FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Sohn, S Kim, W Comeau, DC Wilbur, WJ AF Sohn, Sunghwan Kim, Won Comeau, Donald C. Wilbur, W. John TI Optimal training sets for Bayesian prediction of MeSH (R) assignment SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID CLASSIFIERS; TEXT AB Objectives: The aim of this study was to improve naive Bayes prediction of Medical Subject Headings (MeSH) assignment to documents using optimal training sets found by an active learning inspired method. Design: The authors selected 20 MeSH terms whose occurrences cover a range of frequencies. For each MeSH term, they found an optimal training set, a subset of the whole training set. An optimal training set consists of all documents including a given MeSH term (C-1 class) and those documents not including a given MeSH term (C-1 class) that are closest to the C-1 class. These small sets were used to predict MeSH assignments in the MEDLINE (R) database. Measurements: Average precision was used to compare MeSH assignment using the naive Bayes learner trained on the whole training set, optimal sets, and random sets. The authors compared 95% lower confidence limits of average precisions of naive Bayes with upper bounds for average precisions of a K-nearest neighbor (KNN) classifier. Results: For all 20 MeSH assignments, the optimal training sets produced nearly 200% improvement over use of the whole training sets. In 17 of those MeSH assignments, naive Bayes using optimal training sets was statistically better than a KNN. In 15 of those, optimal training sets performed better than optimized feature selection. Overall naive Bayes averaged 14% better than a KNN for all 20 MeSH assignments. Using these optimal sets with another classifier, C-modified least squares (CMLS), produced an additional 6% improvement over naive Bayes. Conclusion: Using a smaller optimal training set greatly improved learning with naive Bayes. The performance is superior to a KNN. The small training set can be used with other sophisticated learning methods, such as CMLS, where using the whole training set would not be feasible. C1 [Sohn, Sunghwan; Kim, Won; Comeau, Donald C.; Wilbur, W. John] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Sohn, S (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 38A,6N611C,8600 Rockville Pike, Bethesda, MD 20894 USA. EM sohn@ncbi.nlm.nih.gov FU Intramural NIH HHS NR 36 TC 21 Z9 22 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD JUL-AUG PY 2008 VL 15 IS 4 BP 546 EP 553 DI 10.1197/jamia.M2431 PG 8 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 328JM UT WOS:000257794700019 PM 18436913 ER PT J AU Leroy, G Miller, T Rosemblat, G Browne, A AF Leroy, Gondy Miller, Trudi Rosemblat, Graciela Browne, Allen TI A balanced approach to health information evaluation: A vocabulary-based naive Bayes classifier and readability formulas SO JOURNAL OF THE AMERICAN SOCIETY FOR INFORMATION SCIENCE AND TECHNOLOGY LA English DT Article ID CANCER INFORMATION; INTERNET; LITERACY; INSTRUMENTS; QUALITY; CARE; WEB AB Since millions seek health information online, it is vital for this information to be comprehensible. Most studies use readability formulas, which ignore vocabulary, and conclude that online health information is too difficult. We developed a vocabularly-based, naive Bayes classifier to distinguish between three difficulty levels in text. It proved 98% accurate in a 250-document evaluation. We compared our classifier with readability formulas for 90 new documents with different origins and asked representative human evaluators, an expert and a consumer, to judge each document. Average readability grade levels for educational and commercial pages was 10th grade or higher, too difficult according to current literature. In contrast, the classifier showed that 70-90% of these pages were written at an intermediate, appropriate level indicating that vocabulary usage is frequently appropriate in text considered too difficult by readability formula evaluations. The expert considered the pages more difficult for a consumer than the consumer did. C1 [Leroy, Gondy; Miller, Trudi] Claremont Grad Univ, Sch Informat Syst & Technol, Claremont, CA 91730 USA. [Rosemblat, Graciela; Browne, Allen] US Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA. RP Leroy, G (reprint author), Claremont Grad Univ, Sch Informat Syst & Technol, 130 E 9th St, Claremont, CA 91730 USA. EM Gondy.Leroy@cgu.edu; Trudi.Miller@cgu.edu; grosemblat@mail.nih.gov; browne@nlm.nih.gov NR 43 TC 9 Z9 9 U1 2 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1532-2882 J9 J AM SOC INF SCI TEC JI J. Am. Soc. Inf. Sci. Technol. PD JUL PY 2008 VL 59 IS 9 BP 1409 EP 1419 DI 10.1002/asi.20837 PG 11 WC Computer Science, Information Systems; Information Science & Library Science SC Computer Science; Information Science & Library Science GA 319MQ UT WOS:000257168200004 ER PT J AU Lee, J Musyimi, HK Soper, SA Murray, KK AF Lee, Jeonghoon Musyimi, Harrison K. Soper, Steven A. Murray, Kermit K. TI Development of an automated digestion and droplet deposition microfluidic chip for MALDI-TOF MS SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Article ID DESORPTION/IONIZATION MASS-SPECTROMETRY; MONOLITHIC ENZYMATIC MICROREACTOR; CONTINUOUS SAMPLE DEPOSITION; AQUEOUS SOLVENT SYSTEMS; ROTATING BALL INLET; ON-A-CHIP; PROTEIN IDENTIFICATION; CAPILLARY-ELECTROPHORESIS; LIQUID-CHROMATOGRAPHY; HIGH-RESOLUTION AB An automated proteolytic digestion bioreactor and droplet deposition system was constructed with a plastic microfluidic device for off-line interfacing to matrix assisted laser desorption/ ionization time-of-flight mass spectrometry (MALDI-TOF MS). The microfluidic chips were fabricated in poly(methyl methacrylate) (PMMA), using a micromilling machine and incorporated a bioreactor, which was 100 ttm wide, 100 /im deep, and possessed a 4 cm effective channel length (400 nL volume). The chip was operated by pressure-driven flow and mounted on a robotic fraction collector system. The PMMA bioreactor contained surface immobilized trypsin, which was covalently attached to the UV-modified PMMA surface using coupling reagents N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDQ and hydroxysulfosuccinimide (sulfo-NHS). The digested peptides were mixed with a MALDI matrix on-chip and deposited as discrete spots on MALDI targets. The bioreactor provided efficient digestion of a test protein, cytochrome c, at a flow rate of I pL/min, producing a reaction time of -24 s to give adequate sequence coverage for protein identification. Other proteins were also evaluated using this solid-phase bioreactor. The efficiency of digestion was evaluated by monitoring the sequence coverage, which was 64%, 35%, 58%, and 47% for cytochrome