in patients with metastatic melanoma. To explore the mechanism of these in vivo effects, we have studied the changes in lymphocyte phenotype and function in patients receiving anti-CTLA-4 Ab (MDX-010). Patients with stage IV melanoma or renal cell cancer were treated every 3 wk with an anti-CTLA-4 Ab with or without peptide immunization. Pheresis samples were analyzed using flow cytometry to determine lymphocyte cell surface markers. Gene expression analyses and proliferation assays were conducted on purified T cell subsets. Anti-CTLA-4 Ab did not inhibit the suppressive activity of CD4(+)CD25(+) cells in vitro or in vivo. In addition, there was no decrease in the expression of CD4(+)CD25(+) cells in whole PBMC, nor a decrease in Foxp3 gene expression in the CD4(+) or CD4(+)CD25(+) purified cell populations posttreatment. The percentage of CD4(+), CD8(+), CD4(+)CD25(+), and CD4(+)CD25(-) T cells in PBMC expressing the activation marker HLA-DR increased following anti-CTLA-4 Ab administration. Therefore, our results suggest that the antitumor effects of CTLA-4 blockade are due to increased T cell activation rather than inhibition or depletion of T regulatory cells. C1 NCI, Surg Branch, NIH, Bethesda, MD 20814 USA. RP Rosenberg, SA (reprint author), NCI, Surg Branch, NIH, CRC Room 3-3888,10 Ctr Dr,MSC 1201, Bethesda, MD 20814 USA. EM sar@nih.gov FU NCI NIH HHS [Z01 SC003811-31] NR 47 TC 195 Z9 207 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 2005 VL 175 IS 11 BP 7746 EP 7754 PG 9 WC Immunology SC Immunology GA 987UZ UT WOS:000233544200079 PM 16301685 ER PT J AU Raju, R Foote, J Banga, JP Hall, TR Padoa, CJ Dalakas, MC Ortqvist, E Hampe, CS AF Raju, R Foote, J Banga, JP Hall, TR Padoa, CJ Dalakas, MC Ortqvist, E Hampe, CS TI Analysis of GAD65 autoantibodies in Stiff-Person syndrome patients SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GLUTAMIC-ACID-DECARBOXYLASE; DEPENDENT DIABETES-MELLITUS; GAMMA-AMINOBUTYRIC-ACID; ISLET-CELL ANTIBODIES; CEREBELLAR-ATAXIA; DIFFERENT EPITOPES; CLEFT-PALATE; HIGH-LEVEL; EPILEPSY; PLASMAPHERESIS AB Autoantibodies to the 65-kDa isoform of glutamate decarboxylase GAD65 (GAD65Ab) are strong candidates for a pathological role in Stiff-Person syndrome (SPS). We have analyzed the binding specificity of the GAD65Ab in serum and cerebrospinal fluid (CSF) of 12 patients with SPS by competitive displacement studies with GAD65-specific rFab-derived from a number of human and mouse mAbs specific for different determinants on the Ag. We demonstrate considerable differences in the epitope specificity when comparing paired serum and CSF samples, suggesting local stimulation of B cells in the CSF compartment of these patients. Moreover, these autoantibodies strongly inhibit the enzymatic activity of GAD65, thus blocking the formation of the neurotransmitter gamma-aminobutyric acid. The capacity of the sera to inhibit the enzymatic activity of GAD65 correlated with their binding to a conformational C-terminal Ab epitope. Investigation of the inhibitory mechanism revealed that the inhibition could not be overcome by high concentrations of glutamate or the cofactor pyridoxal phosphate, suggesting a noncompetitive inhibitory mechanism. Finally, we identified a linear epitope on amino acids residues 4-22 of GAD65 that was recognized solely by autoantibodies from patients with SPS but not by serum from type I diabetes patients. A mAb (N-GAD65 mAb) recognizing this N-terminal epitope was successfully humanized to enhance its potential therapeutic value by reducing its overall immunogenicity. C1 Univ Washington, Dept Med, Seattle, WA 98195 USA. Natl Inst Neurol Disorders & Stroke, Neuromuscular Dis Sect, NIH, Bethesda, MD 20892 USA. Arrowsmith Technol, Seattle, WA 98103 USA. Kings Coll London, Sch Med, Div Gene & Cell Based Therapy, London WC2R 2LS, England. Univ Witwatersrand, Dept Chem Pathol, Johannesburg, South Africa. Natl Hlth Lab Serv, Johannesburg, South Africa. Karolinska Inst, Dept Women & Child Hlth, Stockholm, Sweden. RP Hampe, CS (reprint author), Univ Washington, Dept Med, Box 357710, Seattle, WA 98195 USA. EM champe@u.washington.edu RI Raju, Raghavan/E-9219-2011 NR 64 TC 80 Z9 81 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 2005 VL 175 IS 11 BP 7755 EP 7762 PG 8 WC Immunology SC Immunology GA 987UZ UT WOS:000233544200080 PM 16301686 ER PT J AU Breman, JG O'Meara, WP AF Breman, JG O'Meara, WP TI Intermittent preventive treatment for malaria in infants: Moving forward, cautiously SO JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material ID PLACEBO-CONTROLLED TRIAL; SULFADOXINE-PYRIMETHAMINE; PLASMODIUM-FALCIPARUM; TANZANIAN INFANTS; CHILDREN; ANEMIA; RESISTANCE; GAMBIA; AREA C1 NIH, Div Int Epidemiol & Populat Studies, Fogiarty Int Ctr, Bethesda, MD 20892 USA. RP Breman, JG (reprint author), NIH, Div Int Epidemiol & Populat Studies, Fogiarty Int Ctr, 16 Ctr Dr, Bethesda, MD 20892 USA. EM jbreman@nih.gov NR 20 TC 4 Z9 4 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 2005 VL 192 IS 11 BP 1869 EP 1871 DI 10.1086/497702 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 980KU UT WOS:000233018200003 PM 16267756 ER PT J AU Baric, I Cuk, M Fumic, K Vugrek, O Allen, RH Glenn, B Maradin, M Pazanin, L Pogribny, I Rados, M Sarnavka, V Schulze, A Stabler, S Wagner, C Zeisel, SH Mudd, SH AF Baric, I Cuk, M Fumic, K Vugrek, O Allen, RH Glenn, B Maradin, M Pazanin, L Pogribny, I Rados, M Sarnavka, V Schulze, A Stabler, S Wagner, C Zeisel, SH Mudd, SH TI S-Adenosylhomocysteine hydrolase deficiency: A second patient, the younger brother of the index patient, and outcomes during therapy SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Article ID CYSTATHIONINE BETA-SYNTHASE; MYELIN BASIC-PROTEIN; TOTAL HOMOCYSTEINE; DNA METHYLATION; METHYLTRANSFERASE DEFICIENCY; METHIONINE METABOLISM; MASS-SPECTROMETRY; FOLATE-DEFICIENCY; GLOBAL DNA; ADENOSYLMETHIONINE AB S-Adenosylhomocysteine (AdoHcy) hydrolase deficiency has been proven in a human only once, in a recently described Croatian boy. Here we report the clinical course and biochemical abnormalities of the younger brother of this proband. This younger brother has the same two mutations in the gene encoding AdoHcy hydrolase, and has been monitored since birth. We report, as well, outcomes during therapy for both patients. The information obtained suggests that the disease starts in utero and is characterized primarily by neuromuscular symptomatology (hypotonia, sluggishness, psychomotor delay, absent tendon reflexes, delayed myelination). The laboratory abnormalities are markedly increased creatine kinase and elevated aminotransferases, as well as specific amino acid aberrations that pinpoint the aetiology. The latter include, most importantly, markedly elevated plasma AdoHcy. Plasma S-adenosylmethionine (AdoMet) is also elevated, as is methionine (although the hypermethioninaemia may be absent or nonsignificant in the first weeks of life). The disease seems to be at least to some extent treatable, as shown by improved myelination and psychomotor development during dietary methionine restriction and supplementation with creatine and phosphatidylcholine. C1 Univ Hosp Ctr, Dept Pediat, Zagreb 10000, Croatia. Univ Zagreb, Sch Med, Zagreb 41001, Croatia. Univ Hosp Ctr, Clin Inst Lab Diag, Zagreb 10000, Croatia. Rudjer Boskovic Inst, Dept Mol Med, Zagreb, Croatia. Univ Colorado, Hlth Sci Ctr, Div Hematol, Denver, CO USA. Vanderbilt Univ, Dept Biochem, Nashville, TN 37232 USA. Dept Vet Affairs Med Ctr, Nashville, TN 37212 USA. Univ Hosp Ctr, Dept Neuropathol, Zagreb, Croatia. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Univ Hosp Ctr, Dept Radiol, Zagreb 10000, Croatia. Univ Childrens Heidelberg, Heidelberg, Germany. Univ N Carolina, Sch Med, Chapel Hill, NC USA. Univ N Carolina, Sch Publ Hlth, Dept Nutr, Chapel Hill, NC 27599 USA. NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. RP Univ Hosp Ctr, Dept Pediat, Kispaticeva 12, Zagreb 10000, Croatia. EM ibaric@kbc-zagreb.hr FU NCRR NIH HHS [M01 RR000046, M01 RR000046-461213]; NIA NIH HHS [AG-09834, R01 AG009834]; NIDDK NIH HHS [DK56359, 5P30 DK26657, P30 DK056350, R01 DK015289, R01 DK055865, R01 DK055865-05, DK15289, DK55865, P30 DK026657, P30 DK056350-08, R37 DK015289] NR 42 TC 46 Z9 47 U1 0 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0141-8955 EI 1573-2665 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PD DEC PY 2005 VL 28 IS 6 BP 885 EP 902 DI 10.1007/s10545-005-0192-9 PG 18 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 006OR UT WOS:000234907300010 PM 16435181 ER PT J AU Kanno, Y Levi, BZ Tamura, T Ozato, K AF Kanno, Y Levi, BZ Tamura, T Ozato, K TI Immune cell-specific amplification of interferon signaling by the IRF-4/8-PU.1 complex SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Article ID SEQUENCE-BINDING-PROTEIN; REGULATORY FACTOR-I; PLASMACYTOID DENDRITIC CELLS; MYELOID PROGENITOR CELLS; IFN-GAMMA; TRANSCRIPTIONAL ACTIVATION; ADAPTIVE IMMUNITY; GENE-EXPRESSION; GP91(PHOX) EXPRESSION; RESPONSIVE ELEMENT AB Both type I interferon (IFN-alpha/beta) and type II IFN ( IFN-gamma) exert many functions that are restricted to immune cells. Thus, they play critical roles in innate and adaptive immunity. IFN regulatory factor-4 (IRF-4) and IRF-8 ( formerly PU. 1 interaction partner [ Pip] and IFN consensus sequence binding domain [ ICSBP], respectively) are immune cell-specific members of the IRF family that regulate the development of myeloid, lymphoid, and dendritic cells. They form a heterodimeric complex with another immune cell-specific transcription factor PU. 1-Spi-1 and regulate transcription of genes in the immune system. This review describes the role of the IRF-8-PU.1 complex in modulating IFN signaling in an immune cell-specific manner. Our studies revealed that some but not all IFN-gamma-inducible genes carry an IFN-gamma activation site ( GAS) element that contains a binding site for the IRF8-PU.1 complex. The IRF-8-PU.1 complex can take part in GAS-mediated transcription and amplify expression of IFN-gamma-responsive genes initiated by Stat1 in macrophages. Similarly, some but not all IFN-alpha/beta-responsive genes are shown to carry an IFN-stimulated response element ( ISRE) that contains an IRF-8-PU.1 binding site. The participation of IRF-8-PU.1 in ISRE-mediated transcription results in the augmentation of IFN-stimulated gene factor 3 ( ISGF3)-induced transcription in macrophages. Thus, GAS and ISRE elements, classically defined as universal IFN-alpha/beta and IFN-gamma response sequences, are not the same, and some harbor an embedded motif for IRF8-PU. 1 binding that functions only in immune cells. Accordingly, the IRF-8-PU.1 complex provides secondary IFN signaling pathways unique to the immune system. Collectively, the contribution of IRF-8 and PU. 1 to IFN-regulated gene expression may in part account for immune cell-specific functions of IFNs. C1 NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. NIAMSD, Mol Immunol & Inflammat Branch, Bethesda, MD 20892 USA. Technion Israel Inst Technol, Dept Food Engn & Biotechnol, IL-32000 Haifa, Israel. RP Ozato, K (reprint author), NICHHD, Lab Mol Growth Regulat, NIH, Bldg 6,Room 2A01 6 Ctr Dr, Bethesda, MD 20892 USA. EM ozatok@nih.gov RI Kanno, Yuka/B-5802-2013; OI Kanno, Yuka/0000-0001-5668-9319 NR 85 TC 77 Z9 77 U1 1 U2 1 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 2005 VL 25 IS 12 BP 770 EP 779 DI 10.1089/jir.2005.25.770 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 000YB UT WOS:000234497300007 PM 16375605 ER PT J AU Connelly, CD Newton, RR Aarons, GA AF Connelly, CD Newton, RR Aarons, GA TI A psychometric examination of English and Spanish versions of the revised conflict tactics scales SO JOURNAL OF INTERPERSONAL VIOLENCE LA English DT Article DE psychometrics; conflict tactics scale-revised; CTS2; intimate partner violence; ethnic groups; cultural groups ID WIFE ASSAULT; 5 SECTORS; PREVALENCE; VIOLENCE; RELIABILITY; DISORDERS; VALIDITY; PARTNER; GENDER; CTS2 AB The psychometric properties of the Revised Conflict Tactics Scales (CTS2) are examined for English-speaking (n = 211) and Spanish-speaking(n = 194)Latino women. Internal consistency of total scale scores is satisfactory (Cronbach's alpha of. 70 to .84). However subscale alphas range from .46 to .80. Confirmatory factor analyses support five factors of negotiation, minor and severe psychological aggression, and minor and severe physical assault. In unconstrained two-group models, loadings are of similar magnitude across language of administration, with the exception of the Physical Assault scales. Unconstrained and constrained model comparisons show scale structure varied by language group for physical assault. Although results of this study show some comparability for English-speaking and Spanish-speaking Latinas, simply combining results across language groups may obscure important differences in rates of endorsement and patterns of responses reflecting cultural, educational, and economic differences. C1 Univ San Diego, Hahn Sch Nursing & Hlth Sci, San Diego, CA 92110 USA. NIMH, Child & Adolescent Serv Res Ctr, Bethesda, MD USA. Calif State Univ Fullerton, Fullerton, CA 92634 USA. RP Connelly, CD (reprint author), Univ San Diego, Hahn Sch Nursing & Hlth Sci, San Diego, CA 92110 USA. FU NIDA NIH HHS [K01 DA015145, K01 DA 15145]; NIMH NIH HHS [MH 01695, MH 50313, MH 55282] NR 22 TC 34 Z9 34 U1 4 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0886-2605 J9 J INTERPERS VIOLENCE JI J. Interpers. Violence PD DEC PY 2005 VL 20 IS 12 BP 1560 EP 1579 DI 10.1177/0886260505280341 PG 20 WC Criminology & Penology; Family Studies; Psychology, Applied SC Criminology & Penology; Family Studies; Psychology GA 981JW UT WOS:000233085900003 PM 16246917 ER PT J AU Zhang, N Oppenheim, JJ AF Zhang, N Oppenheim, JJ TI Crosstalk between chemokines and neuronal receptors bridges immune and nervous systems SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE hyperalgesia; opioid; TRPV1 ID MU-OPIOID RECEPTORS; CAPSAICIN RECEPTOR; HETEROLOGOUS DESENSITIZATION; MICE LACKING; MOLECULAR-CLONING; ION-CHANNEL; RAT-BRAIN; PROTEIN; PAIN; HYPERALGESIA AB Chemokine receptors, a family of Gi protein-coupled receptors responsible for cell migration, are widely expressed by cells of immune and nervous systems. Activation of receptors on the surface of leukocytes, such as opioid, vasoactive intestinal peptide, or adenosine receptors, often has inhibitory effects on chemokine receptors by a mechanism termed heterologous desensitization, resulting in suppression of immune responses. Conversely, activation of chemokine receptors also induces heterologous desensitization of mu-opioid receptors (MOR), a class of key analgesic receptors on neurons. Furthermore, prior exposure of neuronal cells to chemokine treatment enhances the sensitivity of transient receptor potential vanilloid 1 (TRPV1), a heat- and ligand-gated calcium channel, which is critical for sensing of pain. Consequently, during inflammation, activation of chemokine receptors on neurons contributes to hyperalgesia by inhibiting MOR and concomitantly sensitizing TRPV1 via Gi protein-mediated signaling pathways. These observations suggest that the crosstalk between chemokine receptors and neuropeptide membrane receptors serves as a bridge between the immune and nervous systems. C1 NCI, Mol Immunoregulat Lab, Ctr Canc Res, Frederick, MD 21702 USA. Peking Univ, Dept Biol Chem, Beijing 100871, Peoples R China. Peking Univ, State Key Lab Mol Dynam & Stable Struct, Coll Chem, Beijing 100871, Peoples R China. RP Oppenheim, JJ (reprint author), NCI, Mol Immunoregulat Lab, Ctr Canc Res, Bldg 560,Room 21-89A, Frederick, MD 21702 USA. EM Oppenhei@ncifcrf.gov FU Intramural NIH HHS NR 36 TC 48 Z9 49 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 2005 VL 78 IS 6 BP 1210 EP 1214 DI 10.1189/jlb.0405224 PG 5 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 992ZE UT WOS:000233921700005 PM 16204635 ER PT J AU Kobayashi, SD Voyich, JM Whitney, AR DeLeo, FR AF Kobayashi, SD Voyich, JM Whitney, AR DeLeo, FR TI Spontaneous neutrophil apoptosis and regulation of cell survival by granulocyte macrophage-colony stimulating factor SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE inflammation; microarray; polymorphonuclear leukocytes; serum/glucocorticol-regulated kinase ID HUMAN POLYMORPHONUCLEAR LEUKOCYTES; PRIME HUMAN-NEUTROPHILS; GM-CSF; GENE-EXPRESSION; DIFFERENTIATION PROGRAM; IN-VITRO; CLASS-II; BACTERIAL LIPOPOLYSACCHARIDE; PHOSPHOINOSITIDE 3-KINASE; INFLAMMATORY MEDIATORS AB Polymorphonuclear leukocytes (PMNs or neutrophils) are the most prominent cellular component of the innate immune system in humans and produce an array of potent cytotoxic molecules. It is important that neutrophils undergo constitutive (spontaneous) apoptosis as a mechanism to facilitate normal cell turnover and immune system homeostasis. Conversely, several proinflammatory cytokines, including granulocyte macrophage-colony stimulating factor (GM-CSF), prolong neutrophil survival. The molecular mechanisms that regulate PMN apoptosis or survival remain incompletely defined. To that end, we compared global gene expression in human neutrophils during spontaneous apoptosis with that in cells cultured with human GM-CSF. Genes encoding proteins that inhibit apoptosis, such as myeloid cell leukemia sequence 1, caspase 8 and Fas-associated via death domain-like apoptosis regulator (CFLAR), B cell chronic lymphocytic leukemia/lymphoma 2 (BCL2)/ adenovirus E1B 19 kDa-interacting protein 2 (BNIP2), and serum/glucocorticoid-regulated kinase (SGK), were down-regulated coincident with neutrophil apoptosis. In contrast, those encoding apoptosis inhibitor 5, BCL2-like 1, BNIP2, CFLAR, SGK, and tumor necrosis factor alpha-induced protein 8 were up-regulated in PMNs cultured with GM-CSF. Correspondingly, GM-CSF delayed PMN apoptosis (P<0.03), increased cell viability (P<0.03), and prolonged neutrophil phagocytic capacity (P<0.05). Prolonged functional capacity was paralleled by striking up-regulation of proinflammatory genes and proteins, including CD14, CD24, CD66, and human leukocyte antigen-DR. In addition, expression of SGK protein diminished during PMN apoptosis but was restored by culture with GM-CSF, suggesting SGK is involved in leukocyte survival. These studies provide a global view of the molecular events that regulate neutrophil survival and apoptosis. C1 NIAID, Rocky Mt Lab, NIH, Lab Human Bacterial Pathogenesis, Hamilton, MT 59840 USA. RP DeLeo, FR (reprint author), NIAID, Rocky Mt Lab, NIH, Lab Human Bacterial Pathogenesis, 903 S 4th St, Hamilton, MT 59840 USA. EM fdeleo@niaid.nih.gov OI DeLeo, Frank/0000-0003-3150-2516 FU Intramural NIH HHS NR 60 TC 84 Z9 91 U1 1 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD DEC PY 2005 VL 78 IS 6 BP 1408 EP 1418 DI 10.1189/jlb.0605289 PG 11 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 992ZE UT WOS:000233921700026 PM 16204629 ER PT J AU Das, R Kumar, SKK Kumar, A AF Das, R Kumar, SKK Kumar, A TI Use of non-adiabatic geometric phase for quantum computing by NMR SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE quantum computation; geometric phase; fault-tolerant; circuit; controlled phase shift ID NUCLEAR-MAGNETIC-RESONANCE; SEARCH ALGORITHM; EXPERIMENTAL IMPLEMENTATION; BERRY PHASE; COMPUTATION; SPECTROSCOPY; PULSES AB Geometric phases have stimulated researchers for its potential applications in many areas of science. One of them is fault-tolerant quantum computation. A preliminary requisite of quantum computation is the implementation of controlled dynamics of qubits. In controlled dynamics, one qubit undergoes coherent evolution and acquires appropriate phase, depending on the state of other qubits. If the evolution is geometric, then the phase acquired depend only on the geometry of the path executed, and is robust against certain types of error. This phenomenon leads to an inherently fault-tolerant quantum computation. Here we suggest a technique of using non-adiabatic geometric phase for quantum computation, using selective excitation. In a two-qubit system, we selectively evolve a suitable subsystem where the control qubit is in state vertical bar 1 >, through a closed circuit. By this evolution, the target qubit gains a phase controlled by the state of the control qubit. Using the non-adiabatic geometric phase we demonstrate implementation of Deutsch-Jozsa algorithm and Grover's search algorithm in a two-qubit system. (c) 2005 Elsevier Inc. All rights reserved. C1 Indian Inst Sci, NMR Quantum Computat & Quantum Informat Grp, Dept Phys, Bangalore 560012, Karnataka, India. Indian Inst Sci, NMR Res Ctr, Bangalore 560012, Karnataka, India. RP Das, R (reprint author), NCI, Struct Biophys Lab, POB B,Bldg 538, Ft Detrick, MD 21702 USA. EM rdas@ncifcrf.gov; anilnmr@physics.iisc.ernet.in NR 44 TC 14 Z9 14 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 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD DEC PY 2005 VL 177 IS 2 BP 318 EP 328 DI 10.1016/j.nmr.2005.07.025 PG 11 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 993RU UT WOS:000233973400015 PM 16182577 ER PT J AU Silva, AC AF Silva, AC TI Perfusion-based fMRI: Insights from animal models SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article; Proceedings Paper CT International Workshop on Quantitative Cerebral Perfusion Using MRI CY MAR 21-23, 2004 CL Venice, ITALY SP Int Soc Magnet Resonance Med DE functional magnetic resonance imaging; arterial spin labeling; animal models; cerebral blood flow; spatial resolution; temporal resolution ID CEREBRAL-BLOOD-FLOW; FUNCTIONAL MRI; SOMATOSENSORY STIMULATION; RAT-BRAIN; FOREPAW STIMULATION; NMR-SPECTROSCOPY; ARTERIAL WATER; BOLD FMRI; OXYGENATION; CBF AB Modern functional neuroimaging techniques, including functional magnetic resonance imaging (fMRI), positron emission tomography (PET). and optical imaging of intrinsic signals (OIS). rely on a tight coupling between neural activity and cerebral blood flow (CBF) to visualize brain activity using CBF as a Surrogate marker. Because CBF is a uniquely defined physiological parameter, fMRI techniques based on CBF contrast have the advantage of being specific to tissue signal change, and the potential to provide more direct and quantitative measures of brain activation than blood oxygenation level-dependent (BOLD)- or cerebral blood volume (CBV)-based techniques. The changes in CBF elicited by increased neural activity are an excellent: index of the magnitude of electrical activity. Increases in CBF are more closely localized to the foci of increased electrical activity, and occur more promptly to the stimulus than BOLD- or CBV-based contrast. In addition, CBF-based fMRI is less affected by confounds from venous drainage common to BOLD. Animal Studies of brain activation have yielded considerable insights into the advantages of CBF-based fMRI. Based on results provided by animal Studies, CBF fMRI may offer a means of better assessing the magnitude, spatial extent, and temporal response of neural activity, and may be more specific to tissue state. These properties are expected to be particularly useful for longitudinal and quantitative fMRI studies. C1 NINDS, Cerebral Microcirculat Unit, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. RP Silva, AC (reprint author), NINDS, Cerebral Microcirculat Unit, Lab Funct & Mol Imaging, NIH, 10 Ctr Dr,MSC 1065,Bldg 10,Room B1D106, Bethesda, MD 20892 USA. EM silvaa@ninds.nih.gov RI Silva, Afonso/A-7129-2009 FU Intramural NIH HHS NR 38 TC 8 Z9 9 U1 1 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD DEC PY 2005 VL 22 IS 6 BP 745 EP 750 DI 10.1002/jmri.20461 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 990TX UT WOS:000233767200013 PM 16267855 ER PT J AU Duyn, JH van Gelderen, P Talagala, L Koretsky, A de Zwart, JA AF Duyn, JH van Gelderen, P Talagala, L Koretsky, A de Zwart, JA TI Technological advances in MRI measurement of brain perfusion SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article; Proceedings Paper CT International Workshop on Quantitative Cerebral Perfusion Using MRI CY MAR 21-23, 2004 CL Venice, ITALY SP Int Soc Magnet Resonance Med DE MR imaging; perfusion; resolution; coil arrays; parallel imaging ID TO-NOISE RATIO; SIGNAL; COIL; TESLA; ARRAY AB Measurement of brain perfusion using arterial spin labeling (ASL) or dynamic susceptibility contrast (DSC) based MRI has many potential important clinical applications. However, the clinical application of perfusion MRI has been limited by a number of factors, including a relatively poor spatial resolution, limited volume coverage, and low signal-to-noise ratio (SNR). It is difficult to improve any of these aspects because both ASL and DSC methods require rapid image acquisition. In this report, recent methodological developments are discussed that alleviate some of these limitations and make perfusion MRI more Suitable for clinical application. In particular, the availability of high magnetic field strength systems, increased gradient performance, the use of RF coil arrays and parallel imaging, and increasing pulse sequence efficiency allow for increased image acquisition speed and improved SNR. The use of parallel imaging facilitates the trade-off of SNR for increases in spatial resolution. As a demonstration. we obtained DSC and ASL perfusion images at 3.0 T and 7.0 T with multichannel RF coils and parallel imaging, which allowed us to obtain high-quality images with in-plane voxel sizes of 1.5 X 1.5 mm(2). C1 NINDS, Adv MRI Lab, NIH, Bethesda, MD 20892 USA. RP Duyn, JH (reprint author), NINDS, Adv MRI Lab, NIH, Bldg 10,Room B1D724,9000 Rockville Pike, Bethesda, MD 20892 USA. EM jhd@helix.nih.gov RI Duyn, Jozef/F-2483-2010; Koretsky, Alan/C-7940-2015 OI Koretsky, Alan/0000-0002-8085-4756 FU Intramural NIH HHS [Z01 NS002989-08] NR 21 TC 24 Z9 25 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD DEC PY 2005 VL 22 IS 6 BP 751 EP 753 DI 10.1002/jmri.20450 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 990TX UT WOS:000233767200014 PM 16267852 ER PT J AU Petty, HR Kindzelskii, AL Chaiworapongsa, T Petty, AR Romero, R AF Petty, HR Kindzelskii, AL Chaiworapongsa, T Petty, AR Romero, R TI Oxidant release is dramatically increased by elevated glucose concentrations in neutrophils from pregnant women SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE neutrophil; metabolism; hexose monophosphate pathway; reactive oxygen species; NO; glucose; pregnancy ID DIABETES-MELLITUS; MOUSE EMBRYOS; CONGENITAL-MALFORMATIONS; LIPID-PEROXIDATION; OXIDATIVE STRESS; FREE-RADICALS; RAT EMBRYOS; HYPERGLYCEMIA; METABOLISM; COMPLICATIONS AB Objective: To evaluate the mechanism of oxidative stress at glucose levels accompanying diabetic pregnancy. Specifically, we hypothesize that elevated glucose overwhelms hexose monophosphate shunt (HMS) down-regulation observed during pregnancy. Methods: Peripheral blood cells from normal healthy pregnant women were exposed to heightened glucose levels to provide an in vitro model of the effects of diabetic pregnancy. Changes in NAD(P) H, reactive oxygen species (ROS) and nitric oxide (NO) production were evaluated in single cells. Results: Altered metabolic dynamics, as judged by NAD(P)H autofluorescence of neutrophils from both pregnant and nonpregnant women, were observed during incubation with 14 mM glucose, a pathophysiologic level. In parallel, increased production of ROS and NO was observed. The ROS and NO levels attained in cells from pregnant women were greater than those observed in cells from non-pregnant women. Inhibitors of the HMS and NAD( P) H oxidase blocked these effects. These metabolic and oxidant changes required approximately one minute, suggesting that transient glucose spikes during pregnancy could trigger this response. Conclusions: Elevated glucose levels enhance HMS activity and oxidant production in cells from pregnant women. This mechanism may be generally applicable in understanding the role of diabetes in materno-fetal health. C1 Univ Michigan, Sch Med, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48105 USA. Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA. Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. DHHS, NICHHD, Perinatal Res Branch, NIH, Bethesda, MD USA. RP Petty, HR (reprint author), Univ Michigan, Sch Med, Dept Ophthalmol & Visual Sci, 1000 Wall St, Ann Arbor, MI 48105 USA. EM hpetty@umich.edu FU Intramural NIH HHS NR 44 TC 4 Z9 4 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PD DEC PY 2005 VL 18 IS 6 BP 397 EP 404 DI 10.1080/14767050500361679 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 001KN UT WOS:000234532100007 PM 16390806 ER PT J AU Chaiworapongsa, T Romero, R Espinoza, J Kim, YM Edwin, S Bujold, E Gomez, R Kuivaniemi, H AF Chaiworapongsa, T Romero, R Espinoza, J Kim, YM Edwin, S Bujold, E Gomez, R Kuivaniemi, H TI Macrophage migration inhibitory factor in patients with preterm parturition and microbial invasion of the amniotic cavity SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article; Proceedings Paper CT 23rd Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 03-08, 2003 CL SAN FRANCISCO, CA SP Soc Maternal Fetal Med DE amniotic fluid; immunohistochemistry; intrauterine infection; macrophage migration inhibitory factor; MIF; MIF gene expression; parturition; placenta; preterm labor ID MATRIX METALLOPROTEINASES; EXPRESSION; MEMBRANES; SEPSIS; TERM; MIF; HYPERSENSITIVITY; ACTIVATION; INFECTION; MEDIATION AB Objective: Macrophage migration inhibitory factor (MIF) has emerged as an important mediator of septic shock. The administration of MIF increases lethality during endotoxemia, whereas neutralization of this cytokine prevents endotoxic shock and death associated with bacterial infection. The objective of this study was to determine whether there is a change in the amniotic fluid concentration of MIF in intra-amniotic infection and human parturition. Study design: A cross-sectional study was conducted in women in the following categories: (1) mid-trimester (n = 84); (2) preterm labor and intact membranes who delivered at term (n = 33), who delivered preterm (n = 53) and preterm labor with intra-amniotic infection (n = 23); (3) preterm premature rupture of membranes (PROM) with (n = 25) and without intraamniotic infection (n = 26); and (4) term with intact membranes, in labor (n = 52) and not in labor (n = 31). MIF concentrations in amniotic fluid were determined using a sensitive and specific immunoassay. MIF concentrations in maternal plasma were also determined in patients with preterm labor and intact membranes. Immunohistochemistry was conducted in chorioamniotic membranes obtained from a different set of patients presenting with preterm labor with (n = 18) and without (n = 20) histologic chorioamnionitis. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to measure MIF mRNA expression in chorioamniotic membranes of patients with preterm labor with (n = 13) and without (n = 13) histologic chorioamnionitis. Parametric and non-parametric, receiver-operating characteristic (ROC) curve, survival analysis, and Cox regression model were used for analysis. Results: Immunoreactive MIF was detectable in 96% (313/327) of amniotic fluid samples. The concentration of amniotic fluid MIF at term was higher than that in the mid-trimester (p = 0.004). Intra-amniotic infection in women with preterm labor and preterm PROM was associated with a significant increase in median amniotic fluid MIF concentration (p < 0.001 and 0.004, respectively). Patients with preterm labor with sterile amniotic fluid who delivered preterm had a significantly higher median amniotic fluid MIF concentration than those who delivered at term (p = 0.007). Among patients with preterm labor with intact membranes, survival analysis indicated that the median amniocentesis-to-delivery interval was significantly shorter in patients whose amniotic fluid concentrations of MIF were above 302 ng/ml than those below this cutoff value (p < 0.001). Human parturition at term was not associated with changes in the amniotic fluid MIF concentrations (p > 0.05). There was no significant difference in median maternal plasma MIF concentrations among patients with preterm labor and intact membranes who delivered at term, those who delivered preterm, and those who had intra-amniotic infection (p > 0.05 for all comparisons). Immunohistochemistry demonstrated that MIF protein was present in amniotic epithelial cells, and the mean percentage of immunoreactive MIF-staining cells was higher in patients with histologic chorioamnionitis than in those without this lesion (p = 0.03). Similarly, the mean MIF mRNA expression was higher in chorioamniotic membranes obtained from patients with histologic chorioamnionitis than in those without this lesion (p = 0.03). Conclusions: Intra-amniotic infection and preterm parturition, but not term parturition, are associated with a significant increase in amniotic fluid MIF concentrations. Among patients with preterm labor with intact membranes, elevated amniotic fluid concentrations of MIF are associated with intra-amniotic inflammation, histologic chorioamnionitis, and shorter amniocentesis-to-delivery interval. These changes in amniotic fluid were not reflected in maternal plasma. An increased expression of MIF protein and mRNA in chorioamniotic membranes was observed in patients with histologic choricamnionitis. C1 Wayne State Univ, NICHD, DHHS, Perinatol Res Branch,Hutzel Womens Hosp,NIH, Detroit, MI 48201 USA. Wayne State Univ, Hutzel Womens Hosp, Dept Obstet & Gynecol, Detroit, MI USA. Wayne State Univ, Hutzel Womens Hosp, Dept Pathol, Detroit, MI USA. CEDIP, Dept Obstet & Gynecol, Hosp Dr Sotero del Rio, Puente Alto, Chile. Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. RP Romero, R (reprint author), Wayne State Univ, NICHD, DHHS, Perinatol Res Branch,Hutzel Womens Hosp,NIH, 3990 John R,4th Floor, Detroit, MI 48201 USA. EM warfiela@mail.nih.gov OI Kuivaniemi, Helena/0000-0001-5753-8766 FU Intramural NIH HHS; NICHD NIH HHS [Z01 HD002400-14] NR 43 TC 54 Z9 57 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PD DEC PY 2005 VL 18 IS 6 BP 405 EP 416 DI 10.1080/14767050500361703 PG 12 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 001KN UT WOS:000234532100008 PM 16390807 ER PT J AU Shim, SS Romero, R Jun, JK Moon, KC Kim, G Yoon, BH AF Shim, SS Romero, R Jun, JK Moon, KC Kim, G Yoon, BH TI C-reactive protein concentration in vaginal fluid as a marker for intra-amniotic inflammation/infection in preterm premature rupture of membranes SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE C-reactive protein ( CRP); vaginal fluid; intra-amniotic inflammation/infection (IAI); pregnancy outcome; preterm premature rupture of membranes (preterm PROM) ID BLOOD-CELL COUNT; FETAL FIBRONECTIN; INTERLEUKIN-6; INFECTION; AMNIOCENTESIS; PREDICTION; LABOR; DIAGNOSIS; DELIVERY AB Objective: The purpose of this study was to determine whether C-reactive protein (CRP) concentrations in vaginal fluid can identify patients with intra-amniotic inflammation/infection (IAI) and predict adverse outcome in preterm premature rupture of membranes (PROM). Methods: The study population consisted of 121 singleton pregnant women with preterm PROM (436 weeks of gestation) who had an amniocentesis and vaginal fluid collection. A Dacron polyester-tipped applicator was soaked with vaginal fluid for 10 seconds and diluted with 1 mL buffer solution. Amniotic fluid was cultured for aerobic and anaerobic bacteria, as well as mycoplasmas. Vaginal fluid CRP and amniotic fluid matrix metalloproteinase-8 (MMP-8) were determined by specific immunoassays. IAI was defined as an amniotic fluid MMP-8 concentration > 23 ng/mL and/or a positive amniotic fluid culture. Nonparametric tests and survival techniques were used for statistical analysis. Results: Patients with IAI had a significantly higher median vaginal fluid CRP concentration than those without IAI (median (range), 7.8 (0.1 - 1310.1) ng/mL vs. 1.0 (0.1 - 319.4) ng/mL, p < 0.005). The median amniotic fluid white blood cell (WBC) count was significantly higher in patients with a vaginal fluid CRP concentration of 410 ng/mL than in those with a lower concentration (median (range), 82.5 (0 - 8640) cells/mm(3) vs. 2 (0 - > 1000) cells/mm(3), p < 0.001). Patients with vaginal fluid CRP concentration of 410 ng/mL had a significantly shorter sampling-to-delivery interval and higher rates of preterm delivery within five days, funisitis, and histologic chorioamnionitis than did those with a vaginal fluid CRP concentration below this cut-off. A vaginal fluid CRP cut-off of 10 ng/mL had a specificity of 89% and a sensitivity of 45% in the identification of IAI. Conclusion: An elevated CRP concentration in vaginal fluid collected by polyester-tipped applicator is a risk factor for intraamniotic inflammation/infection and impending preterm delivery in preterm PROM. C1 Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul 110744, South Korea. Seoul Natl Univ, Coll Med, Dept Pathol, Seoul 151, South Korea. NICHHD, Perinatol Res Branch, DHHS, NIH, Bethesda, MD USA. RP Yoon, BH (reprint author), Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul 110744, South Korea. EM Yoonbh@snu.ac.kr RI Seoul National University, Pathology/B-6702-2012; Yoon, Bo Hyun/H-6344-2011; Moon, Kyung Chul/J-5465-2012; Jun, Jong Kwan/D-5776-2012 OI Jun, Jong Kwan/0000-0002-0242-1736 NR 20 TC 22 Z9 25 U1 0 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PD DEC PY 2005 VL 18 IS 6 BP 417 EP 422 DI 10.1080/14786430500362231 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 001KN UT WOS:000234532100009 PM 16390808 ER PT J AU Baser, ME Mautner, VF Parry, DM Evans, DGR AF Baser, ME Mautner, VF Parry, DM Evans, DGR TI Methodological issues in longitudinal studies: vestibular schwannoma growth rates in neurofibromatosis 2 SO JOURNAL OF MEDICAL GENETICS LA English DT Review ID ACOUSTIC NEUROMAS; TYPE-2; PREDICTORS AB Four longitudinal studies of vestibular schwannoma (VS) growth rates in neurofibromatosis 2 (NF2) have yielded very different results on the relationship of VS growth rates to age. The studies had different patient eligibility criteria, indices of VS growth rates, VS volumetric methods, and sample sizes. We reanalysed data from two of the longitudinal studies and used data from the population based United Kingdom NF2 Registry to determine the most likely reason for the different results and the actual relationship of VS growth rates to age. We found that the eligibility criterion in one study caused selection bias for slower growing VS. The proper interpretation of the results from the four studies is that VS growth rates in NF2 are highly variable but tend to decrease with increasing age. Clinical trials for VS in NF2 should focus on younger patients because VS growth rates tend to decrease with increasing age, and because faster growing VS are more likely to be excised with increasing age than slower growing VS. C1 Univ Hosp, Dept Maxillofacial Surg, Hamburg, Germany. NCI, Genet Epidemiol Branch, Bethesda, MD 20892 USA. St Marys Hosp, Acad Dept Med Genet, Manchester M13 0JH, Lancs, England. RP 10622 Kinnard Ave 203, Los Angeles, CA 90024 USA. EM michael.baser@verizon.net OI Evans, Gareth/0000-0002-8482-5784 NR 15 TC 10 Z9 11 U1 0 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 EI 1468-6244 J9 J MED GENET JI J. Med. Genet. PD DEC PY 2005 VL 42 IS 12 BP 903 EP 906 DI 10.1136/jmg.2005.031302 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 989PK UT WOS:000233685900003 PM 15831594 ER PT J AU Cha, JH Zou, MF Adkins, EM Rasmussen, SGF Loland, CJ Schoenenberger, B Gether, U Newman, AH AF Cha, JH Zou, MF Adkins, EM Rasmussen, SGF Loland, CJ Schoenenberger, B Gether, U Newman, AH TI Rhodamine-labeled 2 beta-carbomethoxy-3 beta-(3,4-dichlorophenyl)- tropane analogues as high-affinity fluorescent probes for the dopamine transporter SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID RESONANCE ENERGY-TRANSFER; M1 MUSCARINIC RECEPTOR; LIGANDS; SPECTROSCOPY; ANTAGONIST AB Novel fluorescent ligands were synthesized to identify a high-affinity probe that would enable visualization of the dopamine transporter (DAT) in living cells. Fluorescent tags were extended from the N- or 2-position of 2 beta-carbomethoxy-3 beta-(3,4-dichlorophenyl)tropane, using an ethylamino linker. The resulting 2-substituted (5) and N-substituted (9) rhodamine-labeled ligands provided the highest DAT binding affinities expressed in COS-7 cells (K-i = 27 and 18 nM, respectively) in the series. Visualization of the DAT with 5 and 9 was demonstrated by confocal fluorescence laser scanning microscopy in stably transfected HEK293 cells. C1 Natl Inst Drug Abuse, Med Chem Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Univ Copenhagen, Panum Inst, Dept Pharmacol, Mol Pharmacol Grp, DK-2200 Copenhagen, Denmark. Fluka GmbH, CH-9471 Buchs, Switzerland. RP Newman, AH (reprint author), Natl Inst Drug Abuse, Med Chem Sect, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM anewman@intra.nida.nih.gov RI Loland, Claus/E-5975-2014; OI Loland, Claus/0000-0002-1773-1446; Rasmussen, Soren/0000-0002-1853-1841; Gether, Ulrik/0000-0002-0020-3807 FU NIDA NIH HHS [P01 DA12408] NR 18 TC 26 Z9 26 U1 2 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD DEC 1 PY 2005 VL 48 IS 24 BP 7513 EP 7516 DI 10.1021/jm050431y PG 4 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 989EE UT WOS:000233654900002 PM 16302792 ER PT J AU Himmel, DM Das, K Clark, AD Hughes, SH Benjahad, A Oumouch, S Guillemont, J Coupa, S Poncelet, A Csoka, I Meyer, C Andries, K Nguyen, CH Grierson, DS Arnold, E AF Himmel, DM Das, K Clark, AD Hughes, SH Benjahad, A Oumouch, S Guillemont, J Coupa, S Poncelet, A Csoka, I Meyer, C Andries, K Nguyen, CH Grierson, DS Arnold, E TI Crystal structures for HIV-1 reverse transcriptase in complexes with three pyridinone derivatives: A new class of non-nucleoside inhibitors effective against a broad range of drug-resistant strains SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; TEMPLATE-PRIMER UTILIZATION; ANTIBODY FAB FRAGMENT; DOUBLE-STRANDED DNA; IN-VITRO EVALUATION; ANGSTROM RESOLUTION; WILD-TYPE; POSITIONAL ADAPTABILITY; CONFORMATIONAL-CHANGES; MUTANT STRAINS AB In the treatment of AIDS, the efficacy of all drugs, including non-nucleoside inhibitors (NNRTIs) of HIV-1 reverse transcriptase (RT), has been limited by the rapid appearance of drug-resistant viruses. Lys103Asn, Tyr181Cys, and Tyr188Leu are some of the most common RT mutations that cause resistance to NNRTIs in the clinic. We report X-ray crystal structures for RT complexed with three different pyridinone derivatives, R157208, R165481, and R221239, at 2.95, 2.9, and 2.43 angstrom resolution, respectively. All three ligands exhibit nanomolar or subnanomolar inhibitory activity against wild-type RT, but varying activities against drug-resistant mutants. R165481 and R221239 differ from most NNRTIs in that binding does not involve significant contacts with Tyr181. These compounds strongly inhibit wild-type HIV-1 RT and drug-resistant variants, including Tyr181Cys and Lys103Asn RT. These properties result in part from an iodine atom on the pyridinone ring of both inhibitors that interacts with the main-chain carbonyl oxygen of Tyr188. An acrylonitrile substituent on R165481 substantially improves the activity of the compound against wild-type RT (and several mutants) and provides a way to generate novel inhibitors that could interact with conserved elements of HIV-1 RT at the polymerase catalytic site. In R221239, there is a flexible linker to a furan ring that permits interactions with Val106, Phe227, and Pro236. These contacts appear to enhance the inhibitory activity of R221239 against the HIV-1 strains that carry the Val106Ala, Tyr188Leu, and Phe227Cys mutations. C1 Rutgers State Univ, CABM, Piscataway, NJ 08854 USA. Rutgers State Univ, Dept Chem & Chem Biol, Piscataway, NJ 08854 USA. NCI, HIV Drug Resistance Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Ctr Univ Orsay, Lab Pharmacochim, Sect Rech, UMR 176,CNRS,Inst Curie, F-91405 Orsay, France. Johnson & Johnson Pharmaceut Res & Dev, Dept Med Chem, Val De Reuil, France. Johnson & Johnson Pharmaceut Res & Dev, Virol Drug Discovery, B-2340 Beerse, Belgium. RP Rutgers State Univ, CABM, Piscataway, NJ 08854 USA. EM arnold@cabm.rutgers.edu FU NIAID NIH HHS [AI 27690, F32 AI 060300]; NIGMS NIH HHS [P01 GM 066671] NR 56 TC 101 Z9 103 U1 3 U2 18 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 EI 1520-4804 J9 J MED CHEM JI J. Med. Chem. PD DEC 1 PY 2005 VL 48 IS 24 BP 7582 EP 7591 DI 10.1021/jm0500323 PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 989EE UT WOS:000233654900008 PM 16302798 ER PT J AU Moscarelli, M Rupp, A AF Moscarelli, M Rupp, A TI Untitled SO JOURNAL OF MENTAL HEALTH POLICY AND ECONOMICS LA English DT Editorial Material C1 Int Ctr Mental Hlth Policy & Econ, Milan, Italy. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NIMH, Mental Hlth Econ Programme, Div Epidemiol & Serv Res, Rockville, MD 20857 USA. RP Moscarelli, M (reprint author), Int Ctr Mental Hlth Policy & Econ, Milan, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT CENTER MENTAL HEALTH POLICY & ECONOMICS-ICMPE PI MILANO PA VIA DANIELE CRESPI 7, MILANO, 20123, ITALY SN 1091-4358 J9 J MENT HEALTH POLICY JI J. Ment. Health Policy Econ. PD DEC PY 2005 VL 8 IS 4 BP 181 EP 182 PG 2 WC Health Policy & Services; Psychiatry SC Health Care Sciences & Services; Psychiatry GA 998AI UT WOS:000234289800001 PM 16385143 ER PT J AU Yamamura, K Steenbergen, C Murphy, E AF Yamamura, K Steenbergen, C Murphy, E TI Protein kinase C (PKC) activation reduces sarcoplasmic reticulum calcium content and induces cardioprotection SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Meeting Abstract CT 22nd Annual Meeting of the Japanese Section of the International-Society-for-Heart-Research CY DEC 15-17, 2005 CL Osaka, JAPAN SP Int Soc Heart Res, Japanese Sect C1 NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 2005 VL 39 IS 6 BP 1032 EP 1032 PG 1 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 990GY UT WOS:000233732400113 ER PT J AU Woodard, GE Lie, XH Rosado, JA AF Woodard, GE Lie, XH Rosado, JA TI Characteristics of the renal C-type natriuretic peptide receptor in hypertrophied and developing rat kidney SO JOURNAL OF MOLECULAR ENDOCRINOLOGY LA English DT Article ID SMOOTH-MUSCLE-CELLS; PROTEIN-KINASE-A; CLEARANCE RECEPTOR; HYPERTENSIVE-RATS; GUANYLYL CYCLASE; PROLIFERATION; CAMP; INHIBITION AB This study investigates the effect of hypertrophy, using one kidney and one kidney/one clip rats, and development, comparing 3- and 12-week-old rats, on the expression of the 28-amino acid atrial natriuretic peptide (ANP(1-28)) binding sites in rat kidney. Here we report an increased B-max value of glomerular binding sites for ANP(1-28) and C-type natriuretic peptide 1-22 (CNP1-22) in hypertrophied and developing kidney, without modifying their affinity, an effect that was prevented in the presence of the synthetic des[Gln(18), Ser(19), Gly(20), Leu(21), Gly(22)]ANP(4-23)-amide (C-ANF), suggesting that natriuretic peptide receptor (NPR)-C binding sites might be enhanced. The enhanced Bmax was only detected in the high affinity binding site for CNP1-22, which has been identified as the 67 kDa NPR-C-like protein. A similar effect was observed in renal glomeruli from 3-week-old rats compared with 12-week-old rats. Our results indicate that ANP(1-28), CNP1-22 and C-ANF inhibited cAMP synthesis stimulated by the physiological agonists histamine and 5-hydroxytryptamine or directly by forskolin. The inhibitory effect was found to be significantly greater in 1-kidney and 1-kidney/1-clip rats than in controls, and in 3-week-old rats compared with 12-week-old rats. Our observations suggest that this effect must be attributed to the 67 kDa NPR-C-like protein due to the enhanced Bmax values and the reported inhibitory role for this receptor on adenylyl cyclase activity. The enhanced inhibitory role of natriuretic peptides on cAMP synthesis in hypertrophied and developing kidney may influence glomerular function in the rat kidney and suggests a role for the 67 kDa NPR-C-like protein in growth. C1 NIDDKD, NIH, Bethesda, MD 20892 USA. CUNY Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. Univ Extremadura, Dept Physiol, Caceres, Spain. RP Woodard, GE (reprint author), NIDDKD, NIH, Bethesda, MD 20892 USA. EM GeoffreyW@intra.niddk.nih.gov RI Woodard, Geoffrey/A-8608-2009; rosado, juan/H-3488-2015 OI rosado, juan/0000-0002-9749-2325 NR 38 TC 7 Z9 8 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 2005 VL 35 IS 3 BP 519 EP 530 DI 10.1677/jme.1.01871 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 996XU UT WOS:000234210100009 PM 16326837 ER PT J AU Forbes, JG Jin, AJ Ma, K Gutierrez-Cruz, G Tsai, WL Wang, KA AF Forbes, Jeffrey G. Jin, Albert J. Ma, Kan Gutierrez-Cruz, Gustavo Tsai, Wanxia L. Wang, Kuan TI Titin PEVK segment: charge-driven elasticity of the open and flexible polyampholyte SO JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY LA English DT Article; Proceedings Paper CT International Symposium on Muscle Elastic Proteins CY NOV 19-21, 2004 CL Chiba Univ, Chiba, JAPAN HO Chiba Univ ID MUSCLE PROTEIN TITIN; SKELETAL-MUSCLE; MOLECULAR-DYNAMICS; SINGLE MOLECULES; SPRING ELEMENTS; STRIATED-MUSCLE; FORCE; DOMAINS; IDENTIFICATION; IMMUNOGLOBULIN AB The giant protein titin spans half of the sarcomere length and anchors the myosin thick filament to the Z-line of skeletal and cardiac muscles. The passive elasticity of muscle at a physiological range of stretch arises primarily from the extension of the PEVK segment, which is a polyampholyte with dense and alternating-charged clusters. Force spectroscopy studies of a 51 kDa fragment of the human fetal titin PEVK domain (TP1) revealed that when charge interactions were reduced by raising the ionic strength from 35 to 560 mM, its mean persistence length increased from 0.30 +/- 0.04 nm to 0.60 +/- 0.07 nm. In contrast, when the secondary structure of TP1 was altered drastically by the presence of 40 and 80% (v/v) of trifluoroethanol, its force-extension behavior showed no significant shift in the mean persistence length of similar to 0.18 +/- 0.03 nm at the ionic strength of 15 mM. Additionally, the mean persistence length also increased from 0.29 to 0.41 nm with increasing calcium concentration from pCa 5-8 to pCa 3-4. We propose that PEVK is not a simple entropic spring as is commonly assumed, but a highly evolved, gel-like enthalpic spring with its elasticity dominated by the sequence-specific charge interactions. A single polyampholyte chain may be fine-tuned to generate a broad range of molecular elasticity by varying charge pairing schemes and chain configurations. C1 NIAMS, DHHS, Lab Muscle Biol, Muscle Proteom & Nanotechnol Sect,NIH, Bethesda, MD 20892 USA. RP Wang, KA (reprint author), NIAMS, DHHS, Lab Muscle Biol, Muscle Proteom & Nanotechnol Sect,NIH, Bldg 50 Rm 1140, Bethesda, MD 20892 USA. EM wangk@exchange.nih.gov OI Jin, Albert/0000-0003-3826-1081 FU Intramural NIH HHS [Z01 EB000015-01] NR 48 TC 21 Z9 22 U1 0 U2 8 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0142-4319 J9 J MUSCLE RES CELL M JI J. Muscle Res. Cell Motil. PD DEC PY 2005 VL 26 IS 6-8 BP 291 EP 301 DI 10.1007/s10974-005-9035-4 PG 11 WC Cell Biology SC Cell Biology GA 059DI UT WOS:000238713100004 PM 16465472 ER PT J AU Andriamaharavo, NR Andriantsiferana, M Stevenson, PA O'Mahony, G Yeh, HJC Kaneko, T Garraffo, HM Spande, TF Daly, JW AF Andriamaharavo, NR Andriantsiferana, M Stevenson, PA O'Mahony, G Yeh, HJC Kaneko, T Garraffo, HM Spande, TF Daly, JW TI A revised structure for alkaloid 235C isolated from skin extracts of mantellid (Mantella) frogs of Madagascar SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID TANDEM MASS-SPECTROMETRY; DENDROBATID POISON FROGS; PUMILIOTOXIN ALKALOIDS; AMPHIBIAN SKIN; QUINOLIZIDINES; PYRROLIZIDINES; INDOLIZIDINES AB Madagascan frogs of the mantellid genus Mantella have been a rich source of alkaloids derived from dietary arthropods. Two species of frogs, inhabiting swamp forest, contain a unique set of alkaloids, previously proposed, based only on GC-MS and GC-FTIR data, to represent dehydro analogues of the homopumiliotoxins. The major alkaloid of this set, alkaloid 235C (2), now has been isolated in sufficient quantities (ca. 0.3 mg) to allow determination of the structure by NMR analysis. The structure of alkaloid 235C proved to be a 7,8-dehydro-8-desmethylpumiliotoxin. A comparison is presented between the mass, infrared, and (1)H NMR spectra of 235C (2) and a synthetic dehydrohomopumiliotoxin (1), initially proposed incorrectly as the structure for 235C. C1 Univ Antananarivo, Lab Chim Organ Prod Nat, Antananarivo 1001, Madagascar. Queens Univ Belfast, Sch Chem, Belfast BT9 5AG, Antrim, North Ireland. NIDDK, Lab Bioorgan Chem, DHHS, NIH, Bethesda, MD 20892 USA. RP Daly, JW (reprint author), Univ Antananarivo, Lab Chim Organ Prod Nat, Antananarivo 1001, Madagascar. EM jdaly@nih.gov FU Intramural NIH HHS NR 15 TC 6 Z9 6 U1 3 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD DEC PY 2005 VL 68 IS 12 BP 1743 EP 1748 DI 10.1021/np058089f PG 6 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 998ZI UT WOS:000234358000007 PM 16378366 ER PT J AU Meragelman, TL Tucker, KD McCloud, TG Cardellina, JH Shoemaker, RH AF Meragelman, TL Tucker, KD McCloud, TG Cardellina, JH Shoemaker, RH TI Antifungal flavonoids from Hildegardia barteri SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID ISOFLAVONOIDS; RHODODENDRON AB new isoflavan, (3R)-6,2'-dihydroxy-7-methoxy-4',5'-methylenedioxyisoflavan, hildegardiol (1), and two known flavonoids, 2-hydroxymaackiain (2) and farrerol (3), were isolated from the antifungal root extract of Hildegardia barteri. The pterocarpan 2 was largely responsible for the observed antifungal activity. C1 NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21702 USA. NCI, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Cardellina, JH (reprint author), NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21702 USA. EM jcardellina@ncifcrf.gov FU Intramural NIH HHS NR 21 TC 26 Z9 30 U1 1 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD DEC PY 2005 VL 68 IS 12 BP 1790 EP 1792 DI 10.1021/np0503000 PG 3 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 998ZI UT WOS:000234358000019 PM 16378378 ER PT J AU Miller, DW Johnson, JM Solano, SM Hollingsworth, ZR Standaert, DG Young, AB AF Miller, DW Johnson, JM Solano, SM Hollingsworth, ZR Standaert, DG Young, AB TI Absence of alpha-synuclein mRNA expression in normal and multiple system atrophy oligodendroglia SO JOURNAL OF NEURAL TRANSMISSION LA English DT Article; Proceedings Paper CT 2nd International Meeting on MSA CY JUN 17-18, 2004 CL Rome, ITALY DE glial cytoplasmic inclusion; in situ hybridization; synucleinopathy ID GLIAL CYTOPLASMIC INCLUSIONS; CENTRAL-NERVOUS-SYSTEM; A-BETA COMPONENT; PARKINSONS-DISEASE; HUMAN BRAIN; LOCUS TRIPLICATION; PRECURSOR PROTEIN; IMMUNOREACTIVITY; NEUROPATHOLOGY; DEGENERATION AB alpha-Synuclein is a major constituent of glial cytoplasmic inclusions (GCIs), which are pathognomic for multiple system atrophy (MSA). We have previously demonstrated that in normal human brain, alpha-synuclein mRNA has a restricted pattern of neuronal expression and no apparent glial expression. The current study used double-label in situ hybridization to determine if alpha-synuclein mRNA is expressed by oligodendroglia of MSA cases. Analysis of MSA brain tissue revealed depletion of regional signal for this transcript in many brain areas due to extensive neurodegeneration. Cellular analysis of oligodendroglia in crus cerebri, a GCI-rich region ventral to substantia nigra, revealed an absence of alpha-synuclein mRNA signal in control and MSA cases. However, an abundance of this transcript was detected in melanin-containing neurons of substantia nigra. Therefore, oligodendroglia do not express alpha-synuclein mRNA in control and MSA cases suggesting that involvement of alpha-synuclein in GCI pathology of MSA is due to its ectopic presence in oligodendroglia. C1 NIA, Cell Biol & Gene Express Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. Mass Gen Inst Neurodegenerat Dis, Charlestown, MA USA. RP Miller, DW (reprint author), NIA, Cell Biol & Gene Express Sect, Neurogenet Lab, NIH, Bldg 35,Rm 1A-1002,MSC 3707,35 Convent Dr, Bethesda, MD 20892 USA. EM millerda@mail.nih.gov FU NIMH NIH HHS [MH068855]; NINDS NIH HHS [NS038372] NR 32 TC 64 Z9 65 U1 0 U2 4 PU SPRINGER WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0300-9564 J9 J NEURAL TRANSM JI J. Neural Transm. PD DEC PY 2005 VL 112 IS 12 BP 1613 EP 1624 DI 10.1007/s00702-005-0378-1 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 983WJ UT WOS:000233262700003 PM 16284907 ER PT J AU Warren, KE AF Warren, KE TI Molecularly targeted therapy for pediatric brain tumors SO JOURNAL OF NEURO-ONCOLOGY LA English DT Review DE brain tumors; children; EGFR; molecular targets; PDGF; ras; signaling pathways ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITOR; ADVANCED SOLID TUMORS; FARNESYL TRANSFERASE INHIBITORS; HUMAN CANCER-CELLS; PHASE-I; ZD1839 IRESSA; HUMAN GLIOMA; PROTEIN FARNESYLTRANSFERASE; CHILDHOOD MEDULLOBLASTOMA AB Treatment of pediatric brain tumors remains a challenge because of the toxicity associated with conventional treatment and the relative resistance of tumors at the time of recurrence. The traditional approach of administering cytotoxic agents at the maximum tolerated dose is being supplanted by the development of molecularly targeted agents aimed at critical cellular changes that are responsible for the growth and spread of cancer cells. These agents theoretically should be more specific for tumor cells and less toxic to normal cells. While the idea of targeted therapy has generated much excitement in the oncology community, the degree of benefit to patients with central nervous system (CNS) tumors remains unclear. Numerous challenges remain in the development of these agents, including identification of meaningful targets, delivery of agents in sufficient quantity at the target site, and determination of any biologic response to these agents. This article discusses the rationale behind several of these agents and their use in pediatric patients with brain tumors. C1 NCI, Neurooncol Branch, Bethesda, MD 20892 USA. RP Warren, KE (reprint author), NCI, Neurooncol Branch, Bloch Bldg 82,Rm 224,9030 Old Georgetown Rd, Bethesda, MD 20892 USA. EM warrenk@mail.nih.gov NR 108 TC 2 Z9 2 U1 1 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X EI 1573-7373 J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD DEC PY 2005 VL 75 IS 3 BP 335 EP 343 DI 10.1007/s11060-005-6765-5 PG 9 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 988VX UT WOS:000233630500013 ER PT J AU Zhu, XM Wu, KB Rife, L Cawley, NX Brown, B Adams, T Teofilo, K Lillo, C Williams, DS Loh, YP Craft, CM AF Zhu, XM Wu, KB Rife, L Cawley, NX Brown, B Adams, T Teofilo, K Lillo, C Williams, DS Loh, YP Craft, CM TI Carboxypeptidase E is required for normal synaptic transmission from photoreceptors to the inner retina SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE carboxypeptidase E; electroretinography; knockout mouse; retinal photoreceptor; synaptic transmission ID PATHWAY SORTING RECEPTOR; NEUROPEPTIDE-PROCESSING ENZYME; CPE(FAT)/CPE(FAT) MICE; MUSCULAR-DYSTROPHY; SECRETORY GRANULES; GENE-EXPRESSION; CPE(FAT) MICE; FAT MUTATION; RAT RETINA; MOUSE AB Defects in the gene encoding carboxypeptidase E (CPE) in either mouse or human lead to multiple endocrine disorders, including obesity and diabetes. Recent studies on Cpe-/- mice indicated neurological deficits in these animals. As a model system to study the potential role of CPE in neurophysiology, we carried out electroretinography (ERG) and retinal morphological studies on Cpe-/- and Cpe(fat/fat) mutant mice. Normal retinal morphology was observed by light microscopy in both Cpe-/- and Cpe(fat/fat) mice. However, with increasing age, abnormal retinal function was revealed by ERG. Both Cpe-/- and Cpe(fat/fat) animals had progressively reduced ERG response sensitivity, decreased b-wave amplitude and delayed implicit time with age, while maintaining a normal a-wave amplitude. Immunohistochemical staining showed specific localization of CPE in photoreceptor synaptic terminals in wild-type (WT) mice, but in both Cpe-/- and Cpe(fat/fat) mice, CPE was absent in this layer. Bipolar cell morphology and distribution were normal in these mutant mice. Electron microscopy of retinas from Cpe(fat/fat) mice revealed significantly reduced spherule size, but normal synaptic ribbons and synaptic vesicle density, implicating a reduction in total number of vesicles per synapse in the photoreceptors of these animals. These results suggest that CPE is required for normal-sized photoreceptor synaptic terminal and normal signal transmission to the inner retina. C1 Univ So Calif, Mary D Allen Lab Vis Res, Doheny Eye Inst, Dept Ophthalmol,Keck Sch Med, Los Angeles, CA 90033 USA. Univ So Calif, Mary D Allen Lab Vis Res, Doheny Eye Inst, Keck Sch Med,Dept Cell Neurobiol, Los Angeles, CA 90033 USA. NICHD, Cellular Neurobiol Sect, NIH, Bethesda, MD USA. Univ Calif San Diego, Sch Med, Dept Pharmacol, La Jolla, CA 92093 USA. Univ Calif San Diego, Sch Med, Dept Neurosci, La Jolla, CA 92093 USA. RP Zhu, XM (reprint author), Univ So Calif, Mary D Allen Lab Vis Res, Doheny Eye Inst, Dept Ophthalmol,Keck Sch Med, 1355 San Pablo St,DVRC 405, Los Angeles, CA 90033 USA. EM xuemeizh@usc.edu RI Lillo, Concepcion/A-6321-2009 OI Lillo, Concepcion/0000-0001-5814-9826 FU NEI NIH HHS [EY03040, EY07042, EY12598, R01 EY007042] NR 41 TC 19 Z9 19 U1 1 U2 3 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 2005 VL 95 IS 5 BP 1351 EP 1362 DI 10.1111/j.1471-4159.2005.03460.x PG 12 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 982NZ UT WOS:000233170200013 PM 16219026 ER PT J AU Mattson, BJ Bossert, JM Simmons, DE Nozaki, N Nagarkar, D Kreuter, JD Hope, BT AF Mattson, BJ Bossert, JM Simmons, DE Nozaki, N Nagarkar, D Kreuter, JD Hope, BT TI Cocaine-induced CREB phosphorylation in nucleus accumbens of cocaine-sensitized rats is enabled by enhanced activation of extracellular signal-related kinase, but not protein kinase A SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE calcium/ calmodulin kinase; cyclic AMP-dependent protein kinase; Fos; locomotor sensitization; mitogen-activated protein kinase; U0126; Rp-cAMPs ID DEPENDENT GENE-EXPRESSION; C-FOS EXPRESSION; ELEMENT-BINDING PROTEIN; RECEPTOR GLUR1 SUBUNIT; LONG-TERM POTENTIATION; RESPONSE ELEMENT; TRANSCRIPTIONAL REGULATION; BEHAVIORAL SENSITIZATION; SYNAPTIC PLASTICITY; INJECTION STRESS AB Repeated cocaine administration to rats outside their home cages sensitizes the behavioral effects of the drug, and enhances induction of the immediate early gene product Fos in nucleus accumbens. We hypothesized that the same treatment regimen would also enhance cocaine-induced activation of intracellular signaling kinases that phosphorylate cyclic AMP-regulated element-binding protein (CREB), an important mediator of c-fos transcription. Phosphorylation levels of extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK), calcium/calmodulin kinases (CaMKs) II and IV, and CREB were used to assess endogenous functional activity of these signaling molecules in rats behaviorally sensitized outside their home cages. Protein kinase A (PKA)-specific phosphorylation of Ser845 in the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor subunit GluR1 was used to assess endogenous functional activity of PKA. Using western blots and immunohistochemistry, we detected cocaine-induced CREB phosphorylation after repeated cocaine administration, but not after repeated saline administration. Using western blots and MAPK activity assays, we found that cocaine-induced phosphorylation and activation of ERK, but not of CaMKs II or IV or GluR1, was augmented in nucleus accumbens of cocaine-sensitized rats. Unilateral infusions of the MAPK kinase inhibitor U0126 into nucleus accumbens attenuated cocaine-induced ERK and CREB phosphorylation in cocaine-sensitized rats. In contrast, unilateral infusions of the PKA inhibitor Rp-isomer of adenosine-3 ',5 '-cyclicmonophosphorothioate (Rp-cAMPs) did not affect cocaine-induced CREB phosphorylation. Therefore, enhanced activation of ERK, but not PKA, enables and mediates cocaine-induced CREB phosphorylation in nucleus accumbens of rats that are sensitized by repeated cocaine administration outside their home cages. C1 Natl Inst Drug Abuse, Behav Neurosci Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. RP Hope, BT (reprint author), Natl Inst Drug Abuse, Behav Neurosci Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, 5500 Nathan Shock Dr,Bldg C, Baltimore, MD 21224 USA. EM bhope@intra.nida.nih.gov RI Hope, Bruce/A-9223-2010 OI Hope, Bruce/0000-0001-5804-7061 NR 66 TC 89 Z9 90 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 2005 VL 95 IS 5 BP 1481 EP 1494 DI 10.1111/j.1471-4159.2005.03500.x PG 14 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 982NZ UT WOS:000233170200024 PM 16219028 ER PT J AU Kuperstein, F Yakubov, E Dinerman, P Gil, S Eylam, R Salem, N Yavin, E AF Kuperstein, F Yakubov, E Dinerman, P Gil, S Eylam, R Salem, N Yavin, E TI Overexpression of dopamine receptor genes and their products in the postnatal rat brain following maternal n-3 fatty acid dietary deficiency SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE attention deficit hyperactivity disorder; docosahexaenoic acid deficiency; dopamine receptors; gene array; genomic markers; suppression subtractive hybridization ID ALPHA-LINOLENIC ACID; AMYLOID-BETA PEPTIDE; DOCOSAHEXAENOIC ACID; FRONTAL-CORTEX; ARACHIDONIC-ACID; OMEGA-3-FATTY-ACID DEFICIENCY; PREFRONTAL CORTEX; NUCLEUS-ACCUMBENS; LEARNING-ABILITY; CRITICAL PERIODS AB A combination of PCR-Select cDNA subtraction and gene array hybridization was used to identify differentially expressed genomic markers in brains of rats fed for 3 weeks in utero and 2 weeks after birth on an n-3 polyunsaturated fatty acid (PUFA)-deficient diet supplied to dams. Total RNA was isolated, switch mechanism at 5'-end of the RNA transcripts (SMART) applied and used for PCR-Select subtraction of PUFA-deficient and adequately-fed control preparations. Subtracted and amplified ds-cDNA end-products were fragmented, terminally labeled with biotin-ddUTP and hybridized with a RN-U34A gene array. A 10-fold increase in potential genes with log(2)(Tester/Driver) = 1.4 was found compared with traditional gene array technology when the same chip was tested using non-subtracted targets. Reverse transcription-real-time relative PCR confirmed 30% of the transcripts. Among the validated transcripts, D1 and D2 receptors for dopamine (DA), were most prominent among a number of over-expressed neurotransmitter receptors and retinoic acid receptor (RXR alpha-2 and alpha-1). Immunohistochemical staining of brain sections from 2-week-old pups revealed a substantial enrichment of the D2 receptor in discrete regions of the mesolimbic and mesocortical pathways as well as in a large number of brain areas from the n-3 PUFA-deficient pups. Punches of the same areas run on western blots showed similar results. The overwhelming expression of D1 and D2 receptors may be attributed to a behavioral hypersensitivity caused by the possible impairment of DA production during brain development, which may have implications in certain disorders of the nervous system. C1 Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel. NIAAA, Lab Membrane Biochem & Biophys, NIH, Rockville, MD 20852 USA. RP Yavin, E (reprint author), Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel. EM ephraim.yavin@gmx.met NR 73 TC 35 Z9 38 U1 1 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD DEC PY 2005 VL 95 IS 6 BP 1550 EP 1562 DI 10.1111/j.1471-4159.2005.03513.x PG 13 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 987PN UT WOS:000233529900003 PM 16305626 ER PT J AU Markovic-Plese, S Hemmer, B Zhao, YD Simon, R Pinilla, C Martin, R AF Markovic-Plese, S Hemmer, B Zhao, YD Simon, R Pinilla, C Martin, R TI High level of cross-reactivity in influenza virus hemagglutinin-specific CD4+T-cell response: Implications for the initiation of autoimmune response in multiple sclerosis SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE multiple sclerosis; influenza haemagglutinin; immunodominant epitope; molecular mimicry; T-cell receptor repertoire ID MYELIN BASIC-PROTEIN; T-CELL-CLONES; PEPTIDE LIGANDS; ANTIGEN RECOGNITION; MOLECULAR MIMICRY; TRANSGENIC MICE; LYME-DISEASE; AMINO-ACIDS; IDENTIFICATION; TCR AB Viral infections play a role in shaping and maintaining the peripheral T-cell repertoire, as well as ill the initiation Of autoimmune response via mechanisms of molecular mimicry. Ill this Study, we addressed the flexibility of T-cell receptor (TCR) recognition and the degree of structural and sequence homology required for cross-reactive immune response in the induction of autoimmune response. We Studied the extent of cross-reactivity of a CD4+ T-cell clone (TCC) specific for the immunodominant influenza virus hemagglutinin (Flu-HA) peptide derived from a patient with multiple sclerosis (MS) using positional scanning synthetic peptide combinatorial libraries (PS-SCL). We documented cross-reactivity against 14 Flu-HA variants, 11 viral, 15 human, and 3 myelin-derived peptides. Moreover, we identified six naturally Occurring peptides with higher stimulatory potency than the native ligand, implicating high potential for cross-reactivity even for a virus-specific memory TCC. Our Study demonstrates that flexibility of TCR recognition is present even in a clone with a high degree of TCR specificity for all infectious agent. The results have implications for vaccine design and for antigen-specific treatment strategies for autoimmune diseases. (C) 2005 Elsevier B.V. All rights reserved. C1 Univ N Carolina, Dept Neurol, Chapel Hill, NC 27599 USA. NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. Univ Dusseldorf, Dept Neurol, D-40225 Dusseldorf, Germany. NCI, Biometr Res Branch, NIH, Rockville, MD 20854 USA. Torrey Pines Inst Mol Studies & Mixture Sci, San Diego, CA 92121 USA. Hosp Univ Vall dHebron, Neuroimmunol Clin, Barcelona 08035, Spain. RP Markovic-Plese, S (reprint author), Univ N Carolina, Dept Neurol, Chapel Hill, NC 27599 USA. EM markovics@neurology.unc.edu NR 24 TC 28 Z9 29 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD DEC PY 2005 VL 169 IS 1-2 BP 31 EP 38 DI 10.1016/j.jneuroim.2005.07.014 PG 8 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 989PR UT WOS:000233686700004 PM 16150497 ER PT J AU Burnett, TA Mann, EA Stoklosa, JB Ludlow, CL AF Burnett, TA Mann, EA Stoklosa, JB Ludlow, CL TI Self-triggered functional electrical stimulation during swallowing SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID BOLUS VOLUME; LARYNGEAL; COORDINATION; DEGLUTITION; DYSPHAGIA; STROKE; ASPIRATION; VISCOSITY; MOVEMENT; NEURONS AB Burnett, Theresa A., Eric A. Mann, Joseph B. Stoklosa, and Christy L. Ludlow. Self-triggered functional electrical stimulation during swallowing. J Neurophysiol 94: 4011-4018, 2005. First published August 17, 2005; doi: 10.1152/jn. 00025.2005. Hyolaryngeal elevation is essential for airway protection during swallowing and is mainly a reflexive response to oropharyngeal sensory stimulation. Targeted intramuscular electrical stimulation can elevate the resting larynx and, if applied during swallowing, may improve airway protection in dysphagic patients with inadequate hyolaryngeal motion. To be beneficial, patients must synchronize functional electrical stimulation (FES) with their reflexive swallowing and not adapt to FES by reducing the amplitude or duration of their own muscle activity. We evaluated the ability of nine healthy adults to manually synchronize FES with hyolaryngeal muscle activity during discrete swallows, and tested for motor adaptation. Hooked-wire electrodes were placed into the mylo-and thyrohyoid muscles to record electromyographic activity from one side of the neck and deliver monopolar FES for hyolaryngeal elevation to the other side. After performing baseline swallows, volunteers were instructed to trigger FES with a thumb switch in synchrony with their swallows for a series of trials. An experimenter surreptitiously disabled the thumb switch during the final attempt, creating a foil. From the outset, volunteers synchronized FES with the onset of swallow-related thyrohyoid activity (similar to 225 ms after mylohyoid activity onset), preserving the normal sequence of muscle activation. A comparison between average baseline and foil swallows failed to show significant adaptive changes in the amplitude, duration, or relative timing of activity for either muscle, indicating that the central pattern generator for hyolaryngeal elevation is immutable with short term stimulation that augments laryngeal elevation during the reflexive, pharyngeal phase of swallowing. C1 NINDS, Laryngeal & Speech Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Ludlow, CL (reprint author), NINDS, Laryngeal & Speech Sect, Med Neurol Branch, NIH, 10 Ctr Dr,Rm 5D38, Bethesda, MD 20892 USA. EM ludlowc@ninds.nih.gov OI Ludlow, Christy/0000-0002-2015-6171 FU NINDS NIH HHS [Z01 NS-02980, Z01 NS002980] NR 34 TC 25 Z9 31 U1 1 U2 4 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 2005 VL 94 IS 6 BP 4011 EP 4018 DI 10.1152/jn.00025.2005 PG 8 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 984PP UT WOS:000233317100036 PM 16107520 ER PT J AU Heiss, JD Walbridge, S Morrison, P Hampton, RR Sato, S Vortmeyer, A Butman, JA O'Malley, J Vidwan, P Dedrick, RL Oldfield, EH AF Heiss, JD Walbridge, S Morrison, P Hampton, RR Sato, S Vortmeyer, A Butman, JA O'Malley, J Vidwan, P Dedrick, RL Oldfield, EH TI Local distribution and toxicity of prolonged hippocampal infusion of muscimol SO JOURNAL OF NEUROSURGERY LA English DT Article DE epilepsy; infusion test; magnetic resonance imaging; drug delivery system; Macaca mulatta ID CONVECTION-ENHANCED DELIVERY; GLOBUS-PALLIDUS; REGIONAL-DISTRIBUTION; PRIMATE BRAIN; RAT; EPILEPSY; DRUG; INJECTION; PERFUSION; SEIZURES AB Object. The activity of gamma-aminobutyric acid (GABA), the principal inhibitory neurotransmitter, is reduced in the hippocampus in patients with complex partial seizures from mesial temporal sclerosis. To provide preliminary safety and distribution data on using convection-enhanced delivery of agents to treat complex partial seizures and to test the efficacy and safety of regional selective neuronal suppression, the authors infused muscimol, a GABA-A receptor agonist, directly into the hippocampus of nonhuman primates using an integrated catheter electrode. Methods. Ten rhesus monkeys were divided into three groups: 1) use of catheter electrode alone (four monkeys); 2) infusion of escalating concentrations of muscimol followed by vehicle (three monkeys); and 3) infusion of vehicle and subsequent muscimol mixed with muscimol tracer (three monkeys). Infusions were begun 5 days after catheter electrode placement and continued for 5.6 days before switching to the other agent. Head magnetic resonance (MR) images and electroencephalography recordings were obtained before and during the infusions. Brain histological studies and quantitative autoradiography were performed. Neurological function was normal in controls and when muscimol concentrations were 0.125 mM or less, whereas higher concentrations (0.5 and 1 mM) produced reversible apathy and somnolence. Fluid distribution was demonstrated on MR images and muscimol distribution was demonstrated on autoradiographs throughout the hippocampus and adjacent white matter. Conclusions. Targeted modulation of neuronal activity is a reasonable research strategy for the investigation and treatment of medically intractable epilepsy. C1 NINDS, Anim Hlth & Care Sect, NIH, Bethesda, MD USA. NIMH, Neuropsychol Lab, NIH, Bethesda, MD USA. Off Res Serv, Div Bioengn & Phys Sci, Bethesda, MD USA. Clin Ctr Radiol, NIH, Bethesda, MD USA. RP Heiss, JD (reprint author), NINDS, Surg Neurol Branch, Electroencephalog Sect, NIH, 10 Ctr Dr,10-5D37,MSC-1414, Bethesda, MD 20892 USA. EM heissj@ninds.nih.gov RI Butman, John/A-2694-2008; OI Butman, John/0000-0002-1547-9195 FU Intramural NIH HHS [ZIA NS003051-06] NR 47 TC 26 Z9 26 U1 1 U2 4 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD DEC PY 2005 VL 103 IS 6 BP 1035 EP 1045 DI 10.3171/jns.2005.103.6.1035 PG 11 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 990PT UT WOS:000233756400011 PM 16381190 ER PT J AU Tender, GC Vortmeyer, AO Oldfield, EH AF Tender, GC Vortmeyer, AO Oldfield, EH TI Spinal intradural arteriovenous fistulas acquired in late adulthood: absent spinal venous drainage in pathogenesis and pathophysiology - Report of two cases SO JOURNAL OF NEUROSURGERY-SPINE LA English DT Article DE arteriovenous fistula; arteriovenous malformation; terminal filum; lumbar puncture; myelopathy; venous congestion ID CLINICAL-FEATURES; CORD; MALFORMATIONS; VEINS; ARTERIOGRAPHY; COMPLICATION; ANGIOGRAPHY; SURGERY AB Intradural spinal arteriovenous fistulas (AVFs), a subtype of spinal arteriovenous malformation in which there is a direct communication between a spinal artery and a vein on the cord surface or in the subarachnoid space, are generally considered to be congenital lesions caused by maldevelopment of the embryonic vascular system. The authors present the cases of two patients with acquired AVFs of the terminal filum. In each patient an AVF between the distal segment of the anterior spinal artery and its accompanying vein on the terminal filum developed within I year of repeated lumbar myelography that had demonstrated no evidence of abnormal vascularity. In both patients spinal arteriography demonstrated the absence of medullary venous drainage in the thoracolumbar region, which, combined with the arterialized venous input from the AVF, permitted the development of venous congestion and myelopathy. The involved segment of the terminal filum was excised in vitro microarteriography and the histopathological examination demonstrated a single, simple arteriovenous connection in both patients. The findings in these cases indicate that intradural AVF can spontaneously arise in later life. The development of these lesions and/or their clinical manifestation may require not only the presence of the AVF, but also deficiency of medullary spinal venous drainage. The epidemiology and anatomy of intradural AVFs are compatible with an acquired origin in many cases. C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. Louisiana State Univ, Dept Neurosurg, New Orleans, LA USA. RP Oldfield, EH (reprint author), NINDS, Surg Neurol Branch, NIH, 10 Ctr Dr Bldg 10,Room 5D37, Bethesda, MD 20892 USA. EM eo10d@nih.gov NR 33 TC 11 Z9 11 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 1547-5654 J9 J NEUROSURG-SPINE JI J. Neurosurg.