c, bovine serum albumin (BSA), myoglobin, and phosphorylase b, respectively. C1 [Lee, Jeonghoon; Soper, Steven A.; Murray, Kermit K.] Louisiana State Univ, Dept Chem, Baton Rouge, LA 70802 USA. [Musyimi, Harrison K.] NIA, NIH, Baltimore, MD 21224 USA. [Soper, Steven A.] Louisiana State Univ, Dept Mech Engn, Baton Rouge, LA 70802 USA. [Soper, Steven A.] Louisiana State Univ, Ctr BioModular Multi Scale Syst, Baton Rouge, LA 70802 USA. RP Murray, KK (reprint author), Louisiana State Univ, Dept Chem, 232 Choppin Hall, Baton Rouge, LA 70802 USA. EM kkmurray@lsu.edu OI Murray, Kermit/0000-0002-4976-2263 NR 58 TC 36 Z9 36 U1 2 U2 21 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 JUL PY 2008 VL 19 IS 7 BP 964 EP 972 DI 10.1016/j.jasms.2008.03.015 PG 9 WC Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA 329LW UT WOS:000257870100008 PM 18479934 ER PT J AU Liu, MC Liang, YD Chigurupati, S Lathia, JD Pletnikov, M Sun, ZL Crow, M Ross, CA Mattson, MP Rabb, H AF Liu, Manchang Liang, Yideng Chigurupati, Srinivasulu Lathia, Justin D. Pletnikov, Mikhail Sun, Zhaoli Crow, Michael Ross, Christopher A. Mattson, Mark P. Rabb, Hamid TI Acute kidney injury leads to inflammation and functional changes in the brain SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID ACUTE-RENAL-FAILURE; NEUROLOGICAL COMPLICATIONS; UREMIC ENCEPHALOPATHY; BILATERAL-NEPHRECTOMY; MOLECULAR MECHANISMS; ISCHEMIA-REPERFUSION; BEHAVIORAL DEFICITS; G-CSF; HEMODIALYSIS; METABOLISM AB Although neurologic sequelae of acute kidney injury (AKI) are well described, the pathogenesis of acute uremic encephalopathy is poorly understood. This study examined the short-term effect of ischemic AKI on inflammatory and functional changes of the brain in mice by inducing bilateral renal ischemia for 60 min and studying the brains 24 h later. Compared with sham mice, mice with AKI had increased neuronal pyknosis and microgliosis in the brain. AKI also led to increased levels of the proinflammatory chemokines keratinocyte-derived chemoattractant and G-CSF in the cerebral cortex and hippocampus and increased expression of glial fibrillary acidic protein in astrocytes in the cortex and corpus callosum. In addition, extravasation of Evans blue dye into the brain suggested that the blood-brain barrier was disrupted in mice with AKI. Because liver failure also leads to encephalopathy, ischemic liver injury was induced in mice with normal renal function; neuronal pyknosis and glial fibrillary acidic protein expression were not increased, suggesting differential effects on the brain depending on the organ injured. For evaluation of the effects of AKI on brain function, locomotor activity was studied using an open field test. Mice subjected to renal ischemia or bilateral nephrectomy had moderate to severe declines in locomotor activity compared with sham-operated mice. These data demonstrate that severe ischemic AKI induces inflammation and functional changes in the brain. Targeting these pathways could reduce morbidity and mortality in critically ill patients with severe AKI. C1 [Liu, Manchang; Crow, Michael; Rabb, Hamid] Johns Hopkins Univ, Sch Med, Div Nephrol, Dept Med, Baltimore, MD 21205 USA. [Liang, Yideng; Pletnikov, Mikhail; Ross, Christopher A.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Sun, Zhaoli] Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21205 USA. [Chigurupati, Srinivasulu; Lathia, Justin D.; Mattson, Mark P.] Natl Inst Aging Intramural Res Program, Neurosci Lab, Baltimore, MD USA. RP Liu, MC (reprint author), Johns Hopkins Univ, Sch Med, Div Nephrol, Dept Med, 720 Rutland Ave, Baltimore, MD 21205 USA. EM manchang@jhmi.edu RI Mattson, Mark/F-6038-2012 FU Intramural NIH HHS [Z01 AG000313-07]; NHLBI NIH HHS [R01 HL073944, P0 HL073944] NR 43 TC 121 Z9 133 U1 2 U2 7 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JUL PY 2008 VL 19 IS 7 BP 1360 EP 1370 DI 10.1681/ASN.2007080901 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 320VG UT WOS:000257262600018 PM 18385426 ER PT J AU Rankin, JA Grefsheim, SF Canto, CC AF Rankin, Jocelyn A. Grefsheim, Suzanne F. Canto, Candace C. TI The emerging informationist specialty: a systematic review of the literature SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Review ID HEALTH-SCIENCES LIBRARIANS; BIOINFORMATICS SERVICES; CLINICAL INFORMATICIST; BIOMEDICAL-RESEARCH; MEDICAL LIBRARIAN; DECISION-MAKING; CARE; KNOWLEDGE; PROGRAM; SUPPORT AB Purpose: A systematic literature review was conducted to synthesize what is known about informationists, highlight program models, and suggest areas for future research. Methods: Articles retrieved through database searching were reviewed for relevance. Informationist case reports were identified and coded according to an attributes checklist. Data from other retained publications were synthesized under broad themes. The few research studies found were reviewed for level of evidence. Results: Of 113 papers reviewed, the study identified 7 classic and 8 emerging informationist programs. Two major models are apparent, clinical and research, with priorities differing according to program maturity. The literature synthesis also brought together current thinking about informationist qualifications; practice roles; setting characteristics; education and training; organizational, programmatic, and service provider success factors; and challenges and barriers. Program outcomes to date are reported, and future research topics suggested. Specific findings will assist informationist program planners. Conclusions: While the informationist concept remains in the early adopter stage, it appears that domain knowledge, continuous learning, and embedding (working in context) are essential to success. The need for librarians to transition to greater specialization and libraries to emphasize customized service was underscored. A research agenda focused on information management, dissemination, behaviors, and economics is proposed. C1 [Rankin, Jocelyn A.] CDC Informat Ctr, Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. [Grefsheim, Suzanne F.; Canto, Candace C.] NIH, Div Lib Serv, Bethesda, MD 20892 USA. RP Rankin, JA (reprint author), CDC Informat Ctr, Ctr Dis Control & Prevent, 1600 Clifton Rd,Mailstop C04, Atlanta, GA 30333 USA. EM jrankin@cdc.gov; grefshes@nih.gov; cantoc@nih.gov NR 130 TC 25 Z9 27 U1 8 U2 62 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 1536-5050 J9 J MED LIBR ASSOC JI J. Med. Libr. Assoc. PD JUL PY 2008 VL 96 IS 3 BP 194 EP 206 DI 10.3163/1536-5050.96.3.005 PG 13 WC Information Science & Library Science SC Information Science & Library Science GA 340JB UT WOS:000258640800005 PM 18654656 ER PT J AU Blaufox, AD Sleeper, LA Bradley, DJ Breitbart, RE Hordof, A Kanter, RJ Stephenson, EA Stylianou, M