-Spine PD DEC PY 2005 VL 3 IS 6 BP 488 EP 494 DI 10.3171/spi.2005.3.6.0488 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 990PX UT WOS:000233756800013 PM 16381214 ER PT J AU Bagnato, F Butman, JA Mora, CA Gupta, S Yamano, Y Tasciyan, TA Solomon, JM Santos, WJ Stone, RD McFarland, HF Jacobson, S AF Bagnato, F Butman, JA Mora, CA Gupta, S Yamano, Y Tasciyan, TA Solomon, JM Santos, WJ Stone, RD McFarland, HF Jacobson, S TI Conventional magnetic resonance imaging features in patients with tropical spastic paraparesis SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE brain; disability; HTLV-1; magnetic resonance imaging; spinal cord; tropical spastic paraparesis ID I-ASSOCIATED MYELOPATHY; CENTRAL-NERVOUS-SYSTEM; HTLV-1 ASSOCIATED MYELOPATHY; MULTIPLE-SCLEROSIS; NEUROLOGIC DISEASE; SPINAL-CORD; 1-ASSOCIATED MYELOPATHY; CLINICAL-FEATURES; UNITED-KINGDOM; MRI AB Conventional brain and spinal cord magnetic resonance images were performed in 21 patients with human T-cell lymphotropic virus (HTLV)-1 associated myelopathy/tropical spastic paraparesis, to assess the role of conventional magnetic resonance imaging (MRI) in the disease diagnosis. These patients had no other central nervous system conditions or related risk factors at the time of tropical spastic paraparesis diagnosis. Eleven (52.4%) patients showed nonspecific brain abnormalities on T2-weighted images. The majority (77.2%) of brain abnormalities were located in the deep white matter. A transient contrast-enhancing lesion was identified in the brain of only one patient. In the brain of another patient, 9.0% of the T2-hyperintense lesion load was hypointense on the correspondent T1-weighted images. No differences in terms of demographic, biological, or clinical variables were present between patients with abnormal brain images and those with normal brain magnetic resonance images. Spinal cord T2-weighted images were abnormal in three (14.3%) patients. In one of these three patients, a diffuse but transient edema was found along the entire tract of the spinal cord. White matter lesions were present in the central nervous system of 60% of the cases in this study. However, no correlations between magnetic resonance imaging and clinical findings, and no specificity of lesions were observed. Hence, conventional magnetic resonance imaging is a sensitive but not highly specific tool for diagnosis of tropical spastic paraparesis. C1 Warren G Magnuson Clin Ctr, Neuroimmunol Branch, Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. Warren G Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD USA. Med Numer Inc, Sterling, VA USA. RP Jacobson, S (reprint author), Bldg 10,Room 5B-16,9000 Rockville Pike, Bethesda, MD 20892 USA. EM jacobsons@ninds.nih.gov RI Butman, John/A-2694-2008; OI Butman, John/0000-0002-1547-9195 NR 41 TC 22 Z9 23 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD DEC PY 2005 VL 11 IS 6 BP 525 EP 534 DI 10.1080/13550280500385039 PG 10 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 992AI UT WOS:000233855800004 PM 16338746 ER PT J AU Boswell, CA Brechbiel, MW AF Boswell, CA Brechbiel, MW TI Auger electrons: Lethal, low energy, and coming soon to a tumor cell nucleus near you SO JOURNAL OF NUCLEAR MEDICINE LA English DT Editorial Material ID SOMATOSTATIN ANALOGS; CANCER; LOCALIZATION; THERAPY; DOSIMETRY; TOXICITY C1 NCI, NIH, Bethesda, MD 20892 USA. RP Brechbiel, MW (reprint author), NCI, CCR, ROB, Radioimmune & Inorgan Chem Sect, Bldg 10,Room 1B40,10 Ctr Dr, Bethesda, MD 20892 USA. EM martinwb@box-m.nih.gov NR 18 TC 38 Z9 39 U1 0 U2 3 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD DEC PY 2005 VL 46 IS 12 BP 1946 EP 1947 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 991VJ UT WOS:000233842000007 PM 16330556 ER PT J AU Percival, SS Nelson, SA Milner, JA AF Percival, SS Nelson, SA Milner, JA TI Workshop executive summary report SO JOURNAL OF NUTRITION LA English DT Article C1 Univ Florida, Gainesville, FL 32611 USA. Sci Consulting Grp Inc, Gaithersburg, MD 20872 USA. NCI, Div Canc Prevent, Rockville, MD 20852 USA. RP Percival, SS (reprint author), Univ Florida, Gainesville, FL 32611 USA. EM Percival@ufl.edu NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOCIETY NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD DEC PY 2005 VL 135 IS 12 BP 2898S EP 2907S PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 991YZ UT WOS:000233852200025 PM 16317139 ER PT J AU Percival, SS Milner, JA AF Percival, SS Milner, JA TI Opportunities for research SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Workshop on Immunonutrition - Enhancing Tumoricidal Cell activity CY MAR 23, 2005 CL Bethesda, MD SP Div Canc Prevent, NCI, NIH, DHHS C1 Univ Florida, Gainesville, FL 32611 USA. NCI, Div Canc Prevent, Rockville, MD 20852 USA. RP Percival, SS (reprint author), Univ Florida, Gainesville, FL 32611 USA. EM Percival@ufl.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOCIETY NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD DEC PY 2005 VL 135 IS 12 BP 2921S EP 2923S PG 3 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 991YZ UT WOS:000233852200036 PM 16317150 ER PT J AU Merlino, G Poetschke-Klug, H Ichikawa, T Recio, J Zaidi, MR DeFabo, E Noonan, F AF Merlino, G Poetschke-Klug, H Ichikawa, T Recio, J Zaidi, MR DeFabo, E Noonan, F TI Modeling melanoma prevention in the mouse. SO JOURNAL OF NUTRITION LA English DT Meeting Abstract CT International Research Conference on Diet, Nutrition and Cancer CY JUL 14-15, 2005 CL Washington, DC SP Amer Inst Canc Res, World Canc Res Fund Int C1 NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. George Washington Univ, Med Ctr, Dept Environm & Occupat Hlth, Lab Photobiol & Photoimmunol, Washington, DC 20037 USA. RI Zaidi, M. Raza/H-1386-2016 OI Zaidi, M. Raza/0000-0003-0480-3188 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOCIETY NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD DEC PY 2005 VL 135 IS 12 SU S BP 3034S EP 3034S PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 993SS UT WOS:000233975900022 ER PT J AU Grodzinski, P AF Grodzinski, P TI Use of nanotechnologies to advance cancer research. SO JOURNAL OF NUTRITION LA English DT Meeting Abstract CT International Research Conference on Diet, Nutrition and Cancer CY JUL 14-15, 2005 CL Washington, DC SP Amer Inst Canc Res, World Canc Res Fund Int C1 NCI, Alliance Nanotechnol Canc, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOCIETY NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD DEC PY 2005 VL 135 IS 12 SU S BP 3036S EP 3036S PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 993SS UT WOS:000233975900028 ER PT J AU Whiteside, MA Phang, JM AF Whiteside, MA Phang, JM TI Transformation of immortalized, nontumorigenic prostate epithelial cells by a heterocyclic amine commonly occurring in the human diet. SO JOURNAL OF NUTRITION LA English DT Meeting Abstract CT International Research Conference on Diet, Nutrition and Cancer CY JUL 14-15, 2005 CL Washington, DC SP Amer Inst Canc Res, World Canc Res Fund Int C1 NCI, Lab Comparat Carcinogenesis, Metab & Canc Susceptibil Sect, Frederick, MD 21701 USA. NCI, Canc Prevent Fellowship Program, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOCIETY NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD DEC PY 2005 VL 135 IS 12 SU S BP 3038S EP 3039S PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 993SS UT WOS:000233975900035 ER PT J AU van Noord, PAH Ronckers, CM Elias, SG Peeters, PHM AF van Noord, PAH Ronckers, CM Elias, SG Peeters, PHM TI Exposure to the dutch famine of 1944-1945 and shifts in hormonal set points: Parathyroid hormone. SO JOURNAL OF NUTRITION LA English DT Meeting Abstract CT International Research Conference on Diet, Nutrition and Cancer CY JUL 14-15, 2005 CL Washington, DC SP Amer Inst Canc Res, World Canc Res Fund Int C1 NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Julius Ctr UMC, Utrecht, Netherlands. RI Elias, Sjoerd/E-6057-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOCIETY NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD DEC PY 2005 VL 135 IS 12 SU S BP 3041S EP 3042S PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 993SS UT WOS:000233975900045 ER PT J AU McCrary, Q Lin, Q Boushey, CJ Sinha, R Mai, V AF McCrary, Q Lin, Q Boushey, CJ Sinha, R Mai, V TI Diet and microflora composition in African American and caucasian American residents of the eastern shore of Maryland. SO JOURNAL OF NUTRITION LA English DT Meeting Abstract CT International Research Conference on Diet, Nutrition and Cancer CY JUL 14-15, 2005 CL Washington, DC SP Amer Inst Canc Res, World Canc Res Fund Int C1 Univ Maryland Eastern Shore, Princess Anne, MD USA. Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. Purdue Univ, W Lafayette, IN 47907 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RI Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOCIETY NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD DEC PY 2005 VL 135 IS 12 SU S BP 3043S EP 3044S PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 993SS UT WOS:000233975900051 ER PT J AU Zhang, FF Terry, MB Hou, LF Chen, JB Lissowska, J Yeager, M Zatonski, W Chanock, S Chow, WH AF Zhang, FF Terry, MB Hou, LF Chen, JB Lissowska, J Yeager, M Zatonski, W Chanock, S Chow, WH TI MTHFR polymorphisms, dietary folate intake, and stomach cancer risk in a Polish population. SO JOURNAL OF NUTRITION LA English DT Meeting Abstract CT International Research Conference on Diet, Nutrition and Cancer CY JUL 14-15, 2005 CL Washington, DC SP Amer Inst Canc Res, World Canc Res Fund Int C1 NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Columbia Univ, Dept Epidemiol, New York, NY USA. M Sklodowska Curie Inst Oncol, Warsaw, Poland. Ctr Canc, Div Canc Epidemiol & Prevent, Warsaw, Poland. NR 0 TC 0 Z9 0 U1 1 U2 5 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 2005 VL 135 IS 12 SU S BP 3047S EP 3047S PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 993SS UT WOS:000233975900062 ER PT J AU Izevbigie, EB Opata, M Bryant, JL AF Izevbigie, EB Opata, M Bryant, JL TI Deleterious side effects of tamoxifen may be ameliorated by aqueous Vernonia amygdalina leaf extracts. SO JOURNAL OF NUTRITION LA English DT Meeting Abstract CT International Research Conference on Diet, Nutrition and Cancer CY JUL 14-15, 2005 CL Washington, DC SP Amer Inst Canc Res, World Canc Res Fund Int C1 Jackson State Univ, Lab Phytoceut, Dept Biol, Jackson, MS USA. Jackson State Univ, NIH, Ctr Environm Hlth, Jackson, MS USA. Univ Maryland, Inst Human Virol, Baltimore, MD 21201 USA. Univ Maryland, Inst Biotechnol, Baltimore, MD 21201 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOCIETY NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD DEC PY 2005 VL 135 IS 12 SU S BP 3048S EP 3048S PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 993SS UT WOS:000233975900066 ER PT J AU Zhao, CW Andrews, K Holden, J Schweitzer, A Roseland, J Harnly, J Wolf, W Dwyer, J Picciano, MF Betz, J Saldanha, L Yetley, E Fisher, K Radimer, K AF Zhao, CW Andrews, K Holden, J Schweitzer, A Roseland, J Harnly, J Wolf, W Dwyer, J Picciano, MF Betz, J Saldanha, L Yetley, E Fisher, K Radimer, K TI Antioxidant supplements reported in the National Health and Nutrition Examination Survey (NHANES) 1999-2000. SO JOURNAL OF NUTRITION LA English DT Meeting Abstract CT International Research Conference on Diet, Nutrition and Cancer CY JUL 14-15, 2005 CL Washington, DC SP Amer Inst Canc Res, World Canc Res Fund Int C1 USDA, Nutr Data Lab, Beltsville, MD 20705 USA. USDA, Food Composit Lab, Beltsville, MD 20705 USA. NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. Ctr Dis Control, Natl Ctr Hlth Stat, Hyattsville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOCIETY NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD DEC PY 2005 VL 135 IS 12 SU S BP 3055S EP 3056S PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 993SS UT WOS:000233975900088 ER PT J AU Irons, R Carlson, BA Hatfield, DL Davis, CD AF Irons, R Carlson, BA Hatfield, DL Davis, CD TI Dietary selenium homeostasis in mice expressing a mutant Sec tRNA[Ser](Sec) - A model for colon cancer research. SO JOURNAL OF NUTRITION LA English DT Meeting Abstract CT International Research Conference on Diet, Nutrition and Cancer CY JUL 14-15, 2005 CL Washington, DC SP Amer Inst Canc Res, World Canc Res Fund Int C1 NCI, Nutr Sci Res Grp, Rockville, MD USA. NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOCIETY NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD DEC PY 2005 VL 135 IS 12 SU S BP 3059S EP 3060S PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 993SS UT WOS:000233975900100 ER PT J AU Sawyer, RT Abraham, JL Daniloff, E Newman, LS AF Sawyer, RT Abraham, JL Daniloff, E Newman, LS TI Secondary ion mass spectroscopy demonstrates retention of beryllium in chronic beryllium disease granulomas SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID CD4(+) T-CELLS; SENSITIZATION; LOCALIZATION; LUNG; SARCOIDOSIS; MICROSCOPY; ALLELES; TISSUE; ALLOY; MODEL AB Objective: We hypothesized that beryllium (Be) might persist in lung granulomas in patients with chronic beryllium disease (CBD). Methods: A total of 33 Be-exposed ceramics workers underwent transbronchial biopsy. They were classified based on histopathology and Be-lymphocyte proliferation test as CBD or other categories. Lung tissue sections were analyzed using secondary ion mass spectroscopy. Results: Be was detected in the lungs of all Be-exposed groups. Be levels were increased within the granulomas of patients with CBD compared with the Be levels outside granulomas. Notably, Be was detectable in the lungs of CBD patients who had ceased exposure to Be an average of 9 years previously. Conclusions: Be was detected in the lungs of all Be-exposed subjects, with the highest levels of persistent Be inside CBD lung granulomas. Be antigen persistence may help explain the chronicity, of this granulomatous disorder. C1 Natl Jewish Med & Res Ctr, Div Environm & Occupat Hlth Sci, Robert Hollis Lab Environm & Occupat Hlth Sci, Dept Med, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Div Pulm Sci & Crit Care Med, Denver, CO 80262 USA. SUNY Upstate Med Univ, Dept Pathol, Syracuse, NY USA. Univ Colorado, Hlth Sci Ctr, Dept Prevent Med & Biometr, Denver, CO USA. RP Sawyer, RT (reprint author), NIAID, Div Allergy Immunol & Transplantat, NIH, DHHS, 6610 Rockledge Dr,Room 3103, Bethesda, MD 20892 USA. EM sawyerr@niaid.nih.gov FU NCRR NIH HHS [M01 RR00051]; NHLBI NIH HHS [K08 HL03887]; NIEHS NIH HHS [R01 ES-06538, P01 ES11810] NR 36 TC 20 Z9 20 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD DEC PY 2005 VL 47 IS 12 BP 1218 EP 1226 DI 10.1097/01.jom.0000184884.85325.36 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 993GY UT WOS:000233943800006 PM 16340702 ER PT J AU Ward, MH Heineman, EF McComb, RD Weisenburger, DD AF Ward, MH Heineman, EF McComb, RD Weisenburger, DD TI Drinking water and dietary sources of nitrate and nitrite and risk of glioma SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID N-NITROSO COMPOUNDS; DANISH RURAL-POPULATION; CURED MEAT-PRODUCTS; BRAIN-TUMORS; ENDOGENOUS NITROSATION; UNITED-STATES; WELL-WATER; CANCER; NITROSAMINES; EXPOSURE AB Objective. Dietary nitrite has been associated with increased glioma risk; however, drinking water nitrate has not been extensively evaluated. Methods. We conducted a population-based case-control study of adult glioma in Nebraska. Water utility nitrate measurements were linked to residential water source histories. We computed average nitrate exposure over a 20-year period. A food frequency questionnaire was used to assess dietary nitrate and nitrite. Results. Increasing quartiles of the average nitrate level in drinking water were not significantly associated with risk (adjusted odd ratios: 1.4, 1.2, 1.3). Risk was similar among those with both higher and lower intakes of vitamin C, an inhibitor of N-nitroso compound formation. Dietary nitrite intake was not associated with risk. Conclusions: Our study does not support a role for drinking water and dietary sources of nitrate and nitrite in risk of adult glioma. C1 NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. NCI, Div Canc Control & Populat Sci, NIH, DHHS, Bethesda, MD 20892 USA. Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE USA. RP Ward, MH (reprint author), NCI, Occupat & Environm Epidemiol Branch, 6120 Execut Blvd,EPS-8104, Bethesda, MD 20892 USA. EM wardm@mail.nih.gov FU Intramural NIH HHS NR 45 TC 11 Z9 13 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD DEC PY 2005 VL 47 IS 12 BP 1260 EP 1267 DI 10.1097/01.jom.0000184879.67736.ae PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 993GY UT WOS:000233943800011 PM 16340707 ER PT J AU Khoromi, S Patsalides, A Parada, S Salehi, V Meegan, JM Max, MB AF Khoromi, S Patsalides, A Parada, S Salehi, V Meegan, JM Max, MB TI Topiramate in chronic lumbar radicular pain SO JOURNAL OF PAIN LA English DT Article; Proceedings Paper CT 10th World Congress on Pain CY AUG 17-22, 2002 CL SAN DIEGO, CA SP Allergan Inc, AstraZeneca, Eli Lilly & Co, Endo Pharmaceut Inc, Grunenthal GmbH, Janssen Pharmaceut, Pfizer Inc, Pharmacia Corp, Purdue-Mundipharma-Napp Associated Co DE anticonvulsants; chronic sciatica; randomized controlled trials; neuropathic pain ID LOW-BACK-PAIN; DIABETIC-NEUROPATHY; TRIGEMINAL NEURALGIA; CLINICAL PAIN; PRIMARY-CARE; DOUBLE-BLIND; PLACEBO; INTENSITY; EFFICACY; UPDATE AB chronic lumbar radicular pain is the most common neuropathic pain syndrome. This was a double-blind, randomized, 2-period crossover trial of topiramate (50 to 400 mg) and diphenhydramine (6.25 to 50 mg) as active placebo to assess the efficacy of topiramate. Each period consisted of a 4-week escalation, a 2-week maintenance at the highest tolerated dose, and a 2-week taper. Main outcome was the mean daily leg pain score on a 0 to 10 scale during the maintenance period. Global pain relief was assessed on a 6-level category scale. In the 29 of 42 patients who completed the study, topiramate reduced leg pain by a mean of 19% (P =.065). Global pain relief scores were significantly better on topiramate (P <.005). Mean doses were topiramate 200 mg and diphenhydramine 40 mg. We concluded that topiramate treatment might reduce chronic sciatica in some patients but causes frequent side effects and dropouts. We would not recommend topiramate unless studies of alternative regimens showed a better therapeutic ratio. Perspective: The anticonvulsant topiramate might reduce chronic lumbar nerve root pain through effects such as blockade of voltage-gated sodium channels and AMPA/kainite glutamate receptors, modulation of voltage-gated calcium channels, and gamma-aminobutyric acid agonist-like effects. (c) 2005 by the American Pain Society C1 NIH, Dept Hlth & Human Serv, Warren Magnuson Clin Ctr, Dept Radiol, Bethesda, MD 20892 USA. NIH, Dept Hlth & Human Serv, Warren Magnuson Clin Ctr, Dept Nursing, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Pain & Neurosensory Mech Branch, Bethesda, MD USA. RP Khoromi, S (reprint author), NIH, Dept Hlth & Human Serv, Warren Magnuson Clin Ctr, Dept Radiol, Bldg 10,4-1741, Bethesda, MD 20892 USA. EM khoromisu@mail.nih.gov FU Intramural NIH HHS NR 42 TC 67 Z9 72 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD DEC PY 2005 VL 6 IS 12 BP 829 EP 836 DI 10.1016/j.jpain.2005.08.002 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 999HZ UT WOS:000234381700007 PM 16326371 ER PT J AU Han, PKJ Arnold, RM AF Han, PKJ Arnold, RM TI Palliative care services, patient abandonment, and the scope of physicians' responsibilities in end-of-life care SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID NONABANDONMENT; OBLIGATION; EDUCATION; MEDICINE; OUTCOMES; QUALITY; ILL AB Background: Palliative care consultation services are being established at a growing pace in medical centers throughout the country. The intervention of these services may improve the quality of end-of-life care in many ways, but it may also promote an unintended outcome of patient abandonment by primary physicians. Objective: To discuss the nature of patient abandonment in end-of-life care, the moral problems that it poses for palliative care clinicians in their consultative activities, and the implications of patient abandonment for palliative care services. Design: Case study and conceptual analysis of two cases from the experience of the University of Pittsburgh Medical Center Palliative Care Service. Conclusions: The problem of patient abandonment raises deep questions about the proper scope of physicians' responsibilities to dying patients, and unmasks inherent tensions between the goals and functions of palliative medicine services. We offer suggestions on how palliative care services might deal effectively with these tensions, to minimize patient abandonment, and more effectively realize their moral mission. C1 NCI, Canc Prevent Fellowship Program, Div Canc Prevent, NIH, Rockville, MD 20892 USA. Univ Pittsburgh, Div Gen Internal Med, Sect Palliat Care & Med Eth, Pittsburgh, PA USA. RP Han, PKJ (reprint author), NCI, Basic & Biobehav Res Branch, Div Canc Control & Populat Sci, 6130 Execut Blvd,EPN 4097,MSC 7363, Rockville, MD 20892 USA. EM hanp@mail.nih.gov OI Han, Paul/0000-0003-0165-1940 NR 22 TC 8 Z9 10 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD DEC PY 2005 VL 8 IS 6 BP 1238 EP 1245 DI 10.1089/jpm.2005.8.1238 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 045XS UT WOS:000237776600023 PM 16351537 ER PT J AU Emons, JAM Boersma, B Baron, J Wit, JM AF Emons, JAM Boersma, B Baron, J Wit, JM TI Catch-up growth: Testing the hypothesis of delayed growth plate senescence in humans SO JOURNAL OF PEDIATRICS LA English DT Editorial Material ID EPIPHYSEAL FUSION C1 Med Ctr Alkmaar, Dept Pediat, NL-1800 AM Alkmaar, Netherlands. Leiden Univ, Med Ctr, Dept Pediat, Leiden, Netherlands. NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20982 USA. RP Boersma, B (reprint author), Med Ctr Alkmaar, Dept Pediat, POB 501, NL-1800 AM Alkmaar, Netherlands. EM b.boersma@mca.nl NR 13 TC 24 Z9 24 U1 1 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 2005 VL 147 IS 6 BP 843 EP 846 DI 10.1016/j.jpeds.2005.07.033 PG 4 WC Pediatrics SC Pediatrics GA 994XX UT WOS:000234065600030 PM 16356444 ER PT J AU Ohlsson, A Roberts, RS Schmidt, B Davis, P Moddeman, D Saigal, S Solimano, A Vincer, M Wright, L AF Ohlsson, A Roberts, RS Schmidt, B Davis, P Moddeman, D Saigal, S Solimano, A Vincer, M Wright, L CA Trial Indomethacin Prophylaxis Pre TI Male/female differences in indomethacin effects in preterm infants SO JOURNAL OF PEDIATRICS LA English DT Article ID BIRTH AB To test whether indomethacin prophylaxis has sex-mediated effects on severe intraventricular hemorrhage (grade III and IV) and on long-term outcomes in extremely-low-birth-weight infants. A secondary analysis was performed in the entire "Trial of Indomethacin Prophylaxis in Preterms study" cohort. The results suggest a weak differential treatment effect of indomethacin by sex. C1 Univ Toronto, Toronto, ON, Canada. McMaster Univ, Hamilton, ON, Canada. Univ Manitoba, Winnipeg, MB, Canada. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. Dalhousie Univ, Halifax, NS B3H 3J5, Canada. Royal Hosp Women, Melbourne, Vic, Australia. NICHD, Bethesda, MD USA. RP Ohlsson, A (reprint author), Univ Toronto, Toronto, ON, Canada. FU NCRR NIH HHS [M01 RR 00997, M01 RR 00070]; NICHD NIH HHS [U10 HD27851, U10 HD27881, U10 HD21385, U10 HD21364, U10 HD21373, U10 HD27880, U10 HD27904, U10 HD34216] NR 6 TC 16 Z9 17 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD DEC PY 2005 VL 147 IS 6 BP 860 EP 862 DI 10.1016/j.jpeds.2005.07.032 PG 3 WC Pediatrics SC Pediatrics GA 994XX UT WOS:000234065600035 PM 16356449 ER PT J AU Cagli, NA Hakki, SS Dursun, R Toy, H Gokalp, A Ryu, OH Hart, PS Hart, TC AF Cagli, NA Hakki, SS Dursun, R Toy, H Gokalp, A Ryu, OH Hart, PS Hart, TC TI Clinical, genetic, and biochemical findings in two siblings with Papillon-Lefevre Syndrome SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE cathepsin C; cathepsin G; elastase; gene mutation; Papillon-Lefevre Syndrome ID CATHEPSIN-C GENE; FOLLOW-UP; PERIODONTAL-DISEASE; PREPUBERTAL PERIODONTITIS; AGGRESSIVE PERIODONTITIS; MUTATIONS; KERATOSIS; IDENTIFICATION; DEFICIENCY; THERAPY AB Background: Papillon-Lefevre Syndrome (PLS) is an autosomal recessive disease characterized by palmoplantar hyperkeratosis and severe periodontitis affecting both primary and secondary dentitions. Cathepsin C (CTSC) gene mutations are etiologic for PLS. The resultant loss of CTSC function is responsible for the severe periodontal destruction seen clinically. Methods: A 4-year-old female (case 1) and her 10-year-old sister (case 2) presented with palmoplantar skin lesions, tooth mobility, and advanced periodontitis. Based on clinical findings, the cases were diagnosed with PLS. Mutational screening of the CTSC gene was conducted for the cases, and their clinically unaffected parents and brother. Biochemical analysis was performed for CTSC, cathepsin G (CTSG), and elastase activity in neutrophils for all members of the nuclear family. The initial treatment included oral hygiene instruction, scaling and root planing, and systemic amoxicillin-metronidazole therapy. Results: CTSC mutational screening identified a c.415G > A transition mutation. In the homozygous state, this mutation was associated with an almost complete loss of activity of CTSC, CTSG, and elastase. Although monthly visits, including scaling, polishing, and 0.2% chlorhexidine digluconate irrigation were performed to stabilize the periodontal condition, case I lost all her primary teeth. In case 2, some of the permanent teeth could be maintained. Conclusions: This report describes two siblings with a cathepsin C gene mutation that is associated with the inactivity of cathepsin C and several neutrophil serine proteases. The failure of patients to respond to periodontal treatment is discussed in the context of these biological findings. C1 Selcuk Univ, Fac Dent, Dept Periodontol, TR-42079 Konya, Turkey. Selcuk Univ, Fac Med, Dept Dermatol, TR-42079 Konya, Turkey. Selcuk Univ, Fac Med, Dept Pathol, TR-42079 Konya, Turkey. Selcuk Univ, Fac Dent, Dept Pedodont, TR-42079 Konya, Turkey. Natl Inst Dent & Craniofacial Res, Human Craniofacial Genet Sect, NIH, Bethesda, MD USA. Natl Human Genome Res Inst, NIH, Bethesda, MD 20892 USA. RP Hakki, SS (reprint author), Selcuk Univ, Fac Dent, Dept Periodontol, TR-42079 Konya, Turkey. EM sshakki@selcuk.edu.tr NR 37 TC 12 Z9 14 U1 1 U2 2 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 2005 VL 76 IS 12 BP 2322 EP 2329 DI 10.1902/jop.2005.76.12.2322 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 997FD UT WOS:000234229600019 PM 16332247 ER PT J AU DeLozier, TC Lee, SC Coulter, SJ Goh, BC Goldstein, JA AF DeLozier, TC Lee, SC Coulter, SJ Goh, BC Goldstein, JA TI Functional characterization of novel allelic variants of CYP2C9 recently discovered in southeast Asians SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID CYTOCHROME P4502C9; INTERINDIVIDUAL VARIABILITY; GENETIC POLYMORPHISMS; 5'-FLANKING REGION; DRUG-METABOLISM; IN-VITRO; WARFARIN; IDENTIFICATION; SENSITIVITY; POPULATION AB CYP2C9 was recently resequenced in 150 Asian subjects from Singapore. Several new coding variants were reported, and these variants are now named CYP2C9*14 (R125H), CYP2C9*15 (S162X), CYP2C9*16 (T299A), CYP2C9*17 (P382S), CYP2C9*18 (D397A), and CYP2C9*19 (Q454H). The CYP2C9*18 variant also contained an I359L change previously associated with the CYP2C9*3 allele. In this study, we assessed the functional consequences of the new coding changes. cDNAs containing each of the new coding changes were constructed by site-directed mutagenesis and expressed in a bacterial cDNA expression system, the allelic proteins were partially purified, and their ability to hydroxylate a prototype CYP2C9 substrate was assayed. Expression of cDNAs in Escherichia coli containing either the D397A change or the S162X (premature stop codon) could not be detected either spectrally or at the apoprotein level. CYP2C9.14 and CYP2C9.16 exhibited 80 to 90% lower catalytic activity toward tolbutamide at two substrate concentrations compared with wild-type CYP2C9.1. Kinetic analysis confirmed that CYP2C9.14 and CYP2C9.16 have a higher K-m and a > 90% lower intrinsic clearance of tolbutamide compared with wild-type CYP2C9.1. Both CYP2C9.17 and CYP2C9.19 proteins exhibited modest 30 to 40% decreases in catalytic activity toward tolbutamide. Thus, CYP2C9*15 and CYP2C9*18 may represent null alleles, whereas CYP2C9*14 and CYP2C9*16 allelic variants produce proteins that are clearly catalytically defective in vitro, indicating the existence of new defective putative alleles of CYP2C9 in Asians. C1 NIEHS, Human Metab Sect, Lab Pharmacol & Chem, Dept Hlth & Human Serv,NIH, Res Triangle Pk, NC 27709 USA. Natl Univ Singapore Hosp, Dept Hematol Oncol, Singapore, Singapore. RP Goldstein, JA (reprint author), NIEHS, Human Metab Sect, Lab Pharmacol & Chem, Dept Hlth & Human Serv,NIH, POB 12233,A3-02, Res Triangle Pk, NC 27709 USA. EM goldste1@niehs.nih.gov RI Goldstein, Joyce/A-6681-2012; OI Coulter, Sherry/0000-0002-2732-3470 NR 33 TC 50 Z9 53 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD DEC PY 2005 VL 315 IS 3 BP 1085 EP 1090 DI 10.1124/jpet.105.091181 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 984VZ UT WOS:000233335100014 PM 16099926 ER PT J AU Hansen, PB Hashimoto, S Oppermann, M Huang, Y Briggs, JP Schnermann, J AF Hansen, PB Hashimoto, S Oppermann, M Huang, Y Briggs, JP Schnermann, J TI Vasoconstrictor and vasodilator effects of adenosine in the mouse kidney due to preferential activation of A1 or A2 adenosine receptors SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID NITRIC-OXIDE PRODUCTION; RAT RENAL-ARTERY; A(2A) RECEPTORS; AFFERENT ARTERIOLES; ENDOTHELIAL-CELLS; ANGIOTENSIN-II; BLOOD-FLOW; IN-VIVO; AGONISTS; DOGS AB The present experiments in mice were performed to determine the steady- state effects of exogenous adenosine on the vascular resistance of the whole kidney, of superficial blood vessels, and of afferent arterioles. The steady-state effect of an intravenous infusion of adenosine (5, 10, and 20 mu g/min) in wild- type mice was vasodilatation as evidenced by significant reductions of renal and superficial vascular resistance. Resistance decreases were augmented in adenosine 1 receptor (A1AR) -/- mice. Renal vasodilatation by the A2aAR agonist CGS 21680A [2-p-(2-carboxyethyl)phenethyl-amino-5'-N-ethylcarboxamidoadenosine hydrochloride] (0.25, 0.5, and 1 mu g/kg/min) and inhibition of adenosine-induced relaxation by the A2aAR antagonist ZM-241385 [4-(2-[7-amino-2-(2-furyl)[1,2,4] triazolo[2,3-a][1,3,5] triazin-5-yl-amino]ethyl)phenol] (20 mg/kg) suggests that the reduction of renovascular resistance was largely mediated by A2aAR. After treatment with N-omega-nitro-L- arginine methyl ester (L-NAME) adenosine was unable to alter superficial blood flow and resistance significantly indicating that adenosine-induced dilatation is NO- dependent. Absence of a dilatory effect in endothelial nitric-oxide synthase (NOS) -/- mice suggests endothelial NOS as the source of NO. When infused into the subcapsular interstitium, adenosine reduced superficial blood flow through A1AR activation. Adenosine (10(-7) M) constricted isolated perfused afferent arterioles when added to the bath but not when added to the luminal perfusate. Luminal adenosine caused vasoconstriction in the presence of L-NAME or the A2AR antagonist 3,7-dimethyl-1-(2- propynyl)xanthine. Our data show that global elevation of renal adenosine causes steady-state vasorelaxation resulting from adenosine 2 receptor (A2AR)-mediated generation of NO. In contrast, selective augmentation of adenosine around afferent arterioles causes persistent vasoconstriction, indicating A1AR dominance. Thus, adenosine is a renal constrictor only when it can interact with afferent arteriolar A1AR without affecting the bulk of renal A2AR at the same time. C1 NIDDKD, NIH, Bethesda, MD 20892 USA. RP Schnermann, J (reprint author), NIDDKD, NIH, Bldg 10,Room 4D51,10 Ctr Dr,MSC 1370, Bethesda, MD 20892 USA. EM jurgens@intra.niddk.nih.gov RI Briggs, Josephine/B-9394-2009 OI Briggs, Josephine/0000-0003-0798-1190 FU Intramural NIH HHS NR 39 TC 37 Z9 37 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD DEC PY 2005 VL 315 IS 3 BP 1150 EP 1157 DI 10.1124/jpet.105.091017 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 984VZ UT WOS:000233335100022 PM 16120812 ER PT J AU Smith, CM Graham, RA Krol, WL Silver, IS Negishi, M Wang, HB Lecluyse, EL AF Smith, CM Graham, RA Krol, WL Silver, IS Negishi, M Wang, HB Lecluyse, EL TI Differential UGT1A1 induction by chrysin in primary human hepatocytes and HepG2 cells SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID UDP-GLUCURONOSYLTRANSFERASE UGT1A1; ARYL-HYDROCARBON RECEPTOR; DISTAL ENHANCER MODULE; RAT-LIVER MICROSOMES; FLAVONOID CHRYSIN; IN-VITRO; ESTROGEN SYNTHETASE; ANDROSTANE-RECEPTOR; GENE-EXPRESSION; CACO-2 CELLS AB Chrysin, a dietary flavonoid, has been shown to markedly induce UGT1A1 expression and activity in HepG2 and Caco-2 cell lines; thus, it has been suggested to have clinical utility in the treatment of UGT1A1-mediated deficiencies, such as unconjugated hyperbilirubinemia or the prevention of 7-ethyl-10hydroxycamptothecin (SN- 38) toxicity. However, little is known about its induction potential in a more physiologically relevant model system, such as primary hepatocyte culture. In this study, induction of UGT1A1 expression (mRNA, protein, and activity) was investigated in primary human hepatocyte cultures after treatment with chrysin and other prototypical inducers. Endogenous nuclear receptor-mediated UGT1A1 induction was studied using transient transfection reporter assays in primary human hepatocytes and HepG2 cells. Results indicated that induction of UGT1A1 expression was minimal in human hepatocytes treated with chrysin compared with that in HepG2 cells (1.2-versus 11-fold, respectively). Subsequent experiments to determine whether the differential response was due to its metabolic stability revealed strikingly different elimination rate constants between the two cell systems (half-life of 13 min in human hepatocytes versus 122 min in HepG2 cell suspensions). Further study demonstrated that UGT1A1 mRNA expression could be induced in human hepatocyte cultures by either increasing the chrysin dosing frequency or by modulating chrysin metabolism, suggesting that the differential induction observed in hepatocytes and HepG2 cells was due to differences in the metabolic clearance of chrysin. In conclusion, this study suggests that the metabolic stability of chrysin likely would limit its ability to induce UGT1A1 in vivo. C1 Univ N Carolina, Div Drug Delivery & Disposit, Sch Pharm, Chapel Hill, NC 27599 USA. GlaxoSmithKline Inc, Res Triangle Pk, NC USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Wang, HB (reprint author), Univ N Carolina, Div Drug Delivery & Disposit, Sch Pharm, CB 7360,Kerr Hall,Room 2319, Chapel Hill, NC 27599 USA. EM hongbing_wang@unc.edu OI LeCluyse, Edward/0000-0002-2149-8990 FU NIDDK NIH HHS [DK061652] NR 40 TC 26 Z9 27 U1 0 U2 8 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD DEC PY 2005 VL 315 IS 3 BP 1256 EP 1264 DI 10.1124/jpet.105.090795 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 984VZ UT WOS:000233335100035 PM 16135700 ER PT J AU Bourdet, DL Pritchard, JB Thakker, DR AF Bourdet, DL Pritchard, JB Thakker, DR TI Differential substrate and inhibitory activities of ranitidine and famotidine toward human organic cation transporter 1 (hOCT1; SLC22A1), hOCT2 (SLC22A2), and hOCT3 (SLC22A3) SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID CACO-2 CELL MONOLAYERS; N-TETRAALKYLAMMONIUM COMPOUNDS; SINGLE-DOSE PHARMACOKINETICS; FUNCTIONAL-CHARACTERIZATION; H-2-RECEPTOR ANTAGONISTS; H2-RECEPTOR ANTAGONISTS; ANION TRANSPORTER-3; DRUG-INTERACTIONS; ION TRANSPORTERS; RENAL CLEARANCE AB Human organic cation transporters (hOCTs) are expressed in organs of drug absorption and elimination and play an important role in the uptake and elimination of xenobiotics. The purpose of this study was to evaluate the substrate and inhibitory activity of the H-2-receptor antagonists ranitidine and famotidine toward hOCTs and to determine the hOCT isoforms involved in the absorption and elimination of these compounds in humans. Inhibition and substrate specificity of hOCT1, hOCT2, and hOCT3 for ranitidine and famotidine were elucidated in cRNA-injected Xenopus laevis oocytes. Ranitidine and famotidine exhibited similarly potent inhibition of [H-3]1-methyl-4- phenyl pyridinium uptake into hOCT1-expressing (IC50 = 33 and 28 mu M, respectively) and hOCT2-expressing oocytes (IC50 = 76 and 114 mu M, respectively). Famotidine exhibited potent inhibition of hOCT3; in contrast, ranitidine was a moderately weak inhibitor (IC50 = 6.7 and 290 mu M, respectively). [H-3] Ranitidine uptake was stimulated by hOCT1 (K-m = 70 +/- 9 mu M) and to a much smaller extent by hOCT2. No stimulation of [H-3] ranitidine uptake was observed in hOCT3-expressing oocytes. trans-Stimulation and electrophysiology studies suggested that famotidine also is an hOCT1 substrate and exhibits poor or no substrate activity toward hOCT2 and hOCT3. Thus, hOCT1, which is expressed in the intestine and liver, is likely to play a major role in the intestinal absorption and hepatic disposition of ranitidine and famotidine in humans, whereas hOCT2, the major isoform present in the kidney, may play only a minor role in their renal elimination. Famotidine seems to be one of the most potent inhibitors of hOCT3 yet identified. C1 Univ N Carolina, Div Drug Delivery & Disposit, Sch Pharm, Chapel Hill, NC 27599 USA. Natl Inst Hlth, Lab Pharmacol & Chem, Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Thakker, DR (reprint author), Univ N Carolina, Div Drug Delivery & Disposit, Sch Pharm, Kerr Hall,CB 7360, Chapel Hill, NC 27599 USA. EM dhiren_thakker@unc.edu NR 38 TC 54 Z9 58 U1 0 U2 4 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD DEC PY 2005 VL 315 IS 3 BP 1288 EP 1297 DI 10.1124/jpet.105.091223 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 984VZ UT WOS:000233335100038 PM 16141367 ER PT J AU Martinez, ED Rayasam, GV Dull, AB Walker, DA Hager, GL AF Martinez, ED Rayasam, GV Dull, AB Walker, DA Hager, GL TI An estrogen receptor chimera senses ligands by nuclear translocation SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article DE chimera; nuclear translocation; estrogen; glucocorticoid; drug discovery; cell-based assay; high content screen; mobility ID RAT GLUCOCORTICOID-RECEPTORS; GREEN FLUORESCENT PROTEIN; BINDING DOMAIN REVEALS; TUMOR VIRUS PROMOTER; BREAST-CANCER CELLS; HEAT-SHOCK-PROTEIN; LIVING CELLS; PROGESTERONE-RECEPTOR; TRANSCRIPTIONAL ACTIVATION; ENVIRONMENTAL CHEMICALS AB We have developed anew mammalian cell-based assay to screen for ligands of the estrogen receptor. A fluorescently tagged chimera between the glucocorticoid and the estrogen receptors, unlike the constitutively nuclear estrogen receptor, is cytoplasmic in the absence of hormone and translocates to the nucleus in response to estradiol. The chimera maintains specificity for estrogen receptor a ligands and does not show cross-reactivity with other steroids, providing a clean system for drug discovery. Natural and synthetic estrogen receptor a agonists as well as phytoestrogens effectively translocate the receptor to the nucleus in a dose-dependent manner. Antagonists of the estrogen receptor can also transmit the structural signals that result in receptor nuclear translocation. The potency and efficacy of high-affinity ligands can be evaluated in our system by measuring the nuclear translocation of the fluorescently labeled receptor in response to increasing ligand concentrations. The chimera is transcriptionally competent on transient and replicating templates, and is inhibited by estrogen receptor antagonists. Interestingly, the nucleoplasmic mobility of the chimera, determined by FRAP analysis, is faster than that of the wild type estrogen receptor, and the chimera is resistant to ICI immobilization. The translocation properties of this chimera can be utilized in high content screens for novel estrogen receptor modulators. (c) 2005 Elsevier Ltd. All rights reserved. C1 NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. NCI, Basic Res Program, SAIC Frederick Inc, Mol Targets Dev Program, Frederick, MD 21701 USA. RP Hager, GL (reprint author), NCI, Lab Receptor Biol & Gene Express, NIH, Bldg 41,Room B602, Bethesda, MD 20892 USA. EM hagerg@exchange.nih.gov FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 57 TC 17 Z9 18 U1 1 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 2005 VL 97 IS 4 BP 307 EP 321 DI 10.1016/j.jsbmb.2005.06.03 PG 15 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 992AE UT WOS:000233855300001 PM 16162406 ER PT J AU Mooney, MM AF Mooney, MM TI Neoadjuvant and adjuvant chemotherapy for esophageal adenocarcinoma SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Article DE chemotherapy; adjuvant; neoadjuvant therapy; chemoradiation; esophageal cancer ID PREOPERATIVE CHEMOTHERAPY; RADIATION-THERAPY; CANCER; SURGERY; TRIAL; CHEMORADIOTHERAPY; CARCINOMA; CISPLATIN; SURVIVAL; JUNCTION AB The poor outcome associated with surgical resection alone for most patients with locoregional esophageal cancer has generated intensive investigation of combined-modality treatment approaches that include systemic chemotherapy. This review discusses the current role of chemotherapy in the treatment of patients with adenocarcinoma of the esophagus, given in either the pre-operative (neoadjuvant) or post-operative (adjuvant) setting compared to surgery alone, highlighting the results of large, randomized clinical trials that included patients with adenocarcinoma of the esophagus as well as some of the approaches being evaluated with novel therapies in earlier phase clinical trials. Although no definitive recommendations for pre-operative or post-operative treatment can be made for patients with adenocarcinoma of the esophagus based on Outcomes reported in randomized clinical trials performed to date, the results from these trials Suggest chemotherapy or chemoradiation in the perioperative period may have benefit, especially in certain sub-groups. Newer, more effective agents are needed is well as methods to identify which tumors will respond to therapy. Improvement in Outcomes for patients with this disease will require rigorous evaluation of newer multi-modality regimens in well-designed and appropriately powered clinical trials. C1 NCI, Clin Invest Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Mooney, MM (reprint author), NCI, Clin Invest Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, 6130 Execut Blvd,Room 7025,MSC 7436, Bethesda, MD 20892 USA. EM mooneym@ctep.nci.nih.gov NR 35 TC 15 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 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD DEC 1 PY 2005 VL 92 IS 3 BP 230 EP 238 DI 10.1002/jso.20364 PG 9 WC Oncology; Surgery SC Oncology; Surgery GA 989ON UT WOS:000233683500009 PM 16299790 ER PT J AU Schrump, DS Nguyen, DM AF Schrump, DS Nguyen, DM TI Novel molecular targeted therapy for esophageal cancer SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Article DE esophageal cancer; 5 aza 2 ' deoxycytidine; depsipeptide FK228; epigenetics; mitogen activated protein kinase; clinical trial; DNA demethylating agents; HDAC inhibitors ID SQUAMOUS-CELL CARCINOMA; DEPSIPEPTIDE-MEDIATED APOPTOSIS; CPG ISLAND HYPERMETHYLATION; PROMOTER HYPERMETHYLATION; DNA METHYLTRANSFERASES; BARRETTS-ESOPHAGUS; SIGNALING PATHWAY; GENE-EXPRESSION; IN-VITRO; LUNG AB Esophageal cancers are highly lethal neoplasms which are generally refractory to conventional multidisciplinary interventions. Recent elucidation of the mechanisms of esophageal carcinogenesis, as well as preclinical studies utilizing chromatin remodeling agents and inhibitors of oncogene signaling in conjuntction with conventional chemotherapeutic agents provide new opportunities for the development of potentially efficacious molecular targeted therapies for these malignancies. C1 NCI, Thorac Oncol Sect, Surg Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Schrump, DS (reprint author), NCI, Thorac Oncol Sect, Surg Branch, Ctr Canc Res, Bldg 10,Rm 4-3490,10 Ctr Dr MSC 1201, Bethesda, MD 20892 USA. EM David_Schrump@nih.gov NR 43 TC 15 Z9 16 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 2005 VL 92 IS 3 BP 257 EP 261 DI 10.1002/jso.20367 PG 5 WC Oncology; Surgery SC Oncology; Surgery GA 989ON UT WOS:000233683500012 PM 16299785 ER PT J AU Pimpinelli, N Olsen, EA Santucci, M Vonderheid, E Haeffner, AC Stevens, S Burg, G Cerroni, L Dreno, B Glusac, E Guitart, M Heald, PW Kempf, W Knobler, R Lessin, S Sander, C Smoller, BS Telang, G Whittaker, S Iwatsuki, K Obitz, E Takigawa, M Turner, ML Wood, GS AF Pimpinelli, N Olsen, EA Santucci, M Vonderheid, E Haeffner, AC Stevens, S Burg, G Cerroni, L Dreno, B Glusac, E Guitart, M Heald, PW Kempf, W Knobler, R Lessin, S Sander, C Smoller, BS Telang, G Whittaker, S Iwatsuki, K Obitz, E Takigawa, M Turner, ML Wood, GS CA Int Soc Cutaneous Lymphoma TI Defining early mycosis fungoides SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID T-CELL LYMPHOMA; POLYMERASE-CHAIN-REACTION; GRADIENT GEL-ELECTROPHORESIS; SMALL PLAQUE PARAPSORIASIS; RECEPTOR-GAMMA-GENE; SEZARY-SYNDROME; ANTIGEN-EXPRESSION; EN-PLAQUES; PERIPHERAL-BLOOD; PARA-PSORIASIS AB This editorial review summarizes the results of 5 meetings sponsored by the International Society for Cutaneous Lymphonia at which the clinicopathologic and ancillary features of early mycosis fungoides were critically examined. Based Oil this analysis an algorithm was developed for the diagnosis of early mycosis fungoides involving a holistic integration of clinical, histopathologic, immunopathologic, and molecular biological characteristics. A novel aspect of this algorithm is that it relies on multiple types of criteria rather than just one, for example, histopathology. Before its finalization, the proposed diagnostic algorithm will require validation and possibly further refinement at multiple centres during the next several years. It is anticipated that a more standardized approach to the diagnosis of: early mycosis fungoides will have a beneficial impact on the epidemiology, prognostication, treatment and analysis of clinical trials pertaining to this most common type of cutaneous lymphoma. C1 Univ Wisconsin, Dept Dermatol, Madison, WI 53715 USA. Okayama Univ, Okayama, Japan. Univ Aarhus, Dept Dermatol, Aarhus, Denmark. Hamamatsu Univ Sch Med, Dept Dermatol, Hamamatsu, Shizuoka 43131, Japan. Natl Canc Inst, Dermatol Branch, Bethesda, MD USA. Vet Affairs Med Ctr, Madison, WI USA. RP Wood, GS (reprint author), Univ Wisconsin, Dept Dermatol, 1 S Pk,7th Floor, Madison, WI 53715 USA. EM gwood@dermatology.wisc.edu FU NIAMS NIH HHS [AR-02136] NR 95 TC 174 Z9 186 U1 0 U2 9 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD DEC PY 2005 VL 53 IS 6 BP 1053 EP 1063 DI 10.1016/j.jaad.2005.08.057 PG 11 WC Dermatology SC Dermatology GA 990PQ UT WOS:000233756100016 PM 16310068 ER PT J AU Gordon, SM Dionne, RA AF Gordon, SM Dionne, RA TI The integration of clinical research into dental therapeutics - Making treatment decisions SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article DE evidence-based practice; clinical decision making; clinical research; dental therapeutics ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; JAW MUSCLE PAIN; GASTROINTESTINAL TOXICITY; PLASMA-CATECHOLAMINE; RHEUMATOID-ARTHRITIS; EPINEPHRINE; VASOCONSTRICTORS; RESPONSES AB Background. Clinicians make informed theraoeutic decisions in part by assimilating evidence that forms the basis for generally accepted clinical knowledge. Similar to professional training for the practice of dentistry, this requires knowledge of the quality of the evidence and its translation to clinical practice. Description. Evidence-based treatment decisions rely on the ability to understand the differences between clinical practice and clinical research, to critically evaluate the quality of evidence that supports a generally accepted clinical practice, understanding what contributes to the perception of clinical success, and how to select the most appropriate therapy for use in clinical practice. Clinical Implications. Therapeutic decision making is highly dependent on the quality of evidence that is considered when making a judgement and applying it to patient care. Criteria for evaluating clinical research and the findings evolve over time, necessitating periodic review of the foundations on which therapeutic decisions are based. C1 Univ Maryland, Sch Dent, Dept Biomed Sci, Baltimore, MD 21201 USA. NINR, NIH, Bethesda, MD 20892 USA. RP Gordon, SM (reprint author), Univ Maryland, Sch Dent, Dept Biomed Sci, 666 W Baltimore St,Room 4-A-22, Baltimore, MD 21201 USA. EM sgordon@dental.umaryland.edu NR 35 TC 4 Z9 4 U1 1 U2 2 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD DEC PY 2005 VL 136 IS 12 BP 1701 EP 1708 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 994AC UT WOS:000234001000016 PM 16383053 ER PT J AU Penninx, BWJH Pluijm, SMF Lips, P Woodman, R Miedema, K Guralnik, JM Deeg, DJH AF Penninx, BWJH Pluijm, SMF Lips, P Woodman, R Miedema, K Guralnik, JM Deeg, DJH TI Late-life anemia is associated with increased risk of recurrent falls SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE anemia; falls; physical function; muscle strength; longitudinal study ID DWELLING OLDER PERSONS; MUSCLE STRENGTH; PHYSICAL PERFORMANCE; HEMOGLOBIN LEVELS; SKELETAL-MUSCLE; COMMUNITY; DECLINE; WOMEN; ERYTHROPOIETIN; INTERLEUKIN-6 AB OBJECTIVES: To examine whether anemia is associated with a higher incidence of recurrent falls. DESIGN: Prospective cohort study. SETTING: Community-dwelling sample in the Netherlands. PARTICIPANTS: Three hundred ninety-four participants aged 65 to 88 from the Longitudinal Aging Study Amsterdam. MEASUREMENTS: Anemia was defined according to World Health Organization criteria as a hemoglobin concentration less than 12 g/dL in women and less than 13 g/dL in men. Falls were prospectively determined using fall calendars that participants filled out weekly for 3 years. Recurrent fallers were identified as those who fell at least two times within 6 months during the 3-year follow-up. RESULTS: Of the 394 persons, 11.9% (18 women and 29 men) had anemia. The incidence of recurrent falls was 38.3% of anemic persons versus 19.6% of nonanemic persons (P = .004). After adjustment for sex, age, body mass index, and diseases, anemia was significantly associated with a 1.91 times greater risk for recurrent falls (95% confidence interval = 1.09-3.36). Poor physical function (indicated by muscle strength, physical performance, and limitations) partly mediated the association between anemia and incidence of recurrent falls. CONCLUSION: Late-life anemia is common and associated with twice the risk of recurrent falls. Muscle weakness and poor physical performance appear to partly mediate this association. C1 Vrije Univ Amsterdam, EMGO Inst, Med Ctr, Dept Psychiat, NL-1075 BG Amsterdam, Netherlands. Vrije Univ Amsterdam, Ctr Med, Inst Res Extramural Med, NL-1075 BG Amsterdam, Netherlands. Ortho Biotech, Clin Affairs LLC, Ridgewater, NJ USA. Isala Kliniken, Zwolle, Netherlands. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Penninx, BWJH (reprint author), Vrije Univ Amsterdam, EMGO Inst, Med Ctr, Dept Psychiat, Valeriuspl 9, NL-1075 BG Amsterdam, Netherlands. EM brendap@ggzba.nl NR 27 TC 71 Z9 75 U1 0 U2 0 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 2005 VL 53 IS 12 BP 2106 EP 2111 DI 10.1111/j.1532-5415.2005.00491.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 987PL UT WOS:000233529700008 PM 16398894 ER PT J AU Helzner, EP Cauley, JA Pratt, SR Wisniewski, SR Zmuda, JM Talbott, EO de Rekeneire, N Harris, TB Rubin, SM Simonsick, EM Tylavsky, FA Newman, AB AF Helzner, EP Cauley, JA Pratt, SR Wisniewski, SR Zmuda, JM Talbott, EO de Rekeneire, N Harris, TB Rubin, SM Simonsick, EM Tylavsky, FA Newman, AB TI Race and sex differences in age-related hearing loss: The Health, Aging and Body Composition Study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE hearing loss; presbycusis; epidemiology; risk factors; race; sex ID PURE-TONE THRESHOLDS; CIGARETTE-SMOKING; COCHLEAR CAPSULE; MINERAL DENSITY; RISK-FACTORS; NOISE; PREVALENCE; DISEASE; PRESBYACUSIS; EPIDEMIOLOGY AB OBJECTIVES: To determine the prevalence of and risk factors for hearing loss in a sample of 2,052 older adults (aged 73-84; 46.9% male, 37.3% black) enrolled in the Health, Aging and Body Composition (Health ABC) Study. DESIGN: Cross-sectional analysis of a longitudinal cohort study. SETTING: Pittsburgh, Pennsylvania, and Memphis, Tennessee, areas. PARTICIPANTS: Random sample of Medicare beneficiary subjects enrolled in the Health ABC program from 1997 to 1998. They included 2,052 individuals: 660 white men (32.2%), 631 white women (30.8%), 310 black men (15.1%), and 451 black women (22.0%). Participants ranged in age from 73 to 84, with a mean age of 77.5. MEASUREMENTS: Hearing sensitivity was measured using pure-tone threshold testing. Hearing loss was defined based on two averages of hearing thresholds: 500, 1,000, and 2,000 Hz greater than 25-decibel (dB) hearing level (HL) (hearing loss); and 2,000, 4,000, and 8,000 Hz greater than 40-dB HL (high-frequency hearing loss). Potential hearing loss correlates, including demographics, medical history, ototoxic medication use, occupational noise exposure, and lifestyle factors, were collected via questionnaire. RESULTS: The prevalence of hearing loss was 59.9%; the prevalence of high-frequency hearing loss was 76.9%. Hearing loss was most common in white men, followed by white women, black men, and black women. Older age, white race, diabetes mellitus, cerebrovascular disease, smoking, poorer cognitive status, occupational noise exposure, and ear surgery were associated with hearing loss after multivariable adjustment. Race- and sex-specific risk factors included higher blood pressure and occupational noise exposure (white men), poorer cognitive status and smoking (black women), and low total hip bone mineral density (black men). Possible protective factors included salicylate use (overall sample, black men) and moderate alcohol intake (black women). CONCLUSION: Hearing loss was extremely common in this population. Because many of the identified hearing loss risk factors are modifiable, some of the burden associated with hearing loss in older people should be preventable. C1 Univ Pittsburgh, Dept Vet Affairs Pittsburgh Med Ctr, Dept Epidemiol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Vet Affairs Pittsburgh Med Ctr, Dept Commun Disorders & Sci, Pittsburgh, PA 15261 USA. NIA, Epidemiol Demog & Biometry Program, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NIA, Clin Res Branch, Baltimore, MD 21224 USA. Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. RP Helzner, EP (reprint author), Univ Pittsburgh, Dept Vet Affairs Pittsburgh Med Ctr, Dept Epidemiol, Crabtree Hall,130 DeSoto St, Pittsburgh, PA 15261 USA. EM ehelzner@pitt.edu RI Pratt, Sheila/H-7139-2013; Newman, Anne/C-6408-2013; Cauley, Jane/N-4836-2015; OI Newman, Anne/0000-0002-0106-1150; Cauley, Jane/0000-0003-0752-4408; Wisniewski, Stephen/0000-0002-3877-9860; Talbott, Evelyn/0000-0002-5198-7939 FU NIA NIH HHS [N01-AG-6-2102, N01-AG-6-2103, N01-AG-6-2106] NR 48 TC 90 Z9 95 U1 0 U2 21 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 2005 VL 53 IS 12 BP 2119 EP 2127 DI 10.1111/j.1532-5415.2005.00525.x PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 987PL UT WOS:000233529700010 PM 16398896 ER PT J AU Jackson, SN Wang, HYJ Woods, AS AF Jackson, SN Wang, HYJ Woods, AS TI In situ structural characterization of phosphatidylcholines in brain tissue using MALDI-MS/MS SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Article ID ASSISTED-LASER-DESORPTION/IONIZATION; TANDEM MASS-SPECTROMETRY; RAT-BRAIN; PHOSPHOLIPIDS; DESORPTION; TOF; PEPTIDES; LIPIDS AB Phosphatidylcholine (PC) is one of the most abundant classes of phospholipids and is a major component of membranes in biological systems. Recently, PCs have been detected by direct tissue analysis using MALDI-TOFMS. However, these studies did not allow for the structural characterization of PCs in tissue. In the current study, an in situ method for detection and structural analysis of PC species in brain tissue was developed using a MALDI-TOF/TOF mass spectrometer. Initial profiling of lipids in tissue is performed by MALDI-TOFMS, which allows for the assignment of PC species. However, to confirm the structure of the PC species detected in tissue, MALDI-MS/MS analysis was employed. In this work, protonated, sodiated, and potassiated PC species were detected in brain tissue using DHA matrix. MALDI-MS/MS analysis of these species yielded fragments that verified a phosphocholine head group, but did not supply any fragments that would permit the identification of acyl substituents. To obtain more structural information, lithium adducts of PC species were produced using DHA matrix dissolved in 100 mM lithium chloride. MALDI-MS/MS analysis of lithiated PC species produced fragments that allowed for the identification and positional assignment of acyl groups in PC species. C1 Natl Inst Drug Abuse Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Woods, AS (reprint author), Natl Inst Drug Abuse Intramural Res Program, NIH, Baltimore, MD 21224 USA. EM awoods@intra.nida.nih.gov FU Intramural NIH HHS NR 23 TC 122 Z9 126 U1 3 U2 30 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1044-0305 J9 J AM SOC MASS SPECTR JI J. Am. Soc. Mass Spectrom. PD DEC PY 2005 VL 16 IS 12 BP 2052 EP 2056 DI 10.1016/j.jasms.2005.08.014 PG 5 WC Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA 992KX UT WOS:000233883900016 PM 16253515 ER PT J AU Meyers, CM Geanacopoulos, M Holzman, LB Salant, DJ AF Meyers, CM Geanacopoulos, M Holzman, LB Salant, DJ TI Glomerular disease workshop SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID ANTINEUTROPHIL CYTOPLASMIC AUTOANTIBODIES; NEPHROTIC SYNDROME; GENE-EXPRESSION; SLIT DIAPHRAGM; AUTOANTIGEN COMPLEMENTARITY; RENAL-DISEASE; MRL/LPR MICE; VEGF-A; NEPHRIN; GLOMERULONEPHRITIS AB Recent observations regarding intrinsic glomerular cell biology, particularly in the podocyte, have provided exciting new insights into potential pathogenic mechanisms of human glomerular disease. Although both immune and nonimmune mechanisms of glomerular injury have been studied previously, experimental models of disease and recent techniques that provide tools for molecular profiling show great promise for identifying glomerular disease biomarkers. Despite these recent advances, additional work in both basic and clinical studies of glomerular disease is needed to advance the field. Standardization of animal models of distinct forms of glomerular disease would likely facilitate the search for biomarkers. Several factors limit current efforts to implement clinical trials of glomerular disease. Identification of disease biomarkers, development of disease-specific end points, and organization of collaborative clinical groups are critical for ultimately designing and implementing appropriately powered trials of glomerular disease. C1 NIDDK, Div Kidney Urol & Hematol Dis, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Michigan, Sch Med, Dept Internal Med, Div Nephrol, Ann Arbor, MI 48109 USA. Boston Univ, Med Ctr, Renal Sect, Evans Biomed Res Ctr, Boston, MA 02215 USA. RP Meyers, CM (reprint author), NIDDK, Div Kidney Urol & Hematol Dis, NIH, US Dept Hlth & Human Serv, 2 Democracy Pl,6707 Democracy Blvd,Suite 641, Bethesda, MD 20892 USA. EM cm420i@nih.gov OI Salant, David/0000-0002-3866-3120 NR 38 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD DEC PY 2005 VL 16 IS 12 BP 3472 EP 3476 DI 10.1681/ASN.2005090899 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 992ON UT WOS:000233893600005 PM 16267152 ER PT J AU Kessler, SP Hashimoto, S Senanayake, PS Gaughan, C Sen, GC Schnermann, J AF Kessler, SP Hashimoto, S Senanayake, PS Gaughan, C Sen, GC Schnermann, J TI Nephron function in transgenic mice with selective vascular or tubular expression of angiotensin-converting enzyme SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID ACE-DEFICIENT MICE; TUBULOGLOMERULAR FEEDBACK; BLOOD-PRESSURE; MALE-FERTILITY; RATS; TRANSPORT; ISOZYME; GENES AB Angiotensin-converting enzyme (ACE) null mice display aberrant renal pathology. Inadequate formation of angiotensin II (Ang II) results in hypotension, loss of fluid homeostasis, lack of urine concentration, and failure to regulate GFR through the tubuloglomerular feedback (TGF) mechanism. For examining the tissue-specific role of ACE in renal structure and regulation of renal filtrate formation, single-nephron GFR, proximal tubular fluid reabsorption, and TGF responsiveness were determined in mice that expressed ACE in only one tissue. Maximum TGF responses in mice that expressed somatic ACE (sACE) in proximal tubule cells (Gs strain) or germinal ACE in the serum (Pg strain) were reduced significantly compared with wild-type (WT) mice. In contrast, TGF responses in mice that expressed sACE in vascular endothelial cells (Ts strain) were not different from control. Single-nephron GFR was reduced in Ts compared with WT mice, but fractional reabsorption and therefore glomerulotubular balance were not distinguishable. BP responses to exogenous Ang I were diminished in Ts, Gs, and Pg mice, whereas those to Ang II were the same in the different strains. Plasma and renal tissue Ang I of all transgenic mouse strains was significantly higher than WT, whereas Ang II levels were generally lower; aldosterone levels were significantly lower than WT in Ts mice but not in the two other transgenic strains. Our results demonstrate that vascular expression of sACE can largely but not completely restore TGF regulation of GFR. Proximal fluid reabsorption in the chronic absence of proximal tubule ACE is normal. C1 Lerner Res Inst, Dept Mol Genet, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Dept Ophthalm Res, Cleveland, OH 44195 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Kessler, SP (reprint author), Lerner Res Inst, Dept Mol Genet, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM kessles@ccf.org FU Intramural NIH HHS; NHLBI NIH HHS [HL-48258] NR 28 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD DEC PY 2005 VL 16 IS 12 BP 3535 EP 3542 DI 10.1681/ASN.2005020151 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 992ON UT WOS:000233893600013 PM 16221869 ER PT J AU Wang, LM Fields, TA Pazmino, K Dai, QS Burchette, JL Howell, DN Coffman, TM Spurney, RF AF Wang, LM Fields, TA Pazmino, K Dai, QS Burchette, JL Howell, DN Coffman, TM Spurney, RF TI Activation of G alpha q-coupled signaling pathways in glomerular podocytes promotes renal injury SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID FOCAL SEGMENTAL GLOMERULOSCLEROSIS; CONGENITAL NEPHROTIC SYNDROME; ANGIOTENSIN-II; CARDIAC-HYPERTROPHY; CD2-ASSOCIATED PROTEIN; THROMBOXANE RECEPTORS; DIABETIC-NEPHROPATHY; IN-VIVO; MICE; NEPHRIN AB The glomerular podocyte plays a key role in maintaining the integrity of the glomerular filtration barrier. This function may be regulated by activation of cell surface G protein-coupled receptors (GPCR). Studies suggest that podocytes express GPCR that are implicated in the pathogenesis of glomerular diseases. Common to these GPCR systems is activation of phospholipase C through the Gq alpha-subunit (G alpha q). For investigating the role of G alpha q-coupled signaling pathways in promoting renal injury in podocytes, a constitutively active G alpha q subunit (G alpha qQ > L) was expressed in glomerular podocytes using the mouse nephrin promoter. Transgenic (TG) mice demonstrated albuminuria as well as a decrease in both kidney mass and nephron number. By light microscopy, a portion of the TG mice had glomerular abnormalities, including focal to diffuse hypercellularity and segmental sclerosis. Consistent with injury-promoting effects of G alpha qQ > L, there was a significant reduction in podocalyxin mRNA as well as nephrin mRNA and protein levels in glomeruli from TG mice compared with non-TG controls. Expression of the transgene also seemed to increase susceptibility to glomerular injury, because treatment with puromycin aminonucleoside enhanced proteinuria in TG mice compared with non-TG littermate controls (4.2 +/- 1.0 [TG] versus 1.6 +/- 0.3 [non-TG] mg/24 h; P = 0.0161). Thus, activation of G alpha q in glomerular podocytes caused alterations in glomerular histomorphology, albuminuria, decreased nephron mass, and reduced glomerular expression of both nephrin and podocalyxin as well as enhanced susceptibility to glomerular damage induced by puromycin aminonucleoside. It is speculated that G alpha q-coupled signaling cascades may be important effector pathways mediating renal injury. C1 Duke Univ, Med Ctr, Div Nephrol, Dept Med, Durham, NC 27710 USA. Duke Univ, Dept Pathol, Durham, NC 27710 USA. Durham VA Med Ctr, Durham, NC USA. NIH, Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Spurney, RF (reprint author), Duke Univ, Med Ctr, Div Nephrol, Dept Med, Box 3014, Durham, NC 27710 USA. EM spurn002@mc.duke.edu FU NIDDK NIH HHS [R01-DK065956] NR 66 TC 27 Z9 29 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD DEC PY 2005 VL 16 IS 12 BP 3611 EP 3622 DI 10.1681/ASN.2005020167 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 992ON UT WOS:000233893600021 PM 16267159 ER PT J AU Seliger, SL Longstreth, WT Katz, R Manolio, T Fried, LF Shlipak, M Stehman-Breen, CO Newman, A Sarnak, M Gillen, DL Bleyer, A Siscovick, DS AF Seliger, SL Longstreth, WT Katz, R Manolio, T Fried, LF Shlipak, M Stehman-Breen, CO Newman, A Sarnak, M Gillen, DL Bleyer, A Siscovick, DS TI Cystatin C and subclinical brain infarction SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the American-Society-of-Nephrology CY OCT 27-NOV 01, 2004 CL St Louis, MO SP Amer Soc Nephrol ID STAGE RENAL-DISEASE; CARDIOVASCULAR-HEALTH; SERUM CREATININE; ELDERLY-PEOPLE; ROTTERDAM SCAN; OLDER-ADULTS; RISK; STROKE; ATHEROSCLEROSIS; INSUFFICIENCY AB Subclinical brain infarcts (SBI) are common in the elderly and are associated with covert neurologic and cognitive impairment. Although renal impairment is associated with accelerated cerebrovascular disease and an increased risk for clinically apparent brain infarct, few studies have examined the relationship between renal function and SBI, and these m ay have been limited by the inaccuracy of creatinine as a renal function marker. A cross-sectional study was performed among older adults in the Cardiovascular Health Study to examine associations between SBI and two serum markers of renal function: Serum creatinine (SCr) and cystatin C (CysC). Patients had cranial magnetic resonance imaging and renal markers measured in 1992 to 1993. Logistic regression was used to estimate the associations between renal function (estimated by 1/SCr and 1/CysC) and SBI, controlling for potential confounding factors. SBI were present in 789 (28.7%) of 2784 participants. A linear association with SBI was observed for 1/CysC (per 1-SD decrement; odds ratio [OR] 1.20; 95% confidence interval [CI] 1.09 to 1.32; P < 0.001) but not for 1/SCr (OR 1.08; 95% CI 0.98 to 1.19; P = 0.14), for which a quadratic U-shaped association was;suggested (P = 0.004). In a model with both markers, 1/CysC was linearly associated with SBI (OR 1.26; P < 0.001), whereas 1/SCr was not (OR 1.06; P = 0.3). The prevalence of SBI was directly associated with quintile of CysC, whereas the association 'between SCr and SBI was U-shaped, with greater prevalence at high and low levels. Compared with creatinine, CysC, a novel marker of renal function, has a stronger and more direct association with SBI in the elderly. C1 Univ Maryland, Div Nephrol, Baltimore, MD 21201 USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol & Med, Seattle, WA 98195 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Pittsburgh VA Med Ctr, Div Nephrol, Pittsburgh, PA USA. San Francisco VA Med Ctr, Div Gen Internal Med, San Francisco, CA USA. Amgen Inc, Thousand Oaks, CA 91320 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. Tufts Univ New England Med Ctr, Div Nephrol, Boston, MA 02111 USA. Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. Wake Forest Univ, Div Nephrol, Winston Salem, NC 27109 USA. RP Seliger, SL (reprint author), Univ Maryland, Div Nephrol, N3W143,22 S Greene St, Baltimore, MD 21201 USA. EM sseliger@medicine.umaryland.edu RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU NHLBI NIH HHS [N01-HC-15103, N01-HC-35129, N01-HC-85079, N01-HC-85086]; NIDDK NIH HHS [K23-DK063079] NR 31 TC 83 Z9 96 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD DEC PY 2005 VL 16 IS 12 BP 3721 EP 3727 DI 10.1681/ASN.2005010006 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 992ON UT WOS:000233893600033 PM 16236809 ER PT J AU Goncalves, LF Lee, W Espinoza, J Romero, R AF Goncalves, LF Lee, W Espinoza, J Romero, R TI Three- and 4-dimensional ultrasound in obstetric practice - Does it help? SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Review DE 4-dimensional ultrasound; pregnancy; 3-dimensional ultrasound; ultrasound ID FETAL LUNG-VOLUME; SPATIOTEMPORAL IMAGE CORRELATION; CONGENITAL DIAPHRAGMATIC-HERNIA; NUCHAL-TRANSLUCENCY THICKNESS; POWER DOPPLER ULTRASOUND; GESTATIONAL SAC VOLUME; INDIVIDUALIZED GROWTH ASSESSMENT; LETHAL PULMONARY HYPOPLASIA; PREDICTING BIRTH-WEIGHT; BLOOD-FLOW VELOCIMETRY AB Objective. The purpose of this article was to review the published literature on 3-dimensional ultrasound (3DUS) and 4-dimensional ultrasound (4DUS) in obstetrics and determine whether 3DUS adds diagnostic information to what is currently provided by 2-dimensional ultrasound (2DUS) and, if so, in what areas. Methods. A PubMed search was conducted for articles reporting on the use of 3DUS or 4DUS in obstetrics. Seven-hundred six articles were identified, and among those, 525 were actually related to the subject of this review. Articles describing technical developments, clinical studies, reviews, editorials, and studies on fetal behavior or maternal-fetal bonding were reviewed. Results. Three-dimensional ultrasound provides additional diagnostic information for the diagnosis of facial anomalies, especially facial clefts. There is also evidence that 3DUS provides additional diagnostic information in neural tube defects and skeletal malformations. Large studies comparing 2DUS and 3DUS for the diagnosis of congenital anomalies have not provided conclusive results. Preliminary evidence suggests that sonographic tomography may decrease the examination time of the obstetric ultrasound examination, with minimal impact on the visualization rates of anatomic structures. Conclusions. Three-dimensional ultrasound provides additional diagnostic information for the diagnosis of facial anomalies, evaluation of neural tube defects, and skeletal malformations. Additional research is needed to determine the clinical role of 3DUS and 4DUS for the diagnosis of congenital heart disease and central nervous system anomalies. Future studies should determine whether the information contained in the volume data set, by itself, is sufficient to evaluate fetal biometric measurements and diagnose congenital anomalies. C1 Wayne State Univ, NICHHD, Hutzel Womens Hosp, Perinatol Res Branch,Dept Hlth & Human Serv, Detroit, MI 48201 USA. Wayne State Univ, NICHHD, Dept Hlth & Human Serv, Perinatol Res Branch, Detroit, MI 48201 USA. Wayne State Univ, Hutzel Hosp, Dept Obstet & Gynecol, Detroit, MI 48201 USA. William Beaumont Hosp, Div Fetal Imaging, Royal Oak, MI 48072 USA. RP Romero, R (reprint author), Wayne State Univ, NICHHD, Hutzel Womens Hosp, Perinatol Res Branch,Dept Hlth & Human Serv, 3990 John R,Box 4, Detroit, MI 48201 USA. EM warfiela@mail.nih.gov NR 250 TC 55 Z9 58 U1 1 U2 5 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD DEC PY 2005 VL 24 IS 12 BP 1599 EP 1624 PG 26 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 994XM UT WOS:000234064500002 PM 16301717 ER PT J AU Brooks, JP Albert, PS Wilder, RB Gant, DA McLeod, DG Poggi, MM AF Brooks, JP Albert, PS Wilder, RB Gant, DA McLeod, DG Poggi, MM TI Long-term salvage radiotherapy outcome after radical prostatectomy and relapse predictors SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic neoplasms; radiation; prostatectomy; salvage therapy ID LYMPHOVASCULAR INVASION; CLINICAL FAILURES; RADIATION-THERAPY; CANCER; ANTIGEN; PSA; DISEASE; PROGRESSION; ELEVATION; ADJUVANT AB Purpose: We assessed the efficacy of salvage radiotherapy (SRT) and analyzed predictors of biochemical progression-free survival (bPFS) and distant metastasis-free survival in patients with clinically localized disease recurrence after radical prostatectomy. Materials and Methods: The records of 114 patients treated with SRT at 2 institutions between 1991 and 2001 were retrospectively reviewed. Time to biochemical recurrence and to distant metastases was analyzed using the Kaplan-Meier estimation. Candidate predictors of bPFS and distant metastasis-free survival were analyzed using the log rank test and Cox regression. Acute and late complications were scored using Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. Results: At a median followup of 6.3 years (range 1.9 to 13.3) for SRT 4 and 6-year bPFS was 50% (95% CI 42% to 61%) and 33% (95% CI 24% to 43%), respectively. The 6-year actuarial probability of distant metastases after SRT was 14%. Multivariate analysis demonstrated an independent association of increasing Gleason score, lymphovascular invasion and lack of a complete response to SRT with decreased 5-year bDFS. These factors were associated with significantly less 5-year distant metastasis-free survival. Pre-RT prostate specific antigen greater than 2.0 ng/ml was associated with significantly decreased 5-year bDFS and distant metastasis-free survival, although it was not maintained on multivariate analysis. Conclusions: SRT results in durable prostate specific antigen control in select patients. It is well tolerated with few severe late effects. Increasing Gleason score, lymphovascular invasion and lack of a complete response to SRT are significant risks for disease progression requiring additional management. C1 USN, Div Radiat Oncol, Natl Med Ctr, Bethesda, MD 20889 USA. Walter Reed Army Med Ctr, Dept Urol, Washington, DC 20307 USA. Walter Reed Army Med Ctr, Sect Radiat Oncol, Washington, DC 20307 USA. NCI, Biometr Res Branch, Bethesda, MD 20892 USA. RP Poggi, MM (reprint author), USN, Div Radiat Oncol, Natl Med Ctr, 8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM mmpoggi@bethesda.med.navy.mil NR 20 TC 23 Z9 24 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD DEC PY 2005 VL 174 IS 6 BP 2204 EP 2208 DI 10.1097/01.ju.0000181223.99576.ff PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 984HN UT WOS:000233293700033 PM 16280764 ER PT J AU Grubb, RL Behari, A Kim, CM Williams, CR Linehan, WM Coleman, JA AF Grubb, RL Behari, A Kim, CM Williams, CR Linehan, WM Coleman, JA TI Highlights from the Society of Urologic Oncology, 5th Annual Meeting, December 3-4, 2004, Bethesda, Maryland, United States of America SO JOURNAL OF UROLOGY LA English DT Article DE urologic neoplasms; prostatic neoplasms; kidney neoplasms; bladder neoplasms ID RENAL-CELL CANCER; BLADDER-CANCER; PROSTATE-CANCER; CARCINOMA; SUSCEPTIBILITY; PROGRESSION; MUTATIONS; FAMILIES; THERAPY; TRIAL AB Purpose: The fifth annual meeting of the Society of Urologic Oncology was held December 3 and 4, 2004 in Bethesda, Maryland. The program provides a forum for the discussion of important issues in genitourinary malignancies among urologists, radiation oncologists and medical oncologists. Materials and Methods: Agenda topics included kidney cancer, bladder cancer and prostate cancer. Several sessions featured new developments in basic, translational and clinical research. Each session was reviewed for content following the meeting and the highlights were summarized. The Young Urologic Oncologists' Forum was again a successful component of the meeting but it is beyond the scope of this summary. Results: Sessions on kidney cancer focused on molecular genetics and advances in molecular therapeutics. Radio frequency ablation of renal masses was also addressed. Topics discussed in bladder cancer included screening and surgical management. Dr. Donald Skinner received the Huggins Medal and he addressed the society on the management of invasive bladder cancer. Reviewed session topics in prostate cancer included neoadjuvant treatment paradigms, radiation treatment and adjuvant therapy in patients in whom primary treatment has failed. A state-of-the-art lecture addressed hereditary prostate cancer. Conclusions: The Society of Urologic Oncology meeting is unique in its multidisciplinary forum and focus on urological oncology. The meeting this year highlighted emerging trends, and the current state-of-the-art in kidney, bladder and prostate cancer. Additional focus was given to new molecular based diagnostic and therapeutic strategies for genitourinary malignancies. C1 NIH, Urol Oncol Branch, Ctr Canc Res, CRC, Bethesda, MD 20892 USA. RP Coleman, JA (reprint author), NIH, Urol Oncol Branch, Ctr Canc Res, CRC, Bldg 101,Room 2W-5940,MSC 1210,10 Ctr Dr, Bethesda, MD 20892 USA. EM colemanj@mail.nih.gov OI Coleman, Jonathan/0000-0002-6428-7835 NR 20 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD DEC PY 2005 VL 174 IS 6 BP 2330 EP 2333 DI 10.1097/01.ju.0000181828.95803.94 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 984HN UT WOS:000233293700062 PM 16280834 ER PT J AU Vedantham, S Rundback, JH Comerota, AJ Hunter, DW Meissner, MH Hofmann, LV Horne, M Gloviczki, P Andrews, RT Fan, CM Hume, KM Goldhaber, SK Tapson, VF Razavi, MK Min, RJ AF Vedantham, S Rundback, JH Comerota, AJ Hunter, DW Meissner, MH Hofmann, LV Horne, M Gloviczki, P Andrews, RT Fan, CM Hume, KM Goldhaber, SK Tapson, VF Razavi, MK Min, RJ TI Development of a research agenda for endovascular treatment of venous thromboembolism: Proceedings from a multidisciplinary consensus panel SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID DEEP-VEIN THROMBOSIS; CATHETER-DIRECTED THROMBOLYSIS; QUALITY-OF-LIFE; LOWER-EXTREMITY; STREPTOKINASE; THERAPY; HEPARIN; DISEASE; TRIAL C1 Washington Univ, Dept Radiol, Mallinckrodt Inst Radiol, Sch Med, St Louis, MO 63110 USA. Cornell Univ, Dept Vasc & Intervent Radiol, Columbia Presbyterian Med Ctr, New York, NY USA. Cornell Univ, Dept Radiol, Weill Med Coll, New York, NY USA. Univ Michigan, Jobst Vasc Ctr, Toledo, OH USA. Univ Minnesota, Dept Radiol, Minneapolis, MN 55455 USA. Mayo Clin, Coll Med, Div Vasc Surg, Rochester, MN USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. Univ Washington, Dept Vasc & Intervent Radiol, Seattle, WA 98195 USA. Johns Hopkins Univ Hosp, Div Intervent Radiol, Baltimore, MD 21287 USA. NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Dept Vasc Radiol, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. Soc Intervent Radiol Fdn, Fairfax, VA USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. St Joseph Vasc Inst, Orange, CA USA. RP Vedantham, S (reprint author), Washington Univ, Dept Radiol, Mallinckrodt Inst Radiol, Sch Med, 510 S Kingshighway Blvd, St Louis, MO 63110 USA. EM vedanthams@mir.wustl.edu NR 32 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD DEC PY 2005 VL 16 IS 12 BP 1567 EP 1573 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 997CE UT WOS:000234221800001 PM 16371519 ER PT J AU McDermott, MM Guralnik, JM Ferrucci, L Criqui, MH Greenland, P Tian, L Liu, K Tan, J AF McDermott, MM Guralnik, JM Ferrucci, L Criqui, MH Greenland, P Tian, L Liu, K Tan, J TI Functional decline in lower-extremity peripheral arterial disease: Associations with comorbidity, gender, and race SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID ANKLE BRACHIAL INDEX; LEG SYMPTOMS; CLINICAL CHARACTERISTICS; OCCLUSIVE DISEASE; PHYSICAL-ACTIVITY; LONGITUDINAL DATA; 6-MINUTE WALK; CLASSIFICATION; OSTEOARTHRITIS; CRITERIA AB Purpose. To identify comorbidities associated with increased rates of functional decline in persons with lower-extremity peripheral arterial disease (PAD). We also determined whether female sex and black race were associated with greater functional decline than male sex and white race, respectively, in PAD. Methods. Three-hundred ninety-seven men and women with PAD were followed prospectively for a median of 36 months. The presence of comorbid illnesses was determined with medical record review, patient report, medications, laboratory values, and a primary care physician questionnaire. Functional outcomes, measured annually, included the 6-minute walk, usual-paced and fast-paced 4-meter walking speed, and summary performance score. The summary performance score is a composite measure of lower-extremity functioning (score range, 0 to 12; 12 = best). Results: Adjusting for known and potential confounders, PAD patients with pulmonary disease had a significantly greater average annual decline in 6-minute walk performance of -34.02 ft/y (95% confidence interval [CI], -60.42 to -7.63; P = .012), rapid-paced 4-meter walk speed of -0.028 m/s/y (95% CI, -0.054 to -0.001; P = .042), and summary performance score of -0.460/y (95% CI, -0.762 to -0.157; P = .003) compared with those without pulmonary disease. PAD patients with spinal stenosis had a greater average annual decline in 6-minute walk performance of -77.4 ft/y (95% CI, -18.9 to -35.8; P < .001) and usual-paced 4-meter walking velocity of -0.045 m/s/y (95% CI, -0.081 to -0.009; P = .014) compared with participants without spinal stenosis. Conclusion: At 3-year follow-up, pulmonary disease and spinal stenosis were each associated with a significant decline in functioning among persons with PAD. In contrast, female sex and black race were not associated with functional decline among persons with PAD. C1 Northwestern Univ, Dept Med, Feinberg Sch Med, Evanston, IL 60208 USA. Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Evanston, IL 60208 USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. NIA, Lab Clin Epidemiol, Bethesda, MD 20892 USA. Univ Calif San Diego, Dept Family & Prevent Med, San Diego, CA 92103 USA. RP McDermott, MM (reprint author), 675 N St Clair,Ste 18-200, Chicago, IL 60611 USA. EM mdm608@northwestern.edu FU NCRR NIH HHS [RR-00048]; NHLBI NIH HHS [R01-HL64739, R01-HL58099] NR 27 TC 30 Z9 30 U1 3 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD DEC PY 2005 VL 42 IS 6 BP 1131 EP 1137 DI 10.1016/j.jvs.2005.08.010 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 993JB UT WOS:000233949300017 PM 16376203 ER PT J AU Cooney, JC Burgdorfer, W Painter, MK Russell, CL AF Cooney, Joseph C. Burgdorfer, Willy Painter, Martin K. Russell, Cynthia L. TI Tick infestations of the eastern cottontail rabbit (Sylvilagus floridanus) and small rodentia in northwest Alabama and implications for disease transmission SO JOURNAL OF VECTOR ECOLOGY LA English DT Article DE tick/host relationships; rodents; lagomorphs ID DERMACENTOR-VARIABILIS ACARI; MOUNTAIN SPOTTED-FEVER; IXODES-SCAPULARIS ACARI; TENNESSEE VALLEY REGION; BORRELIA-BURGDORFERI; AMBLYOMMA-AMERICANUM; RICKETTSIA-RICKETTSII; UNITED-STATES; SMALL MAMMALS; IXODIDAE AB Studies were conducted over a four-county area of northwest Alabama to determine the association of eastern cottontail rabbits with Dermacentor variabilis, the eastern United States vector of Rocky Mountain spotted fever. A secondary objective was to compare infestations of this tick on rabbits with infestations on commonly encountered rodent species as a means of determining the relative importance of each in the disease transmission cycle. These epidemiologic surveys were conducted in response to reported fatal cases of Rocky Mountain Spotted Fever in two counties of the study area. From 202 eastern cottontail rabbits, 3,956 ticks were collected. Of this total, 79.87% were Haemphysalis leporispalustris, 9.15% Amblyomma americanum, 8.22% Ixodes dentatus, and 2.76% D. variabilis. Only immature stages of D. variabilis were collected from cottontail rabbits. Ticks were collected on rabbits in all months except November, and only one specimen was taken in January. Based on the average number of ticks per host collected in each month, April was the peak month for D. variabilis and I. dentatus. High values for H. leporispalustris also occurred at this time, but even higher values occurred in October and December. The heaviest infestation of A. americanum occurred during the month of August and coincides with the activity period for the larvae of this species. Two hundred sixty-nine of the smaller Rodentia, comprising 13 species, yielded 264 ticks, all D. variabilis, and all but two were immature stages. Five rodent species, Microtus ochragaster Orozomys palustris, Peromyscus gossypinus, Peromyscus leucopus, and Sigmodon hispidus accounted for 95.83% of the ticks collected, and appeared to be preferred hosts for D. variabilis; all five had higher infestation levels per host than did the eastern cottontail rabbit. Data on host relationships in association with seasonal activity are presented. C1 NW Shoals Community Coll, Muscle Shoals, AL 35662 USA. NIAID, US Dept Hlth Educ & Welfare, Publ Hlth Serv, NIH,Epidemiol Branch,Rocky Mt Labs, Hamilton, MT 59840 USA. RP Cooney, JC (reprint author), NW Shoals Community Coll, POB 101 George Wallace Blvd, Muscle Shoals, AL 35662 USA. NR 36 TC 2 Z9 2 U1 3 U2 10 PU SOC VECTOR ECOLOGY PI SANTA ANA PA PO BOX 87, SANTA ANA, CA 92702 USA SN 1081-1710 J9 J VECTOR ECOL JI J. Vector Ecol. PD DEC PY 2005 VL 30 IS 2 BP 171 EP 180 PG 10 WC Entomology SC Entomology GA 082NH UT WOS:000240393100002 PM 16599149 ER PT J AU Uyama, R Hong, SH Nakagawa, T Yazawa, M Kadosawa, T Mochizuki, M Tsujimoto, H Nishimura, R Sasaki, N AF Uyama, R Hong, SH Nakagawa, T Yazawa, M Kadosawa, T Mochizuki, M Tsujimoto, H Nishimura, R Sasaki, N TI Establishment and characterization of eight feline mammary adenocarcinoma cell lines SO JOURNAL OF VETERINARY MEDICAL SCIENCE LA English DT Article DE feline; mammary tumor cell line; primary and metastatic lesion ID INTERMEDIATE FILAMENTS; CARCINOMA; TUMORS; BIOLOGY; CANCER AB Eight new feline mammary adenocarcinoma cell lines derived from either primary or metastatic lesions were established. The morphology of all the cell lines was epithelioid and round to spindle in shape, with cell growth occurring in a monolayer fashion. On immunohistochemistry, these cells reacted with anti-keratin and anti-vimentin antisera. The doubling time of these cells was between 19 and 54 hr. Tumor masses were developed in nude mice by subcutaneous inoculation of the cells that were histologically identical to their original mammary tumor lesions. Telomerase activities measured using the telomeric repeat amplification protocol assay revealed high telemetric activity in all of the cells. C1 Univ Tokyo, Grad Sch Agr & Life Sci, Lab Vet Surg, Bunkyo Ku, Tokyo 1138657, Japan. Univ Tokyo, Grad Sch Agr & Life Sci, Lab Vet Internal Med, Bunkyo Ku, Tokyo 1138657, Japan. Rakuno Gakuen Univ, Fac Vet Med, Lab Compan Anim Clin Med, Ebetsu, Hokkaido 0698501, Japan. Natl Canc Inst, Tumor & Metastasis Biol Sect, Pediat Oncol Branch, Canc Res Ctr,NIH, Rockville, MD 20850 USA. RP Sasaki, N (reprint author), Univ Tokyo, Grad Sch Agr & Life Sci, Lab Vet Surg, Bunkyo Ku, 1-1-1 Yayoi, Tokyo 1138657, Japan. NR 15 TC 11 Z9 11 U1 0 U2 0 PU JAPAN SOC VET SCI PI TOKYO PA UNIV TOKYO, 1-1-1 YAYOI, BUNKYO-KU, TOKYO, 103, JAPAN SN 0916-7250 J9 J VET MED SCI JI J. Vet. Med. Sci. PD DEC PY 2005 VL 67 IS 12 BP 1273 EP 1276 DI 10.1292/jvms.67.1273 PG 4 WC Veterinary Sciences SC Veterinary Sciences GA 002PH UT WOS:000234623000015 PM 16397390 ER PT J AU Resch, W Moss, B AF Resch, W Moss, B TI The conserved poxvirus l3 virion protein is required for transcription of vaccinia virus early genes SO JOURNAL OF VIROLOGY LA English DT Article ID RNA-POLYMERASE; VIRAL TRANSCRIPTION; IN-VITRO; CELLS; EXPRESSION; ENTRY; IDENTIFICATION; PURIFICATION; COMPONENT; ALIGNMENT AB We provide the initial characterization of the product of the vaccinia virus L3L open reading frame (VACWR090), which is conserved in all sequenced members of the poxvirus family. The predicted polypeptide contains no motifs or other features that provided a clue to the role of the L3 protein, and no functional information was available regarding a homolog discovered in Plasmodium falciparum. The U protein was expressed following viral DNA replication, a finding consistent with a putative late promoter sequence, and was packaged as a non-membrane protein in mature virus particles. A recombinant virus, in which the L3L gene was regulated by the Escherichia coli lac operator/repressor system, had a conditional lethal phenotype. The virus replicated in the presence of inducer, but in its absence, the yields of infectious virus were reduced by 99%. When cells were infected without inducer, however, no defect in gene expression or morphogenesis was noted. Virus particles lacking L3, which assembled in the absence of inducer, were indistinguishable from wild-type virions with regard to morphology, major structural proteins, and DNA content but were noninfectious. L3-deficient virions were able to bind and penetrate cells but produced extremely small amounts of viral early mRNA. A defect in transcription was demonstrated by in vitro studies with permeabilized virions, but soluble extracts of L3-deficient virions showed normal levels of template-dependent transcriptional activity, indicating that only transcription of the packaged genome is impaired. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, 4 Ctr Dr,MSC 0445, Bethesda, MD 20892 USA. EM bmoss@nih.gov FU Intramural NIH HHS NR 34 TC 10 Z9 11 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 2005 VL 79 IS 23 BP 14719 EP 14729 DI 10.1128/JVI.79.23.14719-14729.2005 PG 11 WC Virology SC Virology GA 984CE UT WOS:000233279300027 PM 16282472 ER PT J AU Atwood-Moore, A Ejebe, K Levin, HL AF Atwood-Moore, A Ejebe, K Levin, HL TI Specific recognition and cleavage of the plus-strand primer by reverse transcriptase SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; RNASE-H DOMAIN; POLYPURINE TRACT; IN-VIVO; VIRAL-DNA; SCHIZOSACCHAROMYCES-POMBE; RETROTRANSPOSON; INTEGRASE; MECHANISM; PROTEIN AB Reverse transcriptases (RTs) of retroviruses and long terminal repeat (LTR)-retrotransposons possess DNA polymerase and RNase H activities. During reverse transcription these activities are necessary for the programmed sequence of events that include template switching and primer processing. Integrase then inserts the completed cDNA into the genome of the host cell. The RT of the LTR-retrotransposon Tf1 was subjected to random mutagenesis, and the resulting transposons were screened with genetic assays to test which mutations reduced reverse transcription and which inhibited integration. We identified a cluster of mutations in the RNase H domain of RT that were surprising because they blocked integration without reducing cDNA levels. The results of immunoblots demonstrated that these mutations did not reduce levels of RT or integrase. DNA blots showed that the mutations did not lower the amounts of full-length cDNA. The sequences of the 3' ends of the cDNA revealed that mutations within the cluster in RNase H specifically reduced the removal of the polypurine tract (PPT) primer from the ends of the cDNA. These results indicate that primer removal is not a necessary component of reverse transcription. The residues mutated in Tf1 RNase H are conserved in human immunodeficiency virus type 1 and make direct contact with DNA opposite the PPT. Thus, our results identify a conserved element in RT that contacts the PPT and is specifically required for PPT removal. C1 NICHHD, Sect Eukaryot Transposable Elements, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP NICHHD, Sect Eukaryot Transposable Elements, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. EM henry_levin@nih.gov RI Ejebe, Kenechi/I-9238-2016 OI Ejebe, Kenechi/0000-0002-6090-8657 FU Intramural NIH HHS NR 35 TC 14 Z9 14 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD DEC PY 2005 VL 79 IS 23 BP 14863 EP 14875 DI 10.1128/JVI.79.23.14863-14875.2005 PG 13 WC Virology SC Virology GA 984CE UT WOS:000233279300041 PM 16282486 ER PT J AU Mao, HW Lafont, BAP Igarashi, T Nishimura, Y Brown, C Hirsch, V Buckler-White, A Sadjadpour, R Martin, MA AF Mao, HW Lafont, BAP Igarashi, T Nishimura, Y Brown, C Hirsch, V Buckler-White, A Sadjadpour, R Martin, MA TI CD8+ and CD20+ lymphocytes cooperate to control acute simian immunodeficiency virus/human immunodeficiency virus chimeric virus infections in rhesus monkeys: Modulation by major histocompatibility complex genotype SO JOURNAL OF VIROLOGY LA English DT Article ID T-CELL DEPLETION; NEUTRALIZING ANTIBODY-RESPONSES; HUMORAL IMMUNE-RESPONSES; HIV-1 INFECTION; DISEASE PROGRESSION; GENETIC RESTRICTION; CLINICAL-OUTCOMES; PASSIVE TRANSFER; MACAQUES; VIREMIA AB We have previously described two isogenic molecularly cloned simian immunodeficiency virus/human immunodeficiency virus chimeric viruses (SHIVs) that differ from one another by 9 amino acids and direct distinct clinical outcomes in inoculated rhesus monkeys. SHIVDH12R-Clone 7, like other highly pathogenic CXCR4-tropic SHIVs, induces rapid and complete depletions of CD4(+) T lymphocytes and immunodeficiency in infected animals. In contrast, macaques inoculated with SHIVDH12R-Clone 8 experience only partial and transient losses of CD4(+) T cells, show prompt control of their viremia, and remain healthy for periods of time extending for up to 4 years. The contributions of CD8(+) and CD20(+) lymphocytes in suppressing the replication of the attenuated SHIVDH12R-Clone 8 and maintaining a prolonged asymptomatic clinical course was assessed by treating animals with monoclonal antibodies that deplete each lymphocyte subset at the time of virus inoculation. The absence of either CD8(+) or CD20(+) cells during the SHIVDH12R-Clone 8 acute infection resulted in the rapid, complete, and irreversible loss of CD4(+) T cells; sustained high levels of postpeak plasma viremia; and symptomatic disease in Mamu-A*01-negative Indian rhesus monkeys. In Mamu-A*01-positive animals, however, the aggressive, highly pathogenic phenotype was observed only in macaques depleted of CD8(+) cells; SHIVDH12R-Clone 8 was effectively controlled in Mamu-A*01-positive monkeys in the absence of B lymphocytes. Taken together, these results indicate that both CD8(+) and CD20(+) B cells contribute to the control of primate lentiviral infection in Mamu-A*01-negative macaques. Furthermore, the major histocompatibility complex genotype of an infected animal, as exemplified by the Mamu-A*01 allele in this study, has the additional capacity to shift the balance of the composite immune response. C1 NIAID, NIH, Mol Microbiol Lab, Bethesda, MD 20892 USA. RP Martin, MA (reprint author), NIAID, NIH, Mol Microbiol Lab, Bldg 4,Room 315,4 Ctr Dr,MSC 0460, Bethesda, MD 20892 USA. EM malm@nih.gov RI Lafont, Bernard/B-7236-2014 FU Intramural NIH HHS NR 50 TC 25 Z9 27 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 2005 VL 79 IS 23 BP 14887 EP 14898 DI 10.1128/JVI.79.23.14887-14898.2005 PG 12 WC Virology SC Virology GA 984CE UT WOS:000233279300043 PM 16282488 ER PT J AU Pham, QN Biacchesi, S Skiadopoulos, MH Murphy, BR Collins, PL Buchholz, UJ AF Pham, QN Biacchesi, S Skiadopoulos, MH Murphy, BR Collins, PL Buchholz, UJ TI Chimeric recombinant human metapneumoviruses with the nucleoprotein or phosphoprotein open reading frame replaced by that of avian metapneumovirus exhibit improved growth in vitro and attenuation in vivo SO JOURNAL OF VIROLOGY LA English DT Article ID RESPIRATORY SYNCYTIAL VIRUS; VACCINE CANDIDATES; GLYCOPROTEIN GENE; TRACT DISEASE; HOST-RANGE; BOVINE; REPLICATION; PROTEIN; TYPE-3; CHILDREN AB Chimeric versions of recombinant human metapneumovirus (HMPV) were generated by replacing the nucleoprotein (N) or phosphoprotein (P) open reading frame with its counterpart from the closely related avian metapneumovirus (AMPV) subgroup C. In Vero cells, AMPV replicated to an approximately 100-fold-higher titer than HMPV. Surprisingly, the N and P chimeric viruses replicated to a peak titer that was 11- and 25-fold higher, respectively, than that of parental HMPV. The basis for this effect is not known but was not due to obvious changes in the efficiency of gene expression. AMPV and the N and P chimeras were evaluated for replication, immunogenicity, and protective efficacy in hamsters. AMPV was attenuated compared to HMPV in this mammalian host on day 5 postinfection, but not on day 3, and only in the nasal turbinates. In contrast, the N and P chimeras were reduced approximately 100-fold in both the upper and lower respiratory tract on day 3 postinfection, although there was little difference by day 5. The N and P chimeras induced a high level of neutralizing serum antibodies and protective efficacy against HMPV; AMPV was only weakly immunogenic and protective against HMPV challenge, reflecting antigenic differences. In African green monkeys immunized intranasally and intratracheally, the mean peak titer of the P chimera was reduced 100- and 1,000-fold in the upper and lower respiratory tracts, whereas the N chimera was reduced only 10-fold in the lower respiratory tract. Both chimeras were comparable to wild-type HMPV in immunogenicity and protective efficacy. Thus, the P chimera is a promising live HMPV vaccine candidate that paradoxically combines improved growth in vitro with attenuation in vivo. C1 NIAID, Infect Dis Lab, Bethesda, MD 20892 USA. RP Buchholz, UJ (reprint author), Bldg 50,Room 6505,50 S Dr,MSC 8007, Bethesda, MD 20892 USA. EM ubuchholz@niaid.nih.gov RI Biacchesi, Stephane/A-6924-2010 NR 36 TC 40 Z9 51 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 2005 VL 79 IS 24 BP 15114 EP 15122 DI 10.1128/JVI.79.24.15114-15122.2005 PG 9 WC Virology SC Virology GA 997VK UT WOS:000234276700013 PM 16306583 ER PT J AU Silvestri, LS Tortorici, AA Vasquez-Del Carpio, R Patton, JT AF Silvestri, LS Tortorici, AA Vasquez-Del Carpio, R Patton, JT TI Rotavirus glycoprotein NSP4 is a modulator of viral transcription in the infected cell SO JOURNAL OF VIROLOGY LA English DT Article ID NONSTRUCTURAL GLYCOPROTEIN-NS28; VIRUS-REPLICATION; SURFACE-PROTEINS; IN-VIVO; PARTICLES; LOCALIZATION; EXPRESSION; RECEPTOR; RNA; VIROPLASMS AB The outer shell of the rotavirus triple-layered virion is lost during cell entry, yielding a double-layered particle (DLP) that directs synthesis of viral plus-strand RNAs. The plus-strand RNAs act as templates for synthesis of the segmented double-stranded RNA (dsRNA) genome in viral inclusion bodies (viroplasms). The viral endoplasmic reticulum (ER)-resident glycoprotein NSP4 recruits progeny DLPs formed in viroplasms to the ER, where the particles are converted to triple-layered particles (TLPs) via budding. In this study, we have used short interfering RNAs to probe the role of NSP4 in the viral life cycle. Our analysis showed that knockdown of NSP4 expression had no marked effect on the expression of other viral proteins or on the replication of the dsRNA genome segments. However, NSP4 loss of function suppressed viroplasm maturation and caused a maldistribution of nonstructural and structural proteins that normally accumulate in viroplasms. NSP4 loss of function also inhibited formation of packaged virus particles, instead inducing the accumulation of empty particles. Most significant was the observation that NSP4 knockdown led to dramatically increased levels of viral transcription late in the infection cycle. These findings point to a multifaceted role for NSP4 in virus replication, including influencing the development of viroplasms, linking genome packaging with particle assembly, and acting as a modulator of viral transcription. By recruiting transcriptionally active or potentially active DLPs to the ER for conversion to quiescent TLPs, NSP4 acts as a feedback inhibitor down-regulating viral transcription when adequate levels of plus-strand RNAs are available to allow for productive infection. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Patton, JT (reprint author), NIAID, Infect Dis Lab, NIH, 50 South Dr,MSC 8026,Room 6314, Bethesda, MD 20892 USA. EM jpatton@niaid.nih.gov RI Patton, John/P-1390-2014 FU Intramural NIH HHS NR 28 TC 31 Z9 33 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 2005 VL 79 IS 24 BP 15165 EP 15174 DI 10.1128/JVI.79.24.15165-15174.2005 PG 10 WC Virology SC Virology GA 997VK UT WOS:000234276700018 PM 16306588 ER PT J AU Sims, AC Baric, RS Yount, B Burkett, SE Collins, PL Pickles, RJ AF Sims, AC Baric, RS Yount, B Burkett, SE Collins, PL Pickles, RJ TI Severe acute respiratory syndrome coronavirus infection of human ciliated airway epithelia: Role of ciliated cells in viral spread in the conducting airways of the lungs SO JOURNAL OF VIROLOGY LA English DT Article ID MOUSE HEPATITIS-VIRUS; TRANSMISSIBLE GASTROENTERITIS VIRUS; ANGIOTENSIN-CONVERTING ENZYME-2; SARS-ASSOCIATED CORONAVIRUS; GENOME SEQUENCE; FUNCTIONAL RECEPTOR; REVERSE GENETICS; IN-VITRO; DC-SIGN; PROTEIN AB Severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in 2002 as an important cause of severe lower respiratory tract infection in humans, and in vitro models of the lung are needed to elucidate cellular targets and the consequences of viral infection. The SARS-CoV receptor, human angiotensin I-converting enzyme 2 (hACE2), was detected in ciliated airway epithelial cells of human airway tissues derived from nasal or trachcobronchial regions, suggesting that SARS-CoV may infect the proximal airways. To assess infectivity in an in vitro model of human ciliated airway epithelia (HAE) derived from nasal and tracheobronchial airway regions, we generated recombinant SARS-CoV by deletion of open reading frame 7a/7b (ORF7a/ 7b) and insertion of the green fluorescent protein (GFP), resulting in SARS-CoV GFP. SARS-CoV GFP replicated to titers similar to those of wild-type viruses in cell lines. SARS-CoV specifically infected HAE via the apical surface and replicated to titers of 107 PFU/ml by 48 h postinfection. Polyclonal antisera directed against hACE2 blocked virus infection and replication, suggesting that hACE2 is the primary receptor for SARS-CoV infection of HAE. SARS-CoV structural proteins and virions localized to ciliated epithelial cells. Infection was highly cytolytic, as infected ciliated cells were necrotic and shed over time onto the luminal surface of the epithelium. SARS-CoV GFP also replicated to a lesser extent in ciliated cell cultures derived from hamster or rhesus monkey airways. Efficient SARS-CoV infection of ciliated cells in HAE provides a useful in vitro model of human lung origin to study characteristics of SARS-CoV replication and pathogenesis. C1 Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA. Univ N Carolina, Cyst Fibrosis Pulm Res & Treatment Ctr, Chapel Hill, NC 27599 USA. NIAID, Resp Viruses Sect, NIH, Bethesda, MD 20892 USA. RP Sims, AC (reprint author), Univ N Carolina, Dept Epidemiol, 2107 McGavran Greenberg Hall,CB 7435, Chapel Hill, NC 27599 USA. EM sims0018@email.unc.edu FU NIAID NIH HHS [AI059443, 5T32AI07151, AI059136, AI059443-01, P01 AI059443, R01 AI059136, T32 AI007151] NR 75 TC 86 Z9 90 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2005 VL 79 IS 24 BP 15511 EP 15524 DI 10.1128/JVI.79.24.15511-15524.2005 PG 14 WC Virology SC Virology GA 997VK UT WOS:000234276700052 PM 16306622 ER PT J AU Volpato, S Leveille, SG Blaum, C Fried, LP Guralnik, JM AF Volpato, S Leveille, SG Blaum, C Fried, LP Guralnik, JM TI Risk factors for falls in older disabled women with diabetes: The women's health and aging study SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID PERIPHERAL-NERVE DYSFUNCTION; LOWER-EXTREMITY DISABILITY; MINI-MENTAL-STATE; MUSCULOSKELETAL PAIN; ELDERLY PERSONS; US ADULTS; MELLITUS; FRACTURES; COMMUNITY; AGE AB Background. The aim of this Study was to determine whether older disabled women with diabetes have an increased risk of falls compared to women without diabetes and to identify fall risk factors among this high-risk subgroup of patients. Methods. Data are front the Women's Health and Aging Study I (n = 1002, age >= 65 years), a prospective, population-based cohort study of the one third most disabled women in the Baltimore (MD) urban community-dwelling population. Participants were followed semiannually for 3 years. Falls were ascertained at each interview. Diabetes was ascertained by means of a standardized algorithm using multiple sources of information. Results. Baseline prevalence of diabetes was 15.5%. Of the 878 women who participated in at least one follow-up visit and were able to walk at baseline, 64.9% fell at least once during the study and 29.6% experienced two or more falls during a follow-up interval. After adjustment for traditional risk factors, women with diabetes had a higher probability of any fall (odds ratio [OR] 1.38; 95% confidence interval [CI], 1.04-1.81) and of falling two or more times during a follow-up interval (OR 1.69; CI, 1.18-2.43), compared with women without diabetes. Among diabetic women, presence of widespread musculoskeletal pain (OR 5.58; CI, 1.89-16.5), insulin therapy (OR 2.02; CI, 1.10-3.71), overweight (OR 3.50: CI, 1.21-10.1), and poor lower-extremity performance (OR 7.76; CI, 1.03-58.8) were independently associated with increased likelihood of recurrent falls, after adjusting for major risk factors. There were synergistic effects of diabetes and lower-extremity pain and also diabetes and body mass index levels on the risk of failing (p for interactions <.05). Conclusion. Even among disabled older women diabetes is associated with an increased risk of falling, independent of established fall risk factors. In this specific group of older women, pain, high body mass index, and poor lower-extrentity performance are powerful predictors of falling. C1 Univ Ferrara, Dept Clin & Expt Med, Sect Internal Med Gerontol & Geriatr, I-44100 Ferrara, Italy. Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Univ Michigan, Dept Med, Ann Arbor, MI USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD USA. RP Volpato, S (reprint author), Univ Ferrara, Dept Clin & Expt Med, Sect Internal Med Gerontol & Geriatr, Via Savonarola 9, I-44100 Ferrara, Italy. EM vlt@unife.it RI VOLPATO, STEFANO/H-2977-2014 OI VOLPATO, STEFANO/0000-0003-4335-6034 FU NIA NIH HHS [P01 AG004390-21A10016, P01 AG004390] NR 43 TC 84 Z9 84 U1 0 U2 6 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD DEC PY 2005 VL 60 IS 12 BP 1539 EP 1545 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 005RK UT WOS:000234841300006 PM 16424285 ER PT J AU Chen, J Wildman, RP Gu, D Kusek, JW Spruill, M Reynolds, K Liu, D Hamm, LL Whelton, PK He, J AF Chen, J Wildman, RP Gu, D Kusek, JW Spruill, M Reynolds, K Liu, D Hamm, LL Whelton, PK He, J TI Prevalence of decreased kidney function in Chinese adults aged 35 to 74 years SO KIDNEY INTERNATIONAL LA English DT Article DE chronic kidney disease; prevalence; cross-sectional studies; China ID GLOMERULAR-FILTRATION-RATE; NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; RENAL-INSUFFICIENCY; CARDIOVASCULAR-DISEASE; SERUM CREATININE; PREDICTION EQUATION; POPULATION; CLEARANCE; AMERICANS AB Background. Chronic kidney disease (CKD) is a major public health burden in Western countries but little is known about its impact in developing countries. We estimated the prevalence and absolute burden of CKD in the general adult population in China. Methods. A cross-sectional survey was conducted in a nationally representative sample of 15,540 Chinese adults aged 35 to 74 years in 2000 and 2001. Serum creatinine was measured using the modified kinetic Jaffe reaction method at a central laboratory calibrated to the Cleveland Clinic Foundation laboratory. Glomerular filtration rate (GFR) was estimated using the simplified equation developed by the Modification of Diet in Renal Disease study. CKD was defined as an estimated GFR < 60 mL/min/1.73m(2). Results. Overall, the age-standardized prevalences of GFR 60 to 89, 30 to 59, and < 30 mL/min/1.73m(2) were 39.4%, 2.4%, and 0.14%, respectively, in Chinese adults aged 35 to 74 years. The overall prevalence of CKD (GFR < 60 mL/min/1.73m(2)) was 2.53%, representing 11,966,653 persons (1.31% or 3,185,330 men and 3.82% or 8,781,323 women). The age-specific prevalence of CKD was 0.71%, 1.69%, 3.91%, and 8.14% among persons 35 to 44, 45 to 54, 55 to 64, and 65 to 74 years old, respectively. The age-standardized prevalence of CKD was similar in urban (2.60%) and rural (2.52%) residents but was higher in south China (3.05%) than in north China (1.78%) residents. Conclusion. Although the prevalence of CKD in China was relatively low, the population absolute burden is substantial. These data warrant a national program aimed at detection, prevention, and treatment of CKD in China. C1 Tulane Univ, Sch Med, Dept Med, New Orleans, LA 70112 USA. Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA 70112 USA. Tulane Univ, Sch Publ Hlth & Trop Med, Dept Biostat, New Orleans, LA 70112 USA. Chinese Acad Med Sci, Cardiovasc Inst, Beijing 100037, Peoples R China. Chinese Acad Med Sci, Fuwai Hosp, Beijing 100037, Peoples R China. Peking Union Med Coll, Beijing, Peoples R China. NIDDKD, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA. RP Chen, J (reprint author), Tulane Univ, Sch Med, Dept Med, 1430 Tulane Ave,SL-45, New Orleans, LA 70112 USA. EM jchen@tulane.edu NR 33 TC 73 Z9 82 U1 5 U2 11 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD DEC PY 2005 VL 68 IS 6 BP 2837 EP 2845 DI 10.1111/j.1523-1755.2005.00757.x PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 983AU UT WOS:000233204300041 PM 16316361 ER PT J AU Simonsen, L Viboud, C Taylor, R AF Simonsen, L Viboud, C Taylor, R TI Influenza vaccination in elderly people SO LANCET LA English DT Letter C1 NIAID, NIH, Bethesda, MD 20892 USA. Fogarty Int Ctr, NIH, Bethesda, MD 20892 USA. RP Simonsen, L (reprint author), NIAID, NIH, Bethesda, MD 20892 USA. EM lsimonsen@niaid.nih.gov OI Simonsen, Lone/0000-0003-1535-8526 NR 5 TC 14 Z9 14 U1 0 U2 1 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD DEC-JAN PY 2005 VL 366 IS 9503 BP 2086 EP 2086 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 996AE UT WOS:000234146000021 PM 16360785 ER PT J AU Gal, TJ Huang, WY Chen, C Hayes, RB Schwartz, SM AF Gal, TJ Huang, WY Chen, C Hayes, RB Schwartz, SM TI DNA repair gene polymorphisms and risk of second primary neoplasms and mortality in oral cancer patients SO LARYNGOSCOPE LA English DT Article ID SQUAMOUS-CELL CARCINOMA; NECK-CANCER; LUNG-CANCER; FIELD CANCERIZATION; PROMOTER HYPERMETHYLATION; PRIMARY MALIGNANCIES; AERODIGESTIVE TRACT; EXCISION-REPAIR; HEAD; XRCC1 AB Objectives/Hypothesis: We tested the hypothesis that polymorphisms in genes involved in DNA repair pathways are associated with the development of second primary neoplasms of the upper aerodigestive tract (UADT), as well as mortality, in patients previously diagnosed with oral squamous cell cancer (OSCC). Methods: DNA specimens from 279 OSCC patients who had participated in two previous population-based case-control studies were assayed for the following polymorphisms: X-ray repair cross-complementing (XRCC) 1 Arg399Gln, XRCC3 Thr241Met, xeroderma pigmentosum complementing group D (XPD) Lys751Gln, and O-6-methylguanine-DNA methyltransferase (MGMT) Leu84Phe and Val143Ile. Baseline demographic information was obtained from personal interviews and tumor characteristics and treatment were obtained from cancer registry files. Cox proportional hazards models were used to calculate hazards ratio (HR) estimates for each polymorphism in relation to the risk of developing second primary neoplasms at any site, UADT, and head and neck. HRs were also determined for associations with all-cause mortality and oral cancer specific mortality. Results: A significant increased risk of second neoplasms (all sites combined, as well as for UADT sites and for head and neck squamous cell cancers) was observed among XRCC3 241Met allele homozygotes (HR 2.65-3.44, P<.02). No significant association with the development of second neoplasms was observed for the XRCC1 399Gln, XPD 751Gln, or MGMT 84Phe or 143Ile alleles. Although no associations with oral cancer-specific mortality were observed, we found a significant inverse association between all-cause mortality and possessing at least one copy of the XRCC1 399Gln allele (HR 0.68, 95% confidence interval [CI] 0.47-0.97, P=.03), as well as a suggestion of a direct association between all-cause mortality and having one copy of the XRCC3 241Met allele (HR 1.39, 95% CI 0.95-2.03, P=.09). Conclusions: Polymorphisms in the DNA repair enzyme gene XRCC3 241Met was associated with an increased risk of second neoplasms, and polymorphisms of the XRCC1 399Gln gene were associated with a decreased risk of all-cause mortality in patients with primary OSCC. These findings require confirmation in other populations before the clinical implications can be considered. C1 Univ Washington, Dept Otolaryngol Head & Neck Surg, Sch Med, Seattle, WA 98195 USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Washington, DC USA. Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, Washington, DC USA. NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. RP Univ Washington, Dept Otolaryngol Head & Neck Surg, Sch Med, Seattle, WA 98195 USA. EM thomas.gal@lackland.af.mil OI Hayes, Richard/0000-0002-0918-661X FU NCI NIH HHS [CN05230, R01CA48896]; NIDCR NIH HHS [R01 DE12609]; NIEHS NIH HHS [P30ES07033] NR 64 TC 40 Z9 40 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X EI 1531-4995 J9 LARYNGOSCOPE JI Laryngoscope PD DEC PY 2005 VL 115 IS 12 BP 2221 EP 2231 DI 10.1097/01.mlg.0000183736.96004.f7 PG 11 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 996SX UT WOS:000234196100024 PM 16369171 ER PT J AU Aurran-Schleinitz, T Telford, W Perfetto, S Caporaso, N Wilson, W Stetler-Stevenson, MA Zenger, VE Abbasi, F Marti, GE AF Aurran-Schleinitz, T Telford, W Perfetto, S Caporaso, N Wilson, W Stetler-Stevenson, MA Zenger, VE Abbasi, F Marti, GE TI Identification of a new monoclonal B-cell subset in unaffected first-degree relatives in familial chronic lymphocytic leukemia SO LEUKEMIA LA English DT Letter ID LAMBDA-LIGHT CHAIN; DELTA SWITCH; EXPRESS; BLOOD C1 US FDA, Div Cell & Gene Therapies, Off Cellular Tissues & Gene Therapy, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. Inst Paoli Calmettes, Marseille, France. NCI, Flow Cytometry Core Facil, ETIB, NIH, Bethesda, MD 20892 USA. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, Genet Epidemiol Branch, NIH, Bethesda, MD USA. NCI, MOCRU, CCR, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Marti, GE (reprint author), US FDA, Div Cell & Gene Therapies, Off Cellular Tissues & Gene Therapy, Ctr Biol Evaluat & Res, NIH Bldg 29B,Rm 2NN08,8800 Rockville Pike, Bethesda, MD 20014 USA. EM gemarti@helix.nih.gov NR 8 TC 7 Z9 7 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD DEC PY 2005 VL 19 IS 12 BP 2339 EP 2341 DI 10.1038/sj.leu.2403980 PG 3 WC Oncology; Hematology SC Oncology; Hematology GA 986PN UT WOS:000233462300042 PM 16208408 ER PT J AU Ruffin, AB Cogdill, K Kutty, L Hudson-Ochillo, M AF Ruffin, AB Cogdill, K Kutty, L Hudson-Ochillo, M TI Access to electronic health information for the public: Analysis of fifty-three funded projects SO LIBRARY TRENDS LA English DT Article ID OUTREACH; LIBRARIES; PARTNERSHIPS; MODEL AB IN 2000 THE NATIONAL LIBRARY OF MEDICINE (NLM), a component of the National Institutes of Health, funded fifty-three consumer health out-reach projects through the National Network of Libraries of Medicine (NN/LM). The goal of all projects was to improve access to electronic health information for consumers. Drawing on experience gained in the NN/LM public library pilot projects undertaken in 1998-1999, the projects involved medical and public libraries in partnership with a wide range of community organizations, including public health departments, schools, churches, and local professional associations. The projects provided training in the use of MedlinePlus and other health information resources and support for Internet access in a variety of settings. The projects used an array of approaches over an eighteen-month funding period. This article presents descriptive information about the projects, highlights common barriers, and provides an analysis of the effectiveness of methods and approaches used. C1 Natl Lib Med, NNLM, Natl Network Off, Lib Operat Div, Bethesda, MD 20894 USA. RP Ruffin, AB (reprint author), Natl Lib Med, NNLM, Natl Network Off, Lib Operat Div, 8600 Rockville Pike, Bethesda, MD 20894 USA. OI Cogdill, Keith/0000-0002-9863-1657 NR 25 TC 11 Z9 11 U1 1 U2 3 PU GSLIS PUBLICATIONS PI CHAMPAIGN PA 501 E DANIEL ST, CHAMPAIGN, IL 61820-6211 USA SN 0024-2594 J9 LIBR TRENDS JI Libr. Trends PD WIN PY 2005 VL 53 IS 3 BP 434 EP 452 PG 19 WC Information Science & Library Science SC Information Science & Library Science GA 909RV UT WOS:000227879300005 ER PT J AU Shen, J AF Shen, J TI In vivo carbon-13 magnetization transfer effect. Detection of aspartate aminotransferase reaction SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE saturation transfer; C-13 magnetic resonance spectroscopy; aspartate transaminase; brain ID GLUTAMATE; BRAIN; METABOLISM; ENZYMES; NMR; SPECTROSCOPY; COMPARTMENTATION; POLARIZATION; OXALOACETATE; MITOCHONDRIA AB One of the most remarkable achievements of in vivo NMR spectroscopy has been the detection of rapid enzyme-catalyzed exchange reactions using phosphorus-31 magnetic resonance spectroscopy-based magnetization transfer experiments. In this paper, we report, for the first time, the in vivo carbon magnetization transfer (CMT) effect and in vivo detection of the CMT effects of the alpha-ketoglutarate <-> glutamate and the oxaloacetate <-> aspartate reactions, both of which are catalyzed by aspartate aminotransferase. By saturating the carbonyl carbon of a-ketoglutarate at 206 ppm in alpha-chloralose anesthetized adult rat brain, the unidirectional glutamate a-ketoglutarate flux was determined to be 78 +/- 9 mu mol/g/min (mean SD, n = 11) following i.v. infusion of [1,6-C-13(2)]D-glucose. Contribution from aspartate aminotransferase-catalyzed partial reactions to the observed CMT effects was emphasized. Because of the large chemical shift separation between the a-carbons of the amino acids and the carbonyl carbons of the corresponding cognate keto acids, the spillover of the saturation radiofrequency pulses to the alpha-carbon resonances was negligible. The results indicate that the magnetization transfer effects of aspartate aminotransferase-catalyzed reactions can be used as new biomarkers accessible to non-invasive in vivo magnetic resonance spectroscopy techniques. Magn Reson Med 54:1321-1326, 2005. Published 2005 Wiley-Liss, Inc.dagger C1 NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. RP Shen, J (reprint author), NIMH, Mol Imaging Branch, Bldg 10,Room 2D51A,9000 Rockville Pike, Bethesda, MD 20892 USA. EM shenj@intra.nimh.nih.gov FU Intramural NIH HHS NR 30 TC 17 Z9 17 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD DEC PY 2005 VL 54 IS 6 BP 1321 EP 1326 DI 10.1002/mrm.20709 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 989EH UT WOS:000233655200001 PM 16270328 ER PT J AU Kim, S Chi-Fishman, G Barnett, AS Pierpaoli, C AF Kim, S Chi-Fishman, G Barnett, AS Pierpaoli, C TI Dependence on diffusion time of apparent diffusion tensor of ex vivo calf tongue and heart SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE DTI; restricted water diffusion; tongue; heart; diffusion time ID RESTRICTED DIFFUSION; SKELETAL-MUSCLE; COMPARTMENTAL-SYSTEMS; INTRACELLULAR WATER; FIBER ARCHITECTURE; RAT-BRAIN; IN-VIVO; MRI; TISSUE; ORIENTATION AB The time dependence of the apparent diffusion tensor of ex vivo calf heart and tongue was measured for diffusion times (tau(d)) between 32 and 810 ms. The results showed evidence of restricted diffusion in the muscle tissues of both organs. In regions where the myofibers are parallel, the largest eigenvalue (lambda(1)) of the diffusion tensor remained the same for all diffusion times measured, while the other eigenvalues (lambda(2), lambda(3)) decreased by 29-36% between tau(d) = 32 ms and tau(d) = 400 ms. In regions where the fibers cross, the lambda(1) also changed, decreasing by 17% between tau(d) = 32 ms and tau(d) = 400 ms. The restricting compartment size and volume fraction were effectively estimated by fitting the time courses of the eigenvalues to a model consisting of a nonrestricted compartment and a cylindrically restricted compartment. To our knowledge, this study is the first demonstrating diffusion time dependence of measured water diffusion tensor in muscular tissue. With improvement in scanning technology, future studies may permit noninvasive, in vivo detection of changes in muscle myoarchitecture due to disease, treatment, and exercise. Magn Reson Med 54:1387-1396, 2005. Published 2005 Wiley-Liss, Inc.dagger C1 NIH, Phys Disabil Branch, Dept Rehabil Med, Clin Res Ctr, Bethesda, MD 20892 USA. NIMH, NIH, Bethesda, MD 20892 USA. NICHHD, NIH, Bethesda, MD 20892 USA. RP Kim, S (reprint author), NIH, Phys Disabil Branch, Dept Rehabil Med, Clin Res Ctr, 10-6c416,10 Ctr Dr, Bethesda, MD 20892 USA. EM sungheonk@cc.nih.gov RI Pierpaoli, Carlo/E-1672-2011 NR 41 TC 37 Z9 37 U1 1 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD DEC PY 2005 VL 54 IS 6 BP 1387 EP 1396 DI 10.1002/mrm.20676 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 989EH UT WOS:000233655200009 PM 16265644 ER PT J AU Kellman, P McVeigh, ER AF Kellman, P McVeigh, ER TI Image reconstruction in SNR units: A general method for SNR measurement SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE MRI; SNR measurement; SENSE; parallel MRI; phased array; noise ID PHASED-ARRAY; MR-IMAGES; NOISE; SIGNAL; UNFOLD AB The method for phased array image reconstruction of uniform noise images may be used in conjunction with proper image scaling as a means of reconstructing images directly in SNR units. This facilitates accurate and precise SNR measurement on a per pixel basis. This method is applicable to root-sum-of-squares magnitude combining, B-1-weighted combining, and parallel imaging such as SENSE. A procedure for image reconstruction and scaling is presented, and the method for SNR measurement is validated with phantom data. Alternative methods that rely on noise only regions are not appropriate for parallel imaging where the noise level is highly variable across the field-of -view. The purpose of this article is to provide a nuts and bolts procedure for calculating scale factors used for reconstructing images directly in SNR units. The procedure includes scaling for noise equivalent bandwidth of digital receivers, FFTs and associated window functions (raw data filters), and array combining. Magn Reson Med 54:1439-1447, 2005. Published 2005 Wiley-Liss, Inc.dagger C1 NHLBI, Cardiac Energet Lab, DHHS, NIH, Bethesda, MD 20892 USA. RP Kellman, P (reprint author), NHLBI, Cardiac Energet Lab, DHHS, NIH, 10 Ctr Dr,MSC-1061,Bldg 10,Room B1D416, Bethesda, MD 20892 USA. EM kellman@nih.gov FU Intramural NIH HHS [Z01 HL004608-08] NR 16 TC 189 Z9 190 U1 3 U2 17 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD DEC PY 2005 VL 54 IS 6 BP 1439 EP 1447 DI 10.1002/mrm.20713 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 989EH UT WOS:000233655200015 PM 16261576 ER PT J AU Herzka, DA Derbyshire, JA Kellman, P McVeigh, ER AF Herzka, DA Derbyshire, JA Kellman, P McVeigh, ER TI Single heartbeat cardiac tagging for the evaluation of transient phenomena SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE myocardial tagging; myocardial function; fast cardiac imaging; parallel imaging; real time imaging; Valsalva maneuver ID LEFT-VENTRICULAR FUNCTION; REAL-TIME MRI; VALSALVA MANEUVER; BREATH-HOLD; WALL-MOTION; CINE MRI; ECHO; IMAGES; QUANTIFICATION; RECONSTRUCTION AB Many cardiac abnormalities are of a transient nature, creating a beat-to-beat variation in myocardial function. This work presents the cardiac imaging technique for the measurement of regional function during transient cardiac phenomena. All information necessary for the reconstruction of a cine loop is acquired within a single heartbeat, avoiding the temporal blurring introduced by segmented imaging due to the assumption of cardiac cycle periodicity. This method incorporates a gradient-optimized, high-efficiency EPI-SSFP sequence and TSENSE parallel imaging. For acquisitions with readout resolutions of 128,160, 192, and 256 points, the technique produced images with average temporal resolution of 35, 39, 43, and 52 ms and average spatial resolutions of 2.65, 2.12, 1.77, and 1.32 mm in the readout direction, respectively, and 2.88 and 2.08 mm in the phase encode direction for acceleration rates of 3 and 4, respectively. Local apparent strains in the single slice and measurements of ventricular end-systolic and end-diastolic areas were used as quantitative measures to validate the single heartbeat technique. To demonstrate the utility of the sequence, movie loops were acquired for multiple heartbeats in non- breath-held acquisitions as well as during a Valsalva maneuver. A heartbeat-interleaved acquisition allowed for the reconstruction of nonaccelerated images from R contiguous heartbeats. Images reconstructed from such data displayed tag blurring and reduced tag persistence due to motion and interheartbeat variability. Images acquired during the Valsalva maneuver demonstrated apparent beat-to-beat variability, visible both in the images and as changing strain patterns and ventricular volumes. Magn Reson Med 54:1455-1464, 2005. Published 2005 Wiley-Liss, Inc.(dagger) C1 NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA. RP Herzka, DA (reprint author), NHLBI, Cardiac Energet Lab, NIH, MSC-1061,Bldg 10,B1D416, Bethesda, MD 20892 USA. EM herzkad@nih.gov OI Herzka, Daniel/0000-0002-9400-7814 FU Intramural NIH HHS [Z01 HL004608-08] NR 40 TC 4 Z9 5 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD DEC PY 2005 VL 54 IS 6 BP 1455 EP 1464 DI 10.1002/mrm.20719 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 989EH UT WOS:000233655200017 PM 16265635 ER PT J AU Matsumoto, A Matsumoto, S Sowers, AL Koscielniak, JW Trigg, NJ Kuppusamy, P Mitchell, JB Subramanian, S Krishna, MC Matsumoto, K AF Matsumoto, A Matsumoto, S Sowers, AL Koscielniak, JW Trigg, NJ Kuppusamy, P Mitchell, JB Subramanian, S Krishna, MC Matsumoto, K TI Absolute oxygen tension (pO(2)) muscle tissue as determined by in murine fatty and EPR SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE electron paramagnetic resonance; oxygen concentration; spin probe; lithium phthalocyanine; mouse; mammary gland; skeletal muscle ID PREDICTS RADIATION RESPONSE; IN-VIVO; LITHIUM PHTHALOCYANINE; LOCALIZED MEASUREMENTS; ENDOTHELIAL-CELLS; TUMOR HYPOXIA; OXIMETRY; PROBE; CARBOGEN; CANCER AB The absolute partial pressure of oxygen (pO(2)) in the mammary gland pad and femoral muscle of female mice was measured using EPR oximetry at 700 MHz. A small quantity of lithium phthalocyanine (LiPc) crystals was implanted in both mammary and femoral muscle tissue of female C3H mice. Subsequent EPR measurements were carried out 1-30 days after implantation with or without control of core body temperature. The pO(2) values in the tissue became stable 2 weeks after implantation of LiPc crystals. The pO(2) level was found to be higher in the femoral muscle than in the mammary tissue. However, the pO(2) values showed a strong dependence on the core body temperature of the mice. The pO(2) values were responsive to carbogen (95% O-2 5% CO2) breathing even 44-58 days after the implantation of LiPc. The LiPc linewidth was also sensitive to changes in the blood supply even 60 days after implantation of the crystals. This study further validates the use of LiPc crystals and EPR oximetry for long-term non-invasive assessment of pO(2) levels in tissues, underscores the importance of maintaining normal body core temperature during the measurements, and demonstrates that mammary tissue functions at a lower pO(2) level than muscle in female C3H mice. C1 NCI, Radiat Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Lab Proteom & Analyt Technol, Frederick, MD USA. Ohio State Univ, Dept Internal Med, Davis Heart & Lung Res Inst, Columbus, OH 43210 USA. RP Krishna, MC (reprint author), NIH, Bldg 10,Room B3-B69, Bethesda, MD 20892 USA. EM murali@helix.nih.gov NR 36 TC 54 Z9 56 U1 1 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD DEC PY 2005 VL 54 IS 6 BP 1530 EP 1535 DI 10.1002/mrm.20714 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 989EH UT WOS:000233655200024 PM 16276490 ER PT J AU Nezafat, R Kellman, P Derbyshire, JA McVeigh, ER AF Nezafat, R Kellman, P Derbyshire, JA McVeigh, ER TI Real-time blood flow imaging using autocalibrated spiral sensitivity encoding SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE phase contrast; real time imaging; spiral sampling; parallel imaging; auto-calibrated field map ID MRI; SENSE AB A novel spiral phase contrast (PC) technique was developed for high temporal resolution imaging of blood flow without cardiac gating. An autocalibrated spiral sensitivity encoding (SENSE) method is introduced and used to reconstruct PC images. Numerical simulations and a flow phantom study were performed to validate the technique. To study the accuracy of the flow measurement in vivo, a high-resolution cardiac experiment was performed and a subset of undersampled SENSE reconstructed data were reconstructed. Good agreement between the velocity measurement from the fully-sampled and undersampled data was achieved. Real-time experiments were performed to measure blood velocity in the ascending aorta and aortic valve, and during a Valsalva maneuver. The results demonstrate the potential of this technique for real-time flow imaging. C1 NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD USA. RP Nezafat, R (reprint author), NHLBI, Cardiac Energet Lab, NIH, 10 Ctr Dr,MSC-1061,Bldg 10,Room B D412, Bethesda, MD 20892 USA. EM nezafatr@nih.gov FU Intramural NIH HHS [Z01 HL004608-08] NR 19 TC 14 Z9 14 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD DEC PY 2005 VL 54 IS 6 BP 1557 EP 1561 DI 10.1002/mrm.20690 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 989EH UT WOS:000233655200029 PM 16254954 ER PT J AU Acuna-Castillo, C Aravena, M Leiva-Salcedo, E Perez, V Gomez, C Sabaj, V Nishimura, S Perez, C Colombo, A Walter, R Sierra, F AF Acuna-Castillo, C Aravena, M Leiva-Salcedo, E Perez, V Gomez, C Sabaj, V Nishimura, S Perez, C Colombo, A Walter, R Sierra, F TI T-kininogen, a cystatin-like molecule, inhibits ERK-dependent lymphocyte proliferation SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE T lymphocytes; cystatins; T-kininogen; signal transduction; cell proliferation ID CYSTEINE PROTEASE INHIBITOR; ACTIVATION; PHASE; INFLAMMATION; SHIFT; RATS AB Plasma levels of kininogens increase with age in both rats and humans. Kininogens are inhibitors of cysteine proteinases, and filarial cysteine proteinase inhibitors (cystatins) reduce the proliferation of T cells. We evaluated whether T-kininogen (T-KG) might mimic this effect, and here we present data indicating that exposure of either rat splenocytes or Jurkat cells to purified T-KG results in inhibition of both ERK activation and [H-3]-thymidine incorporation, both basal and in response to ConA or PHA. Interestingly, T-KG did not impair [H-3]-thymidine incorporation in response to IL-2, which requires primarily the activation of the JNK and Jak/STAT pathways. These effects were neither the consequence of increased cell death, nor required the activity of kinin receptors. Furthermore, when T cell receptor proximal events were bypassed by the use of PMA plus Calcium ionophore, T-KG no longer inhibited ERK activation, suggesting that inhibition occurs upstream of these events, possibly at the level of membrane associated signal transduction molecules. We conclude that, like filarial cystatins, T-KG inhibits ERK-dependent T cell proliferation, and these observations suggest a possible role for T-KG in immunosenescence. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Univ Chile, Fac Med, Inst Ciencias Biomed, Programa Biol Celular & Mol, Santiago, Chile. Univ Chile, Fac Med, Ctr FONDAP Estudios Mol Celula, Santiago, Chile. Lankenau Inst Med Res, Wynnewood, PA 19096 USA. RP Sierra, F (reprint author), NIA, Biol Aging Program, NIH, 7201 Wisconsin Ave, Bethesda, MD 20892 USA. EM sierraf@nia.nih.gov FU NIA NIH HHS [R01 AG13902] NR 28 TC 15 Z9 16 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD DEC PY 2005 VL 126 IS 12 BP 1284 EP 1291 DI 10.1016/j.mad.2005.07.005 PG 8 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 990AA UT WOS:000233714400005 PM 16140359 ER PT J AU Ishimaru, Y Okada, S Naito, H Nagai, T Yasuoka, A Matsumoto, I Abe, K AF Ishimaru, Y Okada, S Naito, H Nagai, T Yasuoka, A Matsumoto, I Abe, K TI Two families of candidate taste receptors in fishes SO MECHANISMS OF DEVELOPMENT LA English DT Article DE taste receptor; fish; taste bud; phospholipase C-beta 2 ID PUTATIVE PHEROMONE RECEPTORS; BITTER TASTE; ODORANT RECEPTOR; MAMMALIAN SWEET; BUD CELLS; MULTIPLE; MOUSE; IDENTIFICATION; EXPRESSION; EPITHELIUM AB Vertebrates receive tastants, such as sugars, amino acids, and nucleotides, via taste bud cells in epithelia] tissues. In mammals, two families of G protein-coupled receptors for tastants are expressed in taste bud cells-T1Rs for sweet tastants and umami tastants ((L)-amino acids) and T2Rs for bitter tastants. Here, we report two families of candidate taste receptors in fish species, fish T1Rs and T2Rs, which show significant identity to mammalian T1Rs and T2Rs, respectively. Fish T1Rs consist of three types: fish T1R1 and T1R3 that show the highest degrees of identity to mammalian T1R1 and T1R3, respectively, and fish TIR2 that shows almost equivalent identity to both mammalian T1R1 and TIR2. Unlike mammalian T1R2, fish TIR2 consists of two or three members in each species. We also identified two fish T2Rs that show low degrees of identity to mammalian Ms. In situ hybridization experiments revealed that fish T1R and T2R genes were expressed specifically in taste bud cells, but not in olfactory receptor cells. Fish T1R1 and TIR2 genes were expressed in different subsets of taste bud cells, and fish T1R3 gene was co-expressed with either fish T1R1 or TIR2 gene as in the case of mammals. There were also a significant number of cells expressing fish TIR2 genes only. Fish T2R genes were expressed in different cells from those expressing fish T1R genes. These results suggest that vertebrates commonly have two kinds of taste signaling pathways that are defined by the types of taste receptors expressed in taste receptor cells. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Univ Tokyo, Grad Sch Agr & Life Sci, Dept Appl Biol Chem, Bunkyo Ku, Tokyo 1138657, Japan. Natl Inst Environm Hlth Sci, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Ishimaru, Y (reprint author), Univ Tokyo, Grad Sch Agr & Life Sci, Dept Appl Biol Chem, Bunkyo Ku, 1-1-1 Yayoi, Tokyo 1138657, Japan. EM ayishi@mail.ecc.u-tokyo.ac.jp; aka7308@mail.ecc.u-tokyo.ac.jp NR 31 TC 53 Z9 53 U1 2 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD DEC PY 2005 VL 122 IS 12 BP 1310 EP 1321 DI 10.1016/j.mod.2005.07.005 PG 12 WC Developmental Biology SC Developmental Biology GA 000NK UT WOS:000234468700006 PM 16274966 ER PT J AU Matthan, NR Jordan, H Chung, M Lichtenstein, AH Lathrop, DA Lau, J AF Matthan, NR Jordan, H Chung, M Lichtenstein, AH Lathrop, DA Lau, J TI A systematic review and meta-analysis of the impact of omega-3 fatty acids on selected arrhythmia outcomes in animal models SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Review ID POLYUNSATURATED FATTY-ACIDS; DIETARY FISH-OIL; SUDDEN CARDIAC DEATH; VENTRICULAR-FIBRILLATION THRESHOLD; EXPERIMENTAL MYOCARDIAL-INFARCTION; EICOSAPENTAENOIC ACID; DOCOSAHEXAENOIC ACID; NA+ CHANNELS; N-3; ISCHEMIA AB Epidemiological studies and clinical trials report the beneficial effects of fish or fish oil consumption on cardiovascular disease outcomes including sudden death. We performed a systematic review of the literature on controlled animal studies that assessed the effects of omega-3 fatty acids on selected arrhythmia outcomes. On the basis of predetermined criteria, 27 relevant animal studies were identified; 23 of these were feeding studies, and 4 were infusion studies. Across species, fish oil, eicosapentaenoic acid, and/or docosahexaenoic acid appear to have beneficial effects on ventricular tachycardia (VT) and fibrillation (VF) in ischemia- but not reperfusion-induced arrhythmia models; no effect on the incidence of death and infarct size; and inconsistent results with regard to arrhythmia score, VF threshold, ventricular premature beats or length of time in normal sinus rhythm, compared to omega-6, monounsaturated, or saturated fatty acids, and no treatment controls. In a metaanalysis of 13 studies using rat models, fish oil but not alpha-linolenic acid supplementation showed a significant protective effect for ischemia and reperfusion-induced arrhythmias by reducing the incidence of VT and VF. It is not known whether omega-3 fatty-acid supplementation has antiarrhythmic effects in other disease settings not related to ischemia. (c) 2005 Elsevier Inc. All rights reserved. C1 Tufts Univ, USDA, Jean Mayer Human Nutr Res Ctr Aging, Cardiovasc Nutr Lab, Boston, MA 02111 USA. Tufts Univ, New England Med Ctr, Inst Clin Care Res & Hlth Policy Studies, Tufts New England Med Ctr Evidence Based Practice, Boston, MA 02111 USA. NHLBI, Div Heart & Vasc Dis, Heart Res Program, Arrhythmias Ischemia & Sudden Cardiac Death Sci R, Bethesda, MD 20892 USA. RP Matthan, NR (reprint author), Tufts Univ, USDA, Jean Mayer Human Nutr Res Ctr Aging, Cardiovasc Nutr Lab, Boston, MA 02111 USA. EM nirupa.matthan@tufts.edu RI LATHROP, David/A-2758-2008 NR 59 TC 37 Z9 38 U1 2 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD DEC PY 2005 VL 54 IS 12 BP 1557 EP 1565 DI 10.1016/j.metabol.2005.05.026 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 995TU UT WOS:000234127800001 PM 16311086 ER PT J AU Hama, Y Kaji, T Hayakawa, M Kosuda, S AF Hama, Y Kaji, T Hayakawa, M Kosuda, S TI Endovascular stent placement for malignant stenosis and occlusion of the bilateral iliac veins and inferior vena cava after failure of radiation therapy SO MINIMALLY INVASIVE THERAPY & ALLIED TECHNOLOGIES LA English DT Article DE neoplasms; radiation; endovascular; palliative case; terminal care ID VENOUS STENOSIS; MANAGEMENT AB A 70- year- old woman with advanced ureteral carcinoma was referred due to stenosis and occlusion of the bilateral iliac veins and inferior vena cava after failure of radiation therapy. We successfully placed endovascular stents in the bilateral iliac veins and the inferior vena cava. The stents remain patent after five months of follow- up without requiring secondary intervention. As far as we know, this is the first report of radioresistant malignant stenosis of the bilateral iliac veins and the inferior vena cava that was successfully treated with stent placement. C1 NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Natl Def Med Coll, Dept Radiol, Tokorozawa, Saitama 359, Japan. Natl Def Med Coll, Dept Urol, Tokorozawa, Saitama 359, Japan. RP Hama, Y (reprint author), NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bldg 10,Room B3 B69, Bethesda, MD 20892 USA. EM yjhama2005@yahoo.co.jp NR 8 TC 3 Z9 3 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA PO BOX 12 POSTHUSET, NO-0051 OSLO, NORWAY SN 1364-5706 J9 MINIM INVASIV THER JI Minim. Invasive Ther. Allied Technol. PD DEC PY 2005 VL 14 IS 6 BP 372 EP 375 DI 10.1080/13645700500381362 PG 4 WC Surgery SC Surgery GA 991JH UT WOS:000233808900007 PM 16754184 ER PT J AU Levin, BC Sekiguchi, K Tully, LA Chen, TLJ Gropman, A AF Levin, BC Sekiguchi, K Tully, LA Chen, TLJ Gropman, A TI The common deletion found in patient reexamined after 33 years and comparison with complete mtDNA sequences of maternal relatives SO MITOCHONDRION LA English DT Article DE chronic progressive external ophthalmoplegia; CPEO; haplogroup K; mitochondrial DNA (mtDNA); mitochondrial disease; ptosis; ragged-red fibers ID HUMAN MITOCHONDRIAL-DNA; MUTATION AB In 1966, a male (17 years old) was clinically examined at the National Institutes of Health (NIH) and diagnosed with Idiopathic Progressive External Ophthalmoplegia (IPEO). A muscle biopsy showing ragged-red fibers implicated mitochondrial involvement. Since the sequence of human mitochondrial DNA (mtDNA) was not determined until 1981, no genetic confirmation of the disease was possible at that time. In 1999, clinical reexamination and sequencing the entire mtDNA of the patient and living maternal relatives (mother and brother) indicated a progressive mitochondrial myopathy and the presence of the 4977 base pair (bp) deletion (the common deletion) in the patient. Published by Elsevier B.V. on behalf of Mitochondria Research Society. C1 Natl Inst Stand & Technol, Div Biotechnol, Gaithersburg, MD 20899 USA. Natl Res Inst Police Sci, Kashiwa, Chiba, Japan. Natl Inst Justice, Invest & Forens Sci Div, Washington, DC USA. Penn State Univ, Milton S Hershey Med Ctr, Dept Surg, Hershey, PA 17033 USA. Georgetown Univ, Ctr Funct & Mol Imaging, Washington, DC USA. NHGRI, NIH, Bethesda, MD 20892 USA. RP Levin, BC (reprint author), Natl Inst Stand & Technol, Div Biotechnol, 100 Bur Dr,MS 8311, Gaithersburg, MD 20899 USA. EM barbara.levin@nist.gov NR 12 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1567-7249 J9 MITOCHONDRION JI Mitochondrion PD DEC PY 2005 VL 5 IS 6 BP 403 EP 410 DI 10.1016/j.mito.2005.08.001 PG 8 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 997HL UT WOS:000234236000003 PM 16172025 ER PT J AU Kaplan, B Martin, BM Livoff, A Yeremenko, D Livneh, A Cohen, HI AF Kaplan, B Martin, BM Livoff, A Yeremenko, D Livneh, A Cohen, HI TI Gastrointestinal beta(2)microglobulin amyloidosis in hemodialysis patients: biochemical analysis of amyloid proteins in small formalin-fixed paraffin-embedded tissue specimens SO MODERN PATHOLOGY LA English DT Article DE amyloid; beta(2)microglobulin; dialysis-related amyloidosis; electrophoresis; intestine; isoelectrofocusing ID LONG-TERM HEMODIALYSIS; DIALYSIS-RELATED AMYLOIDOSIS; IMMUNOGLOBULIN LIGHT-CHAIN; GLYCATION END-PRODUCTS; BETA(2)-MICROGLOBULIN AMYLOIDOSIS; CHEMICAL-CHARACTERIZATION; BETA-2-MICROGLOBULIN; IDENTIFICATION; PURIFICATION; DEPOSITS AB We present here a first report on the biochemical analysis of intestinal amyloid deposits found in two cases of hemodialysis-related amyloidosis. A new microtechnique was applied for extraction and immunochemical/ chemical characterization of amyloid proteins in small amounts of fixed tissue, thus allowing precise identification of beta(2)microglobulin amyloid (A beta(2)M) in both cases studied. The molecular mass of the identified amyloid beta(2)M was close to that of intact beta(2)M (12 kDa), with no evidence of the products of proteolytic fragmentation of these molecules. The isoelectrofocusing of the purified A beta(2)M demonstrated a shift to more acidic pI as compared to the normal beta(2)M analyzed under the same experimental conditions. The obtained data suggest that the intestinal amyloid deposits in dialysis-related amyloidosis contain disease-specific beta(2)M isoforms, which could play a role in the pathogenesis of amyloid disease. The new methodology used might be useful in obtaining precise diagnosis of amyloidosis that is necessary for appropriate therapy, and also provide new important information on the chemical structure of amyloid proteins. C1 Chaim Sheba Med Ctr, Heller Inst Med Res, IL-52621 Tel Hashomer, Israel. Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel. NIMH, Lab Neurotoxicol, Bethesda, MD USA. Western Galilee Hosp, Nahariya Med Ctr, Dept Pathol, Nahariyya, Israel. RP Kaplan, B (reprint author), Chaim Sheba Med Ctr, Heller Inst Med Res, IL-52621 Tel Hashomer, Israel. EM kaplanb@sheba.health.gov.il NR 40 TC 6 Z9 6 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD DEC PY 2005 VL 18 IS 12 BP 1610 EP 1617 DI 10.1038/modpathol.3800477 PG 8 WC Pathology SC Pathology GA 985IZ UT WOS:000233372100012 PM 16258516 ER PT J AU Cooper, RA Papakrivos, J Lane, KD Fujioka, H Lingelbach, K Wellems, TE AF Cooper, RA Papakrivos, J Lane, KD Fujioka, H Lingelbach, K Wellems, TE TI PfCG2, a Plasmodium falciparum protein peripherally associated with the parasitophorous vacuolar membrane, is expressed in the period of maximum hemoglobin uptake and digestion by trophozoites SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE malaria; endocytosis; phagocytosis; protein trafficking; proteases ID CHLOROQUINE RESISTANCE; MALARIA PARASITE; STREPTOLYSIN-O; ERYTHROCYTE-MEMBRANE; HOST ERYTHROCYTE; FOOD VACUOLE; CG2 GENE; RECOMBINANT FALCIPAIN-2; FEEDING MECHANISM; PLASMEPSIN-II AB A Plasmodium falciparum gene closely linked to the chloroquine resistance locus encodes PfCG2, a predicted 320-330 kDa protein. In the parasitized erythrocyte, PfCG2 expression rises sharply in the trophozoite stage and is detected in electron-dense patches along the parasitophorous vacuolar membrane (PVM), in the cytoplasm and in the digestive vacuole (DV). Results of extraction and partitioning experiments show that PfCG2 is a peripheral membrane protein. Exposure of trophozoite-infected erythrocytes to trypsin-containing buffer after streptolysin O. permeabilization indicates that PfCG2 is exposed to the erythrocyte cytosol at the outer face of the PVM. PfCG2 is highly susceptible to hydrolysis by aspartic and cysteine proteases and shows dose-dependent accumulation in the presence of protease inhibitors. These results suggest that PfCG2 is delivered from the outside face of the PVM to the DV, where it is broken down by parasite proteases. PfCG2 interacts with erythrocyte cytoplasm and may be associated with processes of hemoglobin uptake and digestion by erythrocytic-stage parasites. Published by Elsevier B.V. C1 NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. Univ Marburg, Fachbereich Biol Zool, D-35032 Marburg, Germany. Old Dominion Univ, Dept Biol Sci, Norfolk, VA 23529 USA. Case Western Reserve Univ, Inst Pathol, Cleveland, OH 44106 USA. RP Wellems, TE (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Twinbrook 3, Bethesda, MD 20892 USA. EM twellems@niaid.nih.gov FU Intramural NIH HHS NR 51 TC 9 Z9 11 U1 0 U2 2 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 2005 VL 144 IS 2 BP 167 EP 176 DI 10.1016/j.molbiopara.2005.07.009 PG 10 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA 989ZR UT WOS:000233713400005 PM 16183150 ER PT J AU Carter, CD Kitchen, LE Au, WC Babic, CM Basrai, MA AF Carter, CD Kitchen, LE Au, WC Babic, CM Basrai, MA TI Loss of SOD1 and LYS7 sensitizes Saccharomyces cerevisiae to hydroxyurea and DNA damage agents and downregulates MEC1 pathway effectors SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; ZINC SUPEROXIDE-DISMUTASE; OXIDATIVE STRESS; RIBONUCLEOTIDE REDUCTASE; CHECKPOINT PATHWAYS; BUDDING YEAST; PHYSIOLOGICAL-ROLE; ESCHERICHIA-COLI; NULL MUTANTS; PROTEIN AB Aerobic metabolism produces reactive oxygen species, including superoxide anions, which cause DNA damage unless removed by scavengers such as superoxide dismutases. We show that loss of the Cu,Zn-dependent superoxide dismutase, SOD1, or its copper chaperone, LYS7, confers oxygen-dependent sensitivity to replication arrest and DNA damage in Saccharomyces cerevisiae. We also find that sod] A strains, and to a lesser extent lys7 Delta strains, when arrested with hydroxyurea (HU) show reduced induction of the MEC1 pathway effector Rnr3p and of Hug1p. The HU sensitivity of sod1 Delta and lys7 Delta strains is suppressed by overexpression of TKL1, a transketolase that generates NADPH, which balances redox in the cell and is required for ribonucleotide reductase activity. Our results suggest that the MEC1 pathway in sod1 Delta mutant strains is sensitive to the altered cellular redox state due to increased superoxide anions and establish a new relationship between SOD1, LYS7, and the MEC1-mediated checkpoint response to replication arrest and DNA damage in S. cerevisiae. C1 NCI, Genet Branch, Ctr Canc Res, NIH,Natl Naval Med Ctr, Bethesda, MD 20889 USA. RP Basrai, MA (reprint author), NCI, Genet Branch, Ctr Canc Res, NIH,Natl Naval Med Ctr, Bldg 8,Room 5101,8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM basraim@mail.nih.gov FU Intramural NIH HHS NR 62 TC 22 Z9 24 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 2005 VL 25 IS 23 BP 10273 EP 10285 DI 10.1128/MCB.25.23.10273-10285.2005 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 986MB UT WOS:000233452600006 PM 16287844 ER PT J AU Shyu, YC Lee, TL Ting, CY Wen, SC Hsieh, LJ Li, YC Hwang, JI Lin, CC Shen, CKJ AF Shyu, YC Lee, TL Ting, CY Wen, SC Hsieh, LJ Li, YC Hwang, JI Lin, CC Shen, CKJ TI Sumoylation of p45/NF-E2: Nuclear positioning and transcriptional activation of the mammalian beta-like globin gene locus SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CREB-BINDING-PROTEIN; LEUCINE ZIPPER PROTEIN; HYPERSENSITIVE SITE 2; FACTOR NF-E2; CONTROL REGION; DNA-BINDING; PML BODIES; CHROMOSOME TERRITORIES; ERYTHROLEUKEMIA-CELLS; SUMO-1 MODIFICATION AB NF-E2 is a transcription activator for the regulation of a number of erythroid- and megakaryocytic lineage-specific genes. Here we present evidence that the large subunit of mammalian NF-E2, p45, is sumoylated in vivo in human erythroid K562 cells and in mouse fetal liver. By in vitro sumoylation reaction and DNA transfection experiments, we show that the sumoylation occurs at lysine 368 (K368) of human p45/NF-E2. Furthermore, p45 sumoylation enhances the transactivation capability of NF-E2, and this is accompanied by an increase of the NF-E2 DNA binding affinity. More interestingly, we have found that in K562 cells, the beta-globin gene loci in the euchromatin regions are predominantly colocalized with the nuclear bodies promyelocytic leukemia protein (PML) oncogenic domains that are enriched with the PML, SUMO-1, RNA polymerase H, and sumoylatable p45/NF-E2. Chromatin immunoprecipitation assays further showed that the intact sumoylation site of p45/ NF-E2 is required for its binding to the DNase I-hypersensitive sites of the beta-globin locus control region. Finally, we demonstrated by stable transfection assay that only the wild-type p45, but not its mutant form p45 (K368R), could efficiently rescue beta-globin gene expression in the p45-null, erythroid cell line CB3. These data together point to a model of mammalian P-like globin gene activation by sumoylated p45/NF-E2 in erythroid cells. C1 Acad Sinica, Inst Mol Biol, Taipei 115, Taiwan. Natl Yang Ming Univ, Inst Genet, Taipei 112, Taiwan. Natl Def Univ, Inst Life Sci, Taipei, Taiwan. NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. China Med Univ Hosp, Dept Med Res, Taichung, Taiwan. Chung Shan Med & Dent Coll, Dept Biomed Sci, Taichung, Taiwan. RP Shen, CKJ (reprint author), Acad Sinica, Inst Mol Biol, Taipei 115, Taiwan. EM ckshen@imb.sinica.edu.tw RI Ting, chun-yuan/F-6448-2013; shen, Che-Kun James/L-1343-2015; OI Shyu, Yu-Chiau/0000-0003-1747-2226; Lee, Tung-Liang/0000-0003-1913-1652 NR 65 TC 22 Z9 26 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 2005 VL 25 IS 23 BP 10365 EP 10378 DI 10.1128/MCB.25.23.10365-10378.2005 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 986MB UT WOS:000233452600013 PM 16287851 ER PT J AU Mizugishi, K Yamashita, T Olivera, A Miller, GF Spiegel, S Proia, RL AF Mizugishi, K Yamashita, T Olivera, A Miller, GF Spiegel, S Proia, RL TI Essential role for sphingosine kinases in neural and vascular development SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PROTEIN-COUPLED RECEPTOR; FUNCTIONAL-CHARACTERIZATION; MOLECULAR-CLONING; SPHINGOSINE-1-PHOSPHATE; 1-PHOSPHATE; EXPRESSION; S1P(1); CELLS; ANGIOGENESIS; MATURATION AB Sphingosine-1-phosphate (S1P), an important sphingolipid metabolite, regulates diverse cellular processes, including cell survival, growth, and differentiation. Here we show that S1P signaling is critical for neural and vascular development. Sphingosine kinase-null mice exhibited a deficiency of S1P which severely disturbed neurogenesis, including neural tube closure, and angiogenesis and caused embryonic lethality. A dramatic increase in apoptosis and a decrease in mitosis were seen in the developing nervous system. S1P, receptor-null mice also showed severe defects in neurogenesis, indicating that the mechanism by which SIP promotes neurogenesis is, in part, signaling from the S1P, receptor. Thus, S1P joins a growing list of signaling molecules, such as vascular endothelial growth factor, which regulate the functionally intertwined pathways of angiogenesis and neurogenesis. Our findings also suggest that exploitation of this potent neuronal survival pathway could lead to the development of novel therapeutic approaches for neurological diseases. C1 NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. NIAMS, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. NIH, Div Vet Resources, Bethesda, MD 20892 USA. Virginia Commonwealth Univ, Sch Med, Dept Biochem, Richmond, VA 23298 USA. RP Proia, RL (reprint author), NIDDK, Genet Dev & Dis Branch, NIH, Bldg 10,Rm 9N-314,10 Ctr Dr,MSC 1821, Bethesda, MD 20892 USA. EM proia@nih.gov RI Proia, Richard/A-7908-2012 FU NIGMS NIH HHS [R 37 GM043880] NR 31 TC 379 Z9 387 U1 1 U2 11 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 2005 VL 25 IS 24 BP 11113 EP 11121 DI 10.1128/MCB.25.24.11113-11121.2005 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 990RZ UT WOS:000233762200038 PM 16314531 ER PT J AU Kim, SJ Swanson, MJ Qiu, HF Govind, CK Hinnebusch, AG AF Kim, SJ Swanson, MJ Qiu, HF Govind, CK Hinnebusch, AG TI Activator Gcn4p and Cyc8p/Tup1p are interdependent for promoter occupancy at ARG1 in vivo SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RNA-POLYMERASE-II; TRANSCRIPTIONAL CO-REPRESSOR; TATA-BINDING PROTEIN; SACCHAROMYCES-CEREVISIAE; HISTONE ACETYLTRANSFERASE; CYC8-TUP1 COREPRESSOR; COACTIVATOR COMPLEX; CHROMATIN STRUCTURE; SAGA COACTIVATOR; SRB MEDIATOR AB The Cyc8p/Tup1p complex mediates repression of diverse genes in Saccharomyces cerevisiae and is recruited by DNA binding proteins specific for the different sets of repressed genes. By screening the yeast deletion library, we identified Cyc8p as a coactivator for Gen4p, a transcriptional activator of amino acid biosynthetic genes. Deletion of CYC8 confers sensitivity to an inhibitor of isoleucine/valine biosynthesis and impairs activation of Gcn4p-dependent reporters and authentic amino acid biosynthetic target genes. Deletion of TUP1 produces similar but less severe activation defects in vivo. Although expression of Gcn4p is unaffected by deletion of CYC8, chromatin immunoprecipitation assays reveal a strong defect in binding of Gcn4p at the target genes ARG1 and ARG4 in cyc8 Delta cells and to a lesser extent in tup1 Delta cells. The defects in Gcn4p binding and transcriptional activation in cyc8 Delta cells cannot be overcome by Gcn4p overexpression but are partially suppressed in tup1 Delta cells. The impairment of Gcn4p binding in cyc8 Delta and tup1 Delta cells is severe enough to reduce recruitment of SAGA, Srb mediator, TATA binding protein, and RNA polymerase II to the ARG1 and ARG4 promoters, accounting for impaired transcriptional activation of these genes in both mutants. Cyc8p and Tup1p are recruited to the ARG1 and ARG4 promoters, consistent with a direct role for this complex in stimulating Gcn4p occupancy of the upstream activation sequence (UAS). Interestingly, Gcn4p also stimulates binding of Cyc8p/Tup1p at the 3' ends of these genes, raising the possibility that Cyc8p/Tup1p influences transcription elongation. Our findings reveal a novel coactivator function for Cyc8p/Tup1p at the level of activator binding and suggest that Gcn4p may enhance its own binding to the UAS by recruiting Cyc8p/Tup1p. C1 NICHHD, Lab Gene Regulat & Dev, Bethesda, MD 20892 USA. RP Hinnebusch, AG (reprint author), NIH, Bldg 6A Room B1A13, Bethesda, MD 20892 USA. EM ahinnebusch@nih.gov NR 53 TC 17 Z9 17 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 2005 VL 25 IS 24 BP 11171 EP 11183 DI 10.1128/MCB.25.24.11171-11183.2005 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 990RZ UT WOS:000233762200043 PM 16314536 ER PT J AU Yoon, B Herman, H Hu, B Park, YJ Lindroth, A Bell, A West, AG Chang, YJ Stablewski, A Piel, JC Loukinov, DI Lobanenkov, VV Soloway, PD AF Yoon, B Herman, H Hu, B Park, YJ Lindroth, A Bell, A West, AG Chang, YJ Stablewski, A Piel, JC Loukinov, DI Lobanenkov, VV Soloway, PD TI Rasgrf1 imprinting is regulated by a CTCF-dependent methylation-sensitive enhancer blocker SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DNA METHYLATION; PROTEIN CTCF; H19 GENE; INSULATOR; IGF2; DOMAIN; RNA; BOX; EXPRESSION; UPSTREAM AB Imprinted methylation of the paternal Rasgrf1 allele in mice occurs at a differentially methylated domain (DMD) 30 kbp 5' of the promoter. A repeated sequence 3' of the DMD regulates imprinted methylation, which is required for imprinted expression. Here we identify the mechanism by which methylation controls imprinting. The DMD is an enhancer blocker that binds CTCF in a methylation-sensitive manner. CTCF bound to the unmethylated maternal allele silences expression. CTCF binding to the paternal allele is prevented by repeat-mediated methylation, allowing expression. Optimal in vitro enhancer-blocking activity requires CTCF binding sites. The enhancer blocker can be bypassed in vivo and imprinting abolished by placing an extra enhancer proximal to the promoter. Together, the repeats and the DMD constitute a binary switch that regulates Rasgrf1 imprinting. C1 Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA. Roswell Pk Canc Inst, Dept Mol & Cellular Biol, Buffalo, NY 14263 USA. Padjadjaran State Univ, Hasan Sadikin Gen Hosp, Sch Med, Dept Orthopaed Surg, Bandung, W Java, Indonesia. NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NIAID, Immunopathol Lab, Rockville, MD 20852 USA. RP Soloway, PD (reprint author), Cornell Univ, Div Nutr Sci, 108 Savage Hall, Ithaca, NY 14853 USA. EM pds28@cornell.edu OI West, Adam/0000-0003-3502-7804; Lindroth, Anders/0000-0002-8291-2745 FU NCI NIH HHS [P30CA016056, P30 CA016056, CA98596]; NEI NIH HHS [R01 EY011279, EY11279] NR 29 TC 63 Z9 67 U1 0 U2 5 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 2005 VL 25 IS 24 BP 11184 EP 11190 DI 10.1128/MCB.25.24.11184-11190.2005 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 990RZ UT WOS:000233762200044 PM 16314537 ER PT J AU Lal, A Haynes, SR Gorospe, M AF Lal, A Haynes, SR Gorospe, M TI Clean western blot signals from immunoprecipitated samples SO MOLECULAR AND CELLULAR PROBES LA English DT Article DE heavy Ig chain; light Ig chain; protein A-HRP; protein-G-HRP; background western signals ID BINDING; HUR AB We present a strategy that overcomes the high background arising during Western blotting (WB) detection of proteins obtained through immunoprecipitation (IP). Traditional HRP-conjugated secondary antibodies, which detect the denatured heavy and light antibody chains, produce high background that often mask the signals of interest on WBs. Here, we show that HRP-conjugated Protein A and Protein G, which detect almost exclusively intact antibody molecules, can be effectively used to obtain clean and specific WB signals of target proteins. (C) 2005 Elsevier Ltd. All rights reserved. C1 NIA, Cellular & Mol Biol Lab, IRP, NIH, Baltimore, MD 21224 USA. Uniformed Serv Univ Hlth Sci, Dept Biochem & Mol Biol, Bethesda, MD 20814 USA. RP Lal, A (reprint author), NIA, Cellular & Mol Biol Lab, IRP, NIH, Box 12,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM ashishl@grc.nia.nih.gov FU Intramural NIH HHS; NIA NIH HHS [Z01 AG000511-08]; NIGMS NIH HHS [R01 GM062803, R01 GM62803] NR 8 TC 30 Z9 30 U1 1 U2 7 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0890-8508 J9 MOL CELL PROBE JI Mol. Cell. Probes PD DEC PY 2005 VL 19 IS 6 BP 385 EP 388 DI 10.1016/j.mcp.2005.06.007 PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology GA 987MZ UT WOS:000233523300002 PM 16146684 ER PT J AU Merkulova, TI Kropachev, KY Timofeeva, OA Vasiliev, GV Levashova, ZB Ilnitskaya, SI Kobzev, VF Pakharukova, MY Bryzgalov, LO Kaledin, VI AF Merkulova, TI Kropachev, KY Timofeeva, OA Vasiliev, GV Levashova, ZB Ilnitskaya, SI Kobzev, VF Pakharukova, MY Bryzgalov, LO Kaledin, VI TI Species-specific effects of the hepatocarcinogens 3 '-methyl-4-dimethyl-aminoazobenzene and ortho-aminoazotoluene in mouse and rat liver SO MOLECULAR CARCINOGENESIS LA English DT Article DE hepatocarcinogen; tyrosine aminotransferase; glucocorticoid induction; hepatocyte nuclear factor 3; species-specificity ID TYROSINE AMINOTRANSFERASE GENE; ENRICHED TRANSCRIPTION FACTORS; GLUCOCORTICOID INDUCTION; O-AMINOAZOTOLUENE; MICE; EXPRESSION; PHOSPHORYLATION; DIFFERENTIATION; CARCINOGENESIS; HEPATOCYTES AB The effects of rat-specific hepatocarcinogen 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB), mouse-specific hepatocarcinogen ortho-aminoazotoluene (OAT), non-species-specific hepatocarcinogen diethylnitrosamine (DENA), and non-carcinogenic 4'-methyl-4-dimethylaminoazobenzene (4'-MeDAB) on glucocorticoid induction of tyrosine aminotransferase (TAT) and DNA-binding activity of hepatocyte nuclear factor 3 (HNF3) family of transcription factors were investigated with carcinogen-susceptible and -resistant animals. Species-specific hepatocarcinogens 3'-MeDAB and OAT strongly inhibited glucocorticoid induction of TAT in the liver of susceptible but not resistant animals. DENA, which is highly carcinogenic for the liver of both rats and mice inhibited glucocorticoid induction of TAT in both species, while non-carcinogenic 4'-MeDAB was absolutely ineffective both in rats and mice. The inhibition of TAT activity by the carcinogens was due to reduced levels of TAT mRNA, which is most likely to be a result of the reduced rate of transcription initiation of the TAT gene. In all cases, the TAT inhibition was accompanied by significant reduction of DNA-binding activity of the HNF3 transcription factor, which is known to be critical to glucocorticoid regulation of TAT gene. We also demonstrated that the described species-specific effects of OAT and of T-MeDAB on HNF3 DNA-binding activity may be initiated not only by administration in vivo, but also by their direct administration to homogenate, intact nuclei or nuclear lysate, but not to nuclear extract fraction, obtained by precipitation with 0.32 g/mL of ammonium sulfate (Fraction 1). We showed, that a factor responsible for this effect might be precipitated in 0.32-0.47g/mL interval of ammonium sulfate concentration. In contrast, non-specific hepatocarcinogen DENA was effective upon being added directly to Fraction 1, implying a different mechanism of its action. (c) 2005 Wiley-Liss, Inc. C1 Russian Acad Sci, Inst Cytol & Genet, Siberian Div, Lab Gene Express Control, Novosibirsk 630090, Russia. Russian Acad Sci, Inst Cytol & Genet, Siberian Div, Sect Nucl Acids Chem, Novosibirsk 630090, Russia. Russian Acad Sci, Novosibirsk Bioorgan Chem Inst, Siberian Div, Pharmacogenom Grp, Novosibirsk 630090, Russia. Natl Canc Inst, Comparat Carcinogenesis Lab, Frederick, MD USA. RP Merkulova, TI (reprint author), Russian Acad Sci, Inst Cytol & Genet, Siberian Div, Lab Gene Express Control, Lavrentiev Prospect 6, Novosibirsk 630090, Russia. RI Merkulova, Tatyana/R-9163-2016 NR 47 TC 10 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 2005 VL 44 IS 4 BP 223 EP 232 DI 10.1002/mc.20090 PG 10 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 989EB UT WOS:000233654600001 PM 16267830 ER PT J AU Hu, J Haseebuddin, M Young, M Colburn, NH AF Hu, J Haseebuddin, M Young, M Colburn, NH TI Suppression of p65 phosphorylation coincides with inhibition of I kappa B alpha polyubiquitination and degradation SO MOLECULAR CARCINOGENESIS LA English DT Article DE NF-kappa B; I kappa B alpha; phosphorylation; degradation; ubiquitination ID UBIQUITIN-MEDIATED PROTEOLYSIS; SIGNAL-INDUCED DEGRADATION; 2 DISTINCT MECHANISMS; BETA-TRCP; TRANSCRIPTIONAL ACTIVITY; PROTEIN-DEGRADATION; KINASE-BETA; IKK-BETA; ACTIVATION; CANCER AB Transcription factor nuclear factor-kappa B (NF-kappa B) is held in the cytoplasm in an inactive state by I kappa B inhibitors Oncogenic activation of NF-kappa B is achieved by stimulus-induced ubiquitination and subsequent proteasome-mediated degradation of I kappa B alpha. Once released from the inhibitor, NF-kappa B/p65 enters the nucleus. A pre-requisite for cytokine-induced I kappa B alpha ubiquitination and degradation is the phosphorylation Of I kappa B alpha at S32/S36. Phosphorylation Of I kappa B alpha alone, however, is not sufficient to trigger its degradation, suggesting other events must be required for regulating I kappa B alpha degradation. In this study, we tested the hypothesis that phosphorylation of p65 at 536 is required for TNF-alpha. induced I kappa B alpha proteolysis that in turn controls p65 nuclear translocation. We observed that, without affecting I kappa B alpha phosphorylation, MEK1 inhibitor U0126 treatment inhibited not only p65-S536 phosphorylation but also TNF-alpha-induced polyubiquitination Of I kappa B alpha thereby inhibiting I kappa B alpha degradation. With p65 S536 phosphorylation mutants and mimics, we further observed that the structural mutation of p65 serine 536 to alanine inhibited the recruitment of ubiquitin to the p65-containing complex. As a consequence of suppressing polyubiquitination of the p65-containing complex, degradation of p65 phosphorylation mutant-bound I kappa B alpha was also inhibited. Accordingly, the nuclear translocation of phosphorylation-impaired p65 was significantly reduced. These findings suggest that p65 phosphorylation plays a key role in stimulus-induced I kappa B alpha ubiquitination. Published 2005 Wiley-Liss, Inc.(dagger) C1 NCI, Gene Regulat Sect, Lab Canc Prevent, Canc Res Ctr, Frederick, MD 21702 USA. RP Hu, J (reprint author), NCI, Gene Regulat Sect, Lab Canc Prevent, Canc Res Ctr, Bldg 567,Room 188, Frederick, MD 21702 USA. RI Hu, Jing/M-3130-2014 FU Intramural NIH HHS NR 49 TC 21 Z9 21 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 2005 VL 44 IS 4 BP 274 EP 284 DI 10.1002/mc.20142 PG 11 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 989EB UT WOS:000233654600006 PM 16163708 ER PT J AU Michel, AP Ingrasci, MJ Schemerhorn, BJ Kern, M Le Goff, G Coetzee, M Elissa, N Fontenille, D Vulule, J Lehmann, T Sagnon, NF Costantini, C Besansky, NJ AF Michel, AP Ingrasci, MJ Schemerhorn, BJ Kern, M Le Goff, G Coetzee, M Elissa, N Fontenille, D Vulule, J Lehmann, T Sagnon, NF Costantini, C Besansky, NJ TI Rangewide population genetic structure of the African malaria vector Anopheles funestus SO MOLECULAR ECOLOGY LA English DT Article DE Africa; Anopheles funestus; malaria vector; microsatellites; mitochondrial DNA; population genetics ID RIFT-VALLEY COMPLEX; MICROSATELLITE DATA; PLASMODIUM-FALCIPARUM; DNA POLYMORPHISM; GAMBIAE; MADAGASCAR; DIFFERENTIATION; EVOLUTION; EXPANSION; GROWTH AB Anopheles funestus is a primary vector of malaria in Africa south of the Sahara. We assessed its rangewide population genetic structure based on samples from 11 countries, using 10 physically mapped microsatellite loci, two per autosome arm and the X (N = 548), and 834 bp of the mitochondrial ND5 gene (N = 470). On the basis of microsatellite allele frequencies, we found three subdivisions: eastern (coastal Tanzania, Malawi, Mozambique and Madagascar), western (Burkina Faso, Mali, Nigeria and western Kenya), and central (Gabon, coastal Angola). A. funestus from the southwest of Uganda had affinities to all three subdivisions. Mitochondrial DNA (mtDNA) corroborated this structure, although mtDNA gene trees showed less resolution. The eastern subdivision had significantly lower diversity, similar to the pattern found in the codistributed malaria vector Anopheles gambiae. This suggests that both species have responded to common geographic and/or climatic constraints. The western division showed signatures of population expansion encompassing Kenya west of the Rift Valley through Burkina Faso and Mali. This pattern also bears similarity to A. gambiae, and may reflect a common response to expanding human populations following the development of agriculture. Due to the presumed recent population expansion, the correlation between genetic and geographic distance was weak. Mitochondrial DNA revealed further cryptic subdivision in A. funestus, not detected in the nuclear genome. Mozambique and Madagascar samples contained two mtDNA lineages, designated clade I and clade II, that were separated by two fixed differences and an average of 2% divergence, which implies that they have evolved independently for similar to 1 million years. Clade I was found in all 11 locations, whereas clade II was sampled only on Madagascar and Mozambique. We suggest that the latter clade may represent mtDNA capture by A. funestus, resulting from historical gene flow either among previously isolated and divergent populations or with a related species. C1 Univ Notre Dame, Dept Biol Sci, Ctr Trop Dis Res & Training, Notre Dame, IN 46556 USA. Inst Pasteur Madagascar, Serv Entomol Med, Grp Rech Paludisme, Antananarivo 101, Madagascar. Natl Inst Communicable Dis, Vector Control Reference Unit, ZA-2131 Johannesburg, South Africa. Univ Witwatersrand, Johannesburg, South Africa. Natl Hlth Lab Serv, Div Clin Microbiol & Infect Dis, Sch Pathol, Johannesburg, South Africa. CIRMF, Unite Entomol Med, Franceville, Gabon. Inst Rech Dev, Lab Lutte Insectes Nuisibles, F-34394 Montpellier, France. Kenya Govt Med Res Ctr, Ctr Vector Biol Control Res, Kisumu, Kenya. NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. Ctr Natl Rech Format Paludisme, Ouagadougou, Burkina Faso. Inst Rech Dev, Ouagadougou, Burkina Faso. RP Besansky, NJ (reprint author), Univ Notre Dame, Dept Biol Sci, Ctr Trop Dis Res & Training, Notre Dame, IN 46556 USA. EM nbesansk@nd.edu RI Michel, Andrew/B-5329-2012; FONTENILLE, didier/G-4091-2013; Costantini, Carlo/F-3470-2012; OI Costantini, Carlo/0000-0003-1016-129X; Schemerhorn, Brandon/0000-0003-0247-478X FU NIAID NIH HHS [R01-AI48842] NR 54 TC 46 Z9 47 U1 1 U2 13 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0962-1083 J9 MOL ECOL JI Mol. Ecol. PD DEC PY 2005 VL 14 IS 14 BP 4235 EP 4248 DI 10.1111/j.1365-294X.2005.02754.x PG 14 WC Biochemistry & Molecular Biology; Ecology; Evolutionary Biology SC Biochemistry & Molecular Biology; Environmental Sciences & Ecology; Evolutionary Biology GA 984EW UT WOS:000233286300003 PM 16313589 ER PT J AU O'Shea, PJ Bassett, JHD Sriskantharajah, S Ying, H Cheng, SY Williams, GR AF O'Shea, PJ Bassett, JHD Sriskantharajah, S Ying, H Cheng, SY Williams, GR TI Contrasting skeletal phenotypes in mice with an identical mutation targeted to thyroid hormone receptor alpha 1 or beta SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID GROWTH-FACTOR RECEPTOR-1; BONE-GROWTH; IGF-I; EPIPHYSEAL CHONDROCYTES; POSTNATAL-DEVELOPMENT; SIGNALING PATHWAYS; PLATE CARTILAGE; MESSENGER-RNA; NULL MICE; TR-BETA AB Thyroid hormone (T-3) regulates bone turnover and mineralization in adults and is essential for skeletal development. Surprisingly, we identified a phenotype of skeletal thyrotoxicosis in T-3 receptor beta(PV) (TR beta(PV)) mice in which a targeted frameshift mutation in TR beta results in resistance to thyroid hormone. To characterize mechanisms underlying thyroid hormone action in bone, we analyzed skeletal development in TR alpha 1(PV) mice in which the same PV mutation was targeted to TR alpha 1. In contrast to TR beta(PV) mice, TR alpha 1(PV) mutants exhibited skeletal hypothyroidism with delayed endochondral and intramembranous ossification, severe postnatal growth retardation, diminished trabecular bone mineralization, reduced cortical bone deposition, and delayed closure of the skull sutures. Skeletal hypothyroidism in TR alpha 1(PV) mutants was accompanied by impaired GH receptor and IGF-I receptor expression and signaling in the growth plate, whereas GH receptor and IGF-I receptor expression and signaling were increased in TR alpha 1(PV) mice. These data indicate that GH receptor and IGF-I receptor are physiological targets for T-3 action in bone in vivo. The divergent phenotypes observed in TR alpha 1(PV) and TR beta(PV) mice arise because the pituitary gland is a TR beta-responsive tissue, whereas bone is TR alpha responsive. These studies provide a new understanding of the complex relationship between central and peripheral thyroid status. C1 Univ London Imperial Coll Sci Technol & Med, Mol Endocrinol Grp, London W12 0NN, England. Univ London Imperial Coll Sci Technol & Med, Div Med & Med Res Council, Ctr Clin Sci, London W12 0NN, England. NCI, Mol Biol Lab, Gene Regulat Sect, NIH, Bethesda, MD 20892 USA. RP Williams, GR (reprint author), Univ London Imperial Coll Sci Technol & Med, Mol Endocrinol Grp, Hammersmith Campus, London W12 0NN, England. EM graham.williams@imperial.ac.uk FU Medical Research Council [G108/502] NR 66 TC 74 Z9 74 U1 1 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD DEC PY 2005 VL 19 IS 12 BP 3045 EP 3059 DI 10.1210/me.2005-0224 PG 15 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 986OV UT WOS:000233460500013 PM 16051666 ER PT J AU Ueda, M AF Ueda, M TI Familial hypercholesterolemia SO MOLECULAR GENETICS AND METABOLISM LA English DT Article ID DENSITY-LIPOPROTEIN RECEPTOR; GENE; MANAGEMENT; MUTATIONS; DIAGNOSIS; LDLR C1 NHLBI, Mol Dis Sect, Cardiol Branch, NIH, Bethesda, MD 20892 USA. RP Ueda, M (reprint author), NHLBI, Mol Dis Sect, Cardiol Branch, NIH, Bethesda, MD 20892 USA. EM mueda@mail.nih.gov NR 14 TC 11 Z9 11 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD DEC PY 2005 VL 86 IS 4 BP 423 EP 426 DI 10.1016/j.ymgme.2005.11.003 PG 4 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 997XP UT WOS:000234282500001 PM 16421993 ER PT J AU Bylund, DB Brunton, L Cobbett, P Persky, A Preusch, PC AF Bylund, DB Brunton, L Cobbett, P Persky, A Preusch, PC TI NIGMS-sponsored integrative and organ systems pharmacology: Synopsis of the 2005 experience/anticipation of the 2006 short courses SO MOLECULAR INTERVENTIONS LA English DT Editorial Material C1 Univ Nebraska, Med Ctr, Dept Pharmacol & Expt Neurosci, Omaha, NE 68198 USA. Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA. Michigan State Univ, Dept Pharmacol & Toxicol, E Lansing, MI 48824 USA. Univ N Carolina, Sch Pharm, Div Drug Delivery & Disposit, Chapel Hill, NC USA. NIGMS, Pharmacol Physiol & Biol Chem Div, Bethesda, MD USA. RP Bylund, DB (reprint author), Univ Nebraska, Med Ctr, Dept Pharmacol & Expt Neurosci, 985800 Nebraska Med Ctr, Omaha, NE 68198 USA. EM dbylund@unmc.edu RI Bylund, David/A-9344-2009; Persky, Adam/E-2341-2016 NR 5 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 1534-0384 J9 MOL INTERV JI Mol. Interv. PD DEC PY 2005 VL 5 IS 6 BP 330 EP 333 DI 10.1124/mi.5.6.2 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 003NW UT WOS:000234689900002 PM 16394246 ER PT J AU Buchanan, SK AF Buchanan, SK TI Bacterial metal detectors SO MOLECULAR MICROBIOLOGY LA English DT Editorial Material ID FERRIC CITRATE TRANSPORT; FECA; TONB; MEMBRANE; IRON; INDUCTION; PROTEINS; SYSTEM AB Gram negative bacteria can detect environmental iron using outer membrane transporters (OMTs), and then regulate certain transport genes to take advantage of a readily available iron source. This process begins with an iron complex being bound by an OMT, and results in a signal being sent across the outer membrane, the periplasmic space, and the inner membrane, to a sigma factor that interacts with RNA polymerase and initiates transcription of relevant genes. Many of the interactions contributing to signalling have been observed by genetic and biochemical studies, but structural studies, which potentially show these interactions in molecular detail, have been limited. In this issue, Garcia-Herrero and Vogel describe an NMR structure of the periplasmic domain of an OMT, which had not been seen in previous X-ray crystal structures. This domain transmits the 'iron availability' signal to the next protein in the signal transduction cascade, which sits in the inner membrane and extends into the periplasm. The new structure extends our knowledge of transporter architecture and suggests how signalling may occur across the outer membrane. C1 NIDDK, Mol Biol Lab, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Buchanan, SK (reprint author), NIDDK, Mol Biol Lab, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. EM skbuchan@helix.nih.gov FU Intramural NIH HHS; NIDDK NIH HHS [Z01 DK011003-04] NR 14 TC 5 Z9 6 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD DEC PY 2005 VL 58 IS 5 BP 1205 EP 1209 DI 10.1111/j.1365-2958.2005.04904.x PG 5 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 982OE UT WOS:000233170700001 PM 16313609 ER PT J AU Wess, J AF Wess, J TI Allosteric binding sites on muscarinic acetylcholine receptors SO MOLECULAR PHARMACOLOGY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; M-2 RECEPTORS; SECONDARY HYPERPARATHYROIDISM; SNAKE TOXINS; IDENTIFICATION; MODULATORS; SUBTYPES; LIGANDS; HEMODIALYSIS; PHARMACOLOGY AB In this issue of Molecular Pharmacology, Trankle et al. ( p. 1597) present new findings regarding the existence of a second allosteric site on the M(2) muscarinic acetylcholine receptor ( M(2) mAChR). The M(2) mAChR is a prototypic class A G protein-coupled receptor ( GPCR) that has proven to be a very useful model system to study the molecular mechanisms involved in the binding of allosteric GPCR ligands. Previous studies have identified several allosteric muscarinic ligands, including the acetylcholinesterase inhibitor tacrine and the bis-pyridinium derivative 4,4'-bis-[(2,6-dichloro-benzyloxy-imino)-methyl]1,1'-propane-1,3-diyl-bis-pyridinium dibromide (Duo3), which, in contrast to conventional allosteric muscarinic ligands, display concentration-effect curves with slope factors > 1. By analyzing the interactions of tacrine and Duo3 with other allosteric muscarinic agents predicted to bind to the previously identified 'common' allosteric binding site, Trankle et al. provide evidence suggesting that two allosteric agents and one orthosteric ligand may be able to bind to the M(2) mAChR simultaneously. Moreover, studies with mutant mAChRs indicated that the M(2) receptor epitopes involved in the binding of tacrine and Duo3 may not be identical. Molecular modeling and ligand docking studies suggested that the additional allosteric site probably represents a subdomain of the receptor's allosteric binding cleft. Because allosteric binding sites have been found on many other GPCRs and drugs interacting with these sites are thought to have great therapeutic potential, the study by Trankle et al. should be of considerable general interest. C1 NIH, Mol Signalling Sect, Bioorgan Chem Lab, NIDDK, Bethesda, MD 20892 USA. RP Wess, J (reprint author), NIH, Mol Signalling Sect, Bioorgan Chem Lab, NIDDK, Bldg 8A,Room B1A-05,8 Ctr Dr,MSC 0810, Bethesda, MD 20892 USA. EM jwess@helix.nih.gov NR 32 TC 28 Z9 28 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 2005 VL 68 IS 6 BP 1506 EP 1509 DI 10.1124/mol.105.019141 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 984XH UT WOS:000233340200001 PM 16183853 ER PT J AU Momeni, P Lu, CS Chou, YHW Chang, HC Chen, RS Chen, CC Hsu, JT Singleton, A Hardy, J AF Momeni, P Lu, CS Chou, YHW Chang, HC Chen, RS Chen, CC Hsu, JT Singleton, A Hardy, J TI Taiwanese cases of SCA2 are derived from a single founder SO MOVEMENT DISORDERS LA English DT Article DE SCA2; parkinsonism; ataxic phenotype; haplotype; common founder ID SPINOCEREBELLAR ATAXIA TYPE-2; DISEASE AB We have assessed the haplotypes at the ATXN2 locus in Taiwanese controls and in individuals with SCA2 ataxia with both ataxic and parkinsonian features. Our intention was to determine whether a different ataxin 2 haplotypes predisposed to the two phenotypes. In fact, our analysis showed that all SCA2 mutations carriers had the same ataxin 2 haplotype: haplotype B, which accounts for only 15% of control haplotypes, implying that there is a common founder for all Taiwanese SCA2 patients. (c) 2005 Movement Disorder Society. C1 NIA, Neurogenet Lab, NIH, Bethesda, MD 20952 USA. Chang Gung Mem Hosp, Dept Neurol, Movement Disorders Unit, Taipei 10591, Taiwan. Chang Gung Mem Hosp, Neurosci Res Ctr, Taipei 10591, Taiwan. Chang Gung Mem Hosp, Human Mol Genet Lab, Taipei 10591, Taiwan. Kaohsiung Med Univ, Dept Neurol, Chung Ho Mem Hosp, Kaohsiung, Taiwan. RP Momeni, P (reprint author), NIA, Neurogenet Lab, NIH, 35 Convent Rd,Room 1A1010, Bethesda, MD 20952 USA. EM momeni@mail.nih.gov RI Singleton, Andrew/C-3010-2009; Hardy, John/C-2451-2009 NR 7 TC 4 Z9 4 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 2005 VL 20 IS 12 BP 1633 EP 1636 DI 10.1002/mds.20638 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 994LJ UT WOS:000234033000021 PM 16078202 ER PT J AU Bras, JM Guerreiro, RJ Ribeiro, MH Januario, C Morgadinho, A Oliveira, CR Cunha, L Hardy, J Singleton, A AF Bras, JM Guerreiro, RJ Ribeiro, MH Januario, C Morgadinho, A Oliveira, CR Cunha, L Hardy, J Singleton, A TI G2019S dardarin substitution is a common cause of Parkinson's disease in a Portuguese cohort SO MOVEMENT DISORDERS LA English DT Article DE LRRK2; dardarin; PARK8; Parkinson's disease ID AUTOSOMAL-DOMINANT PARKINSONISM; LRRK2 MUTATION; GENE AB LRRK2 mutations have recently been described in families with Parkinson's disease. Here we show that one of them (G2019S) is present in 6% (7 of 124) unrelated cases of disease in a clinic-based sample series from central Portugal, but not present in 126 controls from the same population. Thus, LRRK2 mutations appear to be a common cause of typical Parkinson's disease and as such will alter clinical practice. (c) 2005 Movement Disorder Society. C1 NIA, Neurogenet Lab, Porter Neurosci Ctr, NIH, Rockville, MD 20852 USA. Coimbra Univ Hosp, Neurol Serv, Coimbra, Portugal. Univ Coimbra, Fac Med, Inst Biochem, Ctr Neurosci & Cell Biol, Coimbra, Portugal. RP Singleton, A (reprint author), NIA, Neurogenet Lab, Porter Neurosci Ctr, NIH, 35 Convent Rd,Room A1A, Rockville, MD 20852 USA. EM singleta@mail.nih.gov RI Bras, Jose/D-3366-2009; Oliveira, Catarina/F-3685-2010; Bras, Jose/A-1428-2011; Singleton, Andrew/C-3010-2009; Hardy, John/C-2451-2009; Guerreiro, Rita/A-1327-2011; Januario Santos, Maria Cristina/O-5939-2015 OI Oliveira, Catarina/0000-0001-6942-4328; Januario Santos, Maria Cristina/0000-0001-5402-3978 NR 14 TC 72 Z9 72 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 2005 VL 20 IS 12 BP 1653 EP 1655 DI 10.1002/mds.20682 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 994LJ UT WOS:000234033000027 PM 16149095 ER PT J AU Gupta, S Solomon, JM Tasciyan, TA Cao, MM Stone, RD Ostuni, JL Ohayon, JM Muraro, PA Frank, JA Richert, ND McFarland, HF Bagnato, F AF Gupta, S Solomon, JM Tasciyan, TA Cao, MM Stone, RD Ostuni, JL Ohayon, JM Muraro, PA Frank, JA Richert, ND McFarland, HF Bagnato, F TI Interferon-beta-Ib effects on re-enhancing lesions in patients with multiple sclerosis SO MULTIPLE SCLEROSIS LA English DT Article DE contrast-enhancing lesions; interferon-beta; lesion sizes; magnetic resonance imaging; multiple sclerosis; re-enhancing lesions ID CENTRAL-NERVOUS-SYSTEM; DISEASE-ACTIVITY; DIAGNOSTIC-CRITERIA; CONTROLLED TRIAL; GADOLINIUM-DTPA; PROGRESSIVE MS; SPIN-ECHO; MRI; ENCEPHALOMYELITIS; ENHANCEMENT AB Interferon-beta (IFN beta) reduces the number and load of new contrast-enhancing lesions (CELs) in patients with multiple sclerosis (MS). However the ability of IFN beta to reduce lesion sizes and re-enhancements of pre-existing CELs has not been examined extensively. Activity of contrast re-enhancing lesions (Re-CELs) and contrast single-enhancing lesions (S-CELs) were monitored in ten patients with relapsing-remitting (RR) MS. These patients underwent monthly post-contrast magnetic resonance imaging (MRIs) for an 18-month natural history phase and an 18-month therapy phase with subcutaneous IFN beta-1b, totaling 37 images per patient. The activity was analysed using the First image as a baseline and registering subsequent active monthly images to the baseline. There was a 76.4% reduction in the number of CELs with IFN beta therapy. The decrease was greater (P = 0.003) for S-CELs (82.3%) than for Re-CELs (57.4%). S-CELs showed no changes in durations of enhancement and maximal lesion sizes with treatment. Exclusively for Re-CELs, IFN beta-1b significantly decreased maximal lesion sizes, total number of enhancement periods and total months of enhancement. Thus, IFN beta appears to be effective in reducing the degree of severity of inflammation among Re-CELs, as reflected by their reduced maximal lesion sizes and durations of enhancement. C1 Natl Inst Neurol Disorders & Stroke, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. New York Med Coll, Valhalla, NY 10595 USA. Med Numer Inc, Sterling, VA USA. NIH, Lab Diagnost Radiol Res, Ctr Clin, Bethesda, MD 20892 USA. RP Bagnato, F (reprint author), Bldg 10,Rm 5B16,9000 Rockville Pike, Bethesda, MD 20892 USA. EM bagnatof@ninds.nih.gov OI Muraro, Paolo/0000-0002-3822-1218 NR 34 TC 8 Z9 8 U1 0 U2 0 PU HODDER ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 1352-4585 J9 MULT SCLER JI Mult. Scler. PD DEC PY 2005 VL 11 IS 6 BP 658 EP 668 DI 10.1191/1352458505ms1229oa PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 990LI UT WOS:000233744100007 PM 16320725 ER PT J AU McFarland, HF Reingold, SC AF McFarland, HF Reingold, SC TI The future of multiple sclerosis therapies: redesigning multiple sclerosis clinical trials in a new therapeutic era SO MULTIPLE SCLEROSIS LA English DT Article DE clinical trials; multiple sclerosis ID SECONDARY PROGRESSIVE MS; OUTCOMES ASSESSMENT; END-POINTS; DISEASE; ENDPOINTS; REVISION AB Due to past success in testing and gaining regulatory approval for a variety of therapies in multiple sclerosis (MS), the conduct of future clinical trials has become increasingly problematic. An international workshop has met to discuss the issues facing the MS clinical trial community and to examine possible new strategies for the design of trials. Particular focus has been placed on trials that either avoid the use of a placebo because of ethical considerations or on designs that allow new therapies to be studied more rapidly or with fewer patients than needed in a conventional placebo-controlled trial. The discussions resulting from the workshop should provide a basis for the examination and implementation of innovative clinical trial designs in MS. C1 Natl Inst Neurol Disorders & Stroke, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. Natl Multiple Sclerosis Soc, New York, NY USA. Sci & Clin Review Associates LLC, New York, NY USA. RP McFarland, HF (reprint author), Natl Inst Neurol Disorders & Stroke, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. EM mcfarlandh@ninds.nih.gov RI Thompson, Alan/C-2654-2008 OI Thompson, Alan/0000-0002-4333-8496 NR 30 TC 16 Z9 16 U1 0 U2 0 PU HODDER ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 1352-4585 J9 MULT SCLER JI Mult. Scler. PD DEC PY 2005 VL 11 IS 6 BP 669 EP 676 DI 10.1191/1352458505ms1231oa PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 990LI UT WOS:000233744100008 PM 16320726 ER PT J AU Sans, N Wang, PY Due, QS Petralia, RS Wang, YX Nakka, S Blumer, JB Macara, IG Wenthold, RJ AF Sans, N Wang, PY Due, QS Petralia, RS Wang, YX Nakka, S Blumer, JB Macara, IG Wenthold, RJ TI Mpins modulates PSD-95 and SAP102 trafficking and influences NMDA receptor surface expression SO NATURE CELL BIOLOGY LA English DT Article ID HETEROTRIMERIC G-PROTEINS; TETRATRICOPEPTIDE REPEAT; CELL-DIVISION; AGS3; MOTIF; PHOSPHORYLATION; IDENTIFICATION; SYNAPSES; COMPLEX; DOMAIN AB Appropriate trafficking and targeting of glutamate receptors (GIuRs) to the postsynaptic density is crucial for synaptic function. We show that mPins (mammalian homologue of Drosophila melanogaster partner of inscuteable) interacts with SAP102 and PSD-95 (two PDZ proteins present in neurons), and functions in the formation of the NMDAR-MAGUK (N-methyl-D-aspartate receptor-membrane-associated guanylate kinase) complex. mPins enhances trafficking of SAP102 and NMDARs to the plasma membrane in neurons. Expression of dominant-negative constructs and short-interfering RNA (siRNA)-mediated knockdown of mPins decreases SAP102 in dendrites and modifies surface expression of NMDARs. mPins changes the number and morphology of dendritic spines and these effects depend on its G alpha i interaction domain, thus implicating G-protein signalling in the regulation of postsynaptic structure and trafficking of GluRs. C1 NIDCD, Neurochem Lab, NIH, Bethesda, MD 20892 USA. Univ Virginia, Sch Med, Ctr Cell Signaling, Charlottesville, VA 22908 USA. Univ Virginia, Sch Med, Dept Pharmacol, Charlottesville, VA 22908 USA. LSU Hlth Sci Ctr, Dept Pharmacol & Expt Therapeut, New Orleans, LA 70112 USA. RP Sans, N (reprint author), INSERM, Inst Neurosci F Magendie, Equipe AVENIR, IFR8, F-33077 Bordeaux, France. EM nathalie.sans@bordeaux.inserm.fr OI Du, Quansheng/0000-0003-4079-8662 FU Intramural NIH HHS; NIGMS NIH HHS [GM070902]; NIMH NIH HHS [F32 MH065092, F32MH65092] NR 38 TC 74 Z9 76 U1 0 U2 1 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 2005 VL 7 IS 12 BP 1179 EP 1190 DI 10.1038/ncb1325 PG 12 WC Cell Biology SC Cell Biology GA 990MW UT WOS:000233748900011 PM 16299499 ER PT J AU Statsuk, AV Bai, RL Baryza, JL Verma, VA Hamel, E Wender, PA Kozmin, SA AF Statsuk, AV Bai, RL Baryza, JL Verma, VA Hamel, E Wender, PA Kozmin, SA TI Actin is the primary cellular receptor of bistramide A SO NATURE CHEMICAL BIOLOGY LA English DT Article ID SKELETAL-MUSCLE FIBERS; KINASE-C-DELTA; LISSOCLINUM-BISTRATUM; MARINE MACROLIDES; PROTEIN; CELLS; CYTOKINESIS; BINDING; DEPSIPEPTIDE; BRYOSTATIN AB Bistramide A ( 1) is a marine natural product with broad, potent antiproliferative effects(1-7). Bistramide A has been reported to selectively activate protein kinase C (PKC) delta, leading to the view that PKC delta is the principal mediator of antiproliferative activity of this natural product(8). Contrary to this observation, we established that bistramide A binds PKCd with low affinity, does not activate this kinase in vitro and does not translocate GFP- PKCd. Furthermore, we identified actin as the cellular receptor of bistramide A. We report that bistramide A disrupts the actin cytoskeleton, inhibits actin polymerization, depolymerizes filamentous F-actin in vitro and binds directly to monomeric G-actin in a 1:1 ratio with a K-d of 7 nM. We also constructed a fully synthetic(9) bistramide A - based affinity matrix and isolated actin as a specific bistramide A - binding protein. This activity provides a molecular explanation for the potent antiproliferative effects of bistramide A, identifying it as a new biochemical tool for studies of the actin cytoskeleton and as a potential lead for development of a new class of antitumor agents(7,10). C1 Univ Chicago, Dept Chem, Chicago, IL 60637 USA. NCI, Toxicol & Pharmacol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21702 USA. Stanford Univ, Dept Chem, Stanford, CA 94305 USA. Stanford Univ, Dept Mol Pharmacol, Stanford, CA 94305 USA. RP Kozmin, SA (reprint author), Univ Chicago, Dept Chem, 5735 S Ellis Ave, Chicago, IL 60637 USA. EM skozmin@uchicago.edu FU NCI NIH HHS [CA31845] NR 30 TC 50 Z9 51 U1 2 U2 14 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1552-4450 J9 NAT CHEM BIOL JI Nat. Chem. Biol. PD DEC PY 2005 VL 1 IS 7 BP 383 EP 388 DI 10.1038/nchembio748 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 986KE UT WOS:000233447700010 PM 16372404 ER PT J AU Theodore, WH AF Theodore, WH TI Brain stimulation for epilepsy SO NATURE CLINICAL PRACTICE NEUROLOGY LA English DT Editorial Material ID ELECTRICAL-STIMULATION; INTRACTABLE EPILEPSY; SEIZURES; THALAMUS C1 NINDS, Clin Epilepsy Sect, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. RP Theodore, WH (reprint author), NINDS, Clin Epilepsy Sect, NIH, Bldg 10 Room 5N-250, Bethesda, MD 20892 USA. EM theodorw@ninds.nih.gov NR 10 TC 8 Z9 9 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1745-834X J9 NAT CLIN PRACT NEURO JI Nat. Clin. Pract. Neurol. PD DEC PY 2005 VL 1 IS 2 BP 64 EP 65 DI 10.1038/ncpneuro0051 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 015DN UT WOS:000235532200003 PM 16932495 ER PT J AU Gao, XJ Bashirova, A Iversen, AKN Phair, J Goedert, JJ Buchbinder, S Hoots, K Vlahov, D Altfeld, M O'Brien, SJ Carrington, M AF Gao, XJ Bashirova, A Iversen, AKN Phair, J Goedert, JJ Buchbinder, S Hoots, K Vlahov, D Altfeld, M O'Brien, SJ Carrington, M TI AIDS restriction HLA allotypes target distinct intervals of HIV-1 pathogenesis SO NATURE MEDICINE LA English DT Article ID VIRUS TYPE-1 INFECTION; T-LYMPHOCYTE RESPONSE; ESCAPE MUTATION; TRANSMISSION; GAG; REVERSION; EVOLUTION AB An effective acquired immune response to infectious agents mediated by HLA-restricted T-cell recognition can target different stages of disease pathogenesis. We show here that three distinct HLA alleles known to alter the overall rate of AIDS progression act during distinct intervals after HIV-1 infection. The discrete timing of HLA allele influence suggests alternative functional mechanisms in immune defense against this dynamic and chronic immunosuppressive disease. C1 NCI, Lab Genom Divers, SAIC Frederick, Basic Res Program, Frederick, MD 21702 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21231 USA. Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, MRC Human Immunol Unit, Oxford OX3 9DS, England. Northwestern Univ, Howard Brown Hlth Ctr, Chicago, IL 60611 USA. Northwestern Univ, Fineberg Sch Med, Chicago, IL 60611 USA. NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. San Francisco Dept Publ Hlth, San Francisco, CA 94102 USA. Univ Texas, Hlth Sci Ctr, Gulf States Hemophilia Ctr, Houston, TX 77030 USA. New York Acad Med, Ctr Urban Epidemiol Studies, New York, NY 10029 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. NCI, Lab Genom Divers, Frederick, MD 21702 USA. RP Carrington, M (reprint author), NCI, Lab Genom Divers, SAIC Frederick, Basic Res Program, POB B, Frederick, MD 21702 USA. EM carringt@ncifcrf.gov FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400]; NIDA NIH HHS [DA 04334] NR 15 TC 134 Z9 137 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD DEC PY 2005 VL 11 IS 12 BP 1290 EP 1292 DI 10.1038/nm1333 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 990WR UT WOS:000233774400025 PM 16288280 ER PT J AU Demierre, MF Higgins, PDR Gruber, SB Hawk, E Lippman, SM AF Demierre, MF Higgins, PDR Gruber, SB Hawk, E Lippman, SM TI Statins and cancer prevention SO NATURE REVIEWS CANCER LA English DT Review ID HMG-COA REDUCTASE; LOVASTATIN-INDUCED APOPTOSIS; COENZYME-A REDUCTASE; AVERAGE CHOLESTEROL LEVELS; CORONARY-HEART-DISEASE; HUMAN-MELANOMA CELLS; MILLION US VETERANS; BREAST-CANCER; IN-VITRO; PROSTATE-CANCER AB Randomized controlled trials for preventing cardiovascular disease indicated that statins had provocative and unexpected benefits for reducing colorectal cancer and melanoma. These findings have led to the intensive study of statins in cancer prevention, including recent, large population-based studies showing statin-associated reductions in overall, colorectal and prostate cancer. Understanding the complex cellular effects (for example, on angiogenesis and inflammation) and the underlying molecular mechanisms of statins (for example, 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase-dependent processes that involve geranylgeranylation of Rho proteins, and HMG-CoA-independent processes that involve lymphocyte-function-associated antigen 1) will advance the development of molecularly targeted agents for preventing cancer. This understanding might also help the development of drugs for other ageing-related diseases with interrelated molecular pathways. C1 Univ Texas, MD Anderson Canc Ctr, Dept Clin Canc Prevent, Houston, TX 77230 USA. Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02118 USA. Univ Michigan, Med Ctr, Dept Internal Med, Div Med & Mol Genet, Ann Arbor, MI 48109 USA. Univ Michigan, Med Ctr, Dept Epidemiol & Human Genet, Ann Arbor, MI 48109 USA. NCI, Off Ctr Training & Resources, Bethesda, MD 20892 USA. RP Lippman, SM (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Clin Canc Prevent, Houston, TX 77230 USA. EM slippman@mdanderson.org RI Higgins, Peter/A-3511-2009 OI Higgins, Peter/0000-0003-1602-4341 NR 127 TC 409 Z9 428 U1 8 U2 48 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD DEC PY 2005 VL 5 IS 12 BP 930 EP 942 DI 10.1038/nrc1751 PG 13 WC Oncology SC Oncology GA 990WS UT WOS:000233774500012 PM 16341084 ER PT J AU Allan, JM Lois, BT AF Allan, JM Lois, BT TI Mechanisms of therapy-related carcinogenesis SO NATURE REVIEWS CANCER LA English DT Review ID ACUTE MYELOID-LEUKEMIA; DNA MISMATCH REPAIR; BREAKPOINT CLUSTER REGION; TOPOISOMERASE-II CLEAVAGE; CELL-CYCLE ARREST; HODGKINS-DISEASE; IONIZING-RADIATION; MICROSATELLITE INSTABILITY; BREAST-CANCER; OVARIAN-CANCER AB Therapy-related cancers, defined as second primary cancers that arise as a consequence of chemotherapy and/or radiotherapy, are unusual in that they have a well-defined aetiology. Knowledge of the specific nature of the initiating exposure and exactly when it occurred has made it easier to identify crucial genetic events and to model these in vitro and in vivo. As such, the study of therapy-related cancers has led to the elucidation of discrete mechanisms of carcinogenesis, including DNA double-strand-break-induced gene translocation and genomic instability conferred by loss of DNA repair. Unsurprisingly, some of these mechanisms seem to operate in the development of sporadic cancers. C1 Univ York, Dept Biol, Epidemiol & Genet Unit, York YO10 5YW, N Yorkshire, England. NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Allan, JM (reprint author), Univ York, Dept Biol, Epidemiol & Genet Unit, York YO10 5YW, N Yorkshire, England. EM Jim.Allan@egu.york.ac.uk RI Allan, James/B-4448-2009 FU Intramural NIH HHS NR 138 TC 141 Z9 146 U1 2 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD DEC PY 2005 VL 5 IS 12 BP 943 EP 955 DI 10.1038/nrc1749 PG 13 WC Oncology SC Oncology GA 990WS UT WOS:000233774500013 PM 16294218 ER PT J AU O'Connor, KA Roth, BL AF O'Connor, KA Roth, BL TI Finding new tricks for old drugs: An efficient route for public-sector drug discovery SO NATURE REVIEWS DRUG DISCOVERY LA English DT Review ID VALVULAR HEART-DISEASE; SEROTONIN RECEPTORS; 5-HT2B RECEPTORS; HUMAN GENOME; FENFLURAMINE; GLUTAMATE; ALS; CEFTRIAXONE; EXPRESSION; PERGOLIDE AB With the annotation of the human genome approaching completion, public-sector researchers - spurred in part by various National Institutes of Health Roadmap Initiatives have become increasingly engaged in drug discovery and development efforts. Although large and diverse chemical libraries of 'drug-like' compounds can be readily screened to yield chemically novel scaffolds, transforming these 'chemical probes' into drugs is a daunting endeavour. A more efficient approach involves screening libraries of approved and off-patent medications; both phenotypic- and molecular target-based screening of 'old drugs' can readily yield compounds that could be immediately used in clinical trials. Using case studies, we describe how this approach has rapidly identified candidate medications suitable for clinical trials in disorders such as progressive multifocal leukoencephalopathy and amyotrophic lateral sclerosis. This approach has also led to the discovery of the molecular targets responsible for serious drug side effects, thereby allowing efficient 'counter-screening' to avoid these side effects. C1 Case Western Reserve Univ, Sch Med, Ctr Comprehens Canc, Dept Biochem, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Ctr Comprehens Canc, Dept Psychiat, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Ctr Comprehens Canc, Dept Neurosci, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, NIMH, Psychoact Drug Screening Program, Cleveland, OH 44106 USA. RP Roth, BL (reprint author), Case Western Reserve Univ, Sch Med, Ctr Comprehens Canc, Dept Biochem, 2109 Adelbert Rd, Cleveland, OH 44106 USA. EM bryan.roth@case.edu RI Roth, Bryan/F-3928-2010 NR 51 TC 124 Z9 126 U1 2 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1776 J9 NAT REV DRUG DISCOV JI Nat. Rev. Drug Discov. PD DEC PY 2005 VL 4 IS 12 BP 1005 EP 1014 DI 10.1038/nrd1900 PG 10 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 990WW UT WOS:000233774900021 PM 16341065 ER PT J AU Finkel, T AF Finkel, T TI Radical medicine: treating ageing to cure disease SO NATURE REVIEWS MOLECULAR CELL BIOLOGY LA English DT Review ID OXIDATIVE STRESS; REACTIVE OXYGEN; LIFE-SPAN; ALZHEIMERS-DISEASE; DNA-DAMAGE; SACCHAROMYCES-CEREVISIAE; CALORIE RESTRICTION; CARDIOVASCULAR RISK; PARKINSONS-DISEASE; SIGNALING PATHWAY AB The incidence of many diseases rises sharply with age. Although clearly separable, ageing and certain age-related diseases might share common mechanisms. Cellular metabolism and subsequent generation of reactive oxygen species might contribute both to the rate at which we age and to our susceptibility to numerous chronic diseases, therefore therapies that directly target the ageing process might provide new ways to treat human diseases. C1 NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. RP Finkel, T (reprint author), NHLBI, Cardiovasc Branch, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM finkelt@nih.gov FU Intramural NIH HHS NR 74 TC 142 Z9 149 U1 2 U2 16 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0072 J9 NAT REV MOL CELL BIO JI Nat. Rev. Mol. Cell Biol. PD DEC PY 2005 VL 6 IS 12 BP 971 EP 976 DI 10.1038/nrm1763 PG 7 WC Cell Biology SC Cell Biology GA 990WU UT WOS:000233774700017 PM 16227974 ER PT J AU Wu, WH Alami, S Luk, E Wu, CH Sen, S Mizuguchi, G Wei, D Wu, C AF Wu, WH Alami, S Luk, E Wu, CH Sen, S Mizuguchi, G Wei, D Wu, C TI Swc2 is a widely conserved H2AZ-binding module essential for ATP-dependent histone exchange SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID CHROMATIN REMODELING COMPLEX; NUCLEOSOME CORE PARTICLE; SACCHAROMYCES-CEREVISIAE; VARIANT H2A.Z; DNA TRANSLOCATION; CRYSTAL-STRUCTURE; H4 ACETYLATION; PROTEIN; HETEROCHROMATIN; CHAPERONES AB The histone variant H2AZ is incorporated preferentially at specific locations in chromatin to modulate chromosome functions. In Saccharomyces cerevisiae, deposition of histone H2AZ is mediated by the multiprotein SWR1 complex, which catalyzes ATP-dependent exchange of nucleosomal histone H2A for H2AZ. Here, we define interactions between SWR1 components and H2AZ, revealing a link between the ATPase domain of Swr1 and three subunits required for the binding of H2AZ. We discovered that Swc2 binds directly to and is essential for transfer of H2AZ. Swc6 and Arp6 are necessary for the association of Swc2 and for nucleosome binding, whereas other subunits, Swc5 and Yaf9, are required for H2AZ transfer but neither H2AZ nor nucleosome binding. Finally, the C-terminal alpha-helix of H2AZ is crucial for its recognition by SWR1. These findings provide insight on the initial events of histone exchange. C1 NCI, Mol Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Wu, C (reprint author), NCI, Mol Cell Biol Lab, Ctr Canc Res, NIH, Bldg 37,Room 6068, Bethesda, MD 20892 USA. EM carlwu@helix.nih.gov RI Sen, Subhojit/I-9033-2012; OI Sen, Subhojit/0000-0001-8457-915X; Luk, Ed/0000-0002-6619-2258 FU Intramural NIH HHS NR 49 TC 129 Z9 135 U1 1 U2 13 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD DEC PY 2005 VL 12 IS 12 BP 1064 EP 1071 DI 10.1038/nsmb1023 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 990WQ UT WOS:000233774300015 PM 16299513 ER PT J AU Yan, Y Wang, Y Tan, Q Lubet, RA You, M AF Yan, Y Wang, Y Tan, Q Lubet, RA You, M TI Efficacy of deguelin and silibinin on benzo(a)pyrene-induced lung tumorigenesis in A/J mice SO NEOPLASIA LA English DT Article DE chemoprevention; deguelin; silibinin; lung cancer; A/J mice ID BRONCHIAL EPITHELIAL-CELLS; PHOSPHATIDYLINOSITOL 3-KINASE/AKT PATHWAY; ENVIRONMENTAL TOBACCO-SMOKE; ATHYMIC NUDE-MICE; PROTEIN-KINASES; TUMOR-GROWTH; CANCER; APOPTOSIS; SILYMARIN; COLON AB We evaluated deguelin and silibinin in A/J mice treated with the tobacco-specific carcinogen benzo(a)pyrene (BP) for their ability to inhibit pulmonary adenoma formation and growth. Animals were treated with either deguelin (5.0 or 10.0 mg/kg body weight, by gavage) or silibinin at doses of 0.05% and 0.1% in the diet, approximately 10 days before a single intraperitoneal dose of BP. We found that oral administration of deguelin reduced tumor multiplicity by 56% and tumor load by 78%, whereas silibinin treatment at doses of 0.05% and 0.1% in the diet did not show any significant efficacy on either tumor multiplicity or tumor load. The result indicates that deguelin significantly inhibits pulmonary adenoma formation and growth in A/J mice. Finding new and effective agents that can prevent lung cancer is urgently needed because cancer of the lungs remains the principal cause of cancer deaths in the United States and because effective chemoprevention of this cancer type remains elusive. Thus, deguelin appears to be a promising new preventive agent for lung cancer and may be considered for further studies in other animal models and in clinical trials. 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, Div Canc Prevent, 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@msnotes.wustl.edu FU NCI NIH HHS [CA058554, CA9696401, R01 CA058554] NR 33 TC 29 Z9 31 U1 1 U2 3 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD DEC PY 2005 VL 7 IS 12 BP 1053 EP 1057 DI 10.1593/neo.05532 PG 5 WC Oncology SC Oncology GA 000KI UT WOS:000234460100003 PM 16354587 ER PT J AU Burrowes, JD Larive, B Chertow, GM Cockram, DB Dwyer, JT Greene, T Kusek, JW Leung, J Rocco, MV AF Burrowes, JD Larive, B Chertow, GM Cockram, DB Dwyer, JT Greene, T Kusek, JW Leung, J Rocco, MV CA HEMO Study Grp TI Self-reported appetite, hospitalization and death in haemodialysis patients: findings from the hemodialysis (HEMO) study SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article DE anorexia; appetite; haemodialysis; malnutrition; morbidity; mortality ID MAINTENANCE HEMODIALYSIS; MEMBRANE FLUX; DIALYSIS; INFLAMMATION; NUTRITION; MODELS AB Background. Anorexia is an important cause of protein-energy malnutrition (PEM) in haemodialysis patients. We investigated whether self-reported appetite was associated with death and hospitalization in subjects enrolled in the Hemodialysis (HEMO) Study. Methods. The HEMO Study was a 7-year, multicentre, randomized trial (N = 1846), which examined the effects of dialysis dose and membrane flux on mortality and morbidity. Three questions from the Appetite and Diet Assessment Tool (ADAT) were used to determine whether appetite had changed over time in the randomized treatment groups. The relations among ADAT scores, dietary protein and energy intakes, biochemical and anthropometric measures, and quality of life were assessed. We used Cox proportional hazards models to evaluate the relative risks of death and hospitalization associated with static and dynamic ADAT scores, adjusted for demographic factors, dose and flux assignments, and co-morbidity. Results. The average length of follow-up was 2.84 years. After adjusting for demographic factors and randomized treatment assignments, there was a significant association between poorer self-reported appetite and death (RR 1.52, 95% CI 1.16-1.98); however, the association became non-significant with further adjustment for co-morbidity (RR 1.23, 95% CI 0.94-1.62). Poorer appetite was unequivocally associated with increased hospitalization rates (multivariable RR 1.35, 95% CI 1.13-1.61). The longitudinal effect of worsening appetite from baseline to 1 year was not associated with mortality or hospitalization rate after adjusting for co-morbidity. Conclusions. The association between appetite and death was confounded by co-morbidity. Self-reported appetite was associated with hospitalization rate in haemodialysis patients and, thus, it may be a useful screening tool for this outcome. Patients who report poor or very poor appetites should be monitored, and they should receive more comprehensive nutritional assessments. C1 Long Isl Univ, Dept Nutr, Sch Hlth Profess & Nursing, Brookville, NY 11548 USA. Cleveland Clin Fdn, Dept Biostat & Epidemiol, Cleveland, OH 44195 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Abbott Labs, Ross Prod Div, Columbus, OH USA. Tufts Univ, Sch Med & Friedman, Boston, MA USA. Tufts Univ, Sch Nutr Sci & Policy, Boston, MA USA. Tufts New England Med ctr, Frances Stern Nutr Ctr, Boston, MA USA. NIDDK, NIH, Bethesda, MD USA. Wake Forest Univ, Sch Med, Dept Internal Med, Winston Salem, NC 27109 USA. RP Burrowes, JD (reprint author), Long Isl Univ, Dept Nutr, Sch Hlth Profess & Nursing, 720 No Blvd,CW Post Campus, Brookville, NY 11548 USA. EM jerrilynn.burrowes@liu.edu OI Dwyer, Johanna/0000-0002-0783-1769 NR 20 TC 75 Z9 77 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD DEC PY 2005 VL 20 IS 12 BP 2765 EP 2774 DI 10.1093/ndt/gfi132 PG 10 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA 985FH UT WOS:000233361800029 PM 16204298 ER PT J AU DelParigi, A Pannacciulli, N Le, DNT Tataranni, PA AF DelParigi, A Pannacciulli, N Le, DNT Tataranni, PA TI In pursuit of neural risk factors for weight gain in humans SO NEUROBIOLOGY OF AGING LA English DT Article; Proceedings Paper CT SPARK Workshop 2004 CY JUL, 2004 CL Bar Harbor, ME DE obesity; positron emission tomography; regional cerebral blood flow; risk factors for weight gain ID POSITRON-EMISSION-TOMOGRAPHY; DOUBLY-LABELED WATER; BODY-WEIGHT; ENERGY-EXPENDITURE; FOOD-INTAKE; LOW-FAT; TASTE PREFERENCES; BRAIN RESPONSES; DIETARY-INTAKE; OBESE SUBJECTS AB Obesity is a multifactorial disease associated with an increased risk of type 2 diabetes, coronary artery disease, cancer, and consequently, with a reduced length of life. Metabolic phenotypes of reduced energy expenditure have been associated with weight gain, but their contribution has been estimated to be relatively small. On the other hand, excessive food intake is likely to be the major determinant of positive energy balances and it is underlied by both non-conscious (homeostatic) and conscious (perceptual, emotional, and cognitive) phenomena processed in the brain. Functional neuroimaging is a promising tool to investigate these neural substrates in humans, because it provides a measurement of state-dependent brain regional activity, bridging the gap between neural events and behavioral responses. Using this technology, a few studies have provided the first evidence of functional differences between obese and lean individuals in the brain's response to energy intake and investigated the presence of neural risk factors of weight gain. (c) 2005 Elsevier Inc. All rights reserved. C1 NIDDK, Obes & Diabet Clin Res Sect, PECRB, US Dept HHS,NIH, Phoenix, AZ USA. RP DelParigi, A (reprint author), Pfizer Inc, Global Res & Dev, Groton, CT 06340 USA. EM angelo.delparigi@pfizer.com NR 59 TC 5 Z9 5 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD DEC PY 2005 VL 26 SU 1 BP S50 EP S55 DI 10.1016/j.neurobiolaaging.2005.09.008 PG 6 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 995SF UT WOS:000234123400012 ER PT J AU Wang, J Xu, GL Slunt, HH Gonzales, V Coonfield, M Fromholt, D Copeland, NG Jenkins, NA Borchelt, DR AF Wang, J Xu, GL Slunt, HH Gonzales, V Coonfield, M Fromholt, D Copeland, NG Jenkins, NA Borchelt, DR TI Coincident thresholds of mutant protein for paralytic disease and protein aggregation caused by restrictively expressed superoxide dismutase cDNA SO NEUROBIOLOGY OF DISEASE LA English DT Article DE FALS; superoxide dismutase; protein aggregation; transgenic mice; disease model ID AMYOTROPHIC-LATERAL-SCLEROSIS; MOTOR-NEURON DEGENERATION; HUMAN ALPHA-SYNUCLEIN; COPPER-BINDING-SITE; TRANSGENIC MICE; IN-VIVO; AMYLOID DEPOSITION; MOUSE MODEL; ALS; ACCUMULATION AB Familial amyotrophic lateral selerosis (FALS) has been modeled in transgenic mice by introducing mutated versions of human genomic DNA encompassing the entire gene for Cu,Zn superoxide dismutase (SOD1). In this setting, the transgene is expressed throughout the body and results in mice that faithfully recapitulate man), pathological and behavioral aspects of FALS. By contrast, transgenic mice made by introducing recombinant vectors, encoding cDNA genes, that target mutant SOD1 expression to motor neurons, only, or astrocytes, only, do not develop disease. Here, we report that mice transgenic for human SOD1 cDNA with the G37R mutation, driven by the mouse prion promoter, develop motor neuron disease. In this model, expression of the transgene is highest in CNS (both neurons and astrocytes) and muscle. The gene was not expressed in cells of the macrophage lineage. Although the highest expressing hemizygous transgenic mice fail to develop disease by 20 months of age, mice homozygous for the transgene show typical ALS-like phenotypes as early as 7 months of age. Spinal cords and brain stems from homozygous animals with motor neuron disease were found to contain aggregated species of mutant SOD1. The establishment of this SOD1-G37R cDNA transgenic model indicates that expression of mutant SOD1 proteins in the neuromuscular unit is sufficient to cause motor neuron disease. The expression levels required to induce disease coincide with the levels required to induce the formation of SOD1 aggregates. (c) 2005 Elsevier Inc. All rights reserved. C1 Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. NCI, Frederick Canc Res & Dev Ctr, Mouse Canc Genet Program, Frederick, MD 21702 USA. RP Borchelt, DR (reprint author), Univ Florida, McKnight Brain Inst, Dept Neurosci, 100 Newell Dr,Room L1-100H,POB 100244, Gainesville, FL 32610 USA. EM borchelt@mbi.ufl.edu NR 46 TC 74 Z9 76 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 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD DEC PY 2005 VL 20 IS 3 BP 943 EP 952 DI 10.1016/j.nbd.2005.06.005 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 990JN UT WOS:000233739100032 PM 16046140 ER PT J AU Fiddick, L Spampinato, MV Grafman, J AF Fiddick, L Spampinato, MV Grafman, J TI Social contracts and precautions activate different neurological systems: An fMRI investigation of deontic reasoning SO NEUROIMAGE LA English DT Article DE functional MRI; neurological system; reasoning; deontic reasoning; social cognition; evolutionary psychology ID WASON SELECTION TASK; FACIAL EXPRESSIONS; BRAIN; IMPAIRMENT; INFERENCE; RESPONSES; COGNITION; EXCHANGE; JUDGMENT; HUMANS AB We conducted an event-related, functional MRI investigation of 12 male's and 12 female's reasoning about conditional deontic rules, rules regulating people's behavior. We employed two different types of rules: social contracts and nonsocial, precautionary rules. Although the rules and the demands of the task were matched in terms of their logical structure, reasoning about social contracts and precautions activated a different constellation of neurological structures. The regions differentially activated by social contracts included dorsomedial PFC (BA 6/8), bilateral ventrolateral PFC (BA 47), the left angular gyrus (BA 39), and left orbitofrontal cortex (BA 10). The regions differentially activated by precautions included bilateral insula, the left lentiform nucleus, posterior cingulate (BA 29/31), anterior cingulate (BA 24) and right postcentral gyrus (BA 3). Collectively, reasoning about prescriptive rules activated the dorsomedial PFC (BA 6/8). The results reinforce the view that human reasoning is not a unified phenomenon, but is content-sensitive. Published by Elsevier Inc. C1 NINDS, Cognit Neurosci Sect, Bethesda, MD 20892 USA. RP Grafman, J (reprint author), NINDS, Cognit Neurosci Sect, Bldg 10,Room 5C20MSC 1440, Bethesda, MD 20892 USA. EM grafmanj@ninds.nih.gov OI Grafman, Jordan H./0000-0001-8645-4457 NR 53 TC 50 Z9 54 U1 1 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD DEC PY 2005 VL 28 IS 4 BP 778 EP 786 DI 10.1016/j.neuroimage.2005.05.033 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 994FC UT WOS:000234015300005 PM 15994098 ER PT J AU Duque, J Hummel, F Celnik, P Murase, N Mazzocchio, R Cohen, LG AF Duque, J Hummel, F Celnik, P Murase, N Mazzocchio, R Cohen, LG TI Transcallosal inhibition in chronic subcortical stroke SO NEUROIMAGE LA English DT Article DE stroke; TMS; interhemispheric inhibition; rehabilitation; motor control ID HUMAN MOTOR CORTEX; TRANSCRANIAL MAGNETIC STIMULATION; NONINVASIVE CORTICAL STIMULATION; INTERHEMISPHERIC INHIBITION; HEMIPARETIC STROKE; CONTROLLED-TRIAL; FOLLOW-UP; RECOVERY; BRAIN; REORGANIZATION AB Movements of the paretic hand in patients with chronic subcortical stroke are associated with high interhemispheric inhibition (IHI) targeting the motor cortex in the lesioned hemisphere relative to healthy controls. The purpose of this investigation was to determine whether this abnormality also involves IHI operating during movements of the non-paretic hand. Here, we studied IHI in the process of generation of voluntary index finger movements by the paretic and non-paretic hands in a simple reaction time paradigm in a group of patients with chronic subcortical stroke. With movements of the nonparetic index finger, IHI targeting the contralateral primary motor cortex ((c)M1) decreased progressively to turn into facilitation at around movement onset, similar to healthy controls. In contrast, movements of the paretic index finger resulted in significantly deeper inhibition at all premovement timings relative to the non-paretic hand. In conclusion, these results document a deeper premovement IHI with paretic than non-paretic hand movements of patients with chronic subcortical stroke, a possible mechanism underlying deficits in motor control. Published by Elsevier Inc. C1 Natl Inst Neurol Disorders & Stroke, Human Cort Physiol Sect, NIH, Bethesda, MD 20817 USA. Univ Louvain, Neurophysiol Lab, Brussels, Belgium. Univ Tokushima, Fac Med, Dept Neurol, Tokushima, Japan. Univ Siena, Dipartimento Sci Neurol & Comportamento, Sez Neurofisiol Clin, Siena, Italy. RP Cohen, LG (reprint author), Natl Inst Neurol Disorders & Stroke, Human Cort Physiol Sect, NIH, Bethesda, MD 20817 USA. EM cohenl@ninds.nih.gov RI Mazzocchio, Riccardo/H-4223-2012 OI Mazzocchio, Riccardo/0000-0002-0628-2868 NR 33 TC 161 Z9 169 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PD DEC PY 2005 VL 28 IS 4 BP 940 EP 946 DI 10.1016/j.neuroimage.2005.06.033 PG 7 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 994FC UT WOS:000234015300019 PM 16084737 ER PT J AU D'Amico, A Benedetti, S Petrini, S Sambuughin, N Boldrini, R Menditto, I Ferrari, M Verardo, M Goldfarb, L Bertini, E AF D'Amico, A Benedetti, S Petrini, S Sambuughin, N Boldrini, R Menditto, I Ferrari, M Verardo, M Goldfarb, L Bertini, E TI Major myofibrillar changes in early onset myopathy due to de novo heterozygous missense mutation in lamin A/C gene SO NEUROMUSCULAR DISORDERS LA English DT Article DE lamin A/C; desmin; myofibrillar myopathy ID FUNCTIONAL CONSEQUENCES; DILATED CARDIOMYOPATHY; PHENOTYPE AB Mutations in the lamin A/C gene (LMNA) have been associated with neuromuscular diseases and more complex syndromes, involving bone and adipose tissue. We report on a case of early onset myopathy due to a heterozygous LMNA mutation in exon 9, characterized by the presence of a marked number of cytoplasmic bodies with extensive myofibrillar abnormalities and Z-disk disruption in skeletal muscle. This case suggests there is a need to increase the list of genes to be screened in patients with myofibrillar myopathy. (C) 2005 Elsevier B.V. All rights reserved. C1 Bambino Gesu Childrens Res Hosp, Dept Lab Med, Unit Mol Med & Pathol, Rome, Italy. Lab Clin Mol Biol Diagnost & Ric San Raffaele, Milan, Italy. IRCCS San Raffaele Sci Inst, Unit Genom Human Dis Diag, Milan, Italy. NINDS, NIH, Bethesda, MD 20892 USA. RP Bertini, E (reprint author), Bambino Gesu Childrens Res Hosp, Dept Lab Med, Unit Mol Med & Pathol, Rome, Italy. EM ebertini@tin.it RI d'amico, adele/J-9203-2016 OI d'amico, adele/0000-0003-2438-2624 NR 10 TC 7 Z9 8 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD DEC PY 2005 VL 15 IS 12 BP 847 EP 850 DI 10.1016/j.nmd.2005.09.007 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 998JD UT WOS:000234313700005 PM 16288872 ER PT J AU Apud, JA Mattay, V Chen, JS Bhaskar, KS Callicott, JH Alce, G Iudicello, J Akbar, N Egan, MF Goldberg, TE Weinberger, DR AF Apud, JA Mattay, V Chen, JS Bhaskar, KS Callicott, JH Alce, G Iudicello, J Akbar, N Egan, MF Goldberg, TE Weinberger, DR TI Comparison of the effects of tolcapone and entacapone on cognition and fMR1 in normal volunteers SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIMH, 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 2005 VL 30 SU 1 BP S159 EP S159 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100419 ER PT J AU Barr, CS Lindell, SG Suomi, SJ Goldman, D Higley, JD AF Barr, CS Lindell, SG Suomi, SJ Goldman, D Higley, JD TI Variation in the rhNPY promoter is associated with differences in CSF levels of NPY and alcohol consumption SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIAAA, Lab Clin & Translat Studies, NIH, 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 2005 VL 30 SU 1 BP S151 EP S151 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100399 ER PT J AU Barr, CS Newman, TK Suomi, SJ Lipsky, R Goldman, D Higley, JD AF Barr, CS Newman, TK Suomi, SJ Lipsky, R Goldman, D Higley, JD TI Association of an ancient CRH gene haplotype with HPA axis activity in rhesus macaques SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIAAA, Lab Clin & Translat Studies, NIH, 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 2005 VL 30 SU 1 BP S96 EP S96 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100262 ER PT J AU Beltaifa, S Webster, MJ Weickert, CS AF Beltaifa, S Webster, MJ Weickert, CS TI NRG-1 protein levels in patients with schizophrenia, bipolar disorder and major depression SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIMH, MiNDS Unit, CBDB, 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 2005 VL 30 SU 1 BP S116 EP S116 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100310 ER PT J AU Brotman, MA Rich, BA Schmajuk, M Monk, CS Mogg, K Bradley, BP Pine, DS Leibenluft, E AF Brotman, MA Rich, BA Schmajuk, M Monk, CS Mogg, K Bradley, BP Pine, DS Leibenluft, E TI Attention bias to threat in bipolar children with or without comorbid anxiety disorders SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RI Brotman, Melissa/H-7409-2013; Monk, Christopher/J-1805-2014 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 2005 VL 30 SU 1 BP S99 EP S100 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100271 ER PT J AU Buckholtz, JW Chen, Q Sust, S Drabant, EM Verchinski, BA Blasi, G Sambataro, F Mattay, VS Weinberger, DR Callicott, JH AF Buckholtz, JW Chen, Q Sust, S Drabant, EM Verchinski, BA Blasi, G Sambataro, F Mattay, VS Weinberger, DR Callicott, JH TI The neural correlates of social decision-making: An event-related fMRI study SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIMH, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA. RI Sambataro, Fabio/E-3426-2010 OI Sambataro, Fabio/0000-0003-2102-416X 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 2005 VL 30 SU 1 BP S160 EP S160 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100422 ER PT J AU Buonanno, A Kwon, OB Vullhorst, D Hoffman, D Longart, M AF Buonanno, A Kwon, OB Vullhorst, D Hoffman, D Longart, M TI Regulation of synaptic plasticity by the NRG-1/ErbB signaling pathway: Possible implications for schizophrenia SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NICHHD, 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 2005 VL 30 SU 1 BP S70 EP S70 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100195 ER PT J AU Callicott, JH Sust, S Tan, HY Mattay, VS Buckholtz, J Egan, MF Weinberger, DR AF Callicott, JH Sust, S Tan, HY Mattay, VS Buckholtz, J Egan, MF Weinberger, DR TI Prefrontal cortex inefficiency during working memory in unaffected siblings of patients with schizophrenia: A replication SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIMH, GCAP, 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 2005 VL 30 SU 1 BP S120 EP S120 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100320 ER PT J AU Cannon, DM Ichise, M Fromm, S Nugent, AC Rollis, D Gandhi, SK Drevets, WC AF Cannon, DM Ichise, M Fromm, S Nugent, AC Rollis, D Gandhi, SK Drevets, WC TI Serotonin transporter binding in unmedicated bipolar disorder subjects using [carbon-11] DASB and positron emission tomography SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIMH, Mood & Anxiety Disorders Program, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. RI Cannon, Dara/C-1323-2009 OI Cannon, Dara/0000-0001-7378-3411 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 2005 VL 30 SU 1 BP S101 EP S102 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100275 ER PT J AU Cassano, HL Hyde, TM Deep-Soboslay, A Kleinman, JE Weickert, CS AF Cassano, HL Hyde, TM Deep-Soboslay, A Kleinman, JE Weickert, CS TI Promoter specific alterations of BDNF mRNA in frontal cortex in patients with schizophrenia SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIMH, NIH, Clin Brain Disorders 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 2005 VL 30 SU 1 BP S120 EP S120 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100321 ER PT J AU Chen, G Creson, T Hao, YL Engel, S Manji, HK AF Chen, G Creson, T Hao, YL Engel, S Manji, HK TI The ERK pathway in left anterior cingulate cortex modulates locomotive and hedonic activities SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIMH, LMP MAP, IRP, NIH, 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 2005 VL 30 SU 1 BP S103 EP S103 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100278 ER PT J AU Chen, JS Lipska, BK Weinberger, DR AF Chen, JS Lipska, BK Weinberger, DR TI New genetic mouse models of schizophrenia: Mimicking cognitive dysfunction by altering susceptibility gene expression SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, 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 2005 VL 30 SU 1 BP S12 EP S13 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100038 ER PT J AU Chen, SA Barr, CS Schwandt, ML Lindell, SG Hommer, D Shoaf, S Suomi, SJ Linnoila, M Higley, JD AF Chen, SA Barr, CS Schwandt, ML Lindell, SG Hommer, D Shoaf, S Suomi, SJ Linnoila, M Higley, JD TI Decreased CNS serotonin turnover, early-life stress, and initial response to ethanol are predictors of ethanol consumption in adolescent rhesus macaques SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIAAA, Lab Clin & Translat Studies, 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 2005 VL 30 SU 1 BP S88 EP S88 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100241 ER PT J AU Choi, SH Bosetti, F AF Choi, SH Bosetti, F TI Enzymes coupled with cyclooxygenase are altered in the brain of cyclooxygenase-1 deficient mice: Implications for neuroprotection in neuropsychiatric disorders SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIA, Brain Physiol & Metab Sect, 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 2005 VL 30 SU 1 BP S266 EP S266 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100691 ER PT J AU Compton, WM Thomas, Y Conway, KP Brodsky, MD AF Compton, WM Thomas, Y Conway, KP Brodsky, MD TI Pain and opioid addiction: Complex relationship SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIDA, 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 2005 VL 30 SU 1 BP S88 EP S89 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100242 ER PT J AU Dickstein, DP Rich, BA Roberson-Nay, R Vinton, DT Berghorst, LH Pine, DS Leibenluft, E AF Dickstein, DP Rich, BA Roberson-Nay, R Vinton, DT Berghorst, LH Pine, DS Leibenluft, E TI Neural activation during encoding of emotional faces in pediatric bipolar disorder SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIMH, Pediat & Dev Neuropsychiat 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 2005 VL 30 SU 1 BP S162 EP S162 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100427 ER PT J AU Du, J Suzuki, K Nagappan, G Wang, Y Lu, B Manji, H AF Du, J Suzuki, K Nagappan, G Wang, Y Lu, B Manji, H TI Lithium normalizes dendritic localization of Val66met polymorphism of brain-derived neurotrophic factor (BDNFmet): Therapeutic implications SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIMH, Mol Pathophysiol Lab, NIH, 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 2005 VL 30 SU 1 BP S107 EP S108 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100289 ER PT J AU Du, J Wei, YL Falke, C Gray, N Szabo, S Yuan, PX Manji, HK AF Du, J Wei, YL Falke, C Gray, N Szabo, S Yuan, PX Manji, HK TI Modulation of AMPA glutamate receptor trafficking by antimanic agents new avenues for drug development SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIMH, Mol Pathophysiol Lab, 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 2005 VL 30 SU 1 BP S52 EP S52 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100147 ER PT J AU Erickson, K Furey, ML Schulkin, J Wood, SE Mah, L Nugent, AC Drevets, WC AF Erickson, K Furey, ML Schulkin, J Wood, SE Mah, L Nugent, AC Drevets, WC TI Influence of low and high dose hydrocortisone infusion on hemodynamic response in amygdala while viewing emotional faces SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIMH, SNMAD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 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 2005 VL 30 SU 1 BP S163 EP S164 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100430 ER PT J AU Finger, E Marsh, A Kamel, N Peschardt, K Vythilingam, M Pine, D Blair, J AF Finger, E Marsh, A Kamel, N Peschardt, K Vythilingam, M Pine, D Blair, J TI Passive avoidance learning and response reversal during tryptophan depletion SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat ID HEALTHY-VOLUNTEERS C1 NIMH, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. NR 5 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 2005 VL 30 SU 1 BP S110 EP S111 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100296 ER PT J AU Furey, ML Drevets, WC AF Furey, ML Drevets, WC TI The old drug scopolamine offers new promise as a potent antidepressant agent: A randomized, placebo-controlled clinical trial SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIMH, Sect Neuroimaging Mood & Anxiety Disorders, NIH, Bethesda, MD 20892 USA. 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 2005 VL 30 SU 1 BP S170 EP S170 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100446 ER PT J AU Giedd, JN AF Giedd, JN TI Structural MRI of typical adolescent brain development SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat 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 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 2005 VL 30 SU 1 BP S68 EP S68 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100189 ER PT J AU Giedd, JN AF Giedd, JN TI Trajectories of anatomic brain development in children and adolescents SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat 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 2 Z9 2 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 2005 VL 30 SU 1 BP S9 EP S9 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100028 ER PT J AU Gogtay, N Greenstein, D Giedd, J Clasen, L Sporn, A Lenane, M Lerch, J Evans, A Rapoport, J AF Gogtay, N Greenstein, D Giedd, J Clasen, L Sporn, A Lenane, M Lerch, J Evans, A Rapoport, J TI The trajectory is the story: Cortical gray matter changes during adolescence in childhood onset schizophrenia evolve into the adult pattern by age 25 SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RI Gogtay, Nitin/A-3035-2008; 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 2005 VL 30 SU 1 BP S128 EP S128 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100342 ER PT J AU Goldberg, SR AF Goldberg, SR TI The endogenous brain cannabinoid system and the motivational control of reinforced behavior SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIDA, Preclin Pharmacol Sect, Behav Neurosci Res Branch, IRP,NIH,DHHS, 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 2005 VL 30 SU 1 BP S68 EP S68 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100187 ER PT J AU Goldman, AL Pezawas, L Chen, G Meyer-Lindenberg, A Goldberg, TE Saad, ZS Mattay, VS Weinberger, DR AF Goldman, AL Pezawas, L Chen, G Meyer-Lindenberg, A Goldberg, TE Saad, ZS Mattay, VS Weinberger, DR TI Integration of emotion-laden and working memory-related information in the prefrontal cortex SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIMH, 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 2005 VL 30 SU 1 BP S172 EP S172 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100450 ER PT J AU Goldman, D Zhou, ZF Kennedy, J Virkkunen, M Robin, R Roy, A Murphy, D Hu, XZ AF Goldman, D Zhou, ZF Kennedy, J Virkkunen, M Robin, R Roy, A Murphy, D Hu, XZ TI Novel functional variation in the serotonin transporter and tryptophan hydroxylase genes and linkage to complex behavioral phenotypes SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIAAA, Neurogenet Lab, NIH, 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 2005 VL 30 SU 1 BP S36 EP S37 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100104 ER PT J AU Gould, TD Picchini, AM O'Donnell, KC Schloesser, RJ Manji, HK AF Gould, TD Picchini, AM O'Donnell, KC Schloesser, RJ Manji, HK TI Mouse strain differences in single dose lithium attenuation of amphetamine hyperactivity SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIMH, Mol Pathophysiol Lab, 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 2005 VL 30 SU 1 BP S172 EP S172 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100452 ER PT J AU Gould, TD Einat, H Picchini, AM ODonnell, KC Schloesser, RJ Manji, HK AF Gould, TD Einat, H Picchini, AM ODonnell, KC Schloesser, RJ Manji, HK TI Targeting glycogen synthase kinase-3 as a treatment for bipolar disorder SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIMH, Mol Pathophysiol Lab, 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 2005 VL 30 SU 1 BP S39 EP S39 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100110 ER PT J AU Heilig, M Hansson, A Sommer, W Terasmaa, A Bjork, K Rimondini, R AF Heilig, M Hansson, A Sommer, W Terasmaa, A Bjork, K Rimondini, R TI Application of functional Genomics to animal models of alcoholism for target discovery and validation SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIAAA, LCTS, NIH, Bethesda, MD USA. RI Rimondini, Roberto/B-2500-2010; Terasmaa, Anton/I-3312-2015 OI Rimondini, Roberto/0000-0003-4099-513X; Terasmaa, Anton/0000-0002-5139-1764 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 2005 VL 30 SU 1 BP S40 EP S41 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100115 ER PT J AU Higley, JD Barr, CS Suomi, SJ AF Higley, JD Barr, CS Suomi, SJ TI CNS serotonergic functioning, alcohol, genotype X by rearing interactions and violence using a nonhuman primate model SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIAAA Intramural, Sect Primate Models Psychopathol, LCTS, NIH, 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 2005 VL 30 SU 1 BP S36 EP S36 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100102 ER PT J AU Honea, RA Meyer-Lindenburg, A Hobbs, K Pezawas, L Verchinski, BA Goldman, AL Mattay, VS Weinberger, DR Callicott, JH AF Honea, RA Meyer-Lindenburg, A Hobbs, K Pezawas, L Verchinski, BA Goldman, AL Mattay, VS Weinberger, DR Callicott, JH TI Temporal and prefrontal cortex gray matter abnormalities in patients with schizophrenia and their unaffected siblings; An optimized voxel-based morphometry study SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIMH, Clin Brain Disorders Branch, 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 2005 VL 30 SU 1 BP S190 EP S191 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100497 ER PT J AU Huffaker, SJ Weinberger, DR AF Huffaker, SJ Weinberger, DR TI Identification of a novel genetic locus at 7q36.1 in strong LD with schizophrenia and the differential expression of the flanking genes, NOS3 and KCNH2 SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIMH, CBDB, 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 2005 VL 30 SU 1 BP S191 EP S191 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100498 ER PT J AU Hyde, TM Mathew, SV Lipska, BK Mitkus, SN Vakkalanka, R Straub, RE Weinberger, DR Kleinman, JE AF Hyde, TM Mathew, SV Lipska, BK Mitkus, SN Vakkalanka, R Straub, RE Weinberger, DR Kleinman, JE TI Allelic variations in NRG1 affect region-specific expression of low affinity nicotinic acetylcholine receptors in the human brain SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIMH, Sect Neuropathol, Clin Brain Disorders Branch, IRP,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 2005 VL 30 SU 1 BP S191 EP S191 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100499 ER PT J AU Innis, R AF Innis, R TI PET imaging of dopamine metabolism and receptors in cortex: Relation to cognitive function in Parkinson s disease SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat 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 2005 VL 30 SU 1 BP S51 EP S51 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100143 ER PT J AU Le Foll, B Goldberg, SR AF Le Foll, B Goldberg, SR TI Ethanol does not affect discriminative stimulus effects of nicotine in rats SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIDA, Preclin Pharmacol Sect, Baltimore, MD USA. RI Le Foll, Bernard/K-2952-2014 OI Le Foll, Bernard/0000-0002-6406-4973 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 2005 VL 30 SU 1 BP S149 EP S150 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100394 ER PT J AU Lehrmann, E Colantuoni, C Hyde, TM Kleinman, JE Becker, KG Freed, WJ AF Lehrmann, E Colantuoni, C Hyde, TM Kleinman, JE Becker, KG Freed, WJ TI Regulation of apolipoprotein L2 in human drug abuse SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIDA, Cellular Neurobiol Res Branch, IRP, NIH,DHHS, 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 2005 VL 30 SU 1 BP S270 EP S270 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100703 ER PT J AU Leibenluft, E Dickstein, D Nelson, E Ernst, M Pine, D AF Leibenluft, E Dickstein, D Nelson, E Ernst, M Pine, D TI Response flexibility in bipolar disorder: A developmental perspective SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat 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 2005 VL 30 SU 1 BP S18 EP S19 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100055 ER PT J AU Lenroot, R Shaw, P Taylor, K Greenstein, D Clasen, L Evans, A Giedd, JN AF Lenroot, R Shaw, P Taylor, K Greenstein, D Clasen, L Evans, A Giedd, JN TI Gender-specific longitudinal changes in cortical thickness in children and adolescents SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIMH, CHP, 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 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 2005 VL 30 SU 1 BP S156 EP S156 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100411 ER PT J AU Lipska, BK Hyde, TM Peters, T Weinberger, DR Kleinman, JE AF Lipska, BK Hyde, TM Peters, T Weinberger, DR Kleinman, JE TI Differential expression in schizophrenic brain of a DISC1 molecular pathway and association with DISC1 SNPs SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat 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 2005 VL 30 SU 1 BP S69 EP S69 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100191 ER PT J AU Low, NC Cui, LH Merikangas, KR AF Low, NC Cui, LH Merikangas, KR TI The familial aggregation anxiety disorders ascertained from the community versus clinics SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIMH, SDGE, 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 2005 VL 30 SU 1 BP S178 EP S179 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100468 ER PT J AU Lu, L Hope, BT Shaham, Y AF Lu, L Hope, BT Shaham, Y TI Role of amygdala ERK in incubation of cocaine craving SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIDA, IRP, Baltimore, MD USA. RI Hope, Bruce/A-9223-2010 OI Hope, Bruce/0000-0001-5804-7061 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 2005 VL 30 SU 1 BP S67 EP S67 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100186 ER PT J AU Marenco, S Jones, DW Barnett, AS Van der Veen, JW Cotton, A Weinberger, DR AF Marenco, S Jones, DW Barnett, AS Van der Veen, JW Cotton, A Weinberger, DR TI Reproducibility of proton spectroscopic imaging (H1-MRSI) at 3Tesla: Effects of corrections for B1 field and partial volume SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIMH, GCAP, CBDB, DHHS, Bethesda, MD 20892 USA. RI Marenco, Stefano/A-2409-2008 OI Marenco, Stefano/0000-0002-2488-2365 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 2005 VL 30 SU 1 BP S220 EP S221 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100570 ER PT J AU Mattay, VS Blasi, G Alce, G Das, S Callicott, JH Kolachana, BS Egan, MF Sambataro, F Meyer-Lindenberg, A Hariri, AR Weinberger, DR AF Mattay, VS Blasi, G Alce, G Das, S Callicott, JH Kolachana, BS Egan, MF Sambataro, F Meyer-Lindenberg, A Hariri, AR Weinberger, DR TI COMT val(158)met polymorphism impacts on reactivity of amygdala to emotion laden stimuli SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIMH, GCAP, IRP, NIH, Bethesda, MD 20892 USA. RI Hariri, Ahmad/D-5761-2011; Sambataro, Fabio/E-3426-2010 OI Sambataro, Fabio/0000-0003-2102-416X 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 2005 VL 30 SU 1 BP S222 EP S222 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100573 ER PT J AU Merikangas, KR Low, NC Cui, LH AF Merikangas, KR Low, NC Cui, LH TI Familial patterns of comorbidity of migraine and affective disorders SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIMH, Intramural Res 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 2005 VL 30 SU 1 BP S182 EP S182 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100476 ER PT J AU Meyer-Lindenberg, A AF Meyer-Lindenberg, A TI Interactions of prefrontal function and dopamine: Multimodal neuroirnaging of genetic modulation SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIMH, GCAP, 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 2005 VL 30 SU 1 BP S51 EP S52 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100144 ER PT J AU Moore, GJ Cortese, BM Glitz, DA Zajac-Benitez, C Quiroz, JA Uhde, TW Drevets, WC Manji, H AF Moore, GJ Cortese, BM Glitz, DA Zajac-Benitez, C Quiroz, JA Uhde, TW Drevets, WC Manji, H TI Lithium increases gray matter in the prefrontal and subgenual prefrontal cortices in treatment responsive bipolar disorder patients SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RI Moore, Gregory/E-7184-2010 OI Moore, Gregory/0000-0001-8541-3194 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 2005 VL 30 SU 1 BP S179 EP S180 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100470 ER PT J AU Newman, AH Zou, MF Cao, JJ Cha, JH Lever, JR Kopajtic, T Katz, JL Parnas, ML Vaughan, R AF Newman, AH Zou, MF Cao, JJ Cha, JH Lever, JR Kopajtic, T Katz, JL Parnas, ML Vaughan, R TI Design, synthesis and application of novel tropane-based photoaffinity labels toward the identification of binding domains on the dopamine transporter SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIDA, Med Chem Sect, IRP, NIH, 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 2005 VL 30 SU 1 BP S210 EP S210 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100543 ER PT J AU Newman, TK Barr, CS Holston, RE Davis, NY Suomi, SJ Goldman, D Higley, JD AF Newman, TK Barr, CS Holston, RE Davis, NY Suomi, SJ Goldman, D Higley, JD TI Multiple novel polymorphisms in the rhesus macaque DRD4 5 ' UTR are associated with impulsive behavior SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIAAA, Lab Clin & Translat Studies, Poolesville, MD USA. 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 2005 VL 30 SU 1 BP S139 EP S139 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100370 ER PT J AU Pezawas, L Goldman, AL Verchinski, BA Mattay, VS Chen, G Hobbs, K Honea, RA Callicott, JS Kolachana, BS Straub, RE Egan, MF Meyer-Lindenberg, A Weinberger, DR AF Pezawas, L Goldman, AL Verchinski, BA Mattay, VS Chen, G Hobbs, K Honea, RA Callicott, JS Kolachana, BS Straub, RE Egan, MF Meyer-Lindenberg, A Weinberger, DR TI Epistasis of SERT & BDNF: A mechanistic model of depression SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat ID VAL66MET POLYMORPHISM; HUMAN-MEMORY; AMYGDALA C1 NIMH, GCAP, NIH, Bethesda, MD 20892 USA. NR 5 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 2005 VL 30 SU 1 BP S231 EP S231 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100598 ER PT J AU Polesskaya, OO Aston, C Sokolov, BP AF Polesskaya, OO Aston, C Sokolov, BP TI Evidence for epigenetic regulation of the 5HT2A receptor gene (5HT2AR). Methylation of allele C-specific CpG sites in 5HT2AR correlates with its expression and eRobust, rapid and relatively sustained antidepressant effects with a single-dose of an NMDA antagonist in treatment-resistant major depression: A double-blind placebo-controlled study expression of DNA methylase DNMT1 SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIDA, NIH, DHHS, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 1 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 2005 VL 30 SU 1 BP S255 EP S255 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100662 ER PT J AU Rao, JS Bazinet, RP Lee, HJ Rapoport, SI AF Rao, JS Bazinet, RP Lee, HJ Rapoport, SI TI Mood stabilizers that downregulate the brain arachidonic acid cascade reduce AP-2 or NF-kappa B transcription factors in rat frontal cortex SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. RI Rao, Jagadeesh/C-1250-2009 NR 2 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 2005 VL 30 SU 1 BP S267 EP S268 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100696 ER PT J AU Rapoport, JL AF Rapoport, JL TI Brain development in childhood onset schizophrenia and their healthy siblings SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIMH, DIRP, 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 2005 VL 30 SU 1 BP S69 EP S69 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100192 ER PT J AU Rapoport, SI Carson, RE Bhattacharjee, A Schapiro, MB Esposito, G Herscovitch, P Eckelman, WC Esposito, G AF Rapoport, SI Carson, RE Bhattacharjee, A Schapiro, MB Esposito, G Herscovitch, P Eckelman, WC Esposito, G TI Imaging neuroinflammation in Alzheimer disease with [1-11C] arachidonic acid and positron emission tomography SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIA, Brain Physiol Metab Sect, NIH, Bethesda, MD 20892 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 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 2005 VL 30 SU 1 BP S225 EP S226 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100584 ER PT J AU Rich, BA Vinton, DT Berghorst, L McClure, EB Pine, DS Leibenluft, E AF Rich, BA Vinton, DT Berghorst, L McClure, EB Pine, DS Leibenluft, E TI Pediatric bipolar disorder and face processing: Neural and behavioral deficits SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIMH, NIH, 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 2005 VL 30 SU 1 BP S233 EP S234 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100604 ER PT J AU Saavedra, JM AF Saavedra, JM TI Blockade of angiotensin II AT1 receptors decreases anxiety and prevents the isolation stress-induced decrease in cortical CRF1 receptors and benzodiazepine binding SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIMH, Pharmacol Sect, 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 2005 VL 30 SU 1 BP S236 EP S236 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100611 ER PT J AU Sambataro, F Kingshott, E Das, S Kolachana, BS Russo, C Mirsky, AF Goldberg, T Egan, MF Meyer-Lindenberg, A Callicott, JH Weinberger, DR Mattay, VS AF Sambataro, F Kingshott, E Das, S Kolachana, BS Russo, C Mirsky, AF Goldberg, T Egan, MF Meyer-Lindenberg, A Callicott, JH Weinberger, DR Mattay, VS TI Effect of catechol-O-methyl transferase val (158)Met polymorphism on information processing in the prefrontal cortex during working memory in the elderly SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIMH, GCAP, IRP, NIH, Bethesda, MD 20892 USA. RI Sambataro, Fabio/E-3426-2010 OI Sambataro, Fabio/0000-0003-2102-416X 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 2005 VL 30 SU 1 BP S81 EP S82 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100224 ER PT J AU Schwandt, ML Barr, CS Suomi, SJ Higley, JD AF Schwandt, ML Barr, CS Suomi, SJ Higley, JD TI Ontogeny of the HPA-axis and monoamine response to acute ethanol challenge in male and female adolescent rhesus macaques SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIAAA, LCTS, Sect Study Primate Models Psychopathol, NIH, 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 2005 VL 30 SU 1 BP S213 EP S214 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100552 ER PT J AU Sei, Y Ren-Patterson, R Li, Z Tunbridge, EM Egan, MF Kolachana, BS Weinberger, DR AF Sei, Y Ren-Patterson, R Li, Z Tunbridge, EM Egan, MF Kolachana, BS Weinberger, DR TI Neuregulin1-induced cell migration of B lymphoblasts: Possible association with schizophrenia SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIMH, GCAP, 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 2005 VL 30 SU 1 BP S252 EP S253 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100655 ER PT J AU Shaw, P Sharp, W Gornick, M Addington, A Greenstein, D Castellanos, X Rapoport, J AF Shaw, P Sharp, W Gornick, M Addington, A Greenstein, D Castellanos, X Rapoport, J TI Genes, brain development and clinical outcome in children with attention deficit/hyperactivity disorder (ADHD) SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RI Shaw, Philip/A-1129-2008 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 2005 VL 30 SU 1 BP S9 EP S10 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100029 ER PT J AU Sibley, DR Hazelwood, LA Free, RB Cabrera, DM AF Sibley, DR Hazelwood, LA Free, RB Cabrera, DM TI Identification and characterization of D2 dopamine receptor interacting proteins SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NINDS, NIH, Bethesda, MD 20892 USA. RI Cabrera, David/I-1013-2014 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 2005 VL 30 SU 1 BP S268 EP S268 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100697 ER PT J AU Spinelli, S Schwandt, M Erickson, K Lindell, S Schulkin, J Gold, P Suomi, SJ Higley, JD AF Spinelli, S Schwandt, M Erickson, K Lindell, S Schulkin, J Gold, P Suomi, SJ Higley, JD TI Relationship between behavior and neurochernical changes in rhesus macaques during a separation paradigm SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 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 2005 VL 30 SU 1 BP S157 EP S157 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100414 ER PT J AU Straub, RE Mayhew, MB Vakkalanka, RK Kolachana, B Goldberg, TE Egan, MF Weinberger, DR AF Straub, RE Mayhew, MB Vakkalanka, RK Kolachana, B Goldberg, TE Egan, MF Weinberger, DR TI MUTED (6p24.3), a protein that binds to dysbindin (DTNBP1, 6p22.3), is strongly associated with schizophrenia and exhibits statistical epistasis with COMT SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIMH, NIH, Bethesda, MD 20892 USA. NR 2 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 2005 VL 30 SU 1 BP S255 EP S256 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100664 ER PT J AU Sunderland, T Mirza, N Putnam, K Huey, ED Bhupali, D Rapoport, JL Soares, H Csako, G Robert, CM AF Sunderland, T Mirza, N Putnam, K Huey, ED Bhupali, D Rapoport, JL Soares, H Csako, G Robert, CM TI Cerebrospinal fluid peptides as biomarkers for presymptomatic AD in "at risk" controls SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat 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 2005 VL 30 SU 1 BP S16 EP S16 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100049 ER PT J AU Sust, S Buckholtz, J Zoltick, B Jones, D Rypma, B Tan, HY Mattay, V Weinberger, DR Callicott, J AF Sust, S Buckholtz, J Zoltick, B Jones, D Rypma, B Tan, HY Mattay, V Weinberger, DR Callicott, J TI Physiological correlates of a non-working memory prefrontal task SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIMH, CBDB, 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 2005 VL 30 SU 1 BP S228 EP S228 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100591 ER PT J AU Tan, HY Chen, Q Sust, S Buckholtz, JW Straub, R Mattay, VS Egan, MF Weinberger, DR Callicott, JH AF Tan, HY Chen, Q Sust, S Buckholtz, JW Straub, R Mattay, VS Egan, MF Weinberger, DR Callicott, JH TI Variation in catecol-O-methyltransferase and GRM3 on working memory load and prefrontal cortical physiology SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIMH, Genes Cognit & Psychosis Program, 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 2005 VL 30 SU 1 BP S263 EP S263 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100683 ER PT J AU Ungerleider, LG Rossi, A Pessoa, L AF Ungerleider, LG Rossi, A Pessoa, L TI The primate prefrontal cortex and the executive control of attention SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat 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 2005 VL 30 SU 1 BP S18 EP S18 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100053 ER PT J AU Verchinski, BA Meyer-Lindenberg, A Pezawas, L Straub, R Honea, R Goldman, AL Hobbs, K Buckholtz, JW Callicott, JH Kolachana, B Mattay, VS Weinberger, DR AF Verchinski, BA Meyer-Lindenberg, A Pezawas, L Straub, R Honea, R Goldman, AL Hobbs, K Buckholtz, JW Callicott, JH Kolachana, B Mattay, VS Weinberger, DR TI Allelic variation of PPP1R1B, encoding DARPP-32, affects human striatal volume and striatal-prefrontal structural connectivity SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIMH, GCAP, 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 2005 VL 30 SU 1 BP S230 EP S230 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100595 ER PT J AU Weickert, CS Law, AJ Beltaifa, S Webster, MJ Harrison, PJ Kleinman, JE Weinberger, DR AF Weickert, CS Law, AJ Beltaifa, S Webster, MJ Harrison, PJ Kleinman, JE Weinberger, DR TI Neuregulin mRNA and protein in patients with schizophrenia SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIMH, MiNDS, CBDB, Bethesda, MD 20892 USA. RI Law, Amanda/G-6372-2012 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 2005 VL 30 SU 1 BP S43 EP S43 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100123 ER PT J AU Weinberger, DR Meyer-Lindenberg, A Mattay, V Joseph, C Berman, KF Kolachana, B Chen, JS Goldberg, T Apud, J Egan, M AF Weinberger, DR Meyer-Lindenberg, A Mattay, V Joseph, C Berman, KF Kolachana, B Chen, JS Goldberg, T Apud, J Egan, M TI COMT in prefrontal cortex and beyond: Genetic studies of cortical DA signaling SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIMH, Genes Cognit & Psychosis Program, 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 2005 VL 30 SU 1 BP S14 EP S14 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100043 ER PT J AU Weinberger, DR Carpenter, W Emanuel, E Gorman, J Muse, R Talan, J Breier, A AF Weinberger, DR Carpenter, W Emanuel, E Gorman, J Muse, R Talan, J Breier, A TI J'Accuse: COI in the news, but what of the accused? SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIMH, 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 2005 VL 30 SU 1 BP S11 EP S11 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100035 ER PT J AU Wint, D Dreher, JC Furman, D Koch, P Kohn, P Egan, M Weinberger, D Berman, KF AF Wint, D Dreher, JC Furman, D Koch, P Kohn, P Egan, M Weinberger, D Berman, KF TI Altered cerebral processing of reward uncertainty in patients with schizophrenia while medication-free and on atypical neuroleptics SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIMH, Sect Integrat Neuroimaging, Bethesda, MD 20892 USA. 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 2005 VL 30 SU 1 BP S262 EP S262 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100681 ER PT J AU Xu, K Yuan, QP Hodgkinson, CA Shen, PH Neuhold, L Ren, ZX Warren, K Goldman, D AF Xu, K Yuan, QP Hodgkinson, CA Shen, PH Neuhold, L Ren, ZX Warren, K Goldman, D TI A large-scale approach for identifying vulnerability genes to alcoholism: A 1536 SNP chip SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIAAA, LNG, NIH, 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 2005 VL 30 SU 1 BP S218 EP S219 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100566 ER PT J AU Zarate, CA Singh, J Carlson, P Brutsche, N Ameli, R Luckenbaugh, D Charney, DS Manji, HK AF Zarate, CA Singh, J Carlson, P Brutsche, N Ameli, R Luckenbaugh, D Charney, DS Manji, HK TI Robust, rapid and relatively sustained antidepressant effects with a single-dose of an NMDA antagonist in treatment-resistant major depression: A double-blind placebo-controlled study SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ Sch Med Dept Psychiat C1 NIMH, Mood & Anxiety Disorders Program, 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 2005 VL 30 SU 1 BP S245 EP S246 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986IA UT WOS:000233442100637 ER PT J AU Fields, RD AF Fields, RD TI Myelination: An overlooked mechanism of synaptic plasticity? SO NEUROSCIENTIST LA English DT Article DE myelin; oligodendrocyte; ATP; purinergic signaling; synaptic plasticity; activity-dependent plasticity; music; environmental enrichment; activity-dependent development ID CORPUS-CALLOSUM; ACTION-POTENTIALS; ADOLESCENT BRAIN; NEURAL IMPULSES; CONDUCTION; PATTERNS; MOLECULE; CHILDREN; CORTEX; VOLUME AB Myelination of the brain continues through childhood into adolescence and early adulthood-the question is, Why? Two new articles provide intriguing evidence that myelination may be an underappreciated mechanism of activity-dependent nervous system plasticity: one study reported increased myelination associated with extensive piano playing, another indicated that rats have increased myelination of the corpus callosum when raised in environments providing increased social interaction and cognitive stimulation. These articles make it clear that activity-dependent effects on myelination cannot be considered strictly a developmental event. They raise the question of whether myelination is an overlooked mechanism of activity-dependent plasticity, extending in humans until at least age 30. It has been argued that regulating the speed of conduction across long fiber tracts would have a major influence on synaptic response, by coordinating the timing of afferent input to maximize temporal summation. The increase in synaptic amplitude could be as large as neurotransmitter-based mechanisms of plasticity, such as LTP. These new findings raise a larger question: How did the oligodendrocytes know they were practicing the piano or that their environment was socially complex? C1 NICHD, Nervous Syst Dev & Plast Sect, NIH, Bethesda, MD 20892 USA. RP Fields, RD (reprint author), NICHD, Nervous Syst Dev & Plast Sect, NIH, Bldg 35,Room 2A211,MSC 3713,35 Lincoln Dr, Bethesda, MD 20892 USA. EM fieldsd@mail.nih.gov FU Intramural NIH HHS; NICHD NIH HHS [Z01 HD000713-11] NR 36 TC 125 Z9 132 U1 8 U2 27 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1073-8584 J9 NEUROSCIENTIST JI Neuroscientist PD DEC PY 2005 VL 11 IS 6 BP 528 EP 531 DI 10.1177/1073858405282304 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 985EK UT WOS:000233359500012 PM 16282593 ER PT J AU Zhang, J Creinin, MD Barnhart, K AF Zhang, J Creinin, MD Barnhart, K CA Management Early Pregnancy Failure TI Medical vs. surgical management of early pregnancy failure - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 NICHHD, Bethesda, MD 20892 USA. Univ Pittsburgh, Pittsburgh, PA 15213 USA. Univ Penn, Philadelphia, PA 19104 USA. RP Zhang, J (reprint author), NICHHD, Bethesda, MD 20892 USA. EM zhangj@mail.nih.gov NR 5 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 1 PY 2005 VL 353 IS 22 BP 2404 EP 2404 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 988EO UT WOS:000233574600017 ER PT J AU Hatsukami, DK Giovino, GA Eissenberg, T Clark, PI Lawrence, D Leischow, S AF Hatsukami, DK Giovino, GA Eissenberg, T Clark, PI Lawrence, D Leischow, S TI Methods to assess potential reduced exposure products SO NICOTINE & TOBACCO RESEARCH LA English DT Review ID ABUSE LIABILITY ASSESSMENT; TOBACCO HARM REDUCTION; SERUM COTININE LEVELS; CIGARETTE-SMOKING; NICOTINE DEPENDENCE; MEDICINAL NICOTINE; DOUBLE-BLIND; DRUG-ABUSE; SMOKERS; CESSATION AB The availability of tobacco products purported to reduce toxin exposure or potentially reduce health risks necessitates the development of methods and identification of biomarkers that can be used to assess these products. These assessments occur on multiple levels and stages, from identifying constituents in the tobacco products and smoke, to human exposure and health effects trials, to postmarketing surveillance. A conference of multidisciplinary experts was convened to present and discuss methods and biomarkers to assess these products and to consider the infrastructure necessary to facilitate the evaluation process. Although no currently available set of measures was thought to be sufficient for determining the relative health risk of potential reduced exposure products, this paper provides a blueprint for future research toward this end. C1 Univ Minnesota, Ctr Canc, Minneapolis, MN 55414 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Virginia Commonwealth Univ, Richmond, VA USA. Battelle Ctr Publ Hlth Res & Evaluat, Baltimore, MD USA. NCI, Bethesda, MD 20892 USA. RP Hatsukami, DK (reprint author), Univ Minnesota, Tobacco Use Res Ctr, 2701 Univ Ave SE,201, Minneapolis, MN 55414 USA. EM hatsu001@umn.edu NR 107 TC 38 Z9 38 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 2005 VL 7 IS 6 BP 827 EP 844 DI 10.1080/14622200500266015 PG 18 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 999HE UT WOS:000234379600003 PM 16298718 ER PT J AU Cannon, DS Baker, TB Piper, ME Scholand, MB Lawrence, DL Drayna, DT McMahon, WM Villegas, GM Caton, TC Coon, H Leppert, MF AF Cannon, DS Baker, TB Piper, ME Scholand, MB Lawrence, DL Drayna, DT McMahon, WM Villegas, GM Caton, TC Coon, H Leppert, MF TI Associations between phenylthiocarbamide gene polymorphisms and cigarette smoking SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID BITTER-TASTE; RECEPTOR GENE; PERCEPTION; SENSITIVITY; ADDICTION AB Phenotypic evidence indicates that the ability to taste the bitter compounds phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PROP) may protect against cigarette smoking. In this study, PTC gene haplotypes were found to be associated with both the odds of being a smoker and the importance of cigarette taste as a smoking motive. Smokers (n = 384) and nonsmokers (n = 183) were genotyped for polymorphisms that affect taste sensitivity to PTC and PROP. The "taster" PAV haplotype, relative to the "nontaster" AVI haplotype, was predicted to be associated with reduced odds of being a smoker and lower taste motivation as measured by the Wisconsin Inventory of Smoking Dependence Motives-68 taste/sensory processes scale. The results did not support the predicted association between the PAV and AVI haplotypes and smoker odds, but the AAV haplotype, which confers intermediate PTC/PROP taste sensitivity, was associated with reduced smoker prevalence (49% vs. 700/o), X-2(1, N= 567) = 10.392, p=.001. The predicted relationship between PAV and AVI and taste motivation was found, F(2, 348)=3.303, p=.038. The results encourage further exploration of the role of taste/sensory processes in tobacco dependence. C1 Univ Utah, Dept Psychiat, Salt Lake City, UT USA. Univ Utah, Div Pulm, Dept Internal Med, Salt Lake City, UT USA. Univ Utah, Dept Genet, Salt Lake City, UT USA. Univ Wisconsin, Dept Psychol, Madison, WI 53706 USA. Natl Inst Deafness & Other Commun Disorders, Rockville, MD USA. RP Cannon, DS (reprint author), Lung Hlth Study Ctr, 410 Chipeta Way,Suite 221, Salt Lake City, UT 84108 USA. EM dale.cannon@hsc.utah.edu OI Coon, Hilary/0000-0002-8877-5446 FU NCI NIH HHS [CA84724] NR 16 TC 42 Z9 43 U1 5 U2 68 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 2005 VL 7 IS 6 BP 853 EP 858 DI 10.1080/14622200500330209 PG 6 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 999HE UT WOS:000234379600005 PM 16298720 ER PT J AU Galban, CJ Maderwald, S Uffmann, K Ladd, ME AF Galban, CJ Maderwald, S Uffmann, K Ladd, ME TI A diffusion tensor imaging analysis of gender differences in water diffusivity within human skeletal muscle SO NMR IN BIOMEDICINE LA English DT Article DE DTI; skeletal muscle; genders; mathematical modeling ID MODERATELY ACTIVE MEN; FORCE-LENGTH CHARACTERISTICS; TIBIALIS ANTERIOR MUSCLE; IN-VIVO; GASTROCNEMIUS-MUSCLE; FIBER ARCHITECTURE; HUMAN CALF; MRI; RELAXATION; WOMEN AB The diffusive properties of adjacent muscles at rest were evaluated in male (n = 12) and fernale (it = 12) subjects using diffusion tensor imaging (DTI). The principle, second and third eigenvalues. trace of the diffusion tensor [Tr(D)], and two anisotropic parameters, ellipsoid eccentricity (e) and fractional anisotropy (FA), of various muscles in the human calf were calculated from the diffusion tensor. Seven muscles were investigated in this study from images acquired of the left calf: the soleus, lateral gastrocnemius, medial gastrocnemius, posterior tibialis, anterior tibialis, extensor digitorum longus and peroneus longus. A mathematical model was also derived that relates the eigenvalues of the diffusion tensor to the muscle fiber Volume fraction, which is defined as the volume of muscle fibers within a well-defined arbitrary Muscle volume. Females on average had higher eigenvalues and Tr(D) compared with males. with the majority of muscles being statistically different between the sexes. In contrast, males on average had higher e and FA than females, with the large plantar flexors-soleus, lateral gastrocnemius, and medial gastrocnemius-producing statistically different results. The behavior of the mathematical model for variations in fiber volume fraction produced similar trends to those seen when the experimental data were fit to the model. The model predicts that a larger volume fraction of skeletal muscle in males is devoted to fibers than in females, but the true underlying Source of the gender discrepancy remains unclear. Although the model does not fully account for other transport processes, it does provide some insight into the limiting factors that affect the diffusion of water in skeletal muscle measured by DTI. Copyright (c) 2005 John Wiley & Sons, Ltd. C1 Univ Hosp Essen, Dept Diagnost & Intervent Radiol, D-45122 Essen, Germany. RP Galban, CJ (reprint author), Drug Delivery & Kinet Resource, Div Bioengn & Phys Sci, NIH, Bldg 13,Rm 3NO5 MSc 5766, Bethesda, MD 20892 USA. EM galbanc@ors.od.nih.gov RI Maderwald, Stefan/B-4241-2011; Ladd, Mark/B-3285-2011 NR 45 TC 51 Z9 61 U1 1 U2 8 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0952-3480 J9 NMR BIOMED JI NMR Biomed. PD DEC PY 2005 VL 18 IS 8 BP 489 EP 498 DI 10.1002/nbm.975 PG 10 WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA 997XE UT WOS:000234281400002 PM 16075414 ER PT J AU Arbab, AS Yocum, GT Rad, AM Khakoo, AY Fellowes, V Read, EJ Frank, JA AF Arbab, AS Yocum, GT Rad, AM Khakoo, AY Fellowes, V Read, EJ Frank, JA TI Labeling of cells with ferumoxides-protamine sulfate complexes does not inhibit function or differentiation capacity of hematopoietic or mesenchymal stem cells SO NMR IN BIOMEDICINE LA English DT Article DE ferumoxides; protamine sulfate; hematopoietic stem cells; mesenchymal stem cells; dendritic cells; colony-forming unit; chondrogenesis ID MR CONTRAST AGENTS; IN-VIVO; MYOCARDIAL-INFARCTION; TRANSFECTION AGENTS; DENDRITIC CELLS; HEPARIN THERAPY; IRON-OXIDES; MOUSE MODEL; HUMAN BLOOD; TRAFFICKING AB Two FDA-approved agents, ferumoxides (Feridex (R)), a suspension of superparamagnetic iron oxide (SPIO) nanoparticles and prolamine sulfate, a drug used to reverse heparin anticoagulation, can be complexed and used to label cells magnetically ex vivo. Labeling stem cells with ferumoxides-protamine sulfate (FePro) complexes allows for non-invasive monitoring by MRI. However, in order for stem cell trials or therapies to be effective. this labeling technique must not inhibit the ability of cells to differentiate. In this study, we examined the effect of FePro labeling on stem cell differentiation. Viability, phenotypic expression and differential capacity of FePro labeled CD34+ hematopoietic stem cells (HSC) and mesenchymal stem cells (MSC) were compared with unlabeled control cells. Colony-forming unit (CFU) assays showed that the capacity to differentiate was equivalent for labeled and unlabeled HSC. Furthermore, labeling did not alter expression of surface phenotypic markers (CD34, CD31. CXCR4, CD20. CD3 and CD14) on HSC, as measured by flow cytometry. SDF-1-induced HSC migration and HSC differentiation to dendritic cells were also unaffected by FePro labeling, Both FePro-labeled and unlabeled MSC were cultured in chondrogenesis-inducing conditions. Alcian blue staining for proteoglycans revealed similar chondrogenic differentiation for both FePro-labeled and unlabeled cells. Furthermore, collagen X proteins, indicators of cartilage formation, were detected at similar levels in both labeled and unlabeled cell pellets. Prussian blue staining confirmed that cells in labeled pellets contained iron oxide, whereas cells in unlabeled pellets did not. It is concluded that FePro labeling does not after the function or differentiation capacity of HSC and MSC. These data increase confidence that MRI studies of FePro-labeled HSC or MSC will provide an accurate representation of in vivo trafficking of unlabeled cells. Copyright (c) 2005 John Wiley & Soils, Ltd. C1 Henry Ford Hlth Syst, Detroit, MI 48202 USA. NIH, Ctr Clin, Expt Neuroimaging Sect, Lab Diagnost Radiol Res, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA. RP Arbab, AS (reprint author), Henry Ford Hlth Syst, 1 Ford Pl, Detroit, MI 48202 USA. EM saali@rad.hfh.edu FU Intramural NIH HHS NR 28 TC 208 Z9 223 U1 2 U2 17 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0952-3480 J9 NMR BIOMED JI NMR Biomed. PD DEC PY 2005 VL 18 IS 8 BP 553 EP 559 DI 10.1002/nbm.991 PG 7 WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA 997XE UT WOS:000234281400009 PM 16229060 ER PT J AU Li, SZ Chen, ZG Zhang, Y Lizak, M Bacher, J Innis, RB Shen, J AF Li, SZ Chen, ZG Zhang, Y Lizak, M Bacher, J Innis, RB Shen, J TI In vivo single-shot, proton-localized C-13 MRS of rhesus monkey brain SO NMR IN BIOMEDICINE LA English DT Article DE magnetic resonance spectroscopy; carbon-13; monkey; brain ID MAGNETIC-RESONANCE-SPECTROSCOPY; DILUTION MASS-SPECTROMETRY; TRICARBOXYLIC-ACID CYCLE; POLARIZATION TRANSFER; CROSS-POLARIZATION; 1.5 T; METABOLISM; NMR; GABA; GLUCOSE AB A single-shot, proton-localized, polarization transfer C-13 spectroscopic method was proposed and implemented on a 4.7 T scanner for studying rhesus monkey brains. The polarization transfer sequence was mostly adiabatic, minimizing signal loss due to B-1 inhomogeneity. RF pulses in polarization transfer were also used for voxel selection of protons with gradient fields. The transferred C-13 magnetization was refocused by additional refocusing adiabatic pulses.. cose solution, C NMR spectra from a 30 mL voxel were acquired for the With the intravenous infusion of D-[1-C-13]glucose resonances of C1 of glucose, C2,3,4 of glutamate and glutamine. The time-resolved turnover of glutamate, glutamine and aspartate from intravenously infused D-[1-C-13] glucose at a temporal resolution of 12 min was demonstrated with excellent spectral resolution and signal-to-noise ratio. Typically, the half-height linewidth of the decoupled C-13 peaks was similar to 4Hz. Data obtained with infusion of sodium [2-C-13]acetate using the proposed polarization transfer method and data from the carboxylic carbon region using non-localized acquisition are also presented. Published in 2005 by John Wiley & Sons, Ltd. C1 NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. NIMH, NIH, Bethesda, MD 20892 USA. Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20892 USA. NIH, Off Res Serv, Bethesda, MD 20892 USA. RP Shen, J (reprint author), NIMH, Mol Imaging Branch, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM shenj@intra.nimh.nih.gov FU Intramural NIH HHS NR 39 TC 11 Z9 11 U1 0 U2 3 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0952-3480 J9 NMR BIOMED JI NMR Biomed. PD DEC PY 2005 VL 18 IS 8 BP 560 EP 569 DI 10.1002/nbm.993 PG 10 WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA 997XE UT WOS:000234281400010 PM 16273509 ER PT J AU Higgins, RD AF Higgins, RD TI Hypoxic ischemic encephalopathy and hypothermia - A critical look SO OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material ID CEREBRAL HYPOTHERMIA; SYSTEMIC HYPOTHERMIA; RANDOMIZED-TRIAL; BRAIN-INJURY; INFANT AB Hypoxic ischemic encephalopathy is a rare condition associated with high neonatal mortality and morbidity. Two randomized clinical trials have recently been published showing potentially promising results with hypothermia for neonatal encephalopathy. Additional clinical trials are underway to test cooling as a therapeutic modality for hypoxic ischemic encephalopathy. Outcome information about infants treated with hypothermia is available for children up to approximately 2 years of age. Longer-term outcome (ie, school age information) is currently lacking with respect to benefit and risk. Therapeutic hypothermia offers a potentially promising therapy for hypoxic ischemic encephalopathy. Hypothermia for encephalopathy should be considered an evolving therapy because of lack of long-term safety and efficacy data. C1 NICHD, Pregnancy & Perinatol Branch, Ctr Dev Biol & Perinatal Med, NIH, Bethesda, MD 20892 USA. RP Higgins, RD (reprint author), NICHD, Pregnancy & Perinatol Branch, Ctr Dev Biol & Perinatal Med, NIH, 6100 Execut Blvd,Room 4B03B,MSC 7510, Bethesda, MD 20892 USA. EM higginsr@mail.nih.gov NR 9 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD DEC PY 2005 VL 106 IS 6 BP 1385 EP 1387 DI 10.1097/01.AOG.0000190206.70375.b4 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 989SX UT WOS:000233695200025 PM 16319267 ER PT J AU Linet, MS Freedman, DM Mohan, AK Doody, MM Ron, E Mabuchi, K Alexander, BH Sigurdson, A Hauptmann, M AF Linet, MS Freedman, DM Mohan, AK Doody, MM Ron, E Mabuchi, K Alexander, BH Sigurdson, A Hauptmann, M TI Incidence of haematopoietic malignancies in US radiologic technologists SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID ATOMIC-BOMB SURVIVORS; ANKYLOSING-SPONDYLITIS; BRITISH RADIOLOGISTS; RADIATION-EXPOSURE; CANCER RISK; MORTALITY; LEUKEMIA; WORKERS; FOLLOW; RATES AB Background: There are limited data on risks of haematopoietic malignancies associated with protracted low-to-moderate dose radiation. Aims: To contribute the first incidence risk estimates for haematopoietic malignancies in relation to work history, procedures, practices, and protective measures in a large population of mostly female medical radiation workers. Methods: The investigators followed up 71 894 ( 77.9% female) US radiologic technologists, first certified during 1926 - 80, from completion of a baseline questionnaire ( 1983 - 89) to return of a second questionnaire ( 1994 - 98), diagnosis of a first cancer, death, or 31 August 1998 ( 731 306 person-years), whichever occurred first. Cox proportional hazards regression was used to compute risks. Results: Relative risks ( RR) for leukaemias other than chronic lymphocytic leukaemia ( non-CLL, 41 cases) were increased among technologists working five or more years before 1950 ( RR = 6.6, 95% CI 1.0 to 41.9, based on seven cases) or holding patients 50 or more times for x ray examination ( RR = 2.6, 95% CI 1.3 to 5.4). Risks of non-CLL leukaemias were not significantly related to the number of years subjects worked in more recent periods, the year or age first worked, the total years worked, specific procedures or equipment used, or personal radiotherapy. Working as a radiologic technologist was not significantly linked with risk of multiple myeloma ( 28 cases), non-Hodgkin's lymphoma ( 118 cases), Hodgkin's lymphoma ( 31 cases), or chronic lymphocytic leukaemia ( 23 cases). Conclusion: Similar to results for single acute dose and fractionated high dose radiation exposures, there was increased risk for non-CLL leukaemias decades after initial protracted radiation exposure that likely cumulated to low-to-moderate doses. C1 NCI, Radiat Epidemiol Branch, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Ctr Biol Evaluat & Res, Off Biostat & Epidemiol, Food & Drug Adm, Rockville, MD USA. Univ Minnesota, Div Occupat & Environm Hlth, Minneapolis, MN USA. RP Linet, MS (reprint author), NCI, Radiat Epidemiol Branch, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS Room 7054, Bethesda, MD 20892 USA. EM linetm@mail.nih.gov FU NCI NIH HHS [N01-CP-15673, N02-CP-81005, N02-CP-81121, N01-CP-51016] NR 35 TC 30 Z9 30 U1 2 U2 8 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1351-0711 EI 1470-7926 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD DEC PY 2005 VL 62 IS 12 BP 861 EP 867 DI 10.1136/oem.2005.020826 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 985HK UT WOS:000233368000009 PM 16299095 ER PT J AU Sen, HN Robinson, MR Fischer, SH AF Sen, HN Robinson, MR Fischer, SH TI CMV retinitis in a patient with Good syndrome SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Article DE Good syndrome; CMV retinitis; polymerase chain reaction; thymoma; immunodeficiency ID HERPES-SIMPLEX ENCEPHALITIS; POLYMERASE-CHAIN-REACTION; CYTOMEGALOVIRUS RETINITIS; OCULAR TOXOPLASMOSIS; CEREBROSPINAL-FLUID; VIRUS-DNA; THYMOMA; IMMUNODEFICIENCY; INFECTIONS AB Purpose: To describe cytomegalovirus (CMV) retinitis in a patient with Good syndrome. Methods: A 48-year-old patient with Good syndrome presented with a necrotizing retinitis in the left eye. Quantitative touchdown real-time polymerase chain reaction (PCR) was performed on aqueous fluid. Results: Quantitative PCR showed 152 copies of CMV per ml and was negative for varicella zoster virus (VZV), Epstein-Barr virus (EBV), herpes simplex virus (HSV-1), and HSV-2. The positive CMV PCR suggested CMV retinitis and the patient was treated with intravitreal ganciclovir injections (2.5 mg/0.05 ml), followed by ganciclovir implant. The retinal lesions showed decreasing activity two weeks after the onset of the therapy. A repeat PCR showed a decreasing number of CMV copies at one and two weeks (122 copies/ml and 0 copies/ml, respectively) that correlated clinically with the decreasing retinitis activity. Conclusions: Quantitative PCR can be useful in diagnosing as well as assessing the response to therapy of CMV retinitis in patients with Good syndrome. C1 NEI, NIH, Bethesda, MD 20892 USA. NIH, Dept Lab Med, Bethesda, MD 20892 USA. RP Sen, HN (reprint author), NEI, NIH, 10 Ctr Dr,Bldg 10,Rm 10N112, Bethesda, MD 20892 USA. EM SenH@nei.nih.gov NR 16 TC 4 Z9 4 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0927-3948 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PD DEC PY 2005 VL 13 IS 6 BP 475 EP 478 DI 10.1080/09273940590950963 PG 4 WC Ophthalmology SC Ophthalmology GA 990AV UT WOS:000233716500010 PM 16321895 ER PT J AU Gwinn, MR Keshava, C Olivero, OA Humsi, JA Poirier, MC Weston, A AF Gwinn, MR Keshava, C Olivero, OA Humsi, JA Poirier, MC Weston, A TI Transcriptional signatures of normal human mammary epithelial cells in response to benzo[a]pyrene exposure: A comparison of three microarray platforms SO OMICS-A JOURNAL OF INTEGRATIVE BIOLOGY LA English DT Article ID CDNA MICROARRAYS; DNA MICROARRAYS AB Microarrays are used to study gene expression in a variety of biological systems. A number of different platforms have been developed, but few studies exist that have directly compared the performance of one platform with another. The goal of this study was to determine array variation by analyzing the same RNA samples with three different array platforms. Using gene expression responses to benzo[a] pyrene exposure in normal human mammary epithelial cells (NHMECs), we compared the results of gene expression profiling using three microarray platforms: photolithographic oligonucleotide arrays (Affymetrix), spotted oligonucleotide arrays (Amersham), and spotted cDNA arrays (NCI). While most previous reports comparing microarrays have analyzed pre-existing data from different platforms, this comparison study used the same sample assayed on all three platforms, allowing for analysis of variation from each array platform. In general, poor correlation was found with corresponding measurements from each platform. Each platform yielded different gene expression profiles, suggesting that while microarray analysis is a useful discovery tool, further validation is needed to extrapolate results for broad use of the data. Also, microarray variability needs to be taken into consideration, not only in the data analysis but also in specific probe selection for each array type. C1 NIOSH, Pathol & Physiol Res Branch, Hlth Effects Lab Div, Ctr Dis Control & Prevent, Morgantown, WV USA. US EPA, Natl Ctr Environm Assessment, Off Res & Dev, Washington, DC 20460 USA. NCI, Carcinogen DNA Interact Sect, LCCTP, NIH, Bethesda, MD 20892 USA. NIOSH, Mol Epidemiol Team, Toxicol Mol Biol Branch, Hlth Effects Lab Div,CDCP, Morgantown, WV USA. RP Weston, A (reprint author), CDC, 1095 Willowdale Rd,Mail Stop L-3014, Morgantown, WV 26506 USA. EM agw8@cdc.gov NR 17 TC 13 Z9 13 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1536-2310 J9 OMICS JI OMICS PD DEC PY 2005 VL 9 IS 4 BP 334 EP 350 DI 10.1089/omi.2005.9.334 PG 17 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 006UG UT WOS:000234922200003 PM 16402892 ER PT J AU Wei, JS Whiteford, CC Cenacchi, N Son, CG Khan, J AF Wei, JS Whiteford, CC Cenacchi, N Son, CG Khan, J TI BBC3 mediates fenretinide-induced cell death in neuroblastoma SO ONCOGENE LA English DT Article DE fenretinide (4-HPR); apoptosis; microarray; BBC3; neuroblastoma; N-[4-hydroxyphenyl]retinamide; PUMA ID INDUCED APOPTOSIS; BH3-ONLY PROTEINS; GENE-EXPRESSION; RETINOIC-ACID; IN-VITRO; LINES; INDUCTION; DIFFERENTIATION; SENSITIVITY; GADD153 AB Fenretinide (4-HPR) is a synthetic retinoid whose apoptosis-inducing effects have been demonstrated in many tumor types. The precise mechanism of its apoptotic action is not fully understood. To further study the mechanism by which 4-HPR exerts its biological effects in neuroblastoma ( NB) and to identify the genes that contribute to the induction of apoptosis, we determined the sensitivity of eight NB cell lines to 4-HPR. Additionally, cDNA microarray analysis was performed on a 4-HPR-sensitive cell line to investigate the temporal changes in gene expression, primarily focusing on the induction of proapoptotic genes. BBC3, a transcriptionally regulated proapoptotic member of the BCL2 family, was the most highly induced proapoptotic gene. Western analysis confirmed the induction of BBC3 protein by 4-HPR. Furthermore, the induction of BBC3 was associated with the sensitivity to this agent in the cell lines tested. Finally we demonstrated that BBC3 alone is sufficient to induce cell death in the 4-HPR-sensitive and resistant NB cell lines, and that siRNA against BBC3 significantly decreases apoptosis induced by 4-HPR. Our results indicate that BBC3 mediates cell death in NB cells in response to 4-HPR. C1 NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. Daejeon Univ, Coll Oriental Med, Dept Internal Med, Taejon, South Korea. RP Khan, J (reprint author), NCI, Pediat Oncol Branch, 8717 Grovemont Circle, Bethesda, MD 20892 USA. EM khanjav@mail.nih.gov RI Khan, Javed/P-9157-2014 OI Khan, Javed/0000-0002-5858-0488 FU NCI NIH HHS [Z01 BC010594-02] NR 33 TC 7 Z9 7 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD DEC 1 PY 2005 VL 24 IS 54 BP 7976 EP 7983 DI 10.1038/sj.onc.1208947 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 989EV UT WOS:000233656600004 PM 16091745 ER PT J AU Novoselov, SV Calvisi, DF Labunskyy, VM Factor, VM Carlson, BA Fomenko, DE Moustafa, ME Hatfield, DL Gladyshev, VN AF Novoselov, SV Calvisi, DF Labunskyy, VM Factor, VM Carlson, BA Fomenko, DE Moustafa, ME Hatfield, DL Gladyshev, VN TI Selenoprotein deficiency and high levels of selenium compounds can effectively inhibit hepatocarcinogenesis in transgenic mice SO ONCOGENE LA English DT Article DE selenoprotein; selenocysteine; selenium; cancer prevention; redox regulation ID GROWTH-FACTOR-ALPHA; CANCER PREVENTION; THIOREDOXIN REDUCTASE; MOUSE MODEL; ACCELERATED HEPATOCARCINOGENESIS; GLUTATHIONE PEROXIDASE-1; PROSTATE-CANCER; LIVER-CANCER; C-MYC; SELENOCYSTEINE AB The micronutrient element selenium ( Se) has been shown to be effective in reducing the incidence of cancer in animal models and human clinical trials. Selenoproteins and low molecular weight Se compounds were implicated in the chemopreventive effect, but specific mechanisms are not clear. We examined the role of Se and selenoproteins in liver tumor formation in TGF alpha/c-Myc transgenic mice, which are characterized by disrupted redox homeostasis and develop liver cancer by 6 months of age. In these mice, both Se deficiency and high levels of Se compounds suppressed hepatocarcinogenesis. In addition, both treatments induced expression of detoxification genes, increased apoptosis and inhibited cell proliferation. Within low-to-optimal levels of dietary Se, tumor formation correlated with expression of most selenoproteins. These data suggest that changes in selenoprotein expression may either suppress or promote tumorigenesis depending on cell type and genotype. Since dietary Se may have opposing effects on cancer, it is important to identify the subjects who will benefit from Se supplementation as well as those who will not. C1 Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. NCI, Expt Carcinogenesis Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Gladyshev, VN (reprint author), Univ Nebraska, Dept Biochem, N 151 Beadle Ctr,1901 Vine St, Lincoln, NE 68588 USA. EM vgladyshev1@unl.edu RI Gladyshev, Vadim/A-9894-2013; OI Novoselov, Sergey/0000-0003-0104-6492 FU NCI NIH HHS [CA080946]; NIA NIH HHS [AG021518]; NIGMS NIH HHS [GM061603] NR 36 TC 74 Z9 75 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD DEC 1 PY 2005 VL 24 IS 54 BP 8003 EP 8011 DI 10.1038/sj.onc.1208940 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 989EV UT WOS:000233656600007 PM 16170372 ER PT J AU Egler, RA Fernandes, E Rothermund, K Sereika, S de Souza-Pinto, N Jaruga, P Dizdaroglu, M Prochownik, EV AF Egler, RA Fernandes, E Rothermund, K Sereika, S de Souza-Pinto, N Jaruga, P Dizdaroglu, M Prochownik, EV TI Regulation of reactive oxygen species, DNA damage, and c-Myc function by peroxiredoxin 1 SO ONCOGENE LA English DT Article DE peroxiredoxin 1; c-Myc; c-Abl; reactive oxygen species; DNA damage; Ras; Omnibank (R) ID LIQUID CHROMATOGRAPHY/MASS SPECTROMETRY; MURINE ERYTHROLEUKEMIA-CELLS; G(1) PHASE PROGRESSION; RAT EMBRYO FIBROBLASTS; TRANSCRIPTION IN-VIVO; HYDROGEN-PEROXIDE; REPRESSES TRANSCRIPTION; GENOMIC INSTABILITY; TUMOR-SUPPRESSOR; OXIDATIVE STRESS AB Overexpression of c-Myc results in transformation and multiple other phenotypes, and is accompanied by the deregulation of a large number of target genes. We previously demonstrated that peroxiredoxin 1 (Prdx1), a scavenger of reactive oxygen species (ROS), interacts with a region of the c-Myc transcriptional regulatory domain that is essential for transformation. This results either in the suppression or enhancement of some c-Myc functions and in the altered expression of select target genes. Most notably, c-Myc-mediated transformation is inhibited, implying a tumor suppressor role for Prdx1. Consistent with this, prdx1 -/- mice develop age-dependent hemolytic anemias and/or malignancies. We now show that erythrocytes and embryonic fibroblasts from these animals contain higher levels of ROS, and that the latter cells show evidence of c-Myc activation, including the ability to be transformed by a ras oncogene alone. In contrast, other primary cells from prdx1 -/- mice do not have elevated ROS, but nonetheless show increased oxidative DNA damage. This apparent paradox can be explained by the fact that ROS localize primarily to the cytoplasm of prdx1 -/- cells, whereas in prdx1 -/- cells, much higher levels of nuclear ROS are seen. We suggest that increased DNA damage and tumor susceptibility in prdx1 -/- animals results from this shift in intracellular ROS. prdx1 -/- mice should be useful in studying the role of oxidative DNA damage in the causation of cancer and its prevention by antioxidants. They should also help in studying the relationship between oncogenes such as c-Myc and DNA damage. C1 Childrens Hosp Pittsburgh, Hematol Oncol Sect, Rangos Res Ctr, Dept Pediat, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Nursing, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15213 USA. NIH, Lab Mol Gerontol, Baltimore, MD 21224 USA. Univ Maryland, Dept Chem & Biochem Engn, Baltimore, MD 21250 USA. Natl Inst Stand & Technol, Chem Sci & Technol Lab, Gaithersburg, MD 20899 USA. Univ Pittsburgh, Med Ctr, Dept Mol Genet & Biochem, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15213 USA. RP Prochownik, EV (reprint author), Childrens Hosp Pittsburgh, Hematol Oncol Sect, Rangos Res Ctr, Dept Pediat, Room 2100,3460 5th Ave, Pittsburgh, PA 15213 USA. EM procev@chp.edu RI Souza-Pinto, Nadja/C-3462-2013; Jaruga, Pawel/M-4378-2015 OI Souza-Pinto, Nadja/0000-0003-4206-964X; FU NHLBI NIH HHS [HL33741]; NICHD NIH HHS [T32 HD042987] NR 99 TC 119 Z9 124 U1 2 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD DEC 1 PY 2005 VL 24 IS 54 BP 8038 EP 8050 DI 10.1038/sj.onc.1208821 PG 13 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 989EV UT WOS:000233656600010 PM 16170382 ER PT J AU Stuart, JR Kawai, H Tsai, KKC Chuang, EY Yuan, ZM AF Stuart, JR Kawai, H Tsai, KKC Chuang, EY Yuan, ZM TI c-Abl regulates early growth response protein (EGR1) in response to oxidative stress SO ONCOGENE LA English DT Article DE c-Abl; EGR1; oxidative stress; tyrosine kinase ID FINGER TRANSCRIPTION FACTOR; TYROSINE KINASE; IONIZING-RADIATION; DNA-DAMAGE; ACTIVATION; GENE; EXPRESSION; P53; UPSTREAM; CELLS AB c-Abl is a tyrosine kinase that can act as a regulator of cell growth and apoptosis in response to stress. Using cell lines expressing c-Abl in an inducible manner, we identified genes whose expression was regulated by c-Abl kinase activity. Microarray analysis indicated that Early Growth Response-1 (EGR1) gene expression is induced by c-Abl kinase activity, which was confirmed at the message and protein levels. Promoter mapping experiments revealed that c-Abl utilizes three distal serum response elements (SREs) in the EGR1 promoter, which are transactivated by mitogen/extracellular receptor kinase (MEK/ERK) signaling. PD 95089, a specific inhibitor of MEK/ERK signaling, attenuated c-Abl-mediated upregulation of EGR1 expression in a dose-dependent manner. Similar results were obtained by using a dominant-negative mutant of mitogen/extracellular kinase. Significantly, hydrogen peroxide-induced EGR1 expression appears to be mediated by c-Abl, as cells expressing dominant negative c-Abl, and c-Abl(-/-) murine embryonic fibroblasts, are completely defective in hydrogen peroxide-induced EGR1 expression. In addition, c-Abl-induced apoptosis is partially mitigated by EGR1 activity, as cells devoid of EGR1 expression undergo reduced rates of c-Abl-induced apoptosis. Together, these results indicate that c-Abl promotes the induction of EGR1 through the MEK/ERK pathway in regulating apoptotic response to oxidative stress. C1 Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA. NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. RP Yuan, ZM (reprint author), Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, 665 Huntington Ave,HSPH-1,Room 508, Boston, MA 02115 USA. EM zyuan@hsph.harvard.edu RI Tsai, Kun-Chih/C-1371-2010 FU NCI NIH HHS [R29 CA85679] NR 33 TC 19 Z9 19 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD DEC PY 2005 VL 24 IS 55 BP 8085 EP 8092 DI 10.1038/sj.onc.1208953 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 991JL UT WOS:000233809400001 PM 16091742 ER PT J AU Helzner, EP Cauley, JA Pratt, SR Wisniewski, SR Talbott, EO Zmuda, JM Harris, TB Rubin, SM Taaffe, DR Tylavsky, FA Newman, AB AF Helzner, EP Cauley, JA Pratt, SR Wisniewski, SR Talbott, EO Zmuda, JM Harris, TB Rubin, SM Taaffe, DR Tylavsky, FA Newman, AB TI Hearing sensitivity and bone mineral density in older adults: the Health, Aging and Body Composition Study SO OSTEOPOROSIS INTERNATIONAL LA English DT Article DE bone mineral density; hearing sensitivity; older adults ID PURE-TONE THRESHOLDS; COCHLEAR CAPSULE; PAGETS-DISEASE; OTOSCLEROSIS; DENSITOMETRY; PREVALENCE; FRACTURES; WOMEN; RISK; RACE AB Bone mineral density (BMD) may be associated with hearing loss in older adults. Demineralization of the cochlear capsule has been associated with hearing loss in those with Paget's disease of the bone and otosclerosis. Osteoporosis may also result in cochlear capsule demineralization. We hypothesized that lower hip BMD and lower heel ultrasound measurements would be associated with hearing loss in a population-based sample of 2,089 older black and white men and women. Bone parameters and hearing function were measured at the fourth clinical follow-up visit. Audiometric threshold testing was used to measure air- and bone-conduction hearing sensitivity. BMD of the hip and its subregions was measured using dual-energy X-ray absorptiometry. Calcaneal bone measurements [broadband ultrasound attenuation (BUA), speed of sound (SOS) and the quantitative ultrasound index (QUI)] were obtained using heel ultrasound. After adjusting for known hearing loss risk factors, no association was found between hearing and any of the bone measurements in whites and black women. In black men, however, lower hip BMD was associated with higher odds of hearing loss; for each standard deviation decrease in total hip BMD, the odds of hearing loss were 1.41 (95% confidence interval 1.08, 1.83), 1.39 (95% CI 1.07, 1.82) for femoral neck BMD and 1.65 (95% CI 1.26, 2.16) for trochanter BMD. Conductive hearing loss was associated with lower heel ultrasound measurements, though only among white men. The results of this study are mixed and inconclusive. Lower BMD of the hip and its subregions was associated with hearing loss among black men, but not among whites or black women. Lower measurements on heel ultrasound were associated with conductive hearing loss, though only among white men. These results suggest that axial and appendicular bone parameters may be modestly associated with hearing loss in older men, but not in women. C1 Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Commun Sci & Disorders, Pittsburgh, PA USA. NIA, Epidmeiol Demog & Biometry Program, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, Prevent Sci Grp, San Francisco, CA 94143 USA. Univ Queensland, Sch Human Movement Studies, Brisbane, Qld, Australia. Univ Tennessee, Dept Prevent Med, Memphis, TN USA. RP Helzner, EP (reprint author), Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. EM ehelzner@pitt.edu RI Pratt, Sheila/H-7139-2013; Newman, Anne/C-6408-2013; Cauley, Jane/N-4836-2015; OI Newman, Anne/0000-0002-0106-1150; Cauley, Jane/0000-0003-0752-4408; Wisniewski, Stephen/0000-0002-3877-9860; Talbott, Evelyn/0000-0002-5198-7939 FU NIA NIH HHS [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106] NR 33 TC 13 Z9 13 U1 1 U2 4 PU SPRINGER LONDON LTD PI GODALMING PA SWEETAPPLE HOUSE CATTESHALL ROAD, GODALMING GU7 3DJ, SURREY, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD DEC PY 2005 VL 16 IS 12 BP 1675 EP 1682 DI 10.1007/s00198-005-1902-8 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 993YZ UT WOS:000233997600028 PM 15883660 ER PT J AU Costantini, M Beccaro, M Merlo, F AF Costantini, M Beccaro, M Merlo, F TI The last three months of life of Italian cancer patients. Methods, sample characteristics and response rate of the Italian Survey of the Dying of Cancer (ISDOC) SO PALLIATIVE MEDICINE LA English DT Article DE caregivers; health service research; health survey; neoplasms; terminal care ID CARE; DEATH; END; SATISFACTION AB Study objective: The Italian Survey of the Dying of Cancer (ISDOC) was undertaken to evaluate the experiences of Italian people dying from cancer during their last three months of life in all settings of care. Study design: A two-stage probability sample was used to estimate end-of-life outcomes of about 160 000 Italian cancer deaths. In the first stage, 30 of the 197 Italian Local Health Districts (LHD) were randomly selected after stratification. In the second stage, a fixed proportion of cancer deaths was randomly drawn from each LHD, and 2000 death certificates of patients who died of cancer were identified. The nonprofessional caregivers were identified and interviewed using a semi-structured questionnaire derived from the Views of Informal Carers - Evaluation of Services (VOICES). Results: Caregivers were successfully identified for 95% of the sample (n = 1900). The caregiver was the child (42.7%), the spouse (36.5%), another family member (17.3%), or a friend (1.5%). Only 3% of the sample had no non-professional support. An interview was obtained for 1289 (64.5%) of the sample, at a median time of 234 days after death ( range: 103 - 374). Higher response rates were associated with home death (67.7%) and with a higher education (>70%). Conversely, a lower response rate was observed when the caregiver was the spouse (56.2%). Response rates ranged from about 80% for letters sent four to six months after the patients' death to about 60% for letters sent after eight months or more. A descriptive analysis of refusals, based on the transcripts of the telephone calls, allowed classification of 61% of refusals for at least one of the two dimensions examined: caregiver psychological suffering and quality of care received by the patient. Psychological suffering was present in 99% of refusals examined for this dimension (48%). Conversely, a poor quality of care was reported by 63% of the refusals examined for this dimension (23%). Conclusion: The ISDOC survey provides a representative picture of the needs and problems associated with the last three months of life of Italian cancer patients. C1 Natl Canc Inst, Clin Epidemiol Unit, I-16132 Genoa, Italy. Natl Canc Inst, Unit Environm Epidemiol, I-16132 Genoa, Italy. RP Costantini, M (reprint author), Natl Canc Inst, Clin Epidemiol Unit, Largo R Benzi 10, I-16132 Genoa, Italy. EM massimo.costantini@istge.it RI Pisanti, Renato/G-6232-2010; costantini, massimo/G-1443-2012; Giorgi Rossi, Paolo/K-6367-2016; OI Giorgi Rossi, Paolo/0000-0001-9703-2460; Pisanti, Renato/0000-0002-8153-2177; costantini, massimo/0000-0002-5293-7079; Bruzzi, Paolo/0000-0002-7874-2077 NR 27 TC 40 Z9 40 U1 1 U2 3 PU HODDER ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 0269-2163 J9 PALLIATIVE MED JI Palliat. Med. PD DEC PY 2005 VL 19 IS 8 BP 628 EP 638 DI 10.1191/0269216305pm1086oa PG 11 WC Health Care Sciences & Services; Public, Environmental & Occupational Health; Medicine, General & Internal SC Health Care Sciences & Services; Public, Environmental & Occupational Health; General & Internal Medicine GA 992ZL UT WOS:000233922400008 PM 16450880 ER PT J AU Alter, BP AF Alter, BP TI Fanconi's Anemia, transplantation, and cancer SO PEDIATRIC TRANSPLANTATION LA English DT Article; Proceedings Paper CT 8th Meeting on Stem Cell Transplantation in Children CY JAN 20-22, 2005 CL Scottsdale, AZ SP Amgen Inc, BioMartin Genzyme LLC DE Fanconi's Anemia; bone marrow transplant; cancer; leukemia; aplastic anemia ID COMPLEMENTATION GROUP AB Patients with Fanconi's Anemia (FA) have high rates of congenital physical abnormalities, bone marrow failure, leukemia, and solid tumors. Stem cell transplant (SCT) is often effective in curing bone marrow failure, but high-risk patients, particularly those whose donor is not a human leukocyte antigen matched sibling, are vulnerable to early mortality from transplant-related complications. Long-term survivors of SCT have risks of solid tumors (particularly of the oral cavity), which are even higher than the already high 'baseline' risk of neoplasia in untransplanted FA patients. In this group, the major types of cancer are head and neck squamous cell carcinomas, and gynecologic malignancies. Rapid evaluation of new SCT preparative regimens would be useful in improving both short-term and long-term results. C1 NCI, Dept Hlth & Human Serv, Clin Genet Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. RP Alter, BP (reprint author), NCI, Dept Hlth & Human Serv, Clin Genet Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. EM alterb@mail.nih.gov NR 19 TC 16 Z9 18 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1397-3142 J9 PEDIATR TRANSPLANT JI Pediatr. Transplant. PD DEC PY 2005 VL 9 SU 7 BP 81 EP 86 DI 10.1111/j.1399-3046.2005.00440.x PG 6 WC Pediatrics; Transplantation SC Pediatrics; Transplantation GA 991HK UT WOS:000233802900011 PM 16305622 ER PT J AU Ehrenkranz, RA Walsh, MC Vohr, BR Jobe, AH Wright, LL Fanaroff, AA Wrage, LA Poole, K AF Ehrenkranz, RA Walsh, MC Vohr, BR Jobe, AH Wright, LL Fanaroff, AA Wrage, LA Poole, K CA Natl Institutes Child Hlth Human D TI Validation of the National Institutes of Health consensus definition of bronchopulmonary dysplasia SO PEDIATRICS LA English DT Article; Proceedings Paper CT Annual Meeting of the Pediatric-Academic-Societies CY APR 28-MAY 13, 2001 CL Baltimore, MD SP Pediat Acad Soc DE bronchopulmonary dysplasia; chronic lung disease; extremely preterm infants; neurodevelopmental ID LOW-BIRTH-WEIGHT; CHRONIC LUNG-DISEASE; NEONATAL RESEARCH NETWORK; PRETERM INFANTS; PREMATURE-INFANTS; MULTICENTER TRIAL; CHILD-HEALTH; RISK-FACTORS; OUTCOMES; DEXAMETHASONE AB Objective. A number of definitions of bronchopulmonary dysplasia (BPD), or chronic lung disease, have been used. A June 2000 National Institute of Child Health and Human Development/National Heart, Lung, and Blood Institute Workshop proposed a severity-based definition of BPD for infants <= 32 weeks' gestational age (GA). Mild BPD was defined as a need for supplemental oxygen (O-2) for >= 28 days but not at 36 weeks' postmenstrual age (PMA) or discharge, moderate BPD as O2 for >= 28 days plus treatment with <= 30% O-2 at 36 weeks' PMA, and severe BPD as O2 for >= 28 days plus >= 30% O-2 and/or positive pressure at 36 weeks' PMA. The objective of this study was to determine the predictive validity of the severity-based, consensus definition of BPD. Methods. Data from 4866 infants (birth weight <= 1000 g, GA <= 32 weeks, alive at 36 weeks' PMA) who were entered into the National Institute of Child Health and Human Development Neonatal Research Network Very Low Birth weight (VLBW) Infant Registry between January 1, 1995 and December 31, 1999, were linked to data from the Network Extremely Low Birth Weight (ELBW) Follow-up Program, in which surviving ELBW infants have a neurodevelopmental and health assessment at 18 to 22 months' corrected age. Linked VLBW Registry and Follow-up data were available for 3848 (79%) infants. Selected follow-up outcomes (use of pulmonary medications, rehospitalization for pulmonary causes, receipt of respiratory syncytial virus prophylaxis, and neurodevelopmental abnormalities) were compared among infants who were identified with BPD defined as O-2 for 28 days (28 days definition), as O-2 at 36 weeks' PMA (36 weeks' definition), and with the consensus definition of BPD. Results. A total of 77% of the neonates met the 28-days definition, and 44% met the 36-weeks definition. Using the consensus BPD definition, 77% of the infants had BPD, similar to the cohort identified by the 28-days definition. A total of 46% of the infants met the moderate (30%) or severe (16%) consensus definition criteria, identifying a similar cohort of infants as the 36-weeks definition. Of infants who met the 28-days definition and 36-weeks definition and were seen at follow-up at 18 to 22 months' corrected age, 40% had been treated with pulmonary medications and 35% had been rehospitalized for pulmonary causes. In contrast, as the severity of BPD identified by the consensus definition worsened, the incidence of those outcomes and of selected adverse neurodevelopmental outcomes increased in the infants who were seen at follow-up. Conclusion. The consensus BPD definition identifies a spectrum of risk for adverse pulmonary and neurodevelopmental outcomes in early infancy more accurately than other definitions. C1 Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06520 USA. Case Western Reserve Univ, Dept Pediat, Cleveland, OH 44106 USA. Brown Univ, Dept Pediat, Providence, RI 02912 USA. Univ Cincinnati, Dept Pediat, Cincinnati, OH USA. NICHHD, Bethesda, MD 20892 USA. RTI Int, Res Triangle Pk, NC USA. RP Ehrenkranz, RA (reprint author), Yale Univ, Sch Med, Dept Pediat, 333 Cedar St,POB 208064, New Haven, CT 06520 USA. EM richard.ehrenkranz@yale.edu FU NCRR NIH HHS [M01 RR 02635, M01 RR 00070, M01 RR 00750, M01 RR 00997, M01 RR 01032, M01 RR 02172, M01 RR 06022, M01 RR 08084]; NICHD NIH HHS [U01 HD36790, U10 HD21364, U10 HD21373, U10 HD21385, U10 HD21397, U10 HD21415, U10 HD27851, U10 HD27853, U10 HD27871, U10 HD27880, U10 HD27904, U10 HD34167, U10 HD34216] NR 47 TC 402 Z9 416 U1 4 U2 16 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 2005 VL 116 IS 6 BP 1353 EP 1360 DI 10.1542/peds.2005-0249 PG 8 WC Pediatrics SC Pediatrics GA 989JH UT WOS:000233668200013 PM 16322158 ER PT J AU Ambalavanan, N Carlo, WA Bobashev, G Mathias, E Liu, B Poole, K Fanaroff, AA Stoll, BJ Ehrenkranz, R Wright, LL AF Ambalavanan, N Carlo, WA Bobashev, G Mathias, E Liu, B Poole, K Fanaroff, AA Stoll, BJ Ehrenkranz, R Wright, LL CA Natl Inst Child Health Human Dev TI Prediction of death for extremely low birth weight neonates SO PEDIATRICS LA English DT Article DE logistic models; neural networks (computer); predictive value; receiver operating characteristic curve ID INTENSIVE-CARE-UNIT; ARTIFICIAL NEURAL-NETWORK; MORTALITY RISK; INFANTS; REGRESSION; ALGORITHM; VIABILITY AB Objective. To compare multiple logistic regression and neural network models in predicting death for extremely low birth weight neonates at 5 time points with cumulative data sets, as follows: scenario A, limited prenatal data; scenario B, scenario A plus additional prenatal data; scenario C, scenario B plus data from the first 5 minutes after birth; scenario D, scenario C plus data from the first 24 hours after birth; scenario E, scenario D plus data from the first 1 week after birth. Methods. Data for all infants with birth weights of 401 to 1000 g who were born between January 1998 and April 2003 in 19 National Institute of Child Health and Human Development Neonatal Research Network centers were used (n = 8608). Twenty-eight variables were selected for analysis (3 for scenario A, 15 for scenario B, 20 for scenario C, 25 for scenario D, and 28 for scenario E) from those collected routinely. Data sets censored for prior death or missing data were created for each scenario and divided randomly into training (70%) and test (30%) data sets. Logistic regression and neural network models for predicting subsequent death were created with training data sets and evaluated with test data sets. The predictive abilities of the models were evaluated with the area under the curve of the receiver operating characteristic curves. Results. The data sets for scenarios A, B, and C were similar, and prediction was best with scenario C (area under the curve: 0.85 for regression; 0.84 for neural networks), compared with scenarios A and B. The logistic regression and neural network models performed similarly well for scenarios A, B, D, and E, but the regression model was superior for scenario C. Conclusions. Prediction of death is limited even with sophisticated statistical methods such as logistic regression and nonlinear modeling techniques such as neural networks. The difficulty of predicting death should be acknowledged in discussions with families and caregivers about decisions regarding initiation or continuation of care. C1 Univ Alabama, Dept Pediat, Birmingham, AL 35249 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. Case Western Reserve Univ, Dept Pediat, Cleveland, OH 44106 USA. Emory Univ, Dept Pediat, Atlanta, GA 30322 USA. Yale Univ, Dept Pediat, New Haven, CT USA. NICHHD, Neonatal Res Network, Bethesda, MD 20892 USA. RP Ambalavanan, N (reprint author), Univ Alabama, Dept Pediat, 525 New Hillman Bldg,619 S 20th St, Birmingham, AL 35249 USA. EM ambal@uab.edu OI Ambalavanan, Namasivayam/0000-0003-0731-9092 FU NCRR NIH HHS [M01 RR00070, M01 RR00750, M01 RR00997, M01 RR01032, M01 RR02172, M01 RR02635, M01 RR06022, M01 RR08084]; NICHD NIH HHS [U10 HD21364, U01 HD36790, U10 HD 40461, U10 HD21373, U10 HD21385, U10 HD21397, U10 HD21415, U10 HD27851, U10 HD27853, U10 HD27856, U10 HD27871, U10 HD27880, U10 HD27881, U10 HD27904, U10 HD34167, U10 HD34216, U10 HD40689] NR 18 TC 39 Z9 41 U1 0 U2 2 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 2005 VL 116 IS 6 BP 1367 EP 1373 DI 10.1542/peds.2004-2099 PG 7 WC Pediatrics SC Pediatrics GA 989JH UT WOS:000233668200015 PM 16322160 ER PT J AU Farrell, MH La Pean, A Ladouceur, L AF Farrell, MH La Pean, A Ladouceur, L TI Content of communication by pediatric residents after newborn genetic screening SO PEDIATRICS LA English DT Article DE communication; genetic testing; newborn screening; patient-doctor communication; quality improvement ID CYSTIC-FIBROSIS; ETHICAL-ISSUES; CHALLENGE AB Background. Newborn screening saves lives, but psychosocial complications after genetic screening have led to doubts about expanding programs. Because complications have been blamed on ineffective communication of results, a population-scale system to ensure communication quality may improve outcomes. The objective of this study was to develop and evaluate a method to assess the content of communication after newborn genetic screening. Methods. We abstracted content data and calculated quantitative scores for 3 communication quality indicators ( key content, early placement of good news, and excessive background content) for 59 transcribed conversations between pediatric residents and simulated parents of an "infant" who was found via newborn screening to carry either cystic fibrosis or sickle cell hemoglobinopathy. Results. Only 8.5% of transcripts contained the key content items that were thought to be necessary for parental understanding; 27.1% included reassuring news about carrier status within the first 10% of content. Scores for 3 quality indicators fell in the low performance range in 35.6%, 30.5%, and 27.1% of transcripts, respectively. The most common topic was background about the disease ( 22% of content statements) even though the infant did not have the disease. Surprisingly, 50% of sickle trait transcripts included counseling about a possible risk for sudden death. Conclusions. Assessment of the content domain of communication quality identified some high-quality communication interspersed with many missed opportunities. If integrated into newborn screening, our method may help to alleviate some of society's ethical concerns about benefit and risk after newborn and other genetic screening. C1 Med Coll Wisconsin, Ctr Patient Care & Outcomes Res, Milwaukee, WI 53226 USA. NINDS, NIH, Neurogenet Branch, Bethesda, MD 20892 USA. NIAID, Div Aids, Int Res Branch, NIH, Bethesda, MD 20892 USA. RP Farrell, MH (reprint author), Med Coll Wisconsin, Ctr Patient Care & Outcomes Res, 8701 Watertown Plank Rd,POB 26509, Milwaukee, WI 53226 USA. EM mfarrell@mail.mcw.edu FU NHLBI NIH HHS [7K01HL072530] NR 34 TC 23 Z9 24 U1 0 U2 7 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 2005 VL 116 IS 6 BP 1492 EP 1498 DI 10.1542/peds.2004-2611 PG 7 WC Pediatrics SC Pediatrics GA 989JH UT WOS:000233668200031 PM 16322176 ER PT J AU La Pean, A Farrell, MH AF La Pean, A Farrell, MH TI Initially misleading communication of carrier results after newborn genetic screening SO PEDIATRICS LA English DT Article DE cystic fibrosis; genetic testing; newborn screening; patient-doctor communication; sickle cell disease ID CYSTIC-FIBROSIS; ETHICAL-ISSUES; KNOWLEDGE; SCHEMATA; RECALL; SKILLS AB Background. Newborn screening saves lives, but the way in which parents learn of a positive screening test is also important for adherence with treatment plans and avoidance of psychosocial complications. The first messages provided to parents may be particularly important for understanding, especially when the infant is found to be a heterozygous carrier for sickle cell hemoglobinopathy ( SCH) or cystic fibrosis ( CF). This study investigated the prevalence of "initially misleading" communication, defined as the inclusion of 1 of 55 "bad-news" content items ( eg, the screening test is positive) before any of 39 "good-news" content items ( eg, the infant is healthy, normal, a carrier, or otherwise without problems). Methods. As part of a larger study of the content of counseling after newborn genetic screening, we used a quantitative, explicit-criteria method to abstract 59 transcribed conversations between pediatric residents and standardized parents of an "infant" who was found through newborn screening to carry either CF or SCH. Results. Of 59 transcripts, 41 were found to be misleading ( at least 1 bad-news content statement before the first good-news content statement). There were significantly more misleading likely-CF-carrier than SCH-carrier transcripts ( 89.7% vs 50%). Among the misleading transcripts, the mean number of misleading statements was 5.5. The mean distance between the first bad-news and first good-news statements was 28.1 statements ( 20.5% of the total duration of counseling). Discussion. The high prevalence of misleading content and the time lag before clarification does not bode well for parental understanding of infant carrier status. Future projects should improve curricula for training programs and develop quality-assurance efforts for community clinicians both to improve parental understanding and help assuage society's fears about the safety of genetic screening technologies. C1 Med Coll Wisconsin, Ctr Patient Care & Outcomes Res, Milwaukee, WI 53226 USA. NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. RP Farrell, MH (reprint author), Med Coll Wisconsin, Ctr Patient Care & Outcomes Res, 8701 Watertown Plank Rd,POB 26509, Milwaukee, WI 53226 USA. EM mfarrell@mail.mcw.edu FU NHLBI NIH HHS [7K01HL072530] NR 34 TC 28 Z9 29 U1 2 U2 7 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 2005 VL 116 IS 6 BP 1499 EP 1505 DI 10.1542/peds.2005-0449 PG 7 WC Pediatrics SC Pediatrics GA 989JH UT WOS:000233668200032 PM 16322177 ER PT J AU Hazra, R Gafni, RI Maldarelli, F Balis, FM Tullio, AN DeCarlo, E Worrell, CJ Steinberg, SM Flaherty, J Yale, K Kearney, BP Zeichner, SL AF Hazra, R Gafni, RI Maldarelli, F Balis, FM Tullio, AN DeCarlo, E Worrell, CJ Steinberg, SM Flaherty, J Yale, K Kearney, BP Zeichner, SL TI Tenofovir disoproxil fumarate and an optimized background regimen of antiretroviral agents as salvage therapy for pediatric HIV infection SO PEDIATRICS LA English DT Article; Proceedings Paper CT 11th Conference on Retroviruses and Opportunistic Infections CY FEB 08-11, 2004 CL San Francisco, CA DE tenofovir; HIV; children; multidrug resistance; bone toxicity ID RANDOMIZED CONTROLLED-TRIAL; BONE-MINERAL CONTENT; REVERSE-TRANSCRIPTASE; HIV-1-INFECTED INDIVIDUALS; EXPERIENCED PATIENTS; COMBINATION THERAPY; PROTEASE INHIBITORS; TREATMENT FAILURE; DRUG-RESISTANCE; RHESUS MACAQUES AB Objectives. Highly active antiretroviral therapy has altered the course of HIV infection among children, but new antiretroviral agents are needed for treatment-experienced children with drug-resistant virus. Tenofovir disoproxil fumarate (DF) is a promising agent for use in pediatric salvage therapy, because of its tolerability, efficacy, and resistance profile. We designed this study to provide preliminary pediatric safety and dosing information on tenofovir DF, while also providing potentially efficacious salvage therapy for heavily treatment-experienced, HIV-infected children. Methods. Tenofovir DF, alone and in combination with optimized background antiretroviral regimens, was studied among 18 HIV-infected children (age range: 8.3-16.2 years) who had progressive disease with >= 2 prior antiretroviral regimens, in a single-center, open-label trial. Tenofovir DF monotherapy for 6 days was followed by the addition of individualized antiretroviral regimens. Subjects were monitored with HIV RNA reverse transcription-polymerase chain reaction, flow cytometry, and routine laboratory studies; monitoring for bone toxicity included measurement of lumbar spine bone mineral density (BMD) with dual-energy x-ray absorptiometry. Subjects were monitored through 48 weeks. Results. Two subjects developed grade 3 elevated hepatic transaminase levels during monotherapy and were removed from the study. The remaining 16 subjects had a median of 4 antiretroviral agents (range: 3-5 agents) added to tenofovir DF. HIV plasma RNA levels decreased from a median pretreatment level of 5.4 log(10) copies per mL (range: 4.1-5.9 log(10) copies per mL) to 4.21 log(10) copies per mL at week 48 (n = 15), with 6 subjects having <400 copies per mL, including 4 with <50 copies per mL. The overall median increases in CD4(+) T cell counts were 58 cells per mm(3) (range: -64 to 589 cells per mm(3)) at week 24 and 0 cells per mm(3) ( range: - 274 to 768 cells per mm(3)) at week 48. The CD4(+) cell responses among the virologic responders were high and sustained. The major toxicity attributed to tenofovir DF was a >6% decrease in BMD for 5 of 15 subjects evaluated at week 48, necessitating the discontinuation of tenofovir DF therapy for 2; all 5 subjects experienced >2 log(10) copies per mL decreases in HIV plasma RNA levels. Conclusions. Tenofovir DF-containing, individualized, highly active antiretroviral therapy regimens were well tolerated and effective among heavily treatmentexperienced, HIV-infected children. Loss of BMD may limit tenofovir DF use among prepubertal patients. C1 NCI, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. NCI, HIV Drug Resistance Program, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. Gilead Sci Inc, Foster City, CA 94404 USA. RP Zeichner, SL (reprint author), NCI, HIV & AIDS Malignancy Branch, NIH, Bldg 10,Room 105255,MSC 1868, Bethesda, MD 20892 USA. EM zeichnes@mail.nih.gov FU Intramural NIH HHS NR 41 TC 50 Z9 52 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 2005 VL 116 IS 6 BP E846 EP E854 DI 10.1542/peds.2005-0975 PG 9 WC Pediatrics SC Pediatrics GA 989JH UT WOS:000233668200089 PM 16291735 ER PT J AU Vaudry, D Hamelink, C Damadzic, R Eskay, RL Gonzalez, B Eiden, LE AF Vaudry, D Hamelink, C Damadzic, R Eskay, RL Gonzalez, B Eiden, LE TI Endogenous PACAP acts as a stress response peptide to protect cerebellar neurons from ethanol or oxidative insult SO PEPTIDES LA English DT Article DE knock-out; granule neurons; development ID CYCLASE-ACTIVATING POLYPEPTIDE; ACTIVITY-DEPENDENT SURVIVAL; GRANULE NEURONS; CELL-SURVIVAL; RAT; EXPRESSION; RECEPTORS; APOPTOSIS; PATHWAY; CORTEX AB The rodent cerebellum is richly supplied with PACAPergic innervation. Exogenous pituitary adenylate cyclase-activating polypeptide (PACAP) increases cerebellar granule cell survival and differentiation in culture, and enhances the number of neuroblasts in the molecular and internal granule cell layers (IGL) when injected postnatally into the cerebellum in vivo. Here, we have investigated the role of endogenous PACAP during cerebellar development by comparing the morphology of normal and PACAP-deficient mouse cerebellum, and the response of cerebellar granule cells from normal and PACAP-deficient mice subjected to neurotoxic insult in culture. There was no difference in cerebellar volume or granule cell number, in I I-day-old wild type versus PACAP-deficient mice. Cultured cerebellar neurons from PACAP-deficient and wild type mice also showed no apparent differences in survival and differentiation either under depolarizing conditions, or non-depolarizing conditions in the presence or absence of either dibutyryl cAMP or 100 nM PACAP. However, cultured cerebellar neurons from PACAP-deficient mice were significantly more sensitive than wild type neurons to ethanol- or hydrogen peroxide-induced toxicity. Differential ethanol toxicity was reversed by addition of 100 nM exogenous PACAP, suggesting that endogenous PACAP has neuroprotective activity in the context of cellular insult or stress. The neuroprotective action of PACAP was mimicked by dibutryl cAMP, indicating that it occurred via activation of adenylate cyclase. These results indicate that PACAP might act to protect the brain from paraphysiological insult, including exposure to toxins or hypoxia. Published by Elsevier Inc. C1 NIMH, Lab Cellular & Mol Regulat, Mol Neurosci Sect, Bethesda, MD 20892 USA. Univ Rouen, INSERM, U413, European Inst Peptide Res IFRMP 23, F-76821 Mont St Aignan, France. RP Eiden, LE (reprint author), NIMH, Lab Cellular & Mol Regulat, Mol Neurosci Sect, 49 Convent Dr,Rm 5A68,MSC 4090,9000 Rockville Pik, Bethesda, MD 20892 USA. EM eidenl@mail.nih.gov RI Gonzalez, Bruno/E-6103-2016; OI Vaudry, David/0000-0003-3567-7452; Eiden, Lee/0000-0001-7524-944X FU Intramural NIH HHS [Z01 MH002386-21] NR 26 TC 46 Z9 48 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD DEC PY 2005 VL 26 IS 12 BP 2518 EP 2524 DI 10.1016/j.peptides.2005.05.015 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 993SX UT WOS:000233976400023 PM 16009465 ER PT J AU Davenport, AP Bonner, TI Foord, SM Harmar, AJ Neubig, RR Pin, JP Spedding, M Kojima, M Kangawa, K AF Davenport, AP Bonner, TI Foord, SM Harmar, AJ Neubig, RR Pin, JP Spedding, M Kojima, M Kangawa, K TI International Union of Pharmacology. LVI. Ghrelin receptor nomenclature, distribution, and function SO PHARMACOLOGICAL REVIEWS LA English DT Review ID HORMONE SECRETAGOGUE RECEPTOR; LEFT-VENTRICULAR DYSFUNCTION; CHRONIC HEART-FAILURE; DES-ACYL GHRELIN; CIRCULATING GHRELIN; CARDIAC CACHEXIA; PEPTIDE; PITUITARY; STOMACH; CELL AB Ghrelin is a 28-amino acid peptide originally isolated from rat stomach and is cleaved from a 117-amino acid precursor. The sequence of the mature peptide from rats and mice differs by two amino acids from that of human ghrelin. Alternative splicing of the ghrelin gene transcript can result in the translation of a second biologically active peptide, des-Gln(14)-ghrelin. Both peptides have a unique post-translational modification, octanoylation of Ser(3), which is essential for the binding to receptors in hypothalamus and pituitary and stimulating the release of growth hormone from the pituitary. The growth hormone secretagogue receptor (GHS-R1a, Swiss-Prot code Q92847, LocusLink ID 2693), a rhodopsin-like seven transmembrane spanning G protein-coupled receptors belonging to Family A, was cloned in 1996 from the pituitary and hypothalamus and shown to be the target of growth hormone secretagogues (GHS), a class of synthetic peptide and non-peptide compounds causing growth hormone release from the anterior pituitary. In 1999, ghrelin was identified as the endogenous cognate ligand for this receptor. The purpose of this review is to propose an official International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR) nomenclature designating GHS-R1a as the ghrelin receptor to follow the convention of naming receptors after the endogenous agonist, abbreviated where necessary to GRLN. C1 Univ Cambridge, Clin Pharmacol Unit, Cambridge, England. NIMH, Genet Lab, Bethesda, MD 20892 USA. GlaxoSmithKline Res & Dev, Stevenage, Herts, England. Univ Edinburgh, Div Neurosci, Edinburgh, Midlothian, Scotland. Univ Edinburgh, Neurosci Res Ctr, Edinburgh, Midlothian, Scotland. Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA. CNRS, Montpellier, France. IRIS, Neuilly Sur Seine, France. Natl Cardiovasc Ctr, Res Inst, Osaka, Japan. RP Davenport, AP (reprint author), Univ Cambridge, Addenbrookes Hosp, Clin Pharmacol Unit, NC IUPHAR Emerging Pharmacol Grp, Cambridge CB2 2QQ, England. EM apd10@medschl.cam.ac.uk RI Davenport, Anthony/A-5773-2008; OI Davenport, Anthony/0000-0002-2096-3117; Spedding, Michael/0000-0002-1248-8221; Harmar, Anthony/0000-0002-3838-9264 NR 41 TC 132 Z9 140 U1 2 U2 7 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 2005 VL 57 IS 4 BP 541 EP 546 DI 10.1124/pr.57.4.1 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 997TG UT WOS:000234270300012 PM 16382107 ER PT J AU Newton, TF De la Garza, R Fong, T Chiang, N Holmes, TH Bloch, DA Anderson, A Elkashef, A AF Newton, TF De la Garza, R Fong, T Chiang, N Holmes, TH Bloch, DA Anderson, A Elkashef, A TI A comprehensive assessment of the safety of intravenous methamphetamine administration during treatment with selegiline SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE selegiline; deprenyl; MAO-B; methamphetamine; treatment; addiction ID MONOAMINE-OXIDASE; COCAINE; DOPAMINE; HUMANS AB Selegiline (L-deprenyl) is a selective irreversible monoamine oxidase B inhibitor shown to be effective in the treatment of Parkinson's and Alzheimer's diseases. Recent evidence suggests that selegiline may also be useful in treating specific aspects of cocaine and nicotine dependence, generating interest in this compound for the treatment of methamphetamine addiction. To investigate this, we performed a randomized, single-blind, placebo-controlled study to evaluate the safety of selegiline treatment (as compared to placebo), concurrent with intravenous methamphetamine (15 or 30 mg). Secondary study objectives included determinations of plasma levels of selegiline and its metabolites, evaluating whether selegiline administration altered the pharmacokinetics of methamphetamine or its metabolites, and evaluating whether selegiline treatment alters the subjective responses to methamphetamine. Twenty-four methamphetamine-dependent participants were randomized to treatment, and 9 of these (N=5 selegiline, N=4 placebo) completed the entire protocol. The principal finding from this study was that intravenous administration of moderate doses of methamphetamine was safely tolerated during treatment with selegiline. No participants had electrocardiogram changes, and there were no meaningful differences in any laboratory values either between groups at screening or as a result of the study procedures. In general, adverse events were mild or moderate, and no subjects were discontinued due to adverse events or serious adverse events. Selegiline treatment did not enhance any of the cardiovascular changes (heart rate, blood pressure) produced by methamphetamine administration. Selegiline treatment slightly increased methamphetamine associated "bad effects" but did not alter any other subjective effects. The elimination half-life of methamphetamine was similar to 12 h, and selegiline did not alter clearance of methamphetamine. The available data suggest that selegiline is likely to be safe if used as a pharmacotherapy for methamphetamine dependence. (C) 2005 Elsevier Inc. All rights reserved. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Natl Inst Drug Abuse, Div Pharmacotherapies & Med Consequences Drug Abu, Bethesda, MD USA. Stanford Univ, Stanford, CA 94305 USA. RP Newton, TF (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. EM tnewton@mednet.ucla.edu RI De La Garza, Richard/B-2489-2014; OI De La Garza, Richard/0000-0003-1943-4469; newton, thomas/0000-0002-3198-5901 FU NCRR NIH HHS [RR 00865]; NIDA NIH HHS [N01DA-00388] NR 23 TC 14 Z9 15 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 2005 VL 82 IS 4 BP 704 EP 711 DI 10.1016/j.pbb.2005.11.012 PG 8 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 015LX UT WOS:000235554000015 PM 16413604 ER PT J AU Zheng, M Zhu, WZ Han, QD Xiao, RP AF Zheng, M Zhu, WZ Han, QD Xiao, RP TI Emerging concepts and therapeutic implications of beta-adrenergic receptor subtype signaling SO PHARMACOLOGY & THERAPEUTICS LA English DT Review DE G protein-coupled receptors; beta-adrenergic receptor subtypes; beta-adrenergic receptor polymorphisin; G proteins; PKA; CaMKII PI3K; apoptosis; hypertrophy; congestive heart failure; beta-blocker therapy ID CHRONIC HEART-FAILURE; RAT VENTRICULAR MYOCYTES; IDIOPATHIC DILATED CARDIOMYOPATHY; PROTEIN-KINASE-A; HUMAN BETA(1)-ADRENERGIC RECEPTOR; RANDOMIZED INTERVENTION TRIAL; FAILING HUMAN HEART; N-TERMINAL KINASES; BETA(2)-ADRENERGIC RECEPTOR; CARDIAC MYOCYTES AB The stimulation of beta-adrenergic receptor (beta AR) plays a pivotal role in regulating myocardial function and morphology in the normal and failing heart. Three genetically and pharmacologically distinct beta AR subtypes, beta(1)AR, beta(2)AR, and beta(3)AR, are identified in various types of cells. While both beta(1)AR and beta(2)AR, the predominant beta AR subtypes expressed in the heart of many mammalian species including human, are Coupled to the G(s)-adenylyl cyclase-cAMP-PKA pathway, beta(2)AR dually activates pertussis toxin-sensitive G(i) proteins. During acute stimulation, beta(2)AR-G(i) coupling partially inhibits the G(s)-mediated positive contractile and relaxant effects via a G(i)-G(beta gamma)-phosphoinositide 3-kinase (PI3K)-dependent mechanism in adult rodent cardiomyocytes. More importantly, persistent beta(1)AR stimulation evokes a multitude of cardiac toxic effects, including myocyte apoptosis and hypertrophy, via a calmodulin-dependent protein kinase II (CaMKII)-, rather than cAMP-PKA-, dependent mechanism in rodent heart in vivo and cultured cardiomyocytes. In contrast, persistent beta(2)AR activation protects myocardium by a cell Survival pathway involving G(i), PI3K, and Akt. In this review, we attempt to highlight the distinct functionalities and signaling mechanisms of these beta AR subtypes and discuss how these subtype-specific properties of beta ARs might affect tile pathogenesis of congestive heart failure (CHF) and tile therapeutic effectiveness of certain beta-blockers in tile treatment of congestive heart failure. (c) 2005 Published by Elsevier Inc. C1 NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Peking Univ, Inst Cardiovasc Sci, Beijing 100083, Peoples R China. Peking Univ, Inst Mol Med, Beijing 100871, Peoples R China. RP Xiao, RP (reprint author), NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM xiaor@grc.nia.nih.gov FU Intramural NIH HHS NR 120 TC 66 Z9 67 U1 2 U2 20 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0163-7258 J9 PHARMACOL THERAPEUT JI Pharmacol. Ther. PD DEC PY 2005 VL 108 IS 3 BP 257 EP 268 DI 10.1016/j.pharmthera.2005.04.006 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 993YT UT WOS:000233996900002 PM 15979723 ER PT J AU Powers, JH AF Powers, JH TI Microbiologic surrogate end points in infectious diseases: Example of acute clinical trials of otitis media trials SO PHARMACOTHERAPY LA English DT Article DE surrogate end points; acute otitis media; tympanocentesis ID STAPHYLOCOCCUS-AUREUS INFECTIONS; BACTERIAL-MENINGITIS; DOUBLE-BLIND; BACTERIOLOGICAL ERADICATION; CARDIOVASCULAR-DISEASE; ANTIBIOTIC-TREATMENT; CHILDREN; THERAPY; MANAGEMENT; MUPIROCIN AB Clinical outcomes that ineasure how patients feet, function, or survive are the most important and relevant outcomes of therapy in clinical trials and in clinical practice. Surrogate end points, which do not directly measure clinical benefit to the patient, may function as Substitutes for clinical end points in clinical trials. Such surrogates are attractive as they may allow measurement of outcomes earlier in time or with a smaller sample size than with clinical outcomes. Microbiologic biomarkers, such as culture results at a specific time after start of therapy, or pharmacodynamic analyses of the effect of drugs on organisms often are proposed as surrogate end points in clinical trials of therapies for infectious diseases. However, evaluation of biomarkers as surrogate end points poses distinct challenges, and only a few biomarkers have been useful replacements for clinical end points. Evaluation of biomarkers as potential surrogate end points first requires an understanding of the differences among measurements of the cause of a disease, risk factors for Outcome, and measurements Of treatment effects. We will discuss the definitions of clinical and surrogate end points and the reasons why surrogate end points may not predict the true clinical benefit of therapies. We will use the example of the biomarker of microbiologic outcomes from tympanocenteses performed during therapy as the sole measure of clinical effectiveness in clinical trials Of acute otitis media to illustrate the challenges in evaluating biomarkers as Surrogate end points. C1 US FDA, Ctr Drug Evaluat & Res, Off Antimicrobial Prod, Rockville, MD 20857 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Powers, JH (reprint author), Ctr Drug Evaluat & Res, Antimicrobial Drug Dev & Resistance Initiat, 10903 New Hampshire Ave,Bldg 22,Room 6400, Silver Spring, MD 20993 USA. EM POWERSJOH@cder.fda.gov NR 67 TC 10 Z9 10 U1 1 U2 1 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD DEC PY 2005 VL 25 IS 12 SU S BP 109S EP 123S DI 10.1592/phco.2005.25.12part2.109S PN 2 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 993FW UT WOS:000233941000003 PM 16305280 ER PT J AU Inbar, Y Benyamini, H Nussinov, R Wolfson, HJ AF Inbar, Y Benyamini, H Nussinov, R Wolfson, HJ TI Combinatorial docking approach for structure prediction of large proteins and multi-molecular assemblies SO PHYSICAL BIOLOGY LA English DT Article; Proceedings Paper CT Workshop on Flexibility in Biomolecules CY MAY 15-18, 2005 CL Tempe, AZ ID GLOBULAR-PROTEINS; PATHWAYS AB Protein folding and protein binding are similar processes. In both, structural units combinatorially associate with each other. In the case of folding, we mostly handle relatively small units, building blocks or domains, that are covalently linked. In the case of multi-molecular binding, the subunits are relatively large and are associated only by non-covalent bonds. Experimentally, the difficulty in the determination of the structures of such large assemblies increases with the complex size and the number of components it contains. Computationally, the prediction of the structures of multi-molecular complexes has largely not been addressed, probably owing to the magnitude of the combinatorial complexity of the problem. Current docking algorithms mostly target prediction of pairwise interactions. Here our goal is to predict the structures of multi-unit associations, whether these are chain-connected as in protein folding, or separate disjoint molecules in the assemblies. We assume that the structures of the single units are known, either through experimental determination or modeling. Our aim is to combinatorially assemble these units to predict their structure. To address this problem we have developed CombDock. CombDock is a combinatorial docking algorithm for the structural units assembly problem. Below, we briefly describe the algorithm and present examples of its various applications to folding and to multi-molecular assemblies. To test the robustness of the algorithm, we use inaccurate models of the structural units, derived either from crystal structures of unbound molecules or from modeling of the target sequences. The algorithm has been able to predict near-native arrangements of the input structural units in almost all of the cases, suggesting that a combinatorial approach can overcome the imperfect shape complementarity caused by the inaccuracy of the models. In addition, we further show that through a combinatorial docking strategy it is possible to enhance the predictions of pairwise interactions involved in a multi-molecular assembly. C1 Tel Aviv Univ, Raymond & Beverly Sackler Fac Exact Sci, Sch Comp Sci, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, Sackler Sch Med, Sackler Inst Mol Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel. NCI, SAIC Frederick Inc, Lab Expt & Computat Biol, Basic Res Program, Frederick, MD 21702 USA. RP Inbar, Y (reprint author), Tel Aviv Univ, Raymond & Beverly Sackler Fac Exact Sci, Sch Comp Sci, IL-69978 Tel Aviv, Israel. EM inbaryuv@tau.ac.il RI Wolfson, Haim/A-1837-2011 FU NCI NIH HHS [N01-CO-12400] NR 19 TC 23 Z9 24 U1 0 U2 0 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 1478-3967 J9 PHYS BIOL JI Phys. Biol. PD DEC PY 2005 VL 2 IS 4 SI SI BP S156 EP S165 DI 10.1088/1478-3975/2/4/S10 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 007UC UT WOS:000234994500011 PM 16280621 ER PT J AU Sardiu, ME Alves, G Yu, YK AF Sardiu, ME Alves, G Yu, YK TI Score statistics of global sequence alignment from the energy distribution of a modified directed polymer and directed percolation problem SO PHYSICAL REVIEW E LA English DT Article ID ACID SUBSTITUTION MATRICES; RANDOM IMPURITIES; PSI-BLAST; SEARCH; CONSTRUCTION; SIMILARITY; PROTEINS AB Sequence alignment is one of the most important bioinformatics tools for modern molecular biology. The statistical characterization of gapped alignment scores has been a long-standing problem in sequence alignment research. Using a variant of the directed path in random media model, we investigate the score statistics of global sequence alignment taking into account, in particular, the compositional bias of the sequences compared. Such statistics are used to distinguish accidental similarity due to compositional similarity from biologically significant similarity. To accommodate the compositional bias, we introduce an extra parameter p indicating the probability for positive matching scores to occur. When p is small, a high scoring alignment obviously cannot come from compositional similarity. When p is large, the highest scoring point within a global alignment tends to be close to the end of both sequences, in which case we say the system percolates. By applying finite-size scaling theory on percolating probability functions of various sizes (sequence lengths), the critical p at infinite size is obtained. For alignment of length t, the fact that the score fluctuation grows as chi t(1/3) is confirmed upon investigating the scaling form of the alignment score. Using the Kolmogorov-Smirnov statistics test, we show that the random variable chi, if properly scaled, follows the Tracy-Widom distributions: Gaussian orthogonal ensemble for p slightly larger than p(c) and Gaussian unitary ensemble for larger p. Although these results deepen our understanding of the distribution of alignment scores, the use of these results in practical applications remains somewhat heuristic and needs to be further developed. Nevertheless, the possibility of characterizing score statistics for modest system size (sequence lengths), via proper reparametrization of alignment scores, is illustrated. C1 Florida Atlantic Univ, Dept Phys, Boca Raton, FL 33431 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Florida Atlantic Univ, Dept Phys, Boca Raton, FL 33431 USA. FU Intramural NIH HHS NR 46 TC 6 Z9 6 U1 0 U2 1 PU AMER PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 2470-0045 EI 2470-0053 J9 PHYS REV E JI Phys. Rev. E PD DEC PY 2005 VL 72 IS 6 AR 061917 DI 10.1103/PhysRevE.72.061917 PN 1 PG 21 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA 008TY UT WOS:000235064800065 PM 16485984 ER PT J AU Wielgus, AR Sarna, T AF Wielgus, AR Sarna, T TI Melanin in human irides of different color and age of donors SO PIGMENT CELL RESEARCH LA English DT Article DE melanin; human iris; eye color; age of donors; ESR spectroscopy; iron; bovine iris; eumelanin; pheomelanin ID ELECTRON-SPIN-RESONANCE; METAL-IONS; LIQUID-CHROMATOGRAPHY; CHEMICAL DEGRADATION; PARKINSONS-DISEASE; EPR INVESTIGATIONS; HYDROXYL RADICALS; UVEAL MELANOCYTES; SUBSTANTIA-NIGRA; SIDEROSIS-BULBI AB Melanin is the main chromophore of the human iris. This pigment is considered to be the most important factor that determines the color of the irides. Previous studies based mainly on chemical degradation methods showed that brown irides contain more melanin than blue ones. In our study, we used electron spin resonance (ESR) spectroscopy to detect and characterize melanin free radical centers and associated iron in human irides. Based on this method, we determined the amount of melanin in the irides and the relative content of iron in iridial melanin as a function of their color, shade, and the age of their donors. Chemical degradation of iridial homogenates enabled us to characterize the structure of eumelanin and determine the content of pheomelanin present in human and bovine irides. The ESR amplitude, the normalized intensity obtained by double integration of the ESR signal of melanin, and the content of the pigment in the irides depended on color and shade of the eyes being 40% higher in the brown group of the irides compared with all other groups. On the other hand, the relative iron content normalized to the melanin content in light blue irides showed a small decrease with age of donors. Melanin in human and bovine irides was mostly composed of eumelanin, and pheomelanin content was of the order of a few percent. Although some differences in the structure of eumelanin present in the human and bovine irides are possible, the results obtained in this study suggest that human irides contain eumelanin with very similar chemical properties. C1 Jagiellonian Univ, Fac Biotechnol, Dept Biophys, PL-30387 Krakow, Poland. NIEHS, Lab Chem & Pharmacol, Res Triangle Pk, NC 27709 USA. RP Sarna, T (reprint author), Jagiellonian Univ, Fac Biotechnol, Dept Biophys, Ul Gronostajowa 7, PL-30387 Krakow, Poland. EM tsarna@mol.uj.edu.pl NR 60 TC 40 Z9 42 U1 2 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0893-5785 J9 PIGM CELL RES JI Pigm. Cell. Res. PD DEC PY 2005 VL 18 IS 6 BP 454 EP 464 DI 10.1111/j.1600-0749.2005.00268.x PG 11 WC Cell Biology; Dermatology SC Cell Biology; Dermatology GA 982HV UT WOS:000233149600008 PM 16280011 ER PT J AU Stadtman, TC AF Stadtman, TC TI Selenoproteins - Tracing the role of a trace element in protein function SO PLOS BIOLOGY LA English DT Editorial Material ID CLOSTRIDIAL GLYCINE REDUCTASE; GLUTATHIONE PEROXIDASE; SELENIUM; SELENOCYSTEINE; IDENTIFICATION; COMPONENT C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Stadtman, TC (reprint author), NHLBI, Biochem Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM tcstadtman@nih.gov NR 11 TC 20 Z9 20 U1 1 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1544-9173 J9 PLOS BIOL JI PLoS. Biol. PD DEC PY 2005 VL 3 IS 12 BP 2077 EP 2079 AR e421 DI 10.1371/journal.pbio.0030421 PG 3 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 992SI UT WOS:000233903800003 PM 16336050 ER PT J AU Jankowsky, JL Slunt, HH Gonzales, V Savonenko, AV Wen, JC Jenkins, NA Copeland, NG Younkin, LH Lester, HA Younkin, SG Borchelt, DR AF Jankowsky, JL Slunt, HH Gonzales, V Savonenko, AV Wen, JC Jenkins, NA Copeland, NG Younkin, LH Lester, HA Younkin, SG Borchelt, DR TI Persistent amyloidosis following suppression of A beta production in a transgenic model of Alzheimer disease SO PLOS MEDICINE LA English DT Article ID GAMMA-SECRETASE INHIBITOR; MOUSE MODEL; MICROGLIAL ACTIVATION; IN-VIVO; GENE-EXPRESSION; PRECURSOR PROTEINS; MEMORY DEFICITS; NERVOUS-SYSTEM; MICE; DEPOSITION AB Background The proteases (secretases) that cleave amyloid-beta (A beta) peptide from the amyloid precursor protein (APP) have been the focus of considerable investigation in the development of treatments for Alzheimer disease. The prediction has been that reducing AP production in the brain, even after the onset of clinical symptoms and the development of associated pathology, will facilitate the repair of damaged tissue and removal of amyloid lesions. However, no long-term studies using animal models of amyloid pathology have yet been performed to test this hypothesis. Methods and Findings We have generated a transgenic mouse model that genetically mimics the arrest of A beta production expected from treatment with secretase inhibitors. These mice overexpress mutant APP from a vector that can be regulated by doxycycline. Under normal conditions, high-level expression of APP quickly induces fulminant amyloid pathology. We show that doxycycline administration inhibits transgenic APP expression by greater than 95% and reduces AP production to levels found in nontransgenic mice. Suppression of transgenic A synthesis in this model abruptly halts the progression of amyloid pathology. However, formation and disaggregation of amyloid deposits appear to be in disequilibrium as the plaques require far longer to disperse than to assemble. Mice in which APP synthesis was suppressed for as long as 6 mo after the formation of AP deposits retain a considerable amyloid load, with little sign of active clearance. Conclusion This study demonstrates that amyloid lesions in transgenic mice are highly stable structures in vivo that are slow to disaggregate. Our findings suggest that arresting AP production in patients with Alzheimer disease should halt the progression of pathology, but that early treatment may be imperative, as it appears that amyloid deposits, once formed, will require additional intervention to clear. C1 Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. CALTECH, Div Biol, Pasadena, CA 91125 USA. Johns Hopkins Univ, Sch Med, Dept Cell Biol, Baltimore, MD USA. NCI, Frederick Canc Res & Dev Ctr, Mouse Canc Genet Program, Frederick, MD USA. Mayo Clin Jacksonville, Jacksonville, FL 32224 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Jankowsky, JL (reprint author), Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. EM jlj2@caltech.edu; borchelt@mbi.ufl.edu FU NIA NIH HHS [K01 AG026144-05, K01 AG026144, K01 AG026144-01, K01 AG026144-02, K01 AG026144-03, K01 AG026144-04, K01 AG26144-01, P01 AG015453, P50 AG005146, P50 AGO5146-20, R01 AG006656, R01 AG006656-16]; NINDS NIH HHS [R01 NS 047225, R01 NS047225] NR 65 TC 125 Z9 127 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD DEC PY 2005 VL 2 IS 12 BP 1318 EP 1333 AR e355 DI 10.1371/journal.pmed.0020355 PG 16 WC Medicine, General & Internal SC General & Internal Medicine GA 003XD UT WOS:000234714700020 PM 16279840 ER PT J AU Sospedra, M Zhao, YD zur Hausen, H Muraro, PA Hamashin, C de Villiers, EM Pinilla, C Martin, R AF Sospedra, Mireia Zhao, Yingdong zur Hausen, Harald Muraro, Paolo A. Hamashin, Christa de Villiers, Ethel-Michele Pinilla, Clemencia Martin, Roland TI Recognition of conserved amino acid motifs of common viruses and its role in autoimmunity SO PLOS PATHOGENS LA English DT Article AB The triggers of autoimmune diseases such as multiple sclerosis ( MS) remain elusive. Epidemiological studies suggest that common pathogens can exacerbate and also induce MS, but it has been difficult to pinpoint individual organisms. Here we demonstrate that in vivo clonally expanded CD4(+) T cells isolated from the cerebrospinal fluid of a MS patient during disease exacerbation respond to a poly-arginine motif of the nonpathogenic and ubiquitous Torque Teno virus. These T cell clones also can be stimulated by arginine-enriched protein domains from other common viruses and recognize multiple autoantigens. Our data suggest that repeated infections with common pathogenic and even nonpathogenic viruses could expand T cells specific for conserved protein domains that are able to cross-react with tissue-derived and ubiquitous autoantigens. C1 NINDS, Cellular Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. NCI, Computat & Syst Biol Grp, Biomet Res Branch, NIH, Bethesda, MD 20892 USA. Deutsch Krebsforschungszentrum, Div Caharacterizat Tumorviruses, D-6900 Heidelberg, Germany. Torrey Pines Inst Mol Studies & Mixture Sci, San Diego, CA USA. RP Martin, R (reprint author), Hosp Univ Hebron, Inst Catalana Rec & Estudis Avancats, Barcelona, Spain. EM roland.martin@icrea.es OI Muraro, Paolo/0000-0002-3822-1218 NR 0 TC 42 Z9 42 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD DEC PY 2005 VL 1 IS 4 BP 335 EP 348 AR e41 DI 10.1371/journal.ppat.0010041 PG 14 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA V42VC UT WOS:000202894000006 PM 16362076 ER PT J AU Beck, KH Hartos, JL Simons-Morton, BG AF Beck, KH Hartos, JL Simons-Morton, BG TI Parent-teen disagreement of parent-imposed restrictions on teen driving after one month of licensure: Is discordance related to risky teen driving? SO PREVENTION SCIENCE LA English DT Article; Proceedings Paper CT 3rd Scientific Meeting of the American-Academy-of-Health-Behavior CY MAR 16-19, 2003 CL ST AUGUSTINE, FL SP Amer Acad Hlth Behav DE adolescent driving; parenting; driving restrictions or limits; concordance ID BRIEF INTERVENTION; DRIVERS; PASSENGERS; 16-YEAR-OLD; INVOLVEMENT; BEHAVIOR AB The purpose of the investigation was to determine if parent-teen discordance for parent-imposed restrictions on driving conditions, driving rules, and the consequences for driving rule violations were related to risky teen driving. A total of 579 parents and their newly licensed teens were interviewed by telephone, 1 month after teens obtained provisional licenses. In multiple regression analyses, the degree of disagreement with parent restrictions on driving conditions and parent-imposed consequences for driving rule violations were negatively associated with a composite measure of teen risky driving. Female parents were negatively associated and male teens were positively associated with risky driving, but discordance with restricted driving conditions was the most important predictor. Discordance may reflect poor parent-teen relations or inadequate communication about parental expectations. The findings suggest that increasing parent-teen concordance on parent-imposed driving restrictions may help reduce risky teen driving. C1 Univ Maryland, Dept Publ & Community Hlth, College Pk, MD 20742 USA. Univ N Carolina, Dept Hlth Behav & Adm, Coll Hlth & Human Serv, Charlotte, NC 28223 USA. NICHD, Prevent Res Branch, DESPR, NIH, Bethesda, MD 20892 USA. RP Beck, KH (reprint author), Univ Maryland, Dept Publ & Community Hlth, 2366 Hlth & Human Perf Bldg, College Pk, MD 20742 USA. EM kbeck1@umd.edu; jlhartos@email.uncc.edu; mortonb@mail.nih.gov FU NIMH NIH HHS [R01-MH49381] NR 32 TC 1 Z9 1 U1 2 U2 2 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1389-4986 J9 PREV SCI JI Prev. Sci. PD DEC PY 2005 VL 6 IS 4 BP 259 EP 267 DI 10.1007/s11121-005-0001-6 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 003AH UT WOS:000234653500001 PM 16416508 ER PT J AU Nallamsetty, S Austin, BP Penrose, KJ Waugh, DS AF Nallamsetty, S Austin, BP Penrose, KJ Waugh, DS TI Gateway vectors for the production of combinatorially-tagged His(6)-MBP fusion proteins in the cytoplasm and periplasm of Escherichia Coli SO PROTEIN SCIENCE LA English DT Article DE immobilized metal affinity chromatography; IMAC; maltose-binding protein; Gateway cloning; fusion tag; structural genomics; TEV protease; expression vector; fusion protein ID MALTOSE-BINDING-PROTEIN; RECOMBINANT PROTEINS; VIRUS PROTEASE; RIBONUCLEASE-A; IN-VIVO; EXPRESSION; PURIFICATION; SOLUBILITY; CHAPERONE; FRAGMENT AB Many proteins that accumulate in the form of insoluble aggregates when they are overproduced in Escherichia coli can be rendered soluble by fusing them to E. coli maltose binding protein (MBP), and this will often enable them to fold in to their biologically active conformations. Yet, although it is an excellent solubility enhancer, MBP is not a particularly good affinity tag for protein purification. To compensate for this shortcoming, we have engineered and successfully tested Gateway destination vectors for the production of dual His(6)MBP-tagged fusion proteins in the cytoplasm and periplasm of E. coli. The MBP moiety improves the yield and solubility of its fusion partners while the hexahistidine tag (His-tag) serves to facilitate their purification. The availability of a vector that targets His(6)MBP fusion proteins to the periplasm expands the utility of this dual tagging approach to include proteins that contain disulfide bonds or are toxic in the bacterial cytoplasm. C1 NCI, Macromol Crystallog Lab, Canc Res Ctr, Frederick, MD 21702 USA. RP Waugh, DS (reprint author), NCI, Macromol Crystallog Lab, Canc Res Ctr, POB B, Frederick, MD 21702 USA. EM waughd@ncifcrf.gov FU Intramural NIH HHS NR 27 TC 91 Z9 96 U1 1 U2 10 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 2005 VL 14 IS 12 BP 2964 EP 2971 DI 10.1110/ps.051718605 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 990RW UT WOS:000233761900004 PM 16322578 ER PT J AU Li, HM Van Vranken, S Zhao, Y Li, Z Guo, Y Eisele, L Li, YX AF Li, HM Van Vranken, S Zhao, Y Li, Z Guo, Y Eisele, L Li, YX TI Crystal structures of T cell receptor beta chains related to rheumatoid arthritis SO PROTEIN SCIENCE LA English DT Article DE TCR; crystal structure; superantigen; rheumatoid arthritis; Mycoplasma arthritidis mitogen; structure/function studies; proteins of the immune system; crystallography; protein crystallization; mutagenesis (site-directed and general); protein structures-new; sedimentation ID COLLAGEN-INDUCED ARTHRITIS; MHC CLASS-II; V-ALPHA DOMAIN; ANTIGEN RECEPTOR; SYNOVIAL-FLUID; 3-DIMENSIONAL STRUCTURE; HLA-DR4 DRA-ASTERISK-0101; MYCOPLASMA SUPERANTIGEN; CONFORMATIONAL-CHANGES; PEPTIDE VACCINATION AB The crystal structures of the V beta 17(+) beta chains of two human T cell receptors (TCRs), originally derived from the synovial fluid (SF4) and tissue (C5-1) of a patient with rheumatoid arthritis (RA), have been determined in native (SF4) and mutant (C5-1(F104 -> Y/C187 -> S)) forms, respectively. These TCR beta chains form homodimers in solution and in crystals. Structural comparison reveals that the main-chain conformations in the CDR regions of the C5-1 and SF4 V beta 17 closely resemble those of a V beta 17 JM22 in a bound form; however, the CDR3 region shows different conformations among these three V beta 17 structures. At the side-chain level, conformational differences were observed at the CDR2 regions between our two ligand-free forms and the bound JM22 form. Other significant differences were observed at the V beta regions 8-12, 40-44, and 82-88 between C5-1/SF4 and JM22 V beta 17, implying that there is considerable variability in the structures of very similar beta chains. Structural alignments also reveal a considerable variation in the V beta-C beta associations, and this may affect ligand recognition. The crystal structures also provide insights into the structure basis of T cell recognition of Mycoplasma arthritidis mitogen (MAM), a superantigen that may be implicated in the development of human RA. Structural comparisons of the V beta domains of known TCR structures indicate that there are significant similarities among V beta regions that are MAM-reactive, whereas there appear to be significant structural differences among those V beta regions that lack MAM-reactivity. It further reveals that CDR2 and framework region (FR) 3 are likely to account for the binding of TCR to MAM. C1 New York State Dept Hlth, Wadsworth Ctr, Albany, NY 12208 USA. SUNY Albany, Sch Publ Hlth, Dept Biomed Sci, Albany, NY 12201 USA. NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. RP Li, HM (reprint author), New York State Dept Hlth, Wadsworth Ctr, 150 New Scotland Ave,CMS-1155, Albany, NY 12208 USA. EM lih@wadsworth.org OI Li, Hongmin/0000-0002-8684-5308 FU NIAID NIH HHS [R01 AI050628-01, AI50628, R01 AI050628] NR 100 TC 6 Z9 7 U1 0 U2 3 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 2005 VL 14 IS 12 BP 3025 EP 3038 DI 10.1110/ps.051748305 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 990RW UT WOS:000233761900010 PM 16260763 ER PT J AU Wu, ZR Delaglio, F Wyatt, K Wistow, G Bax, A AF Wu, ZR Delaglio, F Wyatt, K Wistow, G Bax, A TI Solution structure of gamma S-crystallin by molecular fragment replacement NMR SO PROTEIN SCIENCE LA English DT Article DE alignment; deuteration; liquid crystal; Pf1; relaxation; RDC; residual dipolar coupling; structural proteins; NMR spectroscopy; heteronuclear NMR; new methods; database mining ID RESIDUAL DIPOLAR COUPLINGS; NUCLEAR MAGNETIC-RESONANCE; MACROMOLECULAR STRUCTURE DETERMINATION; ISOTOPICALLY ENRICHED PROTEINS; HIGH-RESOLUTION; LENS CRYSTALLINS; BIOLOGICAL MACROMOLECULES; INDUCED ALIGNMENT; BETA-CRYSTALLIN; CHEMICAL-SHIFTS AB The solution structure of murine gamma S-crystallin (gamma S) has been determined by multidimensional triple resonance NMR spectroscopy, using restraints derived from two sets of dipolar couplings, recorded in different alignment media, and supplemented by a small number of NOE distance restraints. gamma S consists of two topologically similar domains, arranged with an approximate twofold symmetry, and each domain shows close structural homology to closely related (similar to 50% sequence identity) domains found in other members of the gamma-crystallin family. Each domain consists of two four-strand "Greek key" beta-sheets. Although the domains are tightly anchored to one another by the hydrophobic surfaces of the two inner Greek key motifs, the N-arm, the interdomain linker and several turn regions show unexpected flexibility and disorder in solution. This may contribute entropic stabilization to the protein in solution, but may also indicate nucleation sites for unfolding or other structural transitions. The method used for solving the gamma S structure relies on the recently introduced molecular fragment replacement method, which capitalizes on the large database of protein structures previously solved by X-ray crystallography and NMR. C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NEI, Sect Mol Struct & Funct Genom, NIH, Bethesda, MD 20892 USA. Ohio State Univ, Dept Biochem, Columbus, OH 43210 USA. RP Bax, A (reprint author), NIDDK, Chem Phys Lab, NIH, Bldg 5,Room 126, Bethesda, MD 20892 USA. EM bax@nih.gov NR 78 TC 29 Z9 29 U1 2 U2 8 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 2005 VL 14 IS 12 BP 3101 EP 3114 DI 10.1110/ps.051635205 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 990RW UT WOS:000233761900017 PM 16260758 ER PT J AU Grant, BF Hasin, DS Stinson, FS Dawson, DA Ruan, WJ Goldstein, RB Smith, SM Saha, TD Huang, BJ AF Grant, BF Hasin, DS Stinson, FS Dawson, DA Ruan, WJ Goldstein, RB Smith, SM Saha, TD Huang, BJ TI Prevalence, correlates, co-morbidity, and comparative disability of DSM-IV generalized anxiety disorder in the USA: results from the National Epiderniologic Survey on Alcohol and Related Conditions SO PSYCHOLOGICAL MEDICINE LA English DT Article ID COMORBIDITY SURVEY REPLICATION; INTERVIEW SCHEDULE AUDADIS; MENTAL-DISORDERS; UNITED-STATES; PSYCHIATRIC-DISORDERS; LIFETIME PREVALENCE; EPIDEMIOLOGIC SURVEY; PERSONALITY-DISORDERS; MAJOR DEPRESSION; CLINICAL INTERVIEWERS AB Background. This study addressed the prevalences, correlates, co-morbidity and disability of DSM-IV generalized anxiety disorder (GAD) and other psychiatric disorders in a large national survey of the general population, the National Institute on Alcohol Abuse and Alcoholism's (NIAAA) National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). The study presents nationally representative data, for the first time, on prevalence, correlates, co-morbidity, and comparative disability of DSM-IV GAD. Method. Data are taken from a large (n = 43093) representative sample of the adult USA population. Results. Prevalences of 12-month and lifetime GAD were 2(.)1% and 4(.)1%. Being female, middle-aged, widowed/separated/divorced, and low income increased risk, while being Asian, Hispanic, or Black decreased risk. GAD was highly co-morbid with substance use, and other anxiety, mood, and personality disorders. Co-morbidity in GAD was not substantially greater than for most other Axis I and II disorders. Disability and impairment in pure GAD were equivalent to pure mood disorders, but significantly greater than in pure substance use, and other anxiety and personality disorders. Individuals co-morbid for GAD and each mood disorder were more disabled than those with pure forms of GAD or each mood disorder. When co-morbid with GAD, nicotine dependence and other anxiety and personality disorders were not associated with increased disability over that associated with pure GAD, but GAD did show increased disability over that due to each of these disorders in pure form. Conclusions. Associations between GAD and Axis I and II disorders were strong and significant, with variation among specific disorders. Results strongly support GAD as an independent disorder with significant impairment and disability. C1 NIAAA, Lab Epidemiol, Div Intramural Clin & Biol Res, NIH, Bethesda, MD 20892 USA. Columbia Univ, Dept Epidemiol, New York, NY USA. Columbia Univ, Dept Psychiat, New York, NY USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. RP Grant, BF (reprint author), NIAAA, Lab Epidemiol, Div Intramural Clin & Biol Res, NIH, Room 3077,MS 9304,5635 Fishers Lane, Bethesda, MD 20892 USA. EM bgrant@willco.niaaa.nih.gov OI Goldstein, Rise/0000-0002-9603-9473 FU NIAAA NIH HHS [K05AA014221]; NIDA NIH HHS [R01DA018652] NR 82 TC 249 Z9 258 U1 7 U2 35 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD DEC PY 2005 VL 35 IS 12 BP 1747 EP 1759 DI 10.1017/S0033291705006069 PG 13 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 994VK UT WOS:000234059100007 PM 16202187 ER PT J AU Fox, NA Nichols, KE Henderson, HA Rubin, K Schmidt, L Hamer, D Ernst, M Pine, DS AF Fox, NA Nichols, KE Henderson, HA Rubin, K Schmidt, L Hamer, D Ernst, M Pine, DS TI Evidence for a gene-environment interaction in predicting behavioral inhibition in middle childhood SO PSYCHOLOGICAL SCIENCE LA English DT Article ID SEROTONIN TRANSPORTER; SOCIAL SUPPORT; DEPRESSION; CHILDREN; STRESS; POLYMORPHISM; ANXIETY; SHYNESS; MODERATION; AMYGDALA AB Gene-environment interactions are presumed to shape human behavior during early development. However, no human research has demonstrated that such interactions lead to stable individual differences in fear responses. We tested this possibility by focusing on a polymorphism in the promoter region of the gene for the serotonin transporter (5-HTT). This polymorphism has been linked to many indices of serotonin activity. Specifically, we tested the hypothesis that an interaction between children's 5-HTT status and maternal reports of social support predicts inhibited behavior with unfamiliar peers in middle childhood. Results were consistent with this hypothesis: Children with the combination of the short 5-HTT allele and low social support had increased risk for behavioral inhibition in middle childhood. C1 Univ Maryland, Dept Human Dev, College Pk, MD 20742 USA. Univ Miami, Dept Psychol, Coral Gables, FL 33124 USA. McMaster Univ, Dept Psychol, Hamilton, ON, Canada. NCI, Biochem Lab, Canc Res Ctr, Bethesda, MD 20892 USA. RP Fox, NA (reprint author), Univ Maryland, Dept Human Dev, CP 3304,Benjamin Bldg, College Pk, MD 20742 USA. EM fox@umd.edu FU NICHD NIH HHS [HD 17899] NR 27 TC 166 Z9 172 U1 7 U2 25 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0956-7976 J9 PSYCHOL SCI JI Psychol. Sci. PD DEC PY 2005 VL 16 IS 12 BP 921 EP 926 DI 10.1111/j.1467-9280.2005.01637.x PG 6 WC Psychology, Multidisciplinary SC Psychology GA 987LO UT WOS:000233519600001 PM 16313653 ER PT J AU Antoniou, K Papadopoulou-Daifoti, Z Hyphantis, T Papathanasiou, G Bekris, E Marselos, M Panlilio, L Muller, CE Goldberg, SR Ferre, S AF Antoniou, K Papadopoulou-Daifoti, Z Hyphantis, T Papathanasiou, G Bekris, E Marselos, M Panlilio, L Muller, CE Goldberg, SR Ferre, S TI A detailed behavioral analysis of the acute motor effects of caffeine in the rat: involvement of adenosine A(1) and A(2A) receptors SO PSYCHOPHARMACOLOGY LA English DT Article DE caffeine; adenosine A(1) receptor; adenosine A(2A) receptor; motor activity; factor analysis; rat ID NUCLEUS-ACCUMBENS; LOCOMOTOR-ACTIVITY; DOPAMINE RELEASE; MESSENGER-RNA; MICE LACKING; NGFI-B; ANTAGONISTS; BRAIN; GLUTAMATE; AMPHETAMINE AB Rationale: There is no consensus on the contribution of adenosine A(1)t and A(2A) receptor blockade to motor-activating effects of caffeine. Objective: Our aim was to use a detailed and continuous observational method to compare the motor effects induced by caffeine with those induced by selective A(1) and A(2A) receptor antagonists. Methods: The behavioral repertoire induced by systemic administration of caffeine (3, 10, and 30 mg/kg), At receptor antagonist 8-cyclopentyl-1,3-dimethyl-xanthine (CPT; 1.2, 4.8 and 7.2 mg/kg), and A(2A) receptor antagonist 3-(3-hydroxypropyl)-8-(m-methoxystyryl)-7-methyl-1-propargylxanthine phosphate disodium salt (MSX-3; 1, 3, and 10 mg/kg) was analyzed. The effects of pretreatment with the selective A(1) receptor agonist N-6-cyclopentyladenosine (CPA; 0.1 mg/g) and the selective A(2A) receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxyamidoadenosine (CGS 21680; 0.2 mg/kg) on the pattern of motor activation induced by caffeine, CPT, or MSX-3 were also examined. Results: The pattern of behavioral activation induced by caffeine was better mimicked by CPT than by MSX-3. Coadministration of CPT and MSX-3 gave different results depending on the dose and the type of behavioral response. CPA was more effective at decreasing the activating effects of caffeine and CPT than those of CGS 21680. On the other hand, CGS 21680 was more effective at decreasing the activating effects of MSX-3 than those of caffeine or CPT. Factor analysis revealed a complex three-dimensional behavioral profile for caffeine that was similar to the profile for CPT and was different from the profile for MSX-3. Conclusions: The results indicate a predominant role for A(1) receptors in the motor-activating effects of acutely administered caffeine. C1 NIDA, Preclin Pharmacol Sect, Behav Neurosci Branch, Intramural Res Program,NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. Univ Athens, Sch Med, Dept Pharmacol, GR-11527 Athens, Greece. Univ Ioannina, Sch Med, Dept Pharmacol, GR-45110 Ioannina, Greece. Univ Bonn, Inst Pharmaceut, D-53115 Bonn, Germany. RP Ferre, S (reprint author), NIDA, Preclin Pharmacol Sect, Behav Neurosci Branch, Intramural Res Program,NIH,Dept Hlth & Human Serv, POB 5180, Baltimore, MD 21224 USA. EM sferre@intra.nida.nih.gov RI Ferre, Sergi/K-6115-2014; Muller, Christa/C-7748-2014 OI Ferre, Sergi/0000-0002-1747-1779; Muller, Christa/0000-0002-0013-6624 FU Intramural NIH HHS NR 36 TC 49 Z9 50 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD DEC PY 2005 VL 183 IS 2 BP 154 EP 162 DI 10.1007/s00213-005-0173-6 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 992UD UT WOS:000233908600003 PM 16205915 ER PT J AU Siahpush, M Heller, G Singh, G AF Siahpush, M Heller, G Singh, G TI Lower levels of occupation, income and education are strongly associated with a longer smoking duration: Multivariate results from the 2001 Australian National Drug Strategy Survey SO PUBLIC HEALTH LA English DT Article DE smoking cessation; socio-economic status; Australia ID SELF-REPORTED SMOKING; CIGARETTE-SMOKING; CESSATION; HEALTH; VALIDATION; INITIATION; COMMUNITY; MORTALITY; BENEFITS; SMOKERS AB Objective: Our aim was to investigate the association of socio-economic status (SES) with duration of smoking among ever smokers. Study design: We used a subsample of ever smokers (n = 9973) aged 18 + years from the 2001 National Drug Strategy Household Survey (conducted by the Australian Institute of Health and Welfare), which involved a multistage area sample and mainly self-administered questionnaires. Methods: The outcome was smoking duration from onset to cessation. We used survival analysis to predict smoking duration. Results: Results showed that smoking duration from onset to cessation was 14% longer for blue-collar workers than for professionals. Respondents who earned under $300/week smoked for 38% longer than those earning $800+/week. Individuals with less than 10 years of education smoked for 13% longer than those with 12 + years of education. Conclusions: Smokers from lower social strata smoke for much longer durations. This finding and the fact that smoking increases the likelihood of financial stress suggest that tower SES smokers who experience financial stress are more likely to suffer a longer period of compromised living standards than their counterparts in the higher strata. The financial and health burdens of smoking coupled with social inequalities in smoking behaviour suggest that smoking may exacerbate social class differences in health and standards of living. Thus, targeting smoking among disadvantaged groups would not only represent a public health policy but also a social policy to reduce social inequalities. (c) 2005 The Royal Institute of Public Health. Published by Elsevier Ltd. All rights reserved. C1 Canc Council Victoria, Ctr Behav Res Canc, Canc Control Res Inst, Carlton, Vic 3053, Australia. Macquarie Univ, Dept Stat, Sydney, NSW 2109, Australia. NCI, Div Canc Control & Populat Sci, Canc Surveillance Res Program, NIH, Bethesda, MD 20892 USA. RP Siahpush, M (reprint author), Canc Council Victoria, Ctr Behav Res Canc, Canc Control Res Inst, 100 Drummond St, Carlton, Vic 3053, Australia. EM Mohammad.Siahpush@cancervic.org.au NR 28 TC 46 Z9 46 U1 2 U2 7 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0033-3506 J9 PUBLIC HEALTH JI Public Health PD DEC PY 2005 VL 119 IS 12 BP 1105 EP 1110 DI 10.1016/j.puhe.2005.03.004 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 986KF UT WOS:000233447800007 PM 16085150 ER PT J AU Feinendegen, LE Neumann, RD AF Feinendegen, LE Neumann, RD TI Physics must join with biology in better assessing risk from low-dose irradiation SO RADIATION PROTECTION DOSIMETRY LA English DT Article ID DOUBLE-STRAND BREAKS; IONIZING-RADIATION; MICROBEAM IRRADIATION; PROTECTIVE RESPONSES; UNIRRADIATED CELLS; ADAPTIVE RESPONSE; HUMAN-LYMPHOCYTES; HUMAN FIBROBLASTS; REACTIVE OXYGEN; X-RAYS AB This review summarises the complex response of mammalian cells and tissues to low doses of ionising radiation. This thesis encompasses induction of DNA damage, and adaptive protection against both renewed damage and against propagation of damage from the basic level of biological organisation to the clinical expression of detriment. The induction of DNA damage at low radiation doses apparently is proportional to absorbed dose at the physical/chemical level. However, any propagation of such damage to higher levels of biological organisation inherently follows a sigmoid function. Moreover, low-dose-induced inhibition of damage propagation is not linear, but instead follows a dose-effect function typical for adaptive protection, after an initial rapid rise it disappears at doses higher than similar to 0.1-0.2 Gy to cells. The particular biological response duality at low radiation doses precludes the validity of the linear-no-threshold hypothesis in the attempt to relate absorbed dose to cancer. In fact, theory and observation support not only a lower cancer incidence than expected from the linear-no-threshold hypothesis, but also a reduction of spontaneously occurring cancer, a hormetic response, in the healthy individual. C1 Univ Dusseldorf, D-4000 Dusseldorf, Germany. Brookhaven Natl Lab, Upton, NY 11973 USA. NIH, Clin Ctr, Dept Nucl Med, Bethesda, MD USA. RP Feinendegen, LE (reprint author), Univ Dusseldorf, D-4000 Dusseldorf, Germany. EM feinendegen@gmx.net NR 47 TC 15 Z9 17 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0144-8420 J9 RADIAT PROT DOSIM JI Radiat. Prot. Dosim. PD DEC PY 2005 VL 117 IS 4 BP 346 EP 356 DI 10.1093/rpd/nci357 PG 11 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 035MP UT WOS:000237005700002 PM 16244096 ER PT J AU Cruysberg, LPJ Franklin, AJ Sanders, J Self, C Yuan, P Csaky, KG Robinson, MR Kohn, EC Edelhauser, HF AF Cruysberg, LPJ Franklin, AJ Sanders, J Self, C Yuan, P Csaky, KG Robinson, MR Kohn, EC Edelhauser, HF TI Effective transscleral delivery of two retinal anti-angiogenic molecules - Carboxyamido-triazole (CAI) and 2-methoxyestradiol (2ME(2)) SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article ID SUBFOVEAL CHOROIDAL NEOVASCULARIZATION; RANDOMIZED CLINICAL-TRIALS; ENDOGENOUS ESTROGEN METABOLITE; SIGNAL-TRANSDUCTION INHIBITOR; ARGON-LASER PHOTOCOAGULATION; HUMAN SCLERAL PERMEABILITY; CALCIUM INFLUX INHIBITOR; BEAVER-DAM EYE; PHASE-I TRIAL; MACULAR DEGENERATION AB Purpose: To evaluate the human transscleral diffusion and intravitreal delivery of carboxyamido-triazole (CAI) and 2-Methoxyestradiol (2ME(2)). Methods: The transscleral diffusion of two retinal antiangiogenic molecules, CAI and 2ME(2), was measured in vitro to assess their potential transscleral delivery. Varying concentrations and different solvents of CAI and 2ME(2) were placed in the upper compartment of a two-chamber acrylic perfusion apparatus, on the episcleral side of the sclera obtained from human donor eyes. Samples were taken from the lower compartment (uveal side) for up to 24 hours and measured by high performance liquid chromatography. Results: All three solutions that contained CAI efficiently diffused through the sclera with permeability constants that ranged from 2.8 to 5.5 x 10(-6) cm/s. The scleral permeability constant derived for 2ME(2) was 9.96 x 10(-6) cm/s. The permeability constants obtained for both CAI and 2ME(2) are similar to each other as well as to permeability constants measured for other small molecules such as fluorescein and dexamethasone fluorescein. Conclusion: Both CAI and 2ME(2) traverse the sclera efficiently. These data combined with the reported inhibition of posterior segment neovascularization observed with these two molecules demonstrates that CAI and 2ME(2) are good candidate molecules to treat posterior segment neovascularization by local delivery. C1 Emory Univ, Ctr Eye, Dept Ophthalmol, Sch Med, Atlanta, GA 30322 USA. Univ Med Ctr, Maastricht, Netherlands. Retina Specialists, Pensacola, FL USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Pharm, Bethesda, MD 20892 USA. NEI, Bethesda, MD 20892 USA. NCI, Mol Signalling Sect, Pathol Lab, Bethesda, MD 20892 USA. RP Edelhauser, HF (reprint author), Emory Univ, Ctr Eye, Dept Ophthalmol, Sch Med, 1365 B Clifton Rd NE, Atlanta, GA 30322 USA. EM ophthfe@emory.edu FU NEI NIH HHS [P30 EY06360] NR 75 TC 11 Z9 12 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0275-004X J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD DEC PY 2005 VL 25 IS 8 BP 1022 EP 1031 DI 10.1097/00006982-200512000-00011 PG 10 WC Ophthalmology SC Ophthalmology GA 008AQ UT WOS:000235013000011 PM 16340533 ER PT J AU Bondy, CA AF Bondy, CA TI New Issues in the Diagnosis and Management of Turner syndrome SO REVIEWS IN ENDOCRINE & METABOLIC DISORDERS LA English DT Article DE X-chromosome; congenital heart defect; prenatal diagnosis; ovarian failure; short stature ID HOMEOBOX-CONTAINING GENE; PULMONARY VENOUS RETURN; RING-X-CHROMOSOMES; PRENATAL-DIAGNOSIS; GROWTH-HORMONE; SHORT STATURE; CYSTIC HYGROMA; PELVIC ULTRASOUND; OOCYTE DONATION; BLOOD-PRESSURE C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Bondy, CA (reprint author), NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. EM bondyc@mail.nih.gov FU Intramural NIH HHS NR 95 TC 19 Z9 21 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1389-9155 J9 REV ENDOCR METAB DIS JI Rev. Endocr. Metab. Disord. PD DEC PY 2005 VL 6 IS 4 BP 269 EP 280 DI 10.1007/s11154-005-6185-z PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 001HH UT WOS:000234523700003 PM 16311945 ER PT J AU Weed, DL AF Weed, DL TI Weight of evidence: A review of concept and methods SO RISK ANALYSIS LA English DT Review DE causal criteria; methods; quality criteria; risk assessment; systematic reviews; weight of evidence ID OF-EVIDENCE APPROACH; CAUSAL INFERENCE; RESPONSE RELATIONSHIP; RISK-ASSESSMENT; FOLLOW-UP; EXPOSURE; CANCER; EPIDEMIOLOGY; DISEASE; QUALITY AB "Weight of evidence" (WOE) is a common term in the published scientific and policy-making literature, most often seen in the context of risk assessment (RA). Its definition, however, is unclear. A systematic review of the scientific literature was undertaken to characterize the concept. For the years 1994 through 2004, PubMed was searched for publications in which "weight of evidence" appeared in the abstract and/or title. Of the 276 papers that met these criteria, 92 were selected for review: 71 papers published in 2003 and 2004 (WOE appeared in abstract/title) and 21 from 1994 through 2002 (WOE appeared in title). WOE has three characteristic uses in this literature: (1) metaphorical, where WOE refers to a collection of studies or to an unspecified methodological approach; (2) methodological, where WOE points to established interpretative methodologies (e.g., systematic narrative review, meta-analysis, causal criteria, and/or quality criteria for toxicological studies) or where WOE means that "all" rather than some subset of the evidence is examined, or rarely, where WOE points to methods using quantitative weights for evidence; and (3) theoretical, where WOE serves as a label for a conceptual framework. Several problems are identified: the frequent lack of definition of the term "weight of evidence," multiple uses of the term and a lack of consensus about its meaning, and the many different kinds of weights, both qualitative and quantitative, which can be used in RA. A practical recommendation emerges: the WOE concept and its associated methods should be fully described when used. A research agenda should examine the advantages of quantitative versus qualitative weighting schemes, how best to improve existing methods, and how best to combine those methods (e.g.. epidemiology's causal criteria with toxicology's quality criteria). C1 NCI, Rockville, MD 20852 USA. RP Weed, DL (reprint author), NCI, Execut Plaza N,Suite 321,6130 Execut Blvd, Rockville, MD 20852 USA. EM dw102i@nih.gov NR 113 TC 142 Z9 151 U1 5 U2 46 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0272-4332 J9 RISK ANAL JI Risk Anal. PD DEC PY 2005 VL 25 IS 6 BP 1545 EP 1557 DI 10.1111/j.1539-6925.2005.00699.x PG 13 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA 996YF UT WOS:000234211500015 PM 16506981 ER PT J AU Saleem, M Moss, J Egan, JJ AF Saleem, M Moss, J Egan, JJ TI Lung transplantation for rare pulmonary diseases SO SARCOIDOSIS VASCULITIS AND DIFFUSE LUNG DISEASES LA English DT Article; Proceedings Paper CT 1st RIPID International Congress on Rare Pulmonary Diseases and Orphan Drugs in Respiratory Medicine CY FEB 25-26, 2005 CL Milan, ITALY DE lung transplant; sarcoid; lymphangioleiomyomatosis; pulmonary Langerhans Cell Histiocytosis X ID HISTIOCYTOSIS-X; LYMPHANGIOLEIOMYOMATOSIS; SARCOIDOSIS; OUTCOMES; CELLS; CT AB Emphysema, idiopathic pulmonary fibrosis and cystic fibrosis are the major indications for lung transplantation. This article will present an overview of lung transplantation in the context of rare pulmonary diseases, in particular pulmonary sarcoidosis, lymphangioleiomyomatosis (LAM), and pulmonary Langerhans Cell Histiocytosis X (LCH). It will present criteria used in deciding when a patient should be referred and will discuss medical management in the context of lung transplantation. C1 Univ Coll Dublin, Mater Misericordiae Hosp, Dublin 7, Ireland. NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. St Vincents Univ Hosp, Mater Misericordiae Hosp, Adv Lung Dis & Irish Natl Lung Transplant Program, Dublin, Ireland. Univ Coll Dublin, Dublin Mol Med Ctr, Our Ladys Hosp Sick Children, Dublin 2, Ireland. RP Egan, JJ (reprint author), Univ Coll Dublin, Mater Misericordiae Hosp, Eccles St, Dublin 7, Ireland. EM jegan@mater.ie NR 20 TC 0 Z9 0 U1 0 U2 0 PU FONDAZIONE PNEUMOLOGIA U I P ONLUS PI MILANO PA VIA FRUA 15, MILANO, ITALY SN 1124-0490 J9 SARCOIDOSIS VASC DIF JI Sarcoidosis Vasc. Diffus. Lung Dis. PD DEC PY 2005 VL 22 SU 1 BP S85 EP S90 PG 6 WC Respiratory System SC Respiratory System GA 007OS UT WOS:000234979600011 ER PT J AU Steagall, WK Taveira-DaSilva, AM Moss, J AF Steagall, WK Taveira-DaSilva, AM Moss, J TI Clinical and molecular insights into lymphangioleiomyomatosis SO SARCOIDOSIS VASCULITIS AND DIFFUSE LUNG DISEASES LA English DT Article; Proceedings Paper CT 1st RIPID International Congress on Rare Pulmonary Diseases and Orphan Drugs in Respiratory Medicine CY FEB 25-26, 2005 CL Milan, ITALY DE lymphangioleiomyomatosis; tuberin; hamartin; loss of heterozygosity; pulmonary function test; angiomyolipoma; meningioma; metastasis ID TUBEROUS SCLEROSIS COMPLEX; OBSTRUCTIVE PULMONARY-DISEASE; TUMOR-SUPPRESSOR HAMARTIN; SERUM RESPONSE FACTOR; BILATERAL SPONTANEOUS PNEUMOTHORAX; BONE-MINERAL DENSITY; S6 KINASE ACTIVATION; YELLOW NAIL SYNDROME; SMOOTH-MUSCLE-CELLS; HIGH-RESOLUTION CT AB Lymphangioleiomyomatosis (LAM) is a rare disease of women that is characterized by a proliferation of abnormal smooth muscle-like cells (LAM cells), which leads to cystic lung lesions, lymphatic abnormalities, and abdominal tumors (e.g., angiomyolipomas). LAM occurs sporadically or in association with tuberous sclerosis complex, an autosomal dominant syndrome characterized by hamartoma-like tumor growths. The tumor suppressor genes TSC1 and TSC2 have been implicated in the etiology of LAM, as mutations and loss of heterozygosity (LOH) in TSC2 have been detected in LAM cells. TSC1 encodes hamartin, with a postulated role in actin cytoskeleton reorganization. TSC2 encodes tuberin, a protein with roles in cell growth and proliferation, transcriptional activation, and endocytosis. LAM cells, as defined by TSC2 LOH, have been detected in blood and body fluids, and can metastasize. LAM presents insidiously with progressive breathlessness, or dramatically with recurrent pneumothorax, chylothorax, or sudden abdominal hemorrhage. CT scans show numerous thin-walled cysts throughout the lungs, abdominal angiomyolipomas, and lymphangioleiomyomas. Pulmonary function tests show reduced flow rates (FEV1) and diffusion capacity (DLCO). Twenty per cent of patients have positive bronchodilator responses. Exercise testing shows gas-exchange abnormalities, ventilatory limitation, and hypoxemia that may occur with near-normal lung function. Progression of disease is best assessed by measurements of DLCO and FEV 1. In the proper clinical setting, LAM may be diagnosed by a thoraco-abdominal CT scan. Tissue biopsy with special stains (HMB-45) should be reserved for cases with atypical presentations. There is no effective treatment for LAM, but on-going therapeutic trials with rapamyein appear promising. C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Moss, J (reprint author), NHLBI, Pulm Crit Care Med Branch, NIH, Bldg 10,Room 6D03,MSC 1590, Bethesda, MD 20892 USA. EM mossj@nhlbi.nih.gov NR 194 TC 21 Z9 21 U1 0 U2 1 PU MATTIOLI 1885 PI FIDENZA PA VIA DELLA LODESANA 649-SX, FIDENZA, 43046 PR, ITALY SN 1124-0490 J9 SARCOIDOSIS VASC DIF JI Sarcoidosis Vasc. Diffus. Lung Dis. PD DEC PY 2005 VL 22 SU 1 BP S49 EP S66 PG 18 WC Respiratory System SC Respiratory System GA 007OS UT WOS:000234979600008 PM 16457017 ER PT J AU McEvoy, JP Meyer, JM Goff, DC Nasrallah, HA Davis, SA Sullivan, L Meltzer, HY Hsiao, J Stroup, TS Lieberman, JA AF McEvoy, JP Meyer, JM Goff, DC Nasrallah, HA Davis, SA Sullivan, L Meltzer, HY Hsiao, J Stroup, TS Lieberman, JA TI Prevalence of the metabolic syndrome in patients with schizophrenia: Baseline results from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Schizophrenia Trial and comparison with national estimates from NHANES III SO SCHIZOPHRENIA RESEARCH LA English DT Article DE metabolic syndrome; schizophrenia; obesity; cardiovascular; risk ID BODY-MASS INDEX; NUTRITION EXAMINATION SURVEY; VISCERAL FAT DISTRIBUTION; EXCESS MORTALITY; ATYPICAL ANTIPSYCHOTICS; PSYCHIATRIC-PATIENTS; INSULIN SENSITIVITY; MENTAL-DISORDERS; DRUG-NAIVE; HEALTH AB One important risk factor for cardiovascular disease is the metabolic syndrome (MS), yet limited data exist on its prevalence in US patients with schizophrenia. Methods: Using baseline data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Schizophrenia Trial, assessment of MS prevalence was performed based on National Cholesterol Education Program (NCEP) criteria, and also using a fasting glucose threshold of 100 mg/dl (AHA). Subjects with sufficient anthropometric data, data on use of antihypertensives, hypoglycemic medications or insulin, and fasting glucose and lipid values > 8 It from last meal were included in the analysis. Comparative analyses were performed using a randomly selected sample from NHANES III matched I : I on the basis of age, gender and race/ethnicity. Results: Of 1460 CATIE baseline subjects, 689 met analysis criteria. MS prevalence was 40.9% and 42.7%, respectively using the NCEP and AHA derived criteria. In females it was 51.6% and 54.2% using the NCEP and AHA criteria, compared to 36.0% (p =.0002) and 36.6% (p =.0003), respectively for males. 73.4% of all females (including nonfasting subjects) met the waist circumference criterion compared to 36.6% of males. In a logistic regression model with age, race and ethnicity as covariates, CATIE males were 138% more likely to have MS than the NHANES matched sample, and CATIE females 251% more likely than their NHANES counterparts. Even when controlling for differences in body mass index, CATIE males were still 85% more likely to have MS than the NHANES male sample, and CATIE females 137% more likely to have MS than females in NHANES. Conclusions: The metabolic syndrome is highly prevalent in US schizophrenia patients and represents an enormous source of cardiovascular risk, especially for women. Clinical attention must be given to monitoring for this syndrome, and minimizing metabolic risks associated with antipsychotic treatment. (c) 2005 Elsevier B.V. All rights reserved. C1 Univ Calif San Diego, Dept Psychiat, VA San Diego Healthcare Syst, La Jolla, CA 92161 USA. Duke Univ, Dept Psychiat & Behav Sci, John Umstead Hosp, Butner, NC 27509 USA. Harvard Univ, Dept Psychiat, Freedom Trail Clin, Lindemann Mental Hlth Ctr, Boston, MA 02114 USA. Univ Cincinnati, Cincinnati, OH 45267 USA. Quintiles Inc, Morrisville, NC 27560 USA. Boston Univ, Dept Biostat, Boston, MA 02215 USA. Vanderbilt Univ, Psychopharmacol Div, Nashville, TN 37212 USA. NIMH, Adult Psychopharmacol Intevent Program, Bethesda, MD 20892 USA. Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27599 USA. Columbia Univ, Inst Psychiat, Dept Psychiat, New York, NY 10032 USA. RP Meyer, JM (reprint author), Univ Calif San Diego, Dept Psychiat, VA San Diego Healthcare Syst, 3350 La Jolla Village Dr, La Jolla, CA 92161 USA. EM jpmcevoy@dake.edu; jmmeyer@ucsd.edu; goff@psych.mgh.harvard.edu; NASRALHA@ucmail.uc.edu; sonia.davis@quintiles.com; lsull@bu.edu; Herbert.meltzer@vanderbilt.edu; jh23f@nih.gov; scott_stroup@med.unc.edu; JL2616@columbia.edu RI Meltzer, Herbert/E-8131-2013; Stroup, Thomas/F-9188-2014; OI Stroup, Thomas/0000-0002-3123-0672; Sullivan, Lisa/0000-0003-0726-7149 FU NIMH NIH HHS [N01MH90001] NR 50 TC 661 Z9 688 U1 4 U2 33 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD DEC 1 PY 2005 VL 80 IS 1 BP 19 EP 32 DI 10.1016/j.schres.2005.07.014 PG 14 WC Psychiatry SC Psychiatry GA 002KU UT WOS:000234611100004 PM 16137860 ER PT J AU Germain, RN AF Germain, RN TI Imaging dynamic interactions in immune responses SO SEMINARS IN IMMUNOLOGY LA English DT Editorial Material C1 NIAID, NIH, DHHS, Bethesda, MD 20892 USA. RP Germain, RN (reprint author), NIAID, NIH, DHHS, Bldg 10,Room 11N311,10 Ctr Dr MSC-1892, Bethesda, MD 20892 USA. EM rgermain@nih.gov NR 0 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-5323 J9 SEMIN IMMUNOL JI Semin. Immunol. PD DEC PY 2005 VL 17 IS 6 BP 385 EP 386 DI 10.1016/j.smim.2005.10.001 PG 2 WC Immunology SC Immunology GA 993XV UT WOS:000233992400001 PM 16275126 ER PT J AU Germain, RN Castellino, F Chieppa, MC Egen, JG Huang, AYC Koo, LY Hai, Q AF Germain, RN Castellino, F Chieppa, MC Egen, JG Huang, AYC Koo, LY Hai, Q TI An extended vision for dynamic high-resolution intravital immune imaging SO SEMINARS IN IMMUNOLOGY LA English DT Review DE antigen presenting cell; dendritic cell; T cell; chemokine; lymph node; microscopy ID T-CELL-ACTIVATION; GUT EPITHELIAL MONOLAYERS; DENDRITIC CELLS; IN-VIVO; LYMPH-NODES; ANTIGEN PRESENTATION; IMMUNOLOGICAL SYNAPSE; PHYSICAL INTERACTIONS; 2-PHOTON MICROSCOPY; BLOOD-VESSELS AB The past few years have seen the application of confocal and especially two-photon microscopy to the dynamic high-resolution imaging of lymphocytes and antigen presenting cells within organs Such as lymph nodes and thymus. After summarizing some of the published results obtained to date Using, these methods, we describe our view of how this technology will develop and be applied in the near future. This includes its extension to a wide variety of non-lymphoid tissues, to the tracking of functional responses in addition to migratory behavior, to the analysis of Molecular events previously Studied only in vitro, to dissection of the interplay between hematopoietic and stromal elements, to visualization of a wider array of cell types including neutrophils, macrophages, NK cells, NKT cells and others, and to file interaction of the host with infectious agents. Reaching these goals will depend on a combination of new tools for genetic Manipulations, novel fluorescent reporters, enhanced instrumentation, and better surgical techniques for the extended imaging of: live animals. The end result will be a new level of understanding of how orchestrated cell movement and interaction contribute to the physiological and pathological activities of the immune system. Published by Elsevier Ltd C1 NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH,DHHS, Bethesda, MD 20892 USA. RP Germain, RN (reprint author), NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH,DHHS, Bldg 10 Rm 11N311,10 Ctr Dr MSC-1892, Bethesda, MD 20892 USA. EM rgermain@nih.gov RI Chieppa, Marcello/K-4846-2012; OI Egen, Jackson/0000-0003-2053-0837; Huang, Alex/0000-0002-5701-4521 FU Intramural NIH HHS; NIAID NIH HHS [Z01 AI000758-08] NR 85 TC 49 Z9 51 U1 0 U2 4 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-5323 J9 SEMIN IMMUNOL JI Semin. Immunol. PD DEC PY 2005 VL 17 IS 6 BP 431 EP 441 DI 10.1016/j.smim.2005.09.003 PG 11 WC Immunology SC Immunology GA 993XV UT WOS:000233992400006 PM 16216522 ER PT J AU Lynch, JK Han, CJ AF Lynch, JK Han, CJ TI Pediatric stroke: What do we know and what do we need to know? SO SEMINARS IN NEUROLOGY LA English DT Review DE cerebrovascular diseases; child ID SICKLE-CELL-DISEASE; FACTOR-V-LEIDEN; ARTERIAL ISCHEMIC-STROKE; OF-THE-LITERATURE; TISSUE-PLASMINOGEN ACTIVATOR; PROTHROMBIN 20210 G; TERM-FOLLOW-UP; MOYAMOYA-DISEASE; CHILDHOOD STROKE; RISK-FACTORS AB Stroke is a heterogeneous disorder and an important cause of mortality and chronic morbidity in children. Estimates of international incidence rates for childhood stroke have varied widely. Arterial ischemic stroke is reported to be more common than hemorrhagic stroke in children. The clinical presentation of stroke in children differs according to the child's age and stroke type and location. Several risk factors for ischemic and hemorrhagic stroke in children have been reported and include cardiac disorders, blood disorders, vasculopathies, viral infections, and arteriovenous malformations. Current treatment recommendations for stroke in children are based on small nonrandomized trials, adult stroke studies, case series, or consensus or individual expert opinion. Over half of children with stroke will develop lifelong cognitive or motor disability, and up to a third will have a recurrent stroke. International studies have provided important information on stroke in children, but major gaps in our knowledge of the disorder still exist. Currently, there is a need for prospective cohort studies in diverse populations, which utilize a consensus pediatric stroke classification system and a standard evaluation of risk factors and outcome, so that treatment and prevention strategies can be developed. C1 NINDS, Neuroepidemiol Branch, Bethesda, MD 20892 USA. RP Lynch, JK (reprint author), Bldg 10,Room 5S209,10 Ctr Dr,MSC 1447, Bethesda, MD 20892 USA. NR 136 TC 34 Z9 42 U1 1 U2 6 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0271-8235 J9 SEMIN NEUROL JI Semin. Neurol. PD DEC PY 2005 VL 25 IS 4 BP 410 EP 423 DI 10.1055/s-2005-923535 PG 14 WC Clinical Neurology SC Neurosciences & Neurology GA 995DW UT WOS:000234082000010 PM 16341997 ER PT J AU Wu, YW Lynch, JK Nelson, KB AF Wu, YW Lynch, JK Nelson, KB TI Perinatal arterial stroke: Understanding mechanisms and outcomes SO SEMINARS IN NEUROLOGY LA English DT Review DE perinatal arterial stroke; epidemiology; risk factors; outcome ID FACTOR-V-LEIDEN; NEONATAL CEREBRAL INFARCTION; MATERNAL ANTICARDIOLIPIN ANTIBODIES; FULL-TERM INFANTS; ISCHEMIC-STROKE; RISK-FACTORS; PROTEIN-C; METHYLENETETRAHYDROFOLATE REDUCTASE; SINOVENOUS THROMBOSIS; PLACENTAL INFARCTION AB Arterial ischemic infarction occurring around the time of birth is an increasingly recognized cause of neurological disability in children. The rate of arterial infarction in neonates is as high as the annual incidence of large-vessel ischemic stroke in adults. Factors contributing to this increased risk of stroke among neonates include complications that occur before, during, and after delivery. Maternal conditions that have been associated with perinatal stroke in the fetus include prothrombotic disorders, cocaine abuse, and placental complications such as chorioamnionitis and placental vasculopathy. In many cases, the placenta is suspected to be the underlying embolic source for perinatal stroke, although data on placental pathology is often lacking. During the delivery process, an infant may develop a cervical arterial dissection that leads to stroke. Several conditions in the neonatal period predispose to perinatal stroke including prothrombotic disorders, congenital heart disease, meningitis, and systemic infection. Perinatal stroke may present with neonatal seizures during the first weeks of life or may be asymptomatic until months later when the infant is first noted to have pathological handedness. The outcome of perinatal stroke is variable and depends on severity, anatomic localization, and other factors not yet well characterized. As many as 50% of infants with documented stroke recognized in the newborn period do not develop a hemiparesis. The incidence, clinical presentation, pathogenesis, risk factors, and outcome of this increasingly recognized disorder are reviewed. C1 Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94117 USA. NINDS, Neuroepidemiol Branch, Bethesda, MD 20892 USA. RP Wu, YW (reprint author), Univ Calif San Francisco, Dept Neurol, 350 Parnassus Ave,Suite 609, San Francisco, CA 94117 USA. NR 101 TC 48 Z9 49 U1 1 U2 3 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0271-8235 J9 SEMIN NEUROL JI Semin. Neurol. PD DEC PY 2005 VL 25 IS 4 BP 424 EP 434 DI 10.1055/s-2005-923536 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA 995DW UT WOS:000234082000011 PM 16341998 ER PT J AU Fojo, AT Menefee, M AF Fojo, AT Menefee, M TI Microtubule targeting agents: Basic mechanisms of multidrug resistance (MDR) SO SEMINARS IN ONCOLOGY LA English DT Review ID P-GLYCOPROTEIN ANTAGONIST; BETA-TUBULIN; DRUG-RESISTANCE; CELLS RESISTANT; ALPHA-TUBULIN; PHASE-I; PACLITAXEL; EXPRESSION; GENE; ACCUMULATION C1 NCI, Canc Therapeut Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Fojo, AT (reprint author), NCI, Canc Therapeut Branch, Ctr Canc Res, Bldg 10,Room 12C103,10 Ctr Dr, Bethesda, MD 20892 USA. EM tfojo@helix.nih.gov NR 36 TC 63 Z9 65 U1 0 U2 10 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD DEC PY 2005 VL 32 IS 6 SU 7 BP S3 EP S8 DI 10.1053/j.seminoncol.2005.09.010 PG 6 WC Oncology SC Oncology GA 995SJ UT WOS:000234123800002 PM 16360716 ER PT J AU Fojo, AT AF Fojo, AT TI Novel agents for overcoming recurrent breast cancer - Introduction SO SEMINARS IN ONCOLOGY LA English DT Editorial Material ID MULTIDRUG-RESISTANCE; DRUG-RESISTANCE; TRANSPORTERS; EPOTHILONES; PACLITAXEL; MECHANISMS C1 NCI, Canc Therapeut Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Fojo, AT (reprint author), NCI, Canc Therapeut Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NR 21 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD DEC PY 2005 VL 32 IS 6 SU 7 BP S1 EP S2 DI 10.1053/j.seminoncol.2005.09.012 PG 2 WC Oncology SC Oncology GA 995SJ UT WOS:000234123800001 PM 16360715 ER PT J AU Lee, JJ Swain, SM AF Lee, JJ Swain, SM TI Development of novel chemotherapeutic agents to evade the mechanisms of multidrug resistance (MDR) SO SEMINARS IN ONCOLOGY LA English DT Review ID METASTATIC BREAST-CANCER; MICROTUBULE-STABILIZING AGENTS; EPOTHILONE-B ANALOG; PHASE-II; COMBINATION THERAPY; PACLITAXEL; BMS-247550; TRIAL; CAPECITABINE; DOCETAXEL C1 NCI, Canc Therapeut Branch, Ctr Canc Res, NIH, Bethesda, MD 20889 USA. RP Swain, SM (reprint author), NCI, Canc Therapeut Branch, Ctr Canc Res, NIH, 8901 Wisconsin Ave,Bldg 8,Room 5101, Bethesda, MD 20889 USA. EM swains@mail.nih.gov OI Swain, Sandra/0000-0002-1320-3830 NR 34 TC 43 Z9 45 U1 0 U2 10 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD DEC PY 2005 VL 32 IS 6 SU 7 BP S22 EP S26 DI 10.1053/j.seminoncol.2005.09.013 PG 5 WC Oncology SC Oncology GA 995SJ UT WOS:000234123800005 PM 16360719 ER PT J AU Rogers, SM Willis, G Al-Tayyib, A Villarroel, MA Turner, CF Ganapathi, L Zenilman, J Jadack, R AF Rogers, SM Willis, G Al-Tayyib, A Villarroel, MA Turner, CF Ganapathi, L Zenilman, J Jadack, R TI Audio computer assisted interviewing to measure HIV risk behaviours in a clinic population SO SEXUALLY TRANSMITTED INFECTIONS LA English DT Article ID METHODOLOGICAL EXPERIMENT; DRUG-USE; ALCOHOL; SAMPLE; KENYA; MODE AB Objectives: To examine whether audio computer assisted survey interviewing (ACASI) influenced responses to sensitive HIV risk behaviour questions, relative to interviewer administration of those questions (IAQ), among patients attending a sexually transmitted infection (STI) clinic and whether the impact of interview mode on reporting of risk behaviours was homogeneous across subgroups of patients ( defined by age, sex, and previous STI clinic experience). Methods: 1350 clinic patients were assigned to complete a detailed behavioural survey on sexual risk practices, previous STIs and symptoms, condom use, and drug and alcohol use using either ACASI or IAQ. Results: Respondents assigned to ACASI were more likely to report recent risk behaviours such as sex without a condom in the past 24 hours ( adjusted OR = 1.9), anal sex ( adjusted OR = 2.0), and one or more new partners in the past 6 months ( adjusted OR = 1.5) compared to those interviewed by IAQ. The impact of ACASI varied by sex but, contrary to expectations, not by whether the patient had previously visited an STI clinic. Mode of survey administration made little difference within this population in reports of STI knowledge, previous STIs, STI symptoms, or illicit drug use. Conclusion: ACASI provides a useful tool for improving the quality of behavioural data in clinical environments. C1 RTI Int, Program Hlth & Behav Management, Washington, DC 20036 USA. NCI, Div Canc Control & Poulat Sci, Bethesda, MD 20892 USA. CUNY Queens Coll, Flushing, NY 11367 USA. Grad Ctr, Flushing, NY USA. RTI Int, Res Comp Div, Res Triangle Pk, NC USA. Johns Hopkins Bayview Med Ctr, Div Infect Dis, Baltimore, MD USA. Univ Wisconsin, Coll Nursing, Eau Claire, WI 54701 USA. RP Rogers, SM (reprint author), RTI Int, Program Hlth & Behav Management, 1615 M St NW,Suite 740, Washington, DC 20036 USA. EM smr@rti.org FU NIAID NIH HHS [R01-AI46181] NR 20 TC 67 Z9 68 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1368-4973 J9 SEX TRANSM INFECT JI Sex. Transm. Infect. PD DEC 1 PY 2005 VL 81 IS 6 BP 501 EP 507 DI 10.1136/sti.2004.014266 PG 7 WC Infectious Diseases SC Infectious Diseases GA 989PH UT WOS:000233685600014 PM 16326855 ER PT J AU Astor, A Akhtar, T Matallana, MA Muthuswamy, V Olowu, FA Tallo, V Lie, RK AF Astor, A Akhtar, T Matallana, MA Muthuswamy, V Olowu, FA Tallo, V Lie, RK TI Physician migration: views from professionals in Colombia, Nigeria, India, Pakistan and the Philippines SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE physician migration; health policy; developing countries; India; Pakistan; Nigeria; Columbia; The Philippines ID BRAIN-DRAIN; HEALTH-PROFESSIONALS; MEDICAL-PROFESSION; DOCTORS AB There has been much debate recently about several issues related to the migration of physicians from developing to developed countries. However, few studies have been conducted to address these issues in a systematic fashion. In an attempt to begin the process of generating systematic data, we designed and- distributed a questionnaire addressing several core issues surrounding physician migration to respondents selected on the basis of their special expertise or experience in India, Nigeria, Pakistan, Colombia, and the Philippines. The issues addressed relate to the reasons physicians migrate to developed countries, how migration is related to the structure of medical education, the effect that migration has on the health care infrastructure of developing countries, and various policy options for dealing with physician migration. Though responses varied somewhat by country, a desire for increased income, greater access to enhanced technology, an atmosphere of general security and stability, and improved prospects for one's children were the primary motivating factors for physician migration. A majority of respondents believed that physicians in developing counties are provided with highly specialized skills that they can better utilize in developed countries, but respondents were ambivalent with respect to the utility of educational reform. Responses varied significantly by country with regard to whether physician migration results in physician shortages, but there was widespread agreement that it exacerbates shortages in rural and public settings. With respect to policy options, increasing physician income, improving working conditions, requiring physicians to work in their home countries for a period following graduation from medical school, and creating increased collaboration between health ministries in developed and developing countries found the most favor with respondents. (c) 2005 Elsevier Ltd. All rights reserved. C1 NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. Pakistan Med Res Council, Islamabad, Pakistan. Pontif Univ Javeriana, Cendex, Bogota, Colombia. Indian Council Med Res, New Delhi, India. Intellfit Africa Training Ctr, Lagos, Nigeria. RP Lie, RK (reprint author), NIH, Dept Clin Bioeth, Room 1C118,Bldg 10, Bethesda, MD 20892 USA. EM rlie@cc.nih.gov RI Astor, Avi/I-1318-2015 OI Astor, Avi/0000-0002-4720-1841 NR 26 TC 63 Z9 63 U1 1 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD DEC PY 2005 VL 61 IS 12 BP 2492 EP 2500 DI 10.1016/j.socscimed.2005.05.003 PG 9 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 987DO UT WOS:000233498800003 PM 15953667 ER PT J AU Song, L Young, NJ Webb, NE Tuan, RS AF Song, L Young, NJ Webb, NE Tuan, RS TI Origin and characterization of multipotential mesenchymal stem cells derived from adult human trabecular bone SO STEM CELLS AND DEVELOPMENT LA English DT Article ID UMBILICAL-CORD BLOOD; HUMAN ADIPOSE-TISSUE; MICROVASCULAR PERICYTES; IN-VITRO; PROGENITOR CELLS; SELF-RENEWAL; NICHE; DIFFERENTIATION; IDENTIFICATION; MARROW AB Much of the knowledge regarding the regulatory pathways for adult stem cell self-renewal and differentiation has been obtained from the results of in vitro cultures. However, it is unclear if adult stem cells are controlled in the same way under physiological conditions. We examined this issue with respect to the migration of stem cells to tissue injury and how switch from a migratory state to one of proliferation wherein they participate in development. Building on our previous identification of multipotent stem cells in trabecular bone, we have examined the in vitro behavior of these cells within the bone milieu. We found that cell proliferation is inhibited within the trabecular bone niche as cells migrate out of the trabecular bone prior to proliferation. Additionally, multiple cell types were detected in adult trabecular bone, including osteoblasts, osteoclasts, endothelial cells, and Stro-1-positive mesenchymal stem cells. Furthermore, we demonstrated that Stro-1-positive cells migrated out of their native bone niche to generate multipotential stem and progenitor cells during in vitro culture. We conclude that self-renewal and differentiation of adult stem cells in connective tissues are tightly controlled and separately orchestrated processes. A regulatory network of extrinsic factors and intrinsic signals acts to stimulate the exit of stem cells from their niche so that they can localize to sites of wound healing, where they participate in development after functional differentiation. C1 NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Tuan, RS (reprint author), NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Dept Hlth & Human Serv, 50 South Dr,Room 1503,MSC 8022, Bethesda, MD 20892 USA. EM tuanr@mail.nih.gov FU NIAMS NIH HHS [Z01 AR41113] NR 41 TC 36 Z9 39 U1 0 U2 7 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1547-3287 J9 STEM CELLS DEV JI Stem Cells Dev. PD DEC PY 2005 VL 14 IS 6 BP 712 EP 721 DI 10.1089/scd.2005.14.712 PG 10 WC Cell & Tissue Engineering; Hematology; Medicine, Research & Experimental; Transplantation SC Cell Biology; Hematology; Research & Experimental Medicine; Transplantation GA 010IT UT WOS:000235182100012 PM 16433626 ER PT J AU Best, RB Chen, YG Hummer, G AF Best, RB Chen, YG Hummer, G TI Slow protein conformational dynamics from multiple experimental structures: The helix/sheet transition of arc repressor SO STRUCTURE LA English DT Article ID NORMAL-MODE ANALYSIS; ELASTIC-NETWORK MODEL; MOLECULAR-DYNAMICS; FOLDING KINETICS; ENERGY LANDSCAPES; SINGLE-PARAMETER; NATIVE TOPOLOGY; STATE ENSEMBLE; SIMULATION; BINDING AB Conformational transitions underlie the function of many biomolecular systems. Resolving intermediate structural changes, however, is challenging for both experiments and all-atom simulations because the duration of transitions is short relative to the lifetime of the stable species. Simplified descriptions based on a single experimental structure, such as elastic network models or Go models, are not immediately applicable. Here, we develop a general method that combines multiple coarse-grained models to capture slow conformational transitions. Individually, each model describes one of the experimental structures; together, they approximate the complete energy surface. We demonstrate the method for the helix-to-sheet transition in Arc repressor N11L. We find that the transition involves the partial unfolding of the switch region, and rapid refolding into the alternate structure. Transient local unfolding is consistent with the low hydrogen exchange protection factors of the switch region. Also in agreement with experiment, the isomerization occurs independently of the global folding/dimerization transition. C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Hummer, G (reprint author), NIDDK, Chem Phys Lab, NIH, Bldg 5, Bethesda, MD 20892 USA. EM gerhard.hummer@nih.gov RI Hummer, Gerhard/A-2546-2013; Best, Robert/H-7588-2016 OI Hummer, Gerhard/0000-0001-7768-746X; Best, Robert/0000-0002-7893-3543 FU Intramural NIH HHS NR 69 TC 101 Z9 103 U1 2 U2 26 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0969-2126 J9 STRUCTURE JI Structure PD DEC PY 2005 VL 13 IS 12 BP 1755 EP 1763 DI 10.1016/j.str.2005.08.009 PG 9 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 997ZF UT WOS:000234286900006 PM 16338404 ER PT J AU Grover, AC Skarulis, M Alexander, HR Pingpank, JF Javor, ED Chang, R Shawker, M Gorden, P Cochran, C Libutti, SK AF Grover, AC Skarulis, M Alexander, HR Pingpank, JF Javor, ED Chang, R Shawker, M Gorden, P Cochran, C Libutti, SK TI A prospective evaluation of laparoscopic exploration with intraoperative ultrasound as a technique for localizing sporadic insulinomas SO SURGERY LA English DT Article ID INTRAARTERIAL CALCIUM