Vetter, VL Saul, JP AF Blaufox, Andrew D. Sleeper, Lynn A. Bradley, David J. Breitbart, Roger E. Hordof, Allan Kanter, Ronald J. Stephenson, Elizabeth A. Stylianou, Mario Vetter, Victoria L. Saul, J. Philip CA Pediat Heart Network Investigators TI Functional status, heart rate, and rhythm abnormalities in 521 Fontan patients 6 to 18 years of age SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID SINUS NODE DYSFUNCTION; CAVOPULMONARY CONNECTION; ATRIAL TACHYARRHYTHMIAS; OPERATION; ARRHYTHMIA; EXERCISE; OUTCOMES; CHILDREN; DISEASE; ADULTS AB Objectives: Our objective was to determine the relationship between functional outcome and abnormalities of heart rate and rhythm after the Fontan operation. Methods: The National Heart, Lung, and Blood Institute Pediatric Heart Network conducted a cross-sectional analysis of patients who had undergone a Fontan procedure at the 7 network centers. Analysis was based on 521 patients with an electrocardiogram (n = 509) and/or bicycle exercise test ( n 5 404). The Child Health Questionnaire parent report and the oxygen consumption at the anaerobic threshold were used as markers of functional outcome. Results: Various Fontan procedures had been performed: intracardiac lateral tunnel (59%), atriopulmonary connection (14%), extracardiac later tunnel (13%), and extracardiac conduit (11%). Prior volume unloading surgery was performed in 389 patients: bidirectional Glenn (70%) and hemi-Fontan (26%). A history of atrial tachycardia was noted in 9.6% of patients and 13.1% of patients had a pacemaker. Lower resting heart rate and higher peak heart rate were each weakly associated with better functional status, as defined by higher anaerobic threshold (R = -0.18, P = .004, and R = 0.16, P = .007, respectively) and higher Child Health scores for physical functioning (R = -0.18, P < .001, and R = 0.17, P = .002, respectively). Higher anaerobic threshold was also independently associated with younger age and an abnormal P-axis. Resting bradycardia was not associated with anaerobic threshold or Child Health scores. Conclusions: In pediatric patients (6-18 years) after the Fontan procedure, a lower resting heart rate and a higher peak heart rate are each independently associated with better physical function as measured by anaerobic threshold and Child Health scores. However, these correlations are weak, suggesting that other, nonrhythm and nonrate, factors may have a greater impact on the functional outcome of pediatric patients after the Fontan operation. C1 [Blaufox, Andrew D.; Saul, J. Philip] Med Univ S Carolina, Charleston, SC 29425 USA. [Sleeper, Lynn A.] New England Res Inst, Watertown, MA 02172 USA. [Bradley, David J.] Univ Utah, Primary Childrens Med Ctr, Salt Lake City, UT USA. [Breitbart, Roger E.] Childrens Hosp Boston, Boston, MA USA. [Breitbart, Roger E.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Hordof, Allan] Columbia Univ, Childrens Hosp, New York, NY USA. [Kanter, Ronald J.] Duke Univ, Sch Med, Durham, NC USA. [Stephenson, Elizabeth A.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Stylianou, Mario] NHLBI, Bethesda, MD 20892 USA. [Vetter, Victoria L.] Childrens Hosp, Philadelphia, PA 19104 USA. RP Blaufox, AD (reprint author), Schneider Childrens Hosp, Childrens Heart Ctr, 269-01 176th Ave, New Hyde Pk, NY 11040 USA. EM Ablaufox@nshs.edu OI Bradley, David/0000-0003-3607-3423 FU NHLBI NIH HHS [U01 HL068269, U01 HL068269-01, U01 HL068270, U01 HL068270-01, U01 HL068279, U01 HL068279-01, U01 HL068281, U01 HL068281-01, U01 HL068285, U01 HL068285-01, U01 HL068288, U01 HL068288-01, U01 HL068290, U01 HL068290-06, U01 HL068292, U01 HL068292-01, U10 HL109778] NR 26 TC 34 Z9 35 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD JUL PY 2008 VL 136 IS 1 BP 100 EP U87 DI 10.1016/j.jtcvs.2007.12.024 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 322OT UT WOS:000257385900016 PM 18603061 ER PT J AU Johnson, A Sudarshan, S Liu, J Linehan, WM Pinto, PA Bratslavsky, G AF Johnson, Aaron Sudarshan, Sunil Liu, Jack Linehan, W. Marston Pinto, Peter A. Bratslavsky, Gennady TI Feasibility and outcomes of repeat partial nephrectomy SO JOURNAL OF UROLOGY LA English DT Article DE nephrectomy; complications; treatment outcome ID RENAL-CELL CARCINOMA; NEPHRON-SPARING SURGERY; RADIO-FREQUENCY ABLATION; HIPPEL-LINDAU-DISEASE; RADIOFREQUENCY ABLATION; TUMOR SIZE; CANCER AB Purpose: Despite the proven efficacy of nephron sparing surgery, patients with hereditary renal cancer remain at risk for tumor recurrence. Management options for recurrent tumors include completion nephrectomy, ablation and repeat partial nephrectomy. We examine the feasibility and outcomes of repeat partial nephrectomy performed on the same renal unit. Materials and Methods: We retrospectively reviewed the records of 51 attempted repeat partial nephrectomy procedures in 47 patients from 1992 to 2006. Demographic information as well as intraoperative, perioperative and renal functional outcome data were collected. Comparison of preoperative and postoperative renal function was performed using the 2-tailed t test. Results: Major perioperative complications or reoperations occurred in 10 of 51 (19.6%) cases that included 1 perioperative mortality (1.9%). In cases of successful repeat partial nephrectomy there was a statistically significant increase in postoperative serum creatinine (1.35 vs 1.16 mg/dl, p < 0.05), and a significant decrease in creatinine clearance (84.6 vs 95.3 ml per minute, p = 0.05) and renogram split function (52.3% vs 54.8%, p < 0.05). Two patients required long-term hemodialysis (3.9%). Of the 51 renal units 10 (19.6%) required subsequent operations for additional local recurrence or de novo tumor formations with a median time to subsequent surgery of 50 months. Of 47 patients 46 are alive at a median followup of 56 months. Conclusions: Repeat partial nephrectomy is technically feasible. Although there is a statistically significant decrease in postoperative renal functional studies, most patients retained sufficient function to avoid hemodialysis. Repeat partial nephrectomy may provide acceptable oncological control despite the anticipated development of locally recurrent or de novo tumors. C1 [Johnson, Aaron; Sudarshan, Sunil; Liu, Jack; Linehan, W. Marston; Pinto, Peter A.; Bratslavsky, Gennady] NIH, Urol Oncol Branch, Ctr Canc Res, NCI,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Bratslavsky, G (reprint author), NIH, Urol Oncol Branch, Ctr Canc Res, NCI,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM bratslag@mail.nih.gov FU Intramural NIH HHS [Z01 SC006659-25] NR 20 TC 37 Z9 38 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JUL PY 2008 VL 180 IS 1 BP 89 EP 93 DI 10.1016/j.juro.2008.03.030 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 312BK UT WOS:000256643900019 PM 18485404 ER PT J AU Brubaker, L Richter, HE Visco, A Mahajan, S Nygaard, I Braun, TM Barber, MD Menefee, S Schaffer, J Weber, AM Wei, J AF Brubaker, Linda Richter, Holly E. Visco, Anthony Mahajan, Sangeeta Nygaard, Ingrid Braun, Thomas M. Barber, Matthew D. Menefee, Shawn Schaffer, Joseph Weber, Anne M. Wei, John CA Pelvic Floor Disorders Network TI Refractory idiopathic urge urinary incontinence and botulinum A injection SO JOURNAL OF UROLOGY LA English DT Article DE urinary bladder; overactive; questionnaires; botulinum toxin type A; urinary incontinence; female ID NEUROGENIC DETRUSOR OVERACTIVITY; TOXIN INJECTIONS; EXPERIENCE; BLADDER; SYMPTOMS; EFFICACY; WOMEN AB Purpose: We compared 200 U intradetrusor botulinum toxin A vs placebo in women with refractory idiopathic urge incontinence. Materials and Methods: This institutional review board approved, multicenter registered trial randomized women with refractory urge incontinence, detrusor overactivity incontinence and 6 or greater urge incontinence episodes in 3 days to botulinum toxin A or placebo at a 2:1 ratio. Refractory was defined as inadequate symptom control after 2 or more attempts at pharmacotherapy and 1 or more other first line therapies for detrusor overactivity incontinence. The primary outcome measure was time to failure, as evidenced by a Patient Global Impression of Improvement score of 4 or greater at least 2 months after injection, or changes in treatment (initiation or increase) at any time after injection. Safety data, including increased post-void residual volume, defined as more than 200 ml irrespective of symptoms, was obtained at specified time points. Results: Approximately 60% of the women who received botulinum toxin A had a clinical response based on the Patient Global Impression of Improvement. The median duration of their responses was 373 days, significantly longer than the 62 days or less for placebo (p < 0.0001). In the botulinum toxin A group increased post-void residual urine (12 of 28 women or 43%) and urinary tract infection in those with increased post-void residual urine (9 of 12 or 75%) exceeded expected ranges. Further injections were stopped after 43 patients were randomized, including 28 to botulinum toxin A and 15 to placebo. Conclusions: Local injection of 200 U botulinum toxin A was an effective and durable treatment for refractory overactive bladder. However, a transient post-void residual urine increase was experienced in 43% of patients. Botulinum toxin A for idiopathic overactive bladder is still under investigation. C1 Loyola Univ, Med Ctr, Dept Urol, Maywood, IL 60153 USA. Loyola Univ, Med Ctr, Dept Obstet & Gynecol, Maywood, IL 60153 USA. Univ Alabama, Dept Obstet, Birmingham, AL USA. Univ Alabama, Dept Gynecol, Birmingham, AL USA. Univ N Carolina, Chapel Hill, NC USA. Univ Utah, Salt Lake City, UT USA. Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. Cleveland Clin, Obstet Gynecol & Womens Hlth Inst, Cleveland, OH 44106 USA. Case Western Reserve Univ, Dept Obstet & Gynecol, Cleveland, OH 44106 USA. Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA. Univ Calif San Diego, Dept Reprod Med, San Diego, CA 92103 USA. Kaiser Permanente, Dept Obstet & Gynecol, San Diego, CA USA. NICHHD, Contracept & Reprod Hlth Branch, Populat Res Ctr, NIH, Bethesda, MD 20892 USA. RP Brubaker, L (reprint author), Loyola Univ, Med Ctr, Dept Obstet & Gynecol, 2160 S 1st Ave, Maywood, IL 60153 USA. EM Lbrubaker@lumc.edu FU NICHD NIH HHS [1U10 HD54215, 1U10 HD54136, 1U10 HD54214, 1U10 HD54241, 2U01 HD41249, 2U10 HD41250, 2U10 HD41261, 2U10 HD41267, U01 HD041249, U10 HD041248, U10 HD041250, U10 HD041250-06, U10 HD041261, U10 HD041267, U10 HD054136, U10 HD054214, U10 HD054215, U10 HD054241] NR 20 TC 151 Z9 153 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JUL PY 2008 VL 180 IS 1 BP 217 EP 222 DI 10.1016/j.juro.2008.03.028 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 312BK UT WOS:000256643900057 PM 18499184 ER PT J AU Starost, MF Burkholder, TH AF Starost, Matthew F. Burkholder, Tanya H. TI Acalculous and clostridial cholecystitis in a pig SO JOURNAL OF VETERINARY DIAGNOSTIC INVESTIGATION LA English DT Article DE Acalculous cholecystitis; Clostridium perfringens; gallbladder; pigs ID DUODENAL MOTILITY ACTIVITY AB A 21-month-old domestic Hanford pig (Sus scrofa domestica) in a 1-year Study for experimental myocardial infarction was euthanized at the end of the Study. One week earlier, the animal had symptoms and elevated clinical chemistry results Suggestive of hepatobiliary disease, which resolved after medical therapy. At necropsy, the gallbladder was markedly enlarged, discolored, and had a thickened wall. Within the gallbladder, there was abundant friable green-brown material. A Culture of the gallbladder luminal material yielded Clostridium perfringens type A. Histopathology of the gallbladder demonstrated multifocal areas of necrosis of varying depths, admixed with an inflammatory infiltrate that was also observed on the serosa and within the associated adipose tissue. Luminal material was composed of cellular debris and bile sludge admixed with numerous bacterial rods. Smooth-muscle hypertrophy Of numerous small arterioles with narrowed lumina was observed in the gallbladder. A diagnosis of acalculous cholecystitis presumably because of ischemia of the gallbladder with secondary clostridial infection was made. To the authors' knowledge, this is the first reported case of acalculous cholecystitis with evidence of vascular compromise in a pig, as well as cholecystitis secondarily attributed to C. perfringens type A. C1 [Starost, Matthew F.; Burkholder, Tanya H.] NIH, Div Vet Resources, Off Resource Serv, Bethesda, MD 20892 USA. RP Starost, MF (reprint author), NIH, Div Vet Resources, Off Resource Serv, Bldg 28A,Room 106,9000 Rockville Pike, Bethesda, MD 20892 USA. EM starostm@mail.nih.gov FU Intramural Research Program of the National Institutes of Health, Office of Research Services FX The authors would like to thank Jorge Chavez, Annie Merriweather, and Frances Benedetti for technical assistance. This work was supported by the Intramural Research Program of the National Institutes of Health, Office of Research Services. NR 18 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC VETERINARY LABORATORY DIAGNOSTICIANS INC PI TURLOCK PA PO BOX 1522, TURLOCK, CA 95381 USA SN 1040-6387 J9 J VET DIAGN INVEST JI J. Vet. Diagn. Invest. PD JUL PY 2008 VL 20 IS 4 BP 527 EP 530 PG 4 WC Veterinary Sciences SC Veterinary Sciences GA 389ZW UT WOS:000262135100022 PM 18599865 ER PT J AU Yan, YH Kozak, CA AF Yan, Yuhe Kozak, Christine A. TI Novel postentry resistance to AKV ecotropic mouse gammaretroviruses in the African