STIMULATION; PREOPERATIVE LOCALIZATION; RESECTION; ULTRASONOGRAPHY; PANCREAS AB Background. Preoperative imaging studies localize insulinomas in less than 50 % of patients. Arteriography with calcium stimulation and venous sampling (ASVS),regionalizes greater than 90% of insulinomas but requires specialized expertise and an invasive procedure. This prospective study evaluated laparoscopic exploration with IOUS compared with, the other localization procedures in patients with a sporadic insulinoma. Methods. Between March 2001 and October 2004, 14 patients (7 women and 7 men; mean age, 53) with an insulinoma were enrolled in an IRB-approved protocol. Computed tomography, magnetic resonance imaging, ultrasound scan, and arteriography with calcium stimulation and venous sampling were performed preoperatively. A surgeon., blinded to the results of the localizing studies, performed a laparoscopic exploration with intraoperative ultrasound (IOUS). At the completion of the exploration, the success of laparoscopy for localization was scored, and the tumor was resected. Results. Twelve of 14 tumors were localized successfully before laparoscopy (noninvasive, 7 of 14; invasive, 11 of 14). Laparoscopic IOUS localized successfully 12 of 14 tumors. All lesions were resected, and all patients were cured (median, follow-up, 36 months). Conclusion. Laparoscopic IOUS identified 86% of tumors. The authors consider laparoscopic IOUS to be equivalent to ASVS in localizing insulinomas. Further study is therefore warranted to determine the role of laparoscopy with IOUS in the localization and treatment algorithm for patients with sporadic insulinoma. C1 NCI, Surg Metab Sect, Surg Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Radiol, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Libutti, SK (reprint author), NCI, Surg Metab Sect, Surg Branch, Ctr Canc Res,NIH, Bldg 10 4W-5940, Bethesda, MD 20892 USA. EM Steven_Libutti@nih.gov NR 14 TC 26 Z9 31 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD DEC PY 2005 VL 138 IS 6 BP 1003 EP 1008 DI 10.1016/j.surg.2005.09.017 PG 6 WC Surgery SC Surgery GA 998LB UT WOS:000234319000010 PM 16360384 ER PT J AU Rosen, J He, M Umbricht, C Alexander, HR Dackiw, APB Zeiger, MA Libutti, SY AF Rosen, J He, M Umbricht, C Alexander, HR Dackiw, APB Zeiger, MA Libutti, SY TI A six-gene model for differentiating benign from malignant thyroid tumors on the basis of gene expression SO SURGERY LA English DT Article; Proceedings Paper CT 26th Annual Meeting of the American-Association-of-Endocrine-Surgeons CY APR, 2005 CL Cancun, MEXICO SP Amer Assoc Endocrine Surg ID CARCINOMA; CLASSIFICATION; SIGNATURE; NODULES; CANCERS AB Background. Thyroid nodules are common; fine-needle aspirations commonly are read as indeterminate, necessitating surgery to exclude carcinoma. We developed a 6-gene array-based predictor model to diagnose benign versus malignant thyroid lesions. In this study, we verified whether quantitative reverse transcription-polymerase chain reaction (qRT-PCR) using this model reliably can differentiate benign from malignant thyroid nodules. Methods. Molecular profiles of benign (follicular adenomas, hyperblastic nodules) and malignant tumors (papillary thyroid carcinomas, follicular variants of papillary thyroid carcinomas) were analyzed using qRT-PCR from our 6-gene model (kit, Hs.296031, Hs.24183, LSM7, SYNGR2, C21 or f4). The gold standard was standard pathologic criteria. A diagnosis-predictor model was built by using the training samples and was then used to predict the class of 10 additional samples analyzed as unknowns. Results. Our predictor model using 4 7 training samples correctly predicted 9110 unknowns. One sample diagnosed as benign by standard histologic criteria was diagnosed as malignant by our model (sensitivity 75%; specificity, 100%; positive predictive value, 100%; negative predictive value, 85.7%). Conclusions. Molecular diagnosis with our 6-gene model can differentiate between benign and malignant thyroid tumors with high sensitivity and specificity. In combination, these genetic markers may be a reliable test to preoperatively diagnose the malignant Potential of thyroid nodules. C1 NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Dept Surg, Div Endocrine & Oncol Surg, Baltimore, MD 21205 USA. RP Libutti, SY (reprint author), NCI, Surg Branch, Ctr Canc Res, NIH, Bldg 10,Rm 4W-5940,10 Ctr Dr, Bethesda, MD 20892 USA. EM Steven_Libutti@nih.gov NR 18 TC 41 Z9 41 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD DEC PY 2005 VL 138 IS 6 BP 1050 EP 1056 DI 10.1016/j.surg.2005.09.010 PG 7 WC Surgery SC Surgery GA 998LB UT WOS:000234319000022 PM 16360390 ER PT J AU Sakamoto, JH Smith, BR Xie, B Rokhlin, SI Lee, SC Ferrari, M AF Sakamoto, JH Smith, BR Xie, B Rokhlin, SI Lee, SC Ferrari, M TI The molecular analysis of breast cancer utilizing targeted nanoparticle based ultrasound contrast agents SO TECHNOLOGY IN CANCER RESEARCH & TREATMENT LA English DT Article DE breast cancer; HER-2/neu; SKBR-3; ultrasound; contrast agent; and nanoparticle ID IN-SITU HYBRIDIZATION; HER-2/NEU PROTEIN OVEREXPRESSION; INTEROBSERVER REPRODUCIBILITY; OVARIAN-CANCER; CARCINOMA; AMPLIFICATION; PATHOLOGISTS; HERCEPTEST; TUMORS; HER2 AB This study was structured to challenge the hypothesis that nano-sized particulates could be molecularly targeted and bound to the prognostic and predictive HER-2/neu cell membrane receptor to elicit detectable changes in ultrasound response from human breast cancer cells. SKBR-3 human breast cancer cells were enlisted to test the efficacy of the particle conjugation strategy used in this study and ultimately, to provide conclusive remarks regarding the validity of the stated hypothesis. A characterization-mode ultrasound (CMUS) system was used to apply a continuum mechanics based, two-step inversion algorithm to reconstruct the mechanical material properties of four cell/agarose test conditions upon three independent test samples. The four test conditions include: Herceptin (R) conjugated iron oxide nanoparticles bound to cells (HER-con), Herceptin (R) bound to cells (HER), iso-type matched antibody conjugated iron oxide nanoparticles bound to cells (ISO-con), and Cold Flow Buffer mixed with agarose (CFB). The statistical analysis of these ultrasound results supported the ability to differentiate between HER-2/neu positive SKBR-3 cells that have been successfully tagged with Herceptin (R) conjugated iron oxide particles to those that have not demonstrated particle binding. These findings serve as promising proof-of-concept data for the development of a quantitative histopathologic evaluation tool directed towards both in situ and in vivo applications. The ultimate goal of this research is to exploit the molecular expression of the HER-2/neu protein to offer rapid, quantitative ultrasound information concerning the malignancy rating of human breast tissue employing tumor targeting nanoparticle based ultrasound contrast agents. When fully developed, this could potentially help 32,000-63,000 women efficiently find their proper treatment strategy to fight and win their battle against breast cancer. C1 Ohio State Univ, Biomed Engn Ctr, Columbus, OH 43210 USA. Ohio State Univ, Davis Heart & Lung Res Inst, Columbus, OH 43210 USA. Ohio State Univ, Nondestruct Evaluat Program, Columbus, OH 43210 USA. NCI, Bethesda, MD 20892 USA. RP Ferrari, M (reprint author), Ohio State Univ, Biomed Engn Ctr, Rm 110A Davis Heart & Lung Res Lab,473 W 12th Ave, Columbus, OH 43210 USA. EM ferrari@lvd1.bme.ohio-state.edu RI Xie, Bin/D-3590-2009; Lee, Stephen/C-2394-2011; Rokhlin, Stanislav/J-8268-2014 FU NCI NIH HHS [5 R21 CA099089-02] NR 37 TC 28 Z9 28 U1 2 U2 10 PU ADENINE PRESS PI SCHENECTADY PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA SN 1533-0346 J9 TECHNOL CANCER RES T JI Technol. Cancer Res. Treat. PD DEC PY 2005 VL 4 IS 6 BP 627 EP 636 PG 10 WC Oncology SC Oncology GA 001QD UT WOS:000234550500006 PM 16292882 ER PT J AU David, GL Koh, WP Lee, HP Yu, MC London, SJ AF David, GL Koh, WP Lee, HP Yu, MC London, SJ TI Childhood exposure to environmental tobacco smoke and chronic respiratory symptoms in non-smoking adults: The Singapore Chinese Health Study SO THORAX LA English DT Article ID PARENTAL SMOKING; LUNG-FUNCTION; PASSIVE SMOKING; DIETARY FIBER; YOUNG-ADULTS; ASTHMA; DISEASE; PREVALENCE; COHORT; POPULATION AB Background: Childhood exposure to environmental tobacco smoke has been extensively associated with childhood respiratory illness; fewer studies have addressed the effects on adults. Methods: Childhood environmental tobacco smoke exposure in relation to chronic cough, phlegm, and asthma diagnosis was studied in never smokers from a cohort of Singaporeans of Chinese ethnicity aged 45 - 74 years at enrolment from 1993 to 1998. From 1999 to 2004 subjects were interviewed regarding environmental tobacco smoke exposure before and after the age of 18 and the presence and duration of current symptoms of chronic cough and phlegm production and asthma diagnosis. Results: Among 35 000 never smokers, fewer had smoking mothers (19%) than fathers (48%). Although few subjects currently lived (20%) or worked (4%) with smokers, 65% reported living with a daily smoker before the age of 18 years. Living with a smoker before the age of 18 increased the odds of chronic dry cough (149 cases, odds ratio 2.1, 95% CI 1.4 to 3.3) and, to a lesser extent, phlegm, after adjustment for age, sex, dialect group, and current and past exposure to smokers at home and at work after the age of 18. Associations strengthened with higher numbers of smokers in childhood. There was no association with asthma or chronic bronchitis. There was evidence to suggest a stronger association among subjects with a lower adult intake of fibre which has previously been found to be protective for respiratory symptoms. Conclusions: In this large study of non- smokers, living with a smoker in childhood was associated with chronic dry cough and phlegm in adulthood, independent of later exposures to environmental tobacco smoke. C1 Natl Inst Environm Hlth Sci, Epidemiol Branch, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore 117548, Singapore. Univ Minnesota, Ctr Canc, Minneapolis, MN 55455 USA. RP London, SJ (reprint author), Natl Inst Environm Hlth Sci, Epidemiol Branch, NIH, US Dept HHS, POB 12233,Mail Drop A3-05, Res Triangle Pk, NC 27709 USA. EM london2@niehs.nih.gov OI London, Stephanie/0000-0003-4911-5290 FU Intramural NIH HHS; NCI NIH HHS [R01 CA80205]; NIEHS NIH HHS [Z01 ES043012-07, ZO1 ES43012] NR 39 TC 35 Z9 39 U1 0 U2 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0040-6376 EI 1468-3296 J9 THORAX JI Thorax PD DEC PY 2005 VL 60 IS 12 BP 1052 EP 1058 DI 10.1136/thx.2005.042960 PG 7 WC Respiratory System SC Respiratory System GA 985HO UT WOS:000233368400017 PM 16131525 ER PT J AU Balshaw, DM Philbert, M Suk, WA AF Balshaw, DM Philbert, M Suk, WA TI Research strategies for safety evaluation of nanomaterials, part III: Nanoscale technologies for assessing risk and improving public health SO TOXICOLOGICAL SCIENCES LA English DT Article DE nanoscale materials; risk assessment; individual exposure assessment; biological response; public health ID SELF-ASSEMBLED MONOLAYERS; BACTERIAL-CELL ARRAY; SINGLE LIVING CELLS; PEBBLE SENSORS; DENDRIMER NANOCOMPOSITES; COMPUTATIONAL DESIGN; MICROFLUIDIC SYSTEMS; OPTICAL NANOSENSORS; MESOPOROUS SUPPORTS; CHEMICAL-ANALYSIS AB Risk assessment in the environmental health sciences focuses on understanding the nature of environmental exposures and the potential harm posed by those exposures which in turn is determined by the perturbation of biological pathways and the individual's susceptibility to damage. While there are extensive research efforts ongoing in these areas, progress in each is currently slowed by technological limitations including comprehensive assessment of multiple exposures in real time and dynamic assessment of biological response with high temporal and quantitative resolution. This Forum article discusses recent technological innovations capitalizing on the emergent properties of nanoscale materials and their potential adaptation to improving individual exposure assessment, determination of biological response, and environmental remediation. The ultimate goal is to raise the environmental health science community's awareness of these possibilities and encourage the development of improved strategies for assessing risk and improving public health. C1 NIEHS, Ctr Risk & Integrated Sci, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. RP Balshaw, DM (reprint author), NIEHS, Ctr Risk & Integrated Sci, NIH, US Dept HHS, EC-27,POB 12233,79 TW Alexander Dr Suite 3447, Res Triangle Pk, NC 27709 USA. EM Balshaw@niehs.nih.gov NR 40 TC 34 Z9 38 U1 0 U2 14 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD DEC PY 2005 VL 88 IS 2 BP 298 EP 306 DI 10.1093/toxsci/kfi312 PG 9 WC Toxicology SC Toxicology GA 983FC UT WOS:000233215700003 PM 16162851 ER PT J AU Ghanayem, BI McDaniel, LP Churchwell, MI Twaddle, NC Snyder, R Fennell, TR Doerge, DR AF Ghanayem, BI McDaniel, LP Churchwell, MI Twaddle, NC Snyder, R Fennell, TR Doerge, DR TI Role of CYP2E1 in the epoxidation of acrylamide to glycidamide and formation of DNA and hemoglobin adducts SO TOXICOLOGICAL SCIENCES LA English DT Article ID WILD-TYPE MICE; LIQUID-CHROMATOGRAPHY; N-METHYLOLACRYLAMIDE; CYTOCHROME-P450 2E1; B6C3F(1) MICE; F344 RATS; METABOLISM; CARCINOGENICITY; ACRYLONITRILE; TOXICITY AB Acrylamide (AA) is an animal carcinogen, neurotoxin, and reproductive toxin. AA is formed in baked and fried carbohydrate-rich foods. Metabolism of AA occurs via epoxidation to glycidamide (GA) or direct conjugation with glutathione. Using CYP2E1-null mice, recent studies in this laboratory demonstrated that induction of somatic and germ cell mutagenicity in AA-treated mice is dependent on CYP2E1. We hypothesized that AA metabolism to GA is a prerequisite for the induction of AA-induced mutagenicity. Current studies were undertaken to assess the role of CYP2E1 in the epoxidation of AA to GA and the formation of DNA and hemoglobin (HGB) adducts. AA was administered to CYP2E1-null or wild-type mice at 50 mg/kg ip. Mice were euthanized 6 h later and blood and tissues were collected. Using LC-ES/MS/MS, AA, GA, and DNA- and HGB-adducts were measured. While the plasma levels of AA and GA were 115 +/- 14.0 and 1.7 +/- 0.31 mu M in CYP2E1-null mice, they were 0.84 +/- 0.80 and 33.0 +/- 6.3 mu M in the plasma of AA-treated wild-type mice. Administration of AA to wild-type mice caused a large increase in N7-GA-Gua and N3-GA-Ade adducts in the liver, lung, and testes. While traces of N7-GA-Gua adducts were measured in the tissues of AA-treated CYP2E1-null mice, these levels were 52- to 66-fold lower than in wild-type mice. Significant elevation of both AA- and GA-HGB adducts was detected in AA-treated wild-type mice. In AA-treated CYP2E1-null mice, levels of AA-HGB adducts were roughly twice as high as those in wild-type mice. In conclusion, current work demonstrated that CYP2E1 is the primary enzyme responsible for the epoxidation of AA to GA, which leads to the formation of GA-DNA and HGB adducts. C1 NIEHS, Lab Pharmacol & Chem, Natl Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RTI Int, Res Triangle Pk, NC 27709 USA. RP Ghanayem, BI (reprint author), NIEHS, Lab Pharmacol & Chem, Natl Toxicol Program, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM ghanayem@niehs.nih.gov RI Fennell, Tim/D-9936-2013 NR 47 TC 88 Z9 95 U1 1 U2 18 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD DEC PY 2005 VL 88 IS 2 BP 311 EP 318 DI 10.1093/toxsci/kfi307 PG 8 WC Toxicology SC Toxicology GA 983FC UT WOS:000233215700005 PM 16141435 ER PT J AU Diaz, LA Cheong, I Foss, CA Zhang, XS Peters, BA Agrawal, N Bettegowda, C Karim, B Liu, GS Khan, K Huang, X Kohli, M Dang, LH Hwang, P Vogelstein, A Garrett-Mayer, E Kobrin, B Pomper, M Zhou, SB Kinzler, KW Vogelstein, B Huso, DL AF Diaz, LA Cheong, I Foss, CA Zhang, XS Peters, BA Agrawal, N Bettegowda, C Karim, B Liu, GS Khan, K Huang, X Kohli, M Dang, LH Hwang, P Vogelstein, A Garrett-Mayer, E Kobrin, B Pomper, M Zhou, SB Kinzler, KW Vogelstein, B Huso, DL TI Pharmacologic and toxicologic evaluation of C-novyi-NT spores SO TOXICOLOGICAL SCIENCES LA English DT Article ID EXPERIMENTAL CLOSTRIDIUM-NOVYI; VELOCITY MISSILE WOUNDS; APOLIPOPROTEIN-E; SEVERE SEPSIS; GAS-GANGRENE; BACTERIOLYTIC THERAPY; EXPERIMENTAL-TUMORS; SEPTIC SHOCK; SOLID TUMORS; MICE AB Clostridium novyi-NT (C. novyi-NT) spores have been shown to be potent therapeutic agents in experimental tumors of mice and rabbits. In the present study, pharmacologic and toxicologic studies were performed to better understand the factors influencing the efficacy and toxicity of this form of therapy. We found that spores were rapidly cleared from the circulation by the reticuloendothelial system. Even after large doses were administered, no clinical toxicity was observed in healthy mice or rabbits. The spores were also not toxic in mice harboring poorly vascularized non-neoplastic lesions, including myocardial infarcts. In tumor-bearing mice, toxicity appeared related to tumor size and spore dose, as expected with any bacterial infection. However, there was no laboratory or histopathologic evidence of sepsis, and the toxicity could be effectively controlled by simple hydration. C1 Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA. Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21231 USA. Johns Hopkins Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21231 USA. Johns Hopkins Univ, Sch Med, Dept Radiol & Radiol Sci, Baltimore, MD 21231 USA. Johns Hopkins Univ, Sch Med, Dept Comparat Med, Baltimore, MD 21231 USA. Univ Michigan, Dept Oncol, Ann Arbor, MI 48104 USA. NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. RP Zhou, SB (reprint author), Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, 1650 Orleans Ave CRB,Room 590, Baltimore, MD 21231 USA. EM sbzhou@jhmi.edu FU NCI NIH HHS [CA43460, CA062924, CA103175, CA92871]; NCRR NIH HHS [RR00171] NR 44 TC 27 Z9 30 U1 2 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD DEC PY 2005 VL 88 IS 2 BP 562 EP 575 DI 10.1093/toxsci/kfi316 PG 14 WC Toxicology SC Toxicology GA 983FC UT WOS:000233215700030 PM 16162850 ER PT J AU Carey, MA van Pelt, FNAM AF Carey, MA van Pelt, FNAM TI Immunochemical detection of flucloxacillin adduct formation in livers of treated rats SO TOXICOLOGY LA English DT Article DE flucloxacillin; cholestasis; drug-adduct; immunoblotting; ELISA ID CHOLESTATIC HEPATITIS; DAMAGE; DICLOXACILLIN; DERIVATIVES; PENICILLIN; OXACILLIN; PROTEINS; JAUNDICE; THERAPY; BINDING AB Flucloxacillin is a semi-synthetic penicillin widely used in the prophylaxis and treatment of staphylococcal infections. Severe liver reactions, characterised by delayed cholestatic hepatitis and a prolonged course of recovery, a re associated with flucloxacillin therapy. Clinical findings are suggestive of an immune mediated reaction but there exists little supporting experimental evidence. The formation of drug modified hepatic protein adducts has been proposed to play an important role in the hepatotoxicity of many drugs. The aim of the present study was to investigate whether flucloxacillin treatment results in adduct formation in vivo. Flucloxacillin was conjugated to rabbit serum albumin by formation of a penicilloyl determinant and used as an immunogen to raise a polyclonal antiserum specific for flucloxacillin-modified proteins. Antibody specificity was confirmed by competitive enzyme-linked immumosorbent assay (ELISA) with free drug. The antiserum was used in combination with western blotting to detect adduct formation in the livers of flucloxacillin treated rats. Western blot analysis of rat liver subcellular fractions revealed the formation of six flucloxacillin adducts in various subcellular fractions. These studies demonstrate for the first time that treatment with flucloxacillin results in the formation of hepatic protein adducts. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Natl Univ Ireland Univ Coll Cork, Dept Therapeut & Pharmacol, Cork, Ireland. RP Carey, MA (reprint author), Natl Inst Environm Hlth Sci, Lab Resp Biol, Natl Inst Hlth, Res Triangle Pk, NC USA. EM carey1@niehs.nih.gov NR 31 TC 31 Z9 32 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD DEC 1 PY 2005 VL 216 IS 1 BP 41 EP 48 DI 10.1016/j.tox.2005.07.015 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 984NX UT WOS:000233312700006 PM 16112790 ER PT J AU Klein, HG AF Klein, HG TI Margot Kruskall - In memoriam SO TRANSFUSION LA English DT Biographical-Item C1 NIH, Dept Transfus Med, Bethesda, MD 20892 USA. RP Klein, HG (reprint author), NIH, Dept Transfus Med, Bldg 10,Room 1C711, Bethesda, MD 20892 USA. EM HKlein@cc.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD DEC PY 2005 VL 45 IS 12 BP 1982 EP 1983 DI 10.1111/j.1537-2995.2005.00685.x PG 2 WC Hematology SC Hematology GA 987PV UT WOS:000233530700021 ER PT J AU Bruno, DA Dhanireddy, KK Kirk, AD AF Bruno, DA Dhanireddy, KK Kirk, AD TI Challenges in therapeutic strategies for transplantation: Where now from here? SO TRANSPLANT IMMUNOLOGY LA English DT Article DE transplantation; T cell activation; cytotoxicity ID T-CELL-ACTIVATION; DONOR-SPECIFIC TRANSFUSION; NONHUMAN PRIMATE MODEL; MEMORY-LIKE PHENOTYPE; LONG-TERM SURVIVAL; ALLOGRAFT TOLERANCE; COSTIMULATION BLOCKADE; RENAL-TRANSPLANTATION; OPERATIONAL TOLERANCE; LYMPHOCYTE SUBSETS AB The current standard of care in transplantation reliably achieves acceptable graft and patient survival but still depends on life long immunosuppression in most patients. Current strategies employ medications that, in general, inhibit distal events mediating rejection, namely T cell activation and cytotoxicity. They do not typically interfere with initial allorecognition or the factors that influence the direction of an immune response (towards cytotoxicity as opposed to anergy or regulation). Given the exponential amplification of immune responses, these proximal targets may be more efficient in preventing rejection. Recent laboratory investigations have identified several approaches, e.g., costimulation blockade, depletion, and hematopoietic chimerism, that influence the initial stages of the alloimmune response, or establish self-perpetuating means of eliminating rejection without chronic immunosuppression. This manuscript reviews methods of immune manipulation that the authors view as promising for future exploitation and transfer to the clinic. These therapies are similar in that they are viewed as attempts to influence the ability of the body to mount an immune response and its subsequent direction, as opposed to supplying late effector phase inhibition. While it is recognized as unlikely that any one therapy will universally lead to tolerance, the authors propose that these concepts will make immunosuppressive drug minimization more readily successful. (C) 2005 Elsevier B.V. All rights reserved. C1 NIDDKD, Transplantat Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Georgetown Univ Hosp, Dept Surg, Washington, DC 20007 USA. RP Kirk, AD (reprint author), NIDDKD, Transplantat Branch, NIH, Dept Hlth & Human Serv, Bldg 10,Room 5-5750, Bethesda, MD 20892 USA. EM allank@intra.niddk.nih.gov RI Kirk, Allan/B-6905-2012 NR 46 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0966-3274 J9 TRANSPL IMMUNOL JI Transpl. Immunol. PD DEC PY 2005 VL 15 IS 2 BP 149 EP 155 DI 10.1016/j.trim.2005.07.001 PG 7 WC Immunology; Transplantation SC Immunology; Transplantation GA 007GM UT WOS:000234956800008 PM 16412959 ER PT J AU Ferguson, C Larochelle, A Dunbar, CE AF Ferguson, C Larochelle, A Dunbar, CE TI Hematopoietic stem cell gene therapy: dead or alive? SO TRENDS IN BIOTECHNOLOGY LA English DT Review ID BONE-MARROW-TRANSPLANTATION; LONG-TERM HEMATOPOIESIS; BLOOD CD34(+) CELLS; FOAMY VIRUS VECTORS; IN-VIVO; NONHUMAN-PRIMATES; PERIPHERAL-BLOOD; GENOMIC INTEGRATION; LENTIVIRAL VECTOR; PROGENITOR CELLS AB Despite some reports of toxicity in recent clinical trials, many scientists believe that the use of gene therapy in the treatment of congenital genetic defects and acquired disorders has too much potential to abandon. Hematopoietic stem cells (HSCs) have been primary targets for gene therapy owing to their capacity for differentiation and self-renewal, whereby multiple cell lineages can potentially be corrected for the lifetime of an individual. These efforts represent a long-term investment towards broadening physicians' treatment options for patients whose diseases, in particular certain immunodeficiencies, are fatal and where no other therapy is available. We review the recent progress and clinical triumphs as well as the reported toxicity related to insertional mutagenesis. We also discuss the current risk-to-benefit estimates and future strategies to reduce the risks and allow full realization of clinical potential. Scientists are continually revising protocols: going both from 'bench to bedside' and, as strikingly demonstrated by HSC gene therapy, from 'bedside to bench.' C1 NHLBI, Mol Hematopoiesis Sect, NIH, Bethesda, MD 20892 USA. RP Dunbar, CE (reprint author), NHLBI, Mol Hematopoiesis Sect, NIH, Bethesda, MD 20892 USA. EM dunbarc@nhlbi.nih.gov NR 75 TC 16 Z9 17 U1 0 U2 1 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0167-7799 J9 TRENDS BIOTECHNOL JI Trends Biotechnol. PD DEC PY 2005 VL 23 IS 12 BP 589 EP 597 DI 10.1016/j.tibtech.2005.09.005 PG 9 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 994EW UT WOS:000234014600005 PM 16216357 ER PT J AU Kelly, K AF Kelly, K TI The RGK family: a regulatory tail of small GTP-binding proteins SO TRENDS IN CELL BIOLOGY LA English DT Article ID CALCIUM-CHANNEL ACTIVITY; RHO-KINASE PATHWAY; CYTOSKELETAL REORGANIZATION; CALMODULIN; GEM; EXPRESSION; GTPASES; KIR/GEM; REM2; RAD AB RGK proteins are small Ras-related GTP-binding proteins that function as potent inhibitors of voltage-dependent calcium channels, and two members of the family, Gem and Rad, modulate Rho-dependent remodeling of the cytoskeleton. Within the Ras superfamily, RGK proteins have distinct structural and regulatory characteristics. It is an open question as to whether RGK proteins catalyze GTP hydrolysis in vivo. Binding of calmodulin and the 14-3-3 protein to RGK proteins controls downstream pathways. Here, we discuss the structural and functional properties of RGK proteins and highlight recent work by Beguin and colleagues addressing the mechanism of Gem regulation by calmodulin and 14-3-3. C1 NCI, Cell & Canc Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Kelly, K (reprint author), NCI, Cell & Canc Biol Branch, Ctr Canc Res, NIH, Bldg 37,Room 1068, Bethesda, MD 20892 USA. EM kkelly@helix.nih.gov FU Intramural NIH HHS NR 15 TC 41 Z9 41 U1 0 U2 0 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0962-8924 J9 TRENDS CELL BIOL JI Trends Cell Biol. PD DEC PY 2005 VL 15 IS 12 BP 640 EP 643 DI 10.1016/j.tcb.2005.10.002 PG 4 WC Cell Biology SC Cell Biology GA 998KF UT WOS:000234316700004 PM 16242932 ER PT J AU Koonin, EV Martin, W AF Koonin, EV Martin, W TI On the origin of genomes and cells within inorganic compartments SO TRENDS IN GENETICS LA English DT Editorial Material ID UNIVERSAL COMMON ANCESTOR; TRANSITION-METAL SULFIDES; DNA-REPLICATION PROTEINS; MID-ATLANTIC RIDGE; MINIMAL-GENE-SET; HORIZONTAL TRANSFER; LIPID BIOSYNTHESIS; SULFUR-COMPOUNDS; SELFISH OPERONS; IRON SULFIDE AB Building on the model of Russell and Hall for the emergence of life at a warm submarine hydrothermal vent, we suggest that, within a hydrothermally formed system of contiguous iron-sulfide (FeS) compartments, populations of virus-like RNA molecules, which eventually encoded one or a few proteins each, became the agents of both variation and selection. The initial darwinian selection was for molecular self-replication. Combinatorial sorting of genetic elements among compartments would have resulted in preferred proliferation and selection of increasingly complex molecular ensembles - those compartment contents that achieved replication advantages. The last universal common ancestor (LUCA) we propose was not free-living but an inorganically housed assemblage of expressed and replicable genetic elements. The evolution of the enzymatic systems for (i) DNA replication; and (ii) membrane and cell wall biosynthesis, enabled independent escape of the first archaebacterial and eubacterial cells from their hydrothermal hatchery, within which the LUCA itself remained confined. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Univ Dusseldorf, Inst Bot 3, D-4000 Dusseldorf, Germany. RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov RI Martin, William/C-5680-2008; Martin, William /O-5446-2015 OI Martin, William /0000-0003-1478-6449 FU Intramural NIH HHS NR 84 TC 153 Z9 163 U1 3 U2 31 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD DEC PY 2005 VL 21 IS 12 BP 647 EP 654 DI 10.1016/j.tig.2005.09.006 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 989KO UT WOS:000233672700004 PM 16223546 ER PT J AU Gold, SM Mohr, DC Huitinga, I Flachenecker, P Sternberg, EM Heesen, C AF Gold, SM Mohr, DC Huitinga, I Flachenecker, P Sternberg, EM Heesen, C TI The role of stress-response systems for the pathogenesis and progression of MS SO TRENDS IN IMMUNOLOGY LA English DT Review ID PITUITARY-ADRENAL AXIS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; MULTIPLE-SCLEROSIS PATIENTS; BETA-ADRENERGIC-RECEPTOR; BLOOD MONONUCLEAR-CELLS; BETA(2)-ADRENERGIC RECEPTORS; SYMPATHECTOMY AUGMENTS; PSYCHOLOGICAL STRESS; DISEASE PROGRESSION AB Disease progression in multiple sclerosis (MS) - an inflammatory demyelinating and neurodegenerative disease with a presumed T-cell driven autoimmune origin - has long been hypothesized to be associated with stress. However, this notion has only recently been supported by prospective clinical studies. Several clinical and molecular studies in MS and its animal models have recently shown disruptions in the communication between the immune system and the two major stress response systems, the hypothalamo-pituitary-adrenal (HPA) axis and the autonomic nervous system. Insensitivity to glucocorticoid and beta-adrenergic modulation might be involved in overshooting inflammation in MS, whereas hyperactivity of the HPA axis has been linked to neurodegeneration and increased disability. Here, we integrate findings from molecular, cellular, experimental, clinical and epidemiological research to describe the involvement of stress response systems in MS pathogenesis and progression. C1 Univ Hamburg, Hosp Eppendorf, Dept Neurol, D-20246 Hamburg, Germany. Univ Calif Los Angeles, Sch Med, Dept Neurol, Multiple Sclerosis Program, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Ctr Psychoneuroimmunol, Neuropsychiat Inst, Los Angeles, CA 90095 USA. Univ Calif San Francisco, Vet Affairs Med Ctr, Dept Psychiat & Neurol, San Francisco, CA 94121 USA. VUmc, Netherlands Inst Brain Res, NL-1105 AZ Amsterdam, Netherlands. VUmc, MS Ctr, NL-1105 AZ Amsterdam, Netherlands. Neurol Rehabil Zentrum Quellenhof, D-75323 Bad Wildbad, Germany. NIMH, Integrat Neural Immune Program, Sect Neuroendocrine Immunol & Behav, NIH, Rockville, MD 20852 USA. RP Heesen, C (reprint author), Univ Hamburg, Hosp Eppendorf, Dept Neurol, Martinistr 52, D-20246 Hamburg, Germany. EM heesen@uke.uni-hamburg.de OI Gold, Stefan/0000-0001-5188-4799 FU Intramural NIH HHS NR 70 TC 53 Z9 56 U1 2 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4906 J9 TRENDS IMMUNOL JI Trends Immunol. PD DEC PY 2005 VL 26 IS 12 BP 644 EP 652 DI 10.1016/j.it.2005.09.010 PG 9 WC Immunology SC Immunology GA 989KN UT WOS:000233672600007 PM 16214415 ER PT J AU Tonoli, H Barrett, JC AF Tonoli, H Barrett, JC TI CD82 metastasis suppressor gene: a potential target for new therapeutics? SO TRENDS IN MOLECULAR MEDICINE LA English DT Review ID CANCER-CELL-LINES; FREQUENT DOWN-REGULATION; NF-KAPPA-B; PROSTATE-CANCER; TETRASPANIN CD82; KAI1 EXPRESSION; PANCREATIC-CANCER; KAI1/CD82 GENE; T-LYMPHOCYTES; COLON-CANCER AB The transmembrane glycoprotein CD82 is a member of the tetraspanin protein family and is a metastasis suppressor implicated in biological processes ranging from fusion, adhesion and migration to apoptosis and cell-morphology alterations. Downregulation of CD82 expression is associated with the advanced stages of many human cancers and correlates with the acquisition of metastatic potential. Recent studies suggest that complex mechanisms underlie CD82 loss of function, including altered transcriptional regulation, splice variant production and post-translational protein modifications, and indicate a central role for CD82 in controlling metastasis as a 'molecular facilitator'. The diverse array of functions of CD82, the complexity of the regulation of CD82 and the prospects for targeting CD82 as a therapeutic approach for the treatment of a variety of metastatic cancers are discussed. C1 Ctr Canc Res, Lab Biosyst & Canc, NCI, Bethesda, MD 20892 USA. RP Barrett, JC (reprint author), Ctr Canc Res, Lab Biosyst & Canc, NCI, Bethesda, MD 20892 USA. EM barrett@mail.nih.gov FU Intramural NIH HHS NR 67 TC 50 Z9 51 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4914 J9 TRENDS MOL MED JI Trends Mol. Med PD DEC PY 2005 VL 11 IS 12 BP 563 EP 570 DI 10.1016/j.molmed.2005.10.002 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 998LS UT WOS:000234320800007 PM 16271511 ER PT J AU Schulkin, J Morgan, MA Rosen, JB AF Schulkin, J Morgan, MA Rosen, JB TI A neuroendocrine mechanism for sustaining fear SO TRENDS IN NEUROSCIENCES LA English DT Editorial Material ID CORTICOTROPIN-RELEASING HORMONE; MEDIAL PREFRONTAL CORTEX; ACOUSTIC STARTLE REFLEX; CRH MESSENGER-RNA; BED NUCLEUS; STRIA TERMINALIS; PARAVENTRICULAR NUCLEUS; CONDITIONED FEAR; GLUCOCORTICOID-RECEPTOR; RAT-BRAIN AB Fear is an adaptive response to recognition of a potentially dangerous event. Glucocorticoids are essential for maintaining a wide variety of behavioral events by their regulation of numerous genes; one such gene encodes corticotrophin-releasing hormone (CRH). CRH is involved in diverse behavioral responses to changing environmental demands. In this review, we focus on one aspect of glucocorticoid regulation of CRH - namely, fear-related responses to diverse classes of adverse events, such as those represented by contextual and cue-specific stimuli. Three extra-hypothalamic forebrain sites appear crucial for fear-related behavioral responses: the amygdala and the bed nucleus of the stria terminalis for sustaining adaptive fear-related behaviors, and the medial prefrontal cortex for modulating fear-related behaviors. Central regulation of CRH by glucocorticoids is important for adaptive and sustained fear-related behaviors, and its aberration is associated with anxiety and depressive disorders. C1 Georgetown Univ, Dept Phys & Biophys, Washington, DC 20007 USA. Amer Coll Obstetricians & Gynecologists, Dept Res, Washington, DC 20024 USA. NIMH, Clin Neuroendocrinol Branch, Bethesda, MD 20817 USA. Univ Delaware, Dept Psychol, Newark, DE 19716 USA. RP Schulkin, J (reprint author), Georgetown Univ, Dept Phys & Biophys, Washington, DC 20007 USA. EM jschulkin@acog.org NR 69 TC 97 Z9 99 U1 1 U2 11 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD DEC PY 2005 VL 28 IS 12 BP 629 EP 635 DI 10.1016/j.tins.2005.09.009 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 996CG UT WOS:000234151400001 PM 16214230 ER PT J AU Steers, W Diokno, AC Mallett, V Brubaker, L FitzGerald, M Richter, HE Lloyd, LK Albo, M Nager, C Chai, T Johnson, HW Zyczynski, HM Chancellor, M Leng, W Zimmern, P Lemack, G Kraus, S Cespedes, RD Norton, P Kerr, L Tennstedt, S Stoddard, A Kusek, JW Nyberg, LM Weber, AM AF Steers, W Diokno, AC Mallett, V Brubaker, L FitzGerald, M Richter, HE Lloyd, LK Albo, M Nager, C Chai, T Johnson, HW Zyczynski, HM Chancellor, M Leng, W Zimmern, P Lemack, G Kraus, S Cespedes, RD Norton, P Kerr, L Tennstedt, S Stoddard, A Kusek, JW Nyberg, LM Weber, AM CA Urinary Incontinence Treatment Net TI Design of the Stress Incontinence Surgical Treatment Efficacy Trial (SISTER) SO UROLOGY LA English DT Article ID URINARY-INCONTINENCE; WOMEN; DIARY; COLPOCYSTOURETHROPEXY; QUESTIONNAIRE; SURGERY; QUALITY; SOCIETY AB Objectives. To describe the methods and rationale for the first randomized controlled trial conducted by the Urinary Incontinence Treatment Network. Methods. The primary objective of this clinical trial is to compare two commonly performed surgical procedures for stress urinary incontinence-the Burch colposuspension and the autologous rectus fascial sling-for overall treatment success for urinary incontinence and stress-type symptoms of incontinence at 24 months after surgery. Secondary aims include a comparison of complications, quality of life, sexual function, patient satisfaction, costs, and the need for additional treatments or surgery; and an evaluation of the prognostic value of preoperative urodynamic studies. The Stress Incontinence Surgical Treatment Efficacy Trial is being conducted on 655 women with predominant stress urinary incontinence, as determined by history and physical examination, urinary stress test with witnessed leakage, and voiding diary. Administration of all questionnaires and performance of examinations, tests, and both surgical procedures are standardized within and across the clinical centers. Assessments occur preoperatively and at 6 weeks and 3, 6, 12, 18, and 24 months postoperatively. A sample of 655 women ensures 80% power to detect a 12% difference (60% versus 72%) at the 5% significance level. The intent-to-treat analysis will use Fisher's exact test and time-to-failure analyses. Results. Enrollment was completed in June 2004 with 24 months of follow-up to end in June 2006. Conclusions. This is the first large, multicenter randomized clinical trial comparing these two standard-of-care procedures for stress incontinence. C1 New England Res Inst, Watertown, MA 02472 USA. Univ Virginia, Charlottesville, VA USA. William Beaumont Hosp, Royal Oak, MI 48072 USA. Oakwood Hosp, Royal Oak, MI USA. Loyola Univ, Med Ctr, Maywood, IL 60153 USA. Univ Alabama, Birmingham, AL USA. Univ Calif San Diego, San Diego, CA 92103 USA. Univ Maryland, Baltimore, MD 21201 USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Texas SW, Dallas, TX USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Univ Utah, Salt Lake City, UT USA. New England Res Inst, Watertown, MA 02172 USA. NIDDKD, Bethesda, MD 20892 USA. NICHHD, Bethesda, MD 20892 USA. RP Tennstedt, S (reprint author), New England Res Inst, 9 Galen St, Watertown, MA 02472 USA. EM stennstedt@neriscience.com NR 28 TC 54 Z9 54 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD DEC PY 2005 VL 66 IS 6 BP 1213 EP 1217 DI 10.1016/j.urology.2005.06.089 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 995UR UT WOS:000234130200017 ER PT J AU Vitiello, CL Merril, CR Adhya, S AF Vitiello, CL Merril, CR Adhya, S TI An amino acid substitution in a capsid protein enhances phage survival in mouse circulatory system more than a 1000-fold SO VIRUS RESEARCH LA English DT Article ID BACTERIOPHAGE; FATE AB In experiments with germ free mice, free from adaptive antibodies to the bacterial virus lambda phage, titers of the virus in the circulatory system have been reported to decrease by more than 10(9) pfu within 48h of intraperitoneal intravenous or oral administration. Based on these observations, serial passage techniques have been used to select X phage mutants, with 13,000-16,000-fold greater capacity to remain in the mouse circulatory system 24h after intraperitoneal injection. In these prior studies the "long-circulating" phage, designated lambda Argo phage, had at least three mutations including one in the major phage capsid (E) protein, which resulted in the change Of glutamic acid to a lysine at residue 158. In the Current Study, we demonstrate that this single specific Substitution in the E protein is sufficient to confer the "long-circulating" phenotype. The isogenic pair of phage developed in this study consisting of the long-circulating marker-rescued lambda Argo phage, and the parental wild type phage can be used for studies of viral recognition mechanisms of the innate immune system and for the development of more effective antibacterial therapeutic phage strains. Published by Elsevier B.V. C1 NCI, Sect Dev Genet, NIH, Bethesda, MD 20892 USA. NIMH, Sect Biochem Genet, NIH, Bethesda, MD 20892 USA. RP Merril, CR (reprint author), NCI, Sect Dev Genet, NIH, Bethesda, MD 20892 USA. EM merrilc@mail.nih.gov NR 9 TC 36 Z9 37 U1 0 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1702 J9 VIRUS RES JI Virus Res. PD DEC PY 2005 VL 114 IS 1-2 BP 101 EP 103 DI 10.1016/j.virusres.2005.05.014 PG 3 WC Virology SC Virology GA 989AK UT WOS:000233645100012 PM 16055223 ER PT J AU Kyuregyan, KK Poleschuk, VF Zamyatina, NA Isaeva, OV Michailov, MI Ross, S Bukh, J Roggendorf, M Viazov, S AF Kyuregyan, KK Poleschuk, VF Zamyatina, NA Isaeva, OV Michailov, MI Ross, S Bukh, J Roggendorf, M Viazov, S TI Acute GB virus B infection of marmosets is accompanied by mutations in the NS5A protein SO VIRUS RESEARCH LA English DT Article ID HEPATITIS-C VIRUS; SURROGATE MODEL; TAMARIN; AGENT; CHIMPANZEES; VIREMIA; CLONE AB GBV-B, a member of the Flaviviridae family of viruses, is the virus most closely related to HCV, and GBV-B infection in tamarin monkeys might represent a valuable surrogate animal model of HCV infection. In the current study, GBV-B was successfully transmitted to two marmosets (Callithrix jaccus). The infection resulted in viremia of 14- and 17-week duration, respectively, and was accompanied by elevation of isocitrate dehydrogenase activity. These data confirm that marmosets might represent an attractive model for GBV-B infection. The sequence of GBV-B NS5A, which was previously reported to have one of the highest mutation rates during infection in tamarins, was determined for viruses recovered front the inoculum and from marmoset blood samples obtained at weeks 1, 8, and 14 post inoculation in one marmoset and at weeks 2, 8, and 17 post inoculation in the other marmoset. In both animals, we detected four substitutions (R 1945K, K2052G, F2196L, and G2268E), in the virus recovered immediately before viral clearance. Interestingly, two of these mutations (F2196L and G2268E) were described recently for viruses recovered from persistently infected tamarins. Appearance of these mutations presumably reflects a mechanism of immune escape rather than adaptation of the virus to a new host. (c) 2005 Elsevier B.V. All rights reserved. C1 DI Ivanovskii Inst Virol, Moscow 123098, Russia. Gamaleya Inst Epidemiol & Microbiol, Moscow 123098, Russia. Russian Acad Med Sci, Inst Poliomyelitis & Viral Encephalitis, Moscow 142782, Russia. NIAID, Infect Dis Lab, Hepatitis Viruses Sect, Bethesda, MD 20892 USA. Essen Univ Hosp, Inst Virol, D-45122 Essen, Germany. RP Viazov, S (reprint author), DI Ivanovskii Inst Virol, Gamaleya 16, Moscow 123098, Russia. EM sergei.viazov@uni-essen.de RI Mikhailov, Mikhail/E-3531-2014 NR 12 TC 10 Z9 10 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1702 J9 VIRUS RES JI Virus Res. PD DEC PY 2005 VL 114 IS 1-2 BP 154 EP 157 DI 10.1016/j.virusres.2005.06.009 PG 4 WC Virology SC Virology GA 989AK UT WOS:000233645100019 PM 16054723 ER PT J AU Seeliger, MW Beck, SC Pereyra-Munoz, N Dangel, S Tsai, JY Luhmann, UFO van de Pavert, SA Wijnholds, J Samardzija, M Wenzel, A Zrenner, E Narfstrom, K Fahl, E Tanimoto, N Acar, N Tonagel, F AF Seeliger, MW Beck, SC Pereyra-Munoz, N Dangel, S Tsai, JY Luhmann, UFO van de Pavert, SA Wijnholds, J Samardzija, M Wenzel, A Zrenner, E Narfstrom, K Fahl, E Tanimoto, N Acar, N Tonagel, F TI In vivo confocal imaging of the retina in animal models using scanning laser ophthalmoscopy SO VISION RESEARCH LA English DT Article DE scanning-laser ophthalmoscopy; animal models; retinal degenerations; angiography ID NEOVASCULARIZATION; ANGIOGENESIS; SYSTEM; RPE65; MOUSE; GENE AB Scanning-laser ophthalmoscopy is a technique for confocal imaging of the eye in vivo. The use of lasers of different wavelengths allows to obtain information about specific tissues and layers due to their reflection and transmission characteristics. In addition, fluorescent dyes excitable in the blue and infrared range offer a unique access to the vascular structures associated with each layer. In animal models, a further enhancement in specificity can be obtained by GFP expression under control of tissue-specific promotors. Important fields of application are studies in retinal degenerations and the follow-up of therapeutic intervention. (c) 2005 Elsevier Ltd. All rights reserved. C1 Retinal Diagnost Res Grp, Tubingen, Germany. Genet Mol Lab, Tubingen, Germany. Univ Eye Hosp, Dept 2, Tubingen, Germany. NEI, Biol Imaging Core, Bethesda, MD 20892 USA. Univ Zurich, Inst Med Genet, Div Med Mol Genet & Gene Diagnost, Zurich, Switzerland. Netherlands Ophthalm Res Inst, NL-1100 AC Amsterdam, Netherlands. Univ Zurich Hosp, Eye Clin, Lab Retinal Cell Biol, CH-8091 Zurich, Switzerland. Univ Missouri, Coll Vet Med, Dept Med & Surg, Columbia, MO 65211 USA. RP Seeliger, MW (reprint author), Retinal Diagnost Res Grp, Tubingen, Germany. EM see@uni-tuebingen.de RI van de Pavert, Serge/A-7307-2008; Luhmann, Ulrich/D-8905-2012; Samardzija, Marijana/B-9245-2008; OI van de Pavert, Serge/0000-0002-7147-4380; Samardzija, Marijana/0000-0003-0991-4653; Wijnholds, Jan/0000-0003-0099-460X NR 19 TC 113 Z9 113 U1 0 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0042-6989 J9 VISION RES JI Vision Res. PD DEC PY 2005 VL 45 IS 28 BP 3512 EP 3519 DI 10.1016/j.visres.2005.08.014 PG 8 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 997FN UT WOS:000234230600009 PM 16188288 ER PT J AU Adams, C Haidar, D Kamakaka, RT AF Adams, C Haidar, D Kamakaka, RT TI Construction and characterization of a series of vectors for Schizosaccharomyces pombe SO YEAST LA English DT Article DE Schizosaccharomyces pombe; vectors; genomic library ID FISSION YEAST; REPLICATION ORIGIN; ARS ELEMENTS; DNA; PLASMIDS; STRAINS; REGION; GENE AB A set of vectors was created to allow cloning and expression studies in Schizosaccharomyces pombe. These vectors had a uniform backbone with an efficient Sz. pombe ARS, ARS3002, but different selectable markers - his3(+), leu1(+), ade6(+) and ura4(+). The vectors functioned efficiently as autonomously replicating plasmids that could also be converted into integrating vectors. The ura4(+)-containing vector was used to construct a Sz. pombe genomic library. Copyright (c) 2005 John Wiley & Sons, Ltd. C1 NICHHD, Unit Chromatin & Transcript, NIH, Bethesda, MD 20892 USA. RP Kamakaka, RT (reprint author), NICHHD, Unit Chromatin & Transcript, NIH, Bldg 18T,Room 106,18 Lib Dr, Bethesda, MD 20892 USA. EM Rohinton@helix.nih.gov NR 13 TC 8 Z9 8 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0749-503X J9 YEAST JI Yeast PD DEC PY 2005 VL 22 IS 16 BP 1307 EP 1314 DI 10.1002/yea.1332 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology GA 005GA UT WOS:000234809400005 PM 16358314 ER PT J AU Tashiro, T Hasebe, T Kawamura, K Kikuyama, S AF Tashiro, Takahiro Hasebe, Takashi Kawamura, Kosuke Kikuyama, Sakae TI Proteome analysis of the bullfrog (Rana catesbeiana) red blood cells during metamorphic transition SO ZOOLOGICAL SCIENCE LA English DT Meeting Abstract C1 Waseda Univ, Sch Educ, Dept Biol, Shinjyuku Ku, Tokyo 1698050, Japan. Natl Inst Hlth, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ZOOLOGICAL SOC JAPAN PI TOKYO PA TOSHIN-BUILDING, HONGO 2-27-2, BUNKYO-KU, TOKYO, 113-0033, JAPAN SN 0289-0003 J9 ZOOL SCI JI Zool. Sci. PD DEC PY 2005 VL 22 IS 12 BP 1506 EP 1506 PG 1 WC Zoology SC Zoology GA 044DR UT WOS:000237653101569 ER PT J AU Zhu, DM Saul, AJ Miles, AP AF Zhu, DM Saul, AJ Miles, AP TI A quantitative slot blot assay for host cell protein impurities in recombinant proteins expressed in E-coli SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE E. coli host cell proteins; immunoblot; slot blot; vaccine; densitometry; Plasmodium falciparum MSP1; MSP1(42) ID LINKED-IMMUNOSORBENT-ASSAY; DNA; VACCINE AB Residual host cell protein impurities in recombinant proteins intended for human use must be accurately quantified to help establish their safety. We describe a novel means of host cell protein quantitation, in which a slot blot system was employed together with scanning laser densitometry to allow picogram, level sensitivity in detection of residual host cell proteins in unpurified fermentation products and final purified bulk samples. Two allelic forms of merozoite surface protein 1, a promising malaria vaccine candidate antigen currently undergoing evaluation in clinical trials, were expressed in E. coli as clinical grade proteins, refolded, and carried through several chromatographic purification steps. Several lots of these proteins were analyzed with this generic quantitative assay that uses rat polyclonal antibodies generated against soluble and insoluble E. coli proteins. The assay had a detection range of 6.1-1562 ng/mL, with a detection limit of 6.1 ng/mL, comparable to reported ELISA-based methods. This assay proved simple yet very sensitive and accurate, giving highly reproducible results. Thus it is suitable for evaluating host cell protein levels in clinical grade recombinant proteins expressed in E. coli. (c) 2005 Elsevier B.V. All rights reserved. C1 NIAID, Malaria Vaccine Dev Branch, NIH, Rockville, MD 20852 USA. RP Zhu, DM (reprint author), NIAID, Malaria Vaccine Dev Branch, NIH, 5640 Fishers Lane,Twinbrook 1 Room 1118, Rockville, MD 20852 USA. EM dzhu@niaid.nih.gov RI Saul, Allan/I-6968-2013 OI Saul, Allan/0000-0003-0665-4091 NR 14 TC 19 Z9 23 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD NOV 30 PY 2005 VL 306 IS 1-2 BP 40 EP 50 DI 10.1016/j.jim.2005.07.021 PG 11 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 996LD UT WOS:000234174500004 PM 16137696 ER PT J AU Sugase-Miyamoto, Y Richmond, BJ AF Sugase-Miyamoto, Y Richmond, BJ TI Neuronal signals in the monkey basolateral amygdala during reward schedules SO JOURNAL OF NEUROSCIENCE LA English DT Article DE emotion; arousal; motivation; temporal lobe; neurophysiology; visual cue ID ORBITAL PREFRONTAL CORTEX; INFEROTEMPORAL AREA TE; MACAQUE MONKEY; ORBITOFRONTAL CORTEX; RHESUS-MONKEY; PARAHIPPOCAMPAL CORTICES; DOPAMINE NEURONS; RHINAL CORTEX; ALERT MONKEY; RESPONSES AB The amygdala is critical for connecting emotional reactions with environmental events. We recorded neurons from the basolateral complex of two monkeys while they performed visually cued schedules of sequential color discrimination trials, with both valid and random cues. When the cues were valid, the visual cue, which was present throughout each trial, indicated how many trials remained to be successfully completed before a reward. Seventy- six percent of recorded neurons showed response selectivity, with the selectivity depending on some aspects of the current schedule. After a reward, when the monkeys knew that the upcoming cue would be valid, 88 of 246 (36%) neurons responded between schedules, seemingly anticipating the receiving information about the upcoming schedule length. When the cue appeared, 102 of 246 (41%) neurons became selective, at this point encoding information about whether the current trial was the only trial required or how many more trials are needed to obtain a reward. These cue-related responses had a median latency of 120 ms (just between the latencies in inferior temporal visual area TE and perirhinal cortex). When the monkey was releasing a touch bar to complete the trial correctly, 71 of 246 (29%) neurons responded, with responses in the rewarded trials being similar no matter which schedule was ending, thus being sensitive to the reward contingency. Finally, 39 of 246 (16%) neurons responded around the reward. We suggest that basolateral amygdala, by anticipating and then delineating the schedule and representing reward contingency, provide contextual information that is important for adjusting motivational level as a function of immediate behavior goals. C1 NIMH, Neuropsychol Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Natl Inst Adv Ind Sci & Technol, Neurosci Res Inst, Tsukuba, Ibaraki 3058568, Japan. RP Richmond, BJ (reprint author), NIMH, Neuropsychol Lab, NIH, Dept Hlth & Human Serv, Bldg 49,Room 1B80, Bethesda, MD 20892 USA. EM bjr@ln.nimh.nih.gov FU Intramural NIH HHS NR 51 TC 62 Z9 62 U1 3 U2 7 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 30 PY 2005 VL 25 IS 48 BP 11071 EP 11083 DI 10.1523/JNEUROSCI.1796-05.2005 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 988RD UT WOS:000233617500003 PM 16319307 ER PT J AU Yi-Brunozzi, HY Brabazon, DM Lener, D Le Grice, SFJ Marino, JP AF Yi-Brunozzi, HY Brabazon, DM Lener, D Le Grice, SFJ Marino, JP TI A ribose sugar conformational switch in the LTR-retrotransposon Ty3 polypurine tract-containing RNA/DNA hybrid SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID HIV-1 REVERSE-TRANSCRIPTASE; PYRIMIDINE-RICH STRANDS; DOT-RNA HYBRIDS; PURINE-RICH; DNA; INITIATION; SEQUENCE; DUPLEXES; SPECTRA C1 NCI, HIV Drug Resistance Program, Ft Detrick, MD 21702 USA. Loyola Coll, Dept Chem, Baltimore, MD 21210 USA. Univ Maryland, Inst Biotechnol, Ctr Adv Res Biotechnol, Rockville, MD 20850 USA. Natl Inst Stand & Technol, Rockville, MD 20850 USA. RP Le Grice, SFJ (reprint author), NCI, HIV Drug Resistance Program, Ft Detrick, MD 21702 USA. EM slegrice@ncifcrf.gov; marino@umbi.umd.edu FU Intramural NIH HHS; NCI NIH HHS [Z01 BC010492-03]; NIGMS NIH HHS [R01 GM059107, GM59107] NR 15 TC 11 Z9 11 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD NOV 30 PY 2005 VL 127 IS 47 BP 16344 EP 16345 DI 10.1021/ja0534203 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 988RH UT WOS:000233617900002 PM 16305191 ER PT J AU Grishaev, A Wu, J Trewhella, J Bax, A AF Grishaev, A Wu, J Trewhella, J Bax, A TI Refinement of multidomain protein structures by combination of solution small-angle X-ray scattering and NMR data SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID MAGNETIC-RESONANCE-SPECTROSCOPY; MOLECULAR-WEIGHT PROTEINS; BIOLOGICAL MACROMOLECULES; RESOLUTION STRUCTURE; QUATERNARY STRUCTURE; NUCLEIC-ACIDS; CRYSTALLIN; BIOMOLECULES; INFORMATION; ORIENTATION AB Determination of the 3D structures of multidomain proteins by solution NMR methods presents a number of unique challenges related to their larger molecular size and the usual scarcity of constraints at the interdomain interface, often resulting in a decrease in structural accuracy. In this respect, experimental information from small-angle scattering of X-ray radiation in solution (SAXS) presents a suitable complement to the NMR data, as it provides an independent constraint on the overall molecular shape. A computational procedure is described that allows incorporation of such SAXS data into the mainstream high-resolution macromolecular structure refinement. The method is illustrated for a two-domain 177-amino-acid protein, gamma S crystallin, using an experimental SAXS data set fitted at resolutions from similar to 200 angstrom to similar to 30 angstrom. Inclusion of these data during structure refinement decreases the backbone coordinate root-mean-square difference between the derived model and the high-resolution crystal structure of a 54% homologous gamma B crystallin from 1.96 +/- 0.07 angstrom to 1.31 +/- 0.04 angstrom. Combining SAXS data with NMR restraints can be accomplished at a moderate computational expense and is expected to become useful for multidomain proteins, multimeric assemblies, and tight macromolecular complexes. C1 NIDDK, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. Ohio State Univ, Dept Biochem, Columbus, OH 43210 USA. Univ Utah, Dept Chem, Salt Lake City, UT 84112 USA. RP Grishaev, A (reprint author), NIDDK, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. EM grishaev@speck.niddk.nih.gov; bax@nih.gov OI Trewhella, Jill/0000-0002-8555-6766 FU Intramural NIH HHS NR 44 TC 149 Z9 151 U1 1 U2 18 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD NOV 30 PY 2005 VL 127 IS 47 BP 16621 EP 16628 DI 10.1021/ja054342m PG 8 WC Chemistry, Multidisciplinary SC Chemistry GA 988RH UT WOS:000233617900062 PM 16305251 ER PT J AU Zahn, R Buechert, M Overmans, J Talazko, J Specht, K Ko, CW Thiel, T Kaufmann, R Dykierek, P Juengling, F Hull, M AF Zahn, R Buechert, M Overmans, J Talazko, J Specht, K Ko, CW Thiel, T Kaufmann, R Dykierek, P Juengling, F Hull, M TI Mapping of temporal and parietal cortex in progressive nonfluent aphasia and Alzheimer's disease using chemical shift imaging, voxel-based morphometry and positron emission tomography SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE aphasia; primary progressive; Alzheimer's disease; magnetic resonance spectroscopy; magnetic resonance imaging; temporal lobe ID MAGNETIC-RESONANCE SPECTROSCOPY; GRAY-MATTER LOSS; FRONTOTEMPORAL LOBAR DEGENERATION; SEMANTIC MEMORY IMPAIRMENT; MILD COGNITIVE IMPAIRMENT; ADULT HUMAN BRAINS; METABOLIC ABNORMALITIES; N-ACETYLASPARTATE; DEMENTIA; ATROPHY AB Little and controversial evidence is available from neuroimaging studies in progressive nonfluent aphasia (PNA). The goal of this study was to combine information from different imaging modalities in PNA compared with Alzheimer's disease (AD). Chemical shift imaging (CSI), voxel-based morphometry (VBM) and fluorodeoxyglucose positron emission tomography (FDG-PET) were used in 5 PNA, 10 AD patients and 10 normal subjects. Group comparisons revealed left anterior lateral temporal abnormalities (BA20/21) in PNA using CSI, VBM and PET in comparison to normal subjects. AD patients showed more limited hypometabolism within the same area. In addition left lateral parietal (BA40) abnormalities were demonstrated in our PNA as well as our AD group using PET and VBM (AD group only). Combining information from all imaging modalities on a single case basis revealed pathology within the left anterior lateral temporal and lateral parietal lobe both in PNA and AD. PNA and AD patients differed significantly, however, with respect to the frequency of medial temporal lobe and posterior cingulate/ precuneus involvement. Although our results might not be generalizable to all subgroups of PNA, we conclude that medial temporal and posterior cingulate/precurieus cortex pathology as assessed by CSI and VBM or PET distinguish PNA from AD, whereas lateral temporal and parietal areas are involved in both conditions. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Univ Freiburg, Dept Psychiat & Psychotherapy, D-79104 Freiburg, Germany. Univ Freiburg, Dept Radiol, Magnet Resonance Dev & Applicat Ctr, D-79104 Freiburg, Germany. Univ Freiburg, Dept Nucl Med, D-79104 Freiburg, Germany. Univ Bergen, Dept Biol & Med Psychol, N-5009 Bergen, Norway. Inselspital Bern, Dept Nucl Med, CH-3010 Bern, Switzerland. Univ Bern, CH-3010 Bern, Switzerland. RP Zahn, R (reprint author), NINDS, NIH, Cognit Neurosci Sect, Bldg 10,5C205,10 Ctr Dr,MSC 1440, Bethesda, MD 20892 USA. EM zahnr@ninds.nih.gov RI Zahn, Roland/C-4665-2008; Hull, Michael/F-2618-2012; Buechert, Martin/B-3107-2011; Juengling, Freimut/L-8071-2016; Specht, Karsten/C-3762-2009 OI Zahn, Roland/0000-0002-8447-1453; Buechert, Martin/0000-0001-5844-8711; Juengling, Freimut/0000-0002-2538-3074; NR 65 TC 25 Z9 25 U1 0 U2 6 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 NOV 30 PY 2005 VL 140 IS 2 BP 115 EP 131 DI 10.1016/j.pscychresns.2005.08.001 PG 17 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 987RH UT WOS:000233534500002 PM 16253483 ER PT J AU Dunn, RT Willis, MW Benson, BE Repella, JD Kimbrell, TA Ketter, TA Speer, AM Osuch, EA Post, RM AF Dunn, RT Willis, MW Benson, BE Repella, JD Kimbrell, TA Ketter, TA Speer, AM Osuch, EA Post, RM TI Preliminary findings of uncoupling of flow and metabolism in unipolar compared with bipolar affective illness and normal controls SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Review DE unipolar; bipolar; coupling; cerebral metabolism; cerebral blood flow ID CEREBRAL-BLOOD-FLOW; POSITRON EMISSION TOMOGRAPHY; SUBGENUAL PREFRONTAL CORTEX; COMPLEX PARTIAL SEIZURES; CENTRAL NERVOUS-SYSTEM; GLUCOSE-METABOLISM; MOOD-DISORDERS; OXYGEN UTILIZATION; OXIDATIVE-METABOLISM; RAT-BRAIN AB Cerebral metabolism (CMR for glucose or oxygen) and blood flow (CBF) have been reported to be closely correlated in healthy controls. Altered relationships between CMR and CBF have been reported in some brain disease states, but not others. This study examined relationships between global and regional CMRglu vs. CBF in controls and medication-free primary affective disorder patients. Nine bipolars, eight unipolars, and nine healthy controls had [O-15]-water positron emission tomography (PET) scans at rest, and [F-18]-fluorodeoxyglucose PET scans during an auditory continuous performance task. Patients had [O-15]-water and FDG PET scans in tandem the same day; controls had an average of 45 +/- 27 days between scans. Maps of regional coupling were constructed for each subject group. In controls and bipolars, global and virtually all regional correlation coefficients for CMRglu and CBF were positive, albeit more robustly so in controls. However, correlative relationships in unipolars were qualitatively different, such that global and most regional measures of flow and metabolism were not positively related. Unipolars had significantly fewer positive regional correlation coefficients than healthy controls and bipolars. These were significantly different from controls in orbital cortex, anterior cingulate, posterior cingulate, and posterior temporal cortex, and different from bipolars in pregenual anterior cingulate. In unipolars, the degree of flow-metabolism uncoupling was inversely correlated with Hamilton depression scores, indicating the severity of uncoupling was directly related to the severity of depression. These preliminary data suggest abnormal relationships between cerebral metabolism and blood flow globally and regionally in patients with unipolar depression that warrant replication and extension to potential pathophysiological implications. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Somerville, MA 02143 USA. NIMH, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA. Cambridge Hlth Alliance, Ctr Psychopharmacol Res, Somerville, MA 02143 USA. Little Rock Vet Affairs Med Ctr, Little Rock, AR USA. Stanford Univ, Stanford, CA 94305 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. RP Dunn, RT (reprint author), Harvard Univ, Sch Med, Somerville, MA 02143 USA. EM rdunn@challiance.org RI Osuch, Elizabeth/B-5009-2015 OI Osuch, Elizabeth/0000-0001-5946-1862 NR 135 TC 24 Z9 25 U1 0 U2 2 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 NOV 30 PY 2005 VL 140 IS 2 BP 181 EP 198 DI 10.1016/j.pscychresns.2005.07.005 PG 18 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 987RH UT WOS:000233534500007 PM 16257515 ER PT J AU Kitaguchi, T Swartz, KJ AF Kitaguchi, T Swartz, KJ TI An inhibitor of TRPV1 channels isolated from funnel web spider venom SO BIOCHEMISTRY LA English DT Article ID D-ASPARTATE RECEPTOR; AGELENOPSIS-APERTA SPIDER; CGMP-GATED CHANNEL; CAPSAICIN RECEPTOR; VANILLOID RECEPTOR; POTASSIUM CHANNEL; RUTHENIUM RED; CA2+ CHANNELS; ION-CHANNEL; K+ CHANNELS AB Capsaicin receptor channels (TRPV1) are nonselective cation channels that integrate multiple noxious stimuli in sensory neurons. In an effort to identify new inhibitors of these channels we screened a venom library for activity against TRPV1 channels and found robust inhibitory activity in venom from Agelenopsis aperta, a north American funnel web spider. Fractionation of the venom using reversed-phase HPLC resulted in the purification of two acylpolyamine toxins, AG489 and AG505, which inhibit TRPV1 channels from the extracellular side of the membrane. The activity of AG489 was characterized further, and the toxin was found to inhibit TRPV1 channels with a K-i of 0.3 mu M at -40 mV. Inhibition of TRPV1 channels by AG489 is strongly voltage-dependent, with relief of inhibition at positive voltages, consistent with the toxin inhibiting the channel through a pore-blocking mechanism. We used scanning mutagenesis throughout the TM5-TM6 linker, a region thought to form the outer pore of TRPV1 channels, to identify pore mutations that alter toxin affinity. Four mutants dramatically decrease toxin affinity and several mutants increase toxin affinity, consistent with the notion that the TM5-TM6 linker forms the outer vestibule of TRPV1 channels and that AG489 is a pore blocker. C1 NIH, Mol Physiol & Biophys Sect, Porter Neurosci Res Ctr, Natl Inst Neurol Disorders & Stroke, Bethesda, MD 20892 USA. RP Swartz, KJ (reprint author), NIH, Mol Physiol & Biophys Sect, Porter Neurosci Res Ctr, Natl Inst Neurol Disorders & Stroke, 35 Convent Dr,3B 215,MSC 3701, Bethesda, MD 20892 USA. EM swartzk@ninds.nih.gov RI Kitaguchi, Tetsuya/F-5260-2017 FU Intramural NIH HHS [ZIA NS002945-13] NR 44 TC 35 Z9 35 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 29 PY 2005 VL 44 IS 47 BP 15544 EP 15549 DI 10.1021/bi051494l PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 987KI UT WOS:000233516400015 PM 16300403 ER PT J AU Cai, JL Olson, JM Rao, MS Stanley, M Taylor, E Ni, HT AF Cai, JL Olson, JM Rao, MS Stanley, M Taylor, E Ni, HT TI Development of antibodies to human embryonic stem cell antigens SO BMC DEVELOPMENTAL BIOLOGY LA English DT Article ID MOUSE EMBRYOS; ES CELLS; DIFFERENTIATION; EXPRESSION; NANOG; PLURIPOTENCY; LINES AB Background: Using antibodies to specific protein antigens is the method of choice to assign and identify cell lineage through simultaneous analysis of surface molecules and intracellular markers. Embryonic stem cell research can be benefited from using antibodies specific to transcriptional factors/markers that contribute to the "stemness" phenotype or critical for cell lineage. Results: In this report, we have developed and validated antibodies (either monoclonal or polyclonal) specific to human embryonic stem cell antigens and early differentiation transcriptional factors/markers that are critical for cell differentiation into definite lineage. Conclusion: These antibodies enable stem cell biologists to conveniently identify stem cell characteristics and to quantitatively assess differentiation. C1 R&D Syst Inc, Stem Cell Dept, Minneapolis, MN 55413 USA. NIA, Stem Cell Biol Unit, Neurosci Lab, Baltimore, MD 21224 USA. RP Ni, HT (reprint author), R&D Syst Inc, Stem Cell Dept, 614 McKinley Pl, Minneapolis, MN 55413 USA. EM caiji@grc.nia.nih.gov; Judyo@rndsystems.com; raomah@grc.nia.nih.gov; stan0330@tc.umn.edu; evat@rndsystems.com; Jessien@rndsystems.com NR 13 TC 15 Z9 15 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-213X J9 BMC DEV BIOL JI BMC Dev. Biol. PD NOV 29 PY 2005 VL 5 AR 26 DI 10.1186/1471-213X-5-26 PG 7 WC Developmental Biology SC Developmental Biology GA 997WY UT WOS:000234280800001 PM 16316465 ER PT J AU Maloyan, A Sanbe, A Osinska, H Westfall, M Robinson, D Imahashi, K Murphy, E Robbins, J AF Maloyan, A Sanbe, A Osinska, H Westfall, M Robinson, D Imahashi, K Murphy, E Robbins, J TI Mitochondrial dysfunction and apoptosis underlie the pathogenic process in alpha-beta-crystallin desmin-related cardiomyopathy SO CIRCULATION LA English DT Article DE cardiomyopathy; heart diseases; heart failure; molecular biology ID B-CRYSTALLIN; MYOFIBRILLAR MYOPATHY; IN-VIVO; DISEASE; HEART; PROTEIN; DEATH; MICE; METABOLISM; HUNTINGTIN AB Background - Mitochondria and sarcomeres have a well- defined architectural relation that partially depends on the integrity of the cytoskeletal network. An R120G missense mutation in the small heat shock protein alpha- B- crystallin ( CryAB) causes desmin- related cardiomyopathy. Desmin- related cardiomyopathy is characterized by the formation of intracellular aggregates containing CryAB and desmin that are amyloid positive, and disease can be recapitulated in transgenic mice by cardiac- specific expression of the mutant protein. Methods and Results - To understand the resultant pathology, we explored the acute effects of R120G expression both in vitro and in vivo. In vitro, transfection of adult cardiomyocytes with R120G- expressing adenovirus resulted in altered contractile mechanics. In vivo, as the cytoskeletal network is disturbed but before deficits in organ function can be detected, alterations in mitochondrial organization and architecture occur, leading to a reduction in the maximal rate of oxygen consumption with substrates that utilize complex I activity, alterations in the permeability transition pore, and compromised inner membrane potential. Apoptotic pathways are subsequently activated, which eventually results in cardiomyocyte death, dilation, and heart failure. Conclusions - Cardiac chaperone dysfunction acutely leads to altered cardiomyocyte mechanics, perturbations in mitochondrial- sarcomere architecture, and deficits in mitochondrial function, which can result in activation of apoptosis and heart failure. C1 Cincinnati Childrens Hosp, Div Mol Cardiovasc Biol, Cincinnati, OH 45229 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Natl Inst Environm Hlth Sci, Cardiac Surg Sect, Res Triangle Pk, NC USA. Natl Inst Environm Hlth Sci, Lab Signal Transduct, Res Triangle Pk, NC USA. RP Robbins, J (reprint author), Cincinnati Childrens Hosp, Div Mol Cardiovasc Biol, 3333 Burnet Ave, Cincinnati, OH 45229 USA. EM jeff.robbins@cchmc.org FU NHLBI NIH HHS [P01 HL069779, R01 HL066157, T32 HL007825, R01 HL056370, P50 HL074728, P50 HL052318] NR 33 TC 105 Z9 109 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 29 PY 2005 VL 112 IS 22 BP 3451 EP 3461 DI 10.1161/CIRCULATIONHA.105.572552 PG 11 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 988AC UT WOS:000233558300015 PM 16316967 ER EF