pygmy mouse, Mus minutoides SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; LOCUS AFFECTING RESISTANCE; HOST-RANGE RESTRICTIONS; CELL-CULTURES; RETROVIRUS RESTRICTION; ENDOGENOUS RETROVIRUS; FV1; GENE; TRIM5-ALPHA; INFECTION AB Cells of Mus minutoides, an African pygmy mouse of the subgenus Nannomys, are susceptible to ecotropic Moloney and Friend mouse leukemia viruses (MLVs) but not to AK-V-type MLVs. Transfected NM139 ferret cells expressing the mCAT-1 cell surface receptor, with the minCAT-1 substitutions K222Q and V233L, did not restrict AKV MLV. The resistance of M. minutoides cells to AKV MLV was not relieved by inhibitors of glycosylation or by the introduction of NIH 3T3 mCAT-1. Resistance is thus not mediated by receptor sequence variation, expression level, or glycosylation. M. minutoides cells are also infectible with LacZ pseudotypes having AKV Env and Moloney MLV (MoMLV) Gag proteins, further indicating that AKV Env sequence variations do not contribute to the observed block. The pattern of virus resistance in M. minutoides differs from that of the known variants of the Fv1 postentry resistance gene; M. minutoides is equally resistant to N-, B-, and NR-tropic AKV viruses and is equally susceptible to NR- and NB-tropic Friend MLVs. This novel resistance blocks replication before reverse transcription, whereas Fv1 generally restricts replication after reverse transcription; M. minutoides cells produce 2-long-terminal-repeat viral DNA circles and linear viral DNA after infection with MoMLV but not with AKV MLV. Analysis of MoMLV-AKV MLV chimeras determined that the target of resistance is in the virus capsid gene. Mutagenesis demonstrated that restriction is mediated by two amino acid substitutions, H117L and A110R; substitutions at these sites can also be targeted by the resistance genes Fv1 and TRIM5 alpha. M. minutoides cells thus have a novel postentry resistance to AKV MLVs. C1 [Kozak, Christine A.] NIAID, NIH, LMM, Bethesda, MD 20892 USA. RP Kozak, CA (reprint author), NIAID, NIH, LMM, Bldg 4,Room 329,4 Ctr Dr,MSC 0460, Bethesda, MD 20892 USA. EM ckozak@niaid.nih.gov FU Intramural NIH HHS [Z01 AI000300-26] NR 50 TC 7 Z9 7 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 JUL PY 2008 VL 82 IS 13 BP 6120 EP 6129 DI 10.1128/JVI.00202-08 PG 10 WC Virology SC Virology GA 316KC UT WOS:000256947300004 PM 18417580 ER PT J AU Shi, W Huang, Y Sutton-Smith, M Tissot, B Panico, M Morris, HR Dell, A Haslam, SM Boyington, J Graham, BS Yang, ZY Nabell, GJ AF Shi, Wei Huang, Yue Sutton-Smith, Mark Tissot, Berangere Panico, Maria Morris, Howard R. Dell, Anne Haslam, Stuart M. Boyington, Jeffrey Graham, Barney S. Yang, Zhi-Yong Nabell, Gary J. TI A filovirus-unique region of Ebola virus nucleoprotein confers aberrant migration and mediates its incorporation into virions SO JOURNAL OF VIROLOGY LA English DT Article ID INTRINSICALLY UNSTRUCTURED PROTEINS; MARBURG VIRUS; VP40; GLYCOPROTEIN; ASSOCIATION; PREDICTION; PARTICLES; DISORDER; SEQUENCE; CELLS AB The Ebola virus nucleoprotein (NP) is an essential component of the nucleocapsid, required for filovirus particle formation and replication. Together with virion protein 35 (VP35) and VP24, this gene product gives rise to the filamentous nucleocapsid within transfected cells. Ebola virus NP migrates aberrantly, with an apparent molecular mass of 115 kDa, although it is predicted to encode an similar to 85-kDa protein. In this report, we show that two domains of this protein determine this aberrant migration and that this region mediates its incorporation into virions. These regions, amino acids 439 to 492 and amino acids 589 to 739, alter the mobility of Ebola virus NP by sodium dodecyl sulfate-polyacrylamide gel electrophoresis by 5 and 15 kDa, respectively, and confer similar effects on a heterologous protein, LacZ, in a position-independent fashion. Furthermore, when coexpressed with VP40, VP35, and VP24, this region mediated incorporation of NP into released viruslike particles. When fused to chimeric paramyxovirus NPs derived from measles or respiratory syncytial virus, this domain directed these proteins into the viruslike particle. The COOH-terminal NP domain comprises a conserved highly acidic region of NP with predicted disorder, distinguishing Ebola virus NPs from paramyxovirus NPs. The acidic character of this domain is likely responsible for its aberrant biochemical properties. These findings demonstrate that this region is essential for the assembly of the filamentous nucleocapsids that give rise to filoviruses. C1 [Shi, Wei; Huang, Yue; Boyington, Jeffrey; Graham, Barney S.; Yang, Zhi-Yong; Nabell, Gary J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Sutton-Smith, Mark; Tissot, Berangere; Panico, Maria; Morris, Howard R.; Dell, Anne; Haslam, Stuart M.] Univ London Imperial Coll Sci Technol & Med, Fac Nat Sci, Div Mol Biosci, London SW7 2AZ, England. [Morris, Howard R.] M Scan Ltd, Fishponds Close RG41 2TZ, Wokingham, England. RP Nabell, GJ (reprint author), NIAID, Vaccine Res Ctr, NIH, Bldg 40,Rm 4502,MSC-3005,40 Convent Dr, Bethesda, MD 20892 USA. EM gnabel@nih.gov FU Biotechnology and Biological Sciences Research Council; Intramural NIH HHS; Wellcome Trust NR 33 TC 22 Z9 26 U1 1 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2008 VL 82 IS 13 BP 6190 EP 6199 DI 10.1128/JVI.02731-07 PG 10 WC Virology SC Virology GA 316KC UT WOS:000256947300010 PM 18417588 ER PT J AU Wei, CJ Xu, L Kong, WP Shi, W Canis, K Stevens, J Yang, ZY Dell, A Haslam, SM Wilson, IA Nabel, GJ AF Wei, Chih-Jen Xu, Ling Kong, Wing-Pui Shi, Wei Canis, Kevin Stevens, James Yang, Zhi-Yong Dell, Anne Haslam, Stuart M. Wilson, Ian A. Nabel, Gary J. TI Comparative efficacy of neutralizing antibodies elicited by recombinant hemagglutinin proteins from avian H5N1 influenza virus SO JOURNAL OF VIROLOGY LA English DT Article ID PANDEMIC INFLUENZA; IMMUNE-RESPONSES; HEALTHY-ADULTS; VACCINE; IMMUNOGENICITY; CELLS; SPECIFICITY AB Although the human transmission of avian H5N1 virus remains low, the prevalence of this highly pathogenic infection in avian species underscores the need for a preventive vaccine that can be made without eggs. Here, we systematically analyze various forms of recombinant hemagglutinin (HA) protein for their potential efficacy as vaccines. Monomeric, trimeric, and oligomeric H5N1 RA proteins were expressed and purified from either insect or mammalian cells. The immunogenicity of different recombinant HA proteins was evaluated by measuring the neutralizing antibody response. Neutralizing antibodies to H5N1 HA were readily generated in mice immunized with the recombinant HA proteins, but they varied in potency depending on their multimeric nature and cell source. Among the HA proteins, a high-molecular-weight oligomer elicited the strongest antibody response, followed by the trimer; the monomer showed minimal efficacy. The coexpression of another viral surface protein, neuraminidase, did not affect the immunogenicity of the HA oligomer, as expected from the immunogenicity of trimers produced from insect cells. As anticipated, HA expressed in mammalian cells without NA retained the terminal sialic acid residues and failed to bind alpha 2,3-linked sialic acid receptors. Taken together, these results suggest that recombinant HA proteins as individual or oligomeric trimers can elicit potent neutralizing antibody responses to avian H5N1 influenza viruses. C1 [Wei, Chih-Jen; Xu, Ling; Kong, Wing-Pui; Shi, Wei; Yang, Zhi-Yong; Nabel, Gary J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Canis, Kevin; Dell, Anne; Haslam, Stuart M.] Univ London Imperial Coll Sci Technol & Med, Fac Nat Sci, Div Mol Biosci, London SW7 2AZ, England. [Stevens, James; Wilson, Ian A.] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. [Stevens, James; Wilson, Ian A.] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA. RP Nabel, GJ (reprint author), NIAID, Vaccine Res Ctr, NIH, Bldg 40,Room 4502,MSC-3005,40 Convent Dr, Bethesda, MD 20892 USA. EM gnabel@nih.gov FU Biotechnology and Biological Sciences Research Council; Intramural NIH HHS; NIGMS NIH HHS [U54 GM062116]; Wellcome Trust NR 24 TC 86 Z9 90 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2008 VL 82 IS 13 BP 6200 EP 6208 DI 10.1128/JVI.00187-08 PG 9 WC Virology SC Virology GA 316KC UT WOS:000256947300011 PM 18417563 ER PT J AU Norris, KL Youle, RJ AF Norris, Kristi L. Youle, Richard J. TI Cytomegalovirus proteins vMIA and m38.5 link mitochondrial morphogenesis to Bcl-2 family proteins SO JOURNAL OF VIROLOGY LA English DT Article ID CELL-DEATH SUPPRESSION; LOCALIZED INHIBITOR; CONFORMATIONAL-CHANGE; PROAPOPTOTIC BAX; VIRAL HOMOLOGS; X-L; APOPTOSIS; VIRUS; INFECTION; ACTIVATION AB Apoptosis is a host defense mechanism against viruses that can be subverted by viral gene products. Human cytomegalovirus encodes viral mitochondria-localized inhibitor of apoptosis (vMIA; also known as pUL37x1), which is targeted to mitochondria and functions as a potent cell death suppressor by binding to and inhibiting proapoptotic Bcl-2 family members Bax and Bak. vMIA expression also dramatically alters mitochondrial morphology, causing the fragmentation of these organelles. A potential ortholog of vMIA, m38.5, which was identified in murine cytomegallovirus, has been shown to localize to mitochondria and protect against chemically induced apoptosis by unknown mechanisms. Despite sharing negligible homology with vMIA and no region detectably corresponding to the vMIA Bax-binding domain, we find that m38.5, like vMIA, binds to Bax and recruits Bax to mitochondria. Interestingly, m38.5 and vMIA appear to block Bax downstream of translocation to mitochondria and after an initial stage of Bax confomational change. In contrast to vMIA, m38.5 neither binds to Bak nor causes mitochondrial fragmentation. Consistently with Bax-selective inactivation by m38.5, m38.5 fragments mitochondria in Bak knockout (KO) cells and protects Bak KO cells from apoptosis better than Bax KO cells. Thus, vMIA and m38.5 share some, but not all, features of apoptosis regulation through Bcl-2 family interaction and allow the dissection of Bax translocation into discrete steps. C1 [Norris, Kristi L.; Youle, Richard J.] NINDS, Biochem Sect, SNB, NIH, Bethesda, MD 20892 USA. RP Youle, RJ (reprint author), NINDS, Biochem Sect, SNB, NIH, 35 Convent Dr,Room 2C 917, Bethesda, MD 20892 USA. EM ler@ninds.nih.gov NR 51 TC 38 Z9 42 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 JUL PY 2008 VL 82 IS 13 BP 6232 EP 6243 DI 10.1128/JVI.02710-07 PG 12 WC Virology SC Virology GA 316KC UT WOS:000256947300014 PM 18417572 ER PT J AU Nelson, GE Wagenaar, TR Moss, B AF Nelson, Gretchen E. Wagenaar, Timothy R. Moss, Bernard TI A conserved sequence within the H2 subunit of the vaccinia virus entry/fusion complex is important for interaction with the A28 subunit and infectivity SO JOURNAL OF VIROLOGY LA English DT Article ID CELL-CELL FUSION; INTRACELLULAR MATURE VIRION; SURFACE HEPARAN-SULFATE; MEMBRANE-FUSION; ENVELOPE GLYCOPROTEIN; ESSENTIAL COMPONENT; INFLUENZA-VIRUS; PROTEIN BINDS; ENTRY; GENE AB The recently described vaccinia virus entry/fusion complex (EFC) comprises at least eight polypeptides that are conserved in all poxviruses. Neither the structure of the complex nor the roles of individual subunits are known. Here we provide evidence for an interaction between the H2 and A28 subunits in the context of a virus infection as well as in uninfected cells transfected with plasmids expressing the corresponding genes. We focused on a highly conserved 21-amino acid-segment in H2 that is flanked by cysteine residues. The effect of amino acid substitutions within the 21-amino-acid segment was determined by an infectivity complementation assay using a conditional H2-null mutant of vaccinia virus. Mutations that had no, moderate, or large negative effects on complementation were found. The latter group included glutamic acid substitutions of leucine and individual glycines and alanine substitution of both glycines within a LGYSG sequence. Mutations with the most pronounced effect on infectivity disrupted the interaction of H2 with A28 to the greatest extent in both infected and uninfected cells. These data indicate that the LGYSG sequence is important for the interaction of H2 with A28 and suggest that this sequence is buried within the EFC complex. C1 [Nelson, Gretchen E.; Wagenaar, Timothy R.; Moss, Bernard] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, 33 North Dr,MSC 3210, Bethesda, MD 20892 USA. EM bmoss@nih.gov FU Intramural NIH HHS NR 41 TC 16 Z9 19 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 JUL PY 2008 VL 82 IS 13 BP 6244 EP 6250 DI 10.1128/JVI.00434-08 PG 7 WC Virology SC Virology GA 316KC UT WOS:000256947300015 PM 18417576 ER PT J AU Rulli, SJ Mirro, J Hill, SA Lloyd, P Gorelick, RJ Coffin, JM Derse, D Rein, A AF Rulli, Samuel J., Jr. Mirro, Jane Hill, Shawn A. Lloyd, Patricia Gorelick, Robert J. Coffin, John M. Derse, David Rein, Alan TI Interactions of murine APOBEC3 and human APOBEC3G with murine leukemia viruses SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-1 REVERSE TRANSCRIPTION; VIF PROTEIN; ENDOGENOUS RETROVIRUSES; CYTIDINE DEAMINATION; ZINC-FINGER; GENOMIC RNA; TYPE-1; DNA; RESTRICTION; RETROTRANSPOSITION AB APOBEC3 proteins are cytidine deaminases which help defend cells against retroviral infections. One antiviral mechanism involves deaminating dC residues in minus-strand DNA during reverse transcription, resulting in G-to-A mutations in the coding strand. We investigated the effects of mouse APOBEC3 (mA3) and human APOBEC3G (hA3G) upon Moloney murine leukemia virus (MLV). We find that mA3 inactivates MLV but is significantly less effective against MLV than is hA3G. In contrast, mA3 is as potent against human immunodeficiency virus type 1 (HIV-1, lacking the protective Vif protein) as is hA3G. The two APOBEC3 proteins are packaged to similar extents in MLV particles. Dose-response profiles imply that a single APOBEC3 molecule (or oligomer) is sufficient to inactivate an MLV particle. The inactivation of MLV by mA3 and hA3G is accompanied by relatively small reductions in the amount of viral DNA in infected cells. Although hA3G induces significant levels of G-to-A mutations in both MLV and HIV DNAs, and mA3 induces these mutations in HIV DNA, no such mutations were detected in DNA synthesized by MLV inactivated by mA3. Thus, MLV has apparently evolved to partially resist the antiviral effects of mA3 and to totally resist the ability of mA3 to induce G-to-A mutation in viral DNA. Unlike the resistance of HIV-1 and human T-cell leukemia virus type 1 to hA3G, the resistance of MLV to mA3 is not mediated by the exclusion of APOBEC from the virus particle. The nature of its resistance and the mechanism of inactivation of MLV by mA3 are completely unknown. C1 [Rulli, Samuel J., Jr.; Mirro, Jane; Hill, Shawn A.; Derse, David; Rein, Alan] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. [Lloyd, Patricia] SAIC Frederick Inc, Basic Res Lab, Frederick, MD 21702 USA. [Gorelick, Robert J.] SAIC Frederick Inc, AIDS Vaccine Program, Frederick, MD 21702 USA. [Coffin, John M.] Tufts Univ, Dept Microbiol, Boston, MA 02111 USA. RP Rein, A (reprint author), NCI, HIV Drug Resistance Program, POB B, Frederick, MD 21702 USA. EM rein@ncifcrf.gov FU Intramural NIH HHS [Z01 BC010511-05, Z01 BC010512-05]; NCI NIH HHS [N01-CO-12400, N01CO12400] NR 54 TC 45 Z9 45 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2008 VL 82 IS 13 BP 6566 EP 6575 DI 10.1128/JVI.01357-07 PG 10 WC Virology SC Virology GA 316KC UT WOS:000256947300044 PM 18448535 ER PT J AU Ambrose, Z Compton, L Piatak, M Lu, D Alvord, WG Lubomirski, MS Hildreth, JEK Lifson, JD Miller, CJ KewalRamani, VN AF Ambrose, Zandrea Compton, Lara Piatak, Michael, Jr. Lu, Ding Alvord, W. Gregory Lubomirski, Mariusz S. Hildreth, James E. K. Lifson, Jeffrey D. Miller, Christopher J. KewalRamani, Vineet N. TI Incomplete protection against simian immunodeficiency virus vaginal transmission in rhesus macaques by a topical antiviral agent revealed by repeat challenges SO JOURNAL OF VIROLOGY LA English DT Article ID LIPID RAFTS; SHIV CHALLENGE; MEMBRANE CHOLESTEROL; HIV PATHOGENESIS; CCR5 INHIBITOR; TYPE-1; INFECTION; ANTIBODY; IMMUNIZATION; MONKEYS AB The rising prevalence of human immunodeficiency virus type 1 (HIV-1) infection in women, especially in resource-limited settings, accentuates the need for accessible, inexpensive, and female-controlled preexposure prophylaxis strategies to prevent mucosal transmission of the virus. While many compounds can inactivate HIV-1 in vitro, evaluation in animal models for mucosal transmission of virus may help identify which approaches will be effective in vivo. Macaques challenged intravaginally with pathogenic simian immunodeficiency virus (SIVmuc251) provide a model to preclinically evaluate candidate microbicides. 2-Hydroxypropyl-beta-cyclodextrin (BCD) prevents HIV-1 and SIV infection of target cells at subtoxic doses in vitro. Consistent with these findings, intravaginal challenge of macaques with SIVmac251 preincubated with BCD prevented mucosal transmission, as measured by plasma viremia and antiviral antibodies, through 10 weeks postchallenge. In an initial challenge, BCD applied topically prior to SIVmac251 prevented intravaginal transmission of virus compared to controls (P < 0.0001). However, upon a second virus challenge following BCD pretreatment, the majority of the previously protected animals became infected. The mechanism through which animals become infected at a frequency similar to that of controls after prior exposure to BCD and SIVmac251 in subsequent intravaginal virus challenges (P = 0.63), despite the potent antiviral properties of BCD, remains to be determined. These results highlight the unpredictability of antiviral compounds as topical microbicides and suggest that repeated exposures to candidate treatments should be considered for in vivo evaluation. C1 [Ambrose, Zandrea; KewalRamani, Vineet N.] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. [Compton, Lara; Lu, Ding; Miller, Christopher J.] Univ Calif Davis, Calif Natl Primate Res Ctr, Davis, CA 95616 USA. [Compton, Lara; Lu, Ding; Miller, Christopher J.] Univ Calif Davis, Ctr Comparat Med, Davis, CA 95616 USA. [Piatak, Michael, Jr.; Lifson, Jeffrey D.] SAIC Frederick Inc, AIDS Vaccine Program, NCI, Frederick, MD 21702 USA. [Alvord, W. Gregory; Lubomirski, Mariusz S.] Data Management Serv Inc, NCI, Frederick, MD 21702 USA. [Hildreth, James E. K.] Mehany Med Coll, Nashville, TN 37208 USA. RP Ambrose, Z (reprint author), Univ Pittsburgh, Div Infect Dis, 817B Scaife Hall, Pittsburgh, PA 15261 USA. EM ambrosez@dom.pitt.edu; vineet@ncifcrf.gov FU Intramural NIH HHS; NCI NIH HHS [N01CO12400, N01-CO-12400]; NCRR NIH HHS [U51RR00169, P51 RR000169] NR 47 TC 5 Z9 6 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 JUL PY 2008 VL 82 IS 13 BP 6591 EP 6599 DI 10.1128/JVI.02730-07 PG 9 WC Virology SC Virology GA 316KC UT WOS:000256947300047 PM 18434406 ER PT J AU Chevalier, SA Ko, NL Calattini, S Mallet, A Prevost, MC Kehn, K Brady, JN Kashanchi, F Gessain, A Mahieux, R AF Chevalier, Sebastien Alain Ko, Nga Ling Calattini, Sara Mallet, Adeline Prevost, Marie-Christine Kehn, Kylene Brady, John N. Kashanchi, Fatah Gessain, Antoine Mahieux, Renaud TI Construction and characterization of a human T-cell lymphotropic virus type 3 infectious molecular clone SO JOURNAL OF VIROLOGY LA English DT Article ID COMPLETE NUCLEOTIDE-SEQUENCE; CERCOCEBUS-TORQUATUS; PAPIO-HAMADRYAS; LEUKEMIA-VIRUS; CAMEROON; IDENTIFICATION; STLV-PH969; FEATURES; BABOONS; AFRICA AB We and others have uncovered the existence of human T-cell lymphotropic virus type 3 (HTLV-3). We have now generated an HTLV-3 proviral clone. We established that gag, env, pol, pro, and tax/rex as well as minus-strand mRNAs are present in cells transfected with the HTLV-3 clone. HTLV-3 p24(gag) protein is detected in the cell culture supernatant. Transfection of 293T-long terminal repeat (LTR)-green fluorescent protein (GFP) cells with the HTLV-3 clone promotes formation of syncytia, a hallmark of Env expression, together with the appearance of fluorescent cells, demonstrating that Tax is expressed. Viral particles are visible by electron microscopy. These particles are infectious, as demonstrated by infection experiments with purified virions. C1 [Chevalier, Sebastien Alain; Ko, Nga Ling; Calattini, Sara; Gessain, Antoine; Mahieux, Renaud] Inst Pasteur, Dept Virol, CNRS URA 3015, Unite Epidemiol & Physiopathol Virus Oncogenes, F-75015 Paris, France. [Kehn, Kylene; Kashanchi, Fatah; Mahieux, Renaud] George Washington Univ, Med Ctr, Dept Microbiol Immunol & Trop Med, Washington, DC 20037 USA. [Kehn, Kylene; Kashanchi, Fatah; Mahieux, Renaud] George Washington Univ, Med Ctr, Dept Biochem, Washington, DC 20037 USA. [Chevalier, Sebastien Alain; Brady, John N.] NCI, NIH, LCO, VTB, Bethesda, MD 20892 USA. RP Mahieux, R (reprint author), Inst Pasteur, INSERM, CNRS, URA 3015,Unite Epidemiol & Physiopathol Virus Onc, 28 Rue Docteur Roux, F-75724 Paris 15, France. EM rmahieux@pasteur.fr RI Kehn-Hall, Kylene/I-5752-2013 FU NIAID NIH HHS [R21 AI072495, AI072495-01] NR 24 TC 9 Z9 9 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 JUL PY 2008 VL 82 IS 13 BP 6747 EP 6752 DI 10.1128/JVI.00247-08 PG 6 WC Virology SC Virology GA 316KC UT WOS:000256947300061 PM 18417569 ER PT J AU Kaufman, DR Goudsmit, J Holterman, L Ewald, BA Denholtz, M Devoy, C Giri, A Grandpre, LE Heraud, JM Franchini, G Seaman, MS Havenga, MJE Barouch, DH AF Kaufman, David R. Goudsmit, Jaap Holterman, Lennart Ewald, Bonnie A. Denholtz, Matthew Devoy, Colleen Giri, Ayush Grandpre, Lauren E. Heraud, Jean-Michel Franchini, Genoveffa Seaman, Michael S. Havenga, Menzo J. E. Barouch, Dan H. TI Differential antigen requirements for protection against systemic and intranasal vaccinia virus challenges in mice SO JOURNAL OF VIROLOGY LA English DT Article ID 2 INFECTIOUS FORMS; SMALLPOX VACCINATION; NONHUMAN-PRIMATES; ANTIBODY-RESPONSES; UNITED-STATES; ADENOVIRUS; IMMUNITY; VECTORS; MONKEYPOX; IMMUNOGENICITY AB The development of a subunit vaccine for smallpox represents a potential strategy to avoid the safety concerns associated with replication-competent vaccinia virus. Preclinical studies to date with subunit smallpox vaccine candidates, however, have been limited by incomplete information regarding protective antigens and the requirement for multiple boost immunizations to afford protective immunity. Here we explore the protective efficacy of replication-incompetent, recombinant adenovirus serotype 35 (rAd35) vectors expressing the vaccinia virus intracellular mature virion (IMV) antigens A27L and L1R and extracellular enveloped virion (EEV) antigens A33R and B5R in a murine vaccinia virus challenge model. A single immunization with the rAd35-L1R vector effectively protected mice against a lethal systemic vaccinia virus challenge. The rAd35-L1R vector also proved more efficacious than the combination of four rAd35 vectors expressing A27L, L1R, A33R, and B5R. Moreover, serum containing L1R-specific neutralizing antibodies afforded postexposure prophylaxis after systemic vaccinia virus infection. In contrast, the combination of rAd35-L1R and rAd35-B5R vectors was required to protect mice against a lethal intranasal vaccinia virus challenge, suggesting that both IMV- and EEV-specific immune responses are important following intranasal infection. Taken together, these data demonstrate that different protective antigens are required based on the route of vaccinia virus challenge. These studies also suggest that rAd vectors warrant further assessment as candidate subunit smallpox vaccines. C1 [Kaufman, David R.; Ewald, Bonnie A.; Denholtz, Matthew; Devoy, Colleen; Giri, Ayush; Grandpre, Lauren E.; Seaman, Michael S.; Barouch, Dan H.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02215 USA. [Goudsmit, Jaap; Holterman, Lennart; Havenga, Menzo J. E.] Crucell Holland BV, NL-2301 CA Leiden, Netherlands. [Heraud, Jean-Michel; Franchini, Genoveffa] NCI, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Barouch, DH (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Res E Room 213,330 Brookline Ave, Boston, MA 02215 USA. EM dbarouch@bidmc.harvard.edu RI HERAUD, Jean-Michel/O-1464-2013 OI HERAUD, Jean-Michel/0000-0003-1107-0859 FU NIAID NIH HHS [AI058727, AI066305, AI066924, R01 AI058727, R01 AI066924, T32 AI007387, U19 AI066305] NR 31 TC 24 Z9 24 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2008 VL 82 IS 14 BP 6829 EP 6837 DI 10.1128/JVI.00353-08 PG 9 WC Virology SC Virology GA 324UQ UT WOS:000257545300005 PM 18448519 ER PT J AU Zhang, MY Vu, BK Choudhary, A Lu, H Humbert, M Ong, H Alam, M Ruprecht, RM Quinnan, G Jiang, S Montefiori, DC Mascola, JR Broder, CC Haynes, BF Dimitrov, DS AF Zhang, Mei-Yun Vu, Bang K. Choudhary, Anil Lu, Hong Humbert, Michael Ong, Helena Alam, Munir Ruprecht, Ruth M. Quinnan, Gerald Jiang, Shibo Montefiori, David C. Mascola, John R. Broder, Christopher C. Haynes, Barton F. Dimitrov, Dimiter S. TI Cross-reactive human immunodeficiency virus type 1-neutralizing human monoclonal antibody that recognizes a novel conformational epitope on gp41 and lacks reactivity against self-antigens SO JOURNAL OF VIROLOGY LA English DT Article ID NEUTRALIZING ANTI-GP41 2F5; PROXIMAL EXTERNAL REGION; ENVELOPE GLYCOPROTEIN; PHAGE LIBRARY; HIV-1 GP41; PHOSPHATIDYLINOSITOL PHOSPHATE; BINDING; FUSION; DIVERSE; INFECTION AB Broadly cross-reactive human immunodeficiency virus (HIV)-neutralizing antibodies are infrequently elicited in infected humans. The two best-characterized gp41-specific cross-reactive neutralizing human monoclonal antibodies, 4E10 and 2F5, target linear epitopes in the membrane-proximal external region (MPER) and bind to cardiolipin and several other autoantigens. It has been hypothesized that, because of such reactivity to self-antigens, elicitation of 2F5 and 4E10 and similar antibodies by vaccine immunogens based on the MPER could be affected by tolerance mechanisms. Here, we report the identification and characterization of a novel anti-gp41 monoclonal antibody, designated m44, which neutralized most of the 22 HIV type 1 (HIV-1) primary isolates from different clades tested in assays based on infection of peripheral blood mononuclear cells by replication-competent virus but did not bind to cardiolipin and phosphatidylserine in an enzyme-linked immunosorbent assay and a Biacore assay nor to any protein or DNA autoantigens tested in Luminex assays. m44 bound to membrane-associated HIV-1 envelope glycoproteins (Envs), to recombinant Envs lacking the transmembrane domain and cytoplasmic tail (gp140s), and to gp41 structures containing five-helix bundles and six-helix bundles, but not to N-heptad repeat trimers, suggesting that the C-heptad repeat is involved in m44 binding. In contrast to 2F5, 4E10, and Z13, m44 did not bind to any significant degree to denatured gp140 and linear peptides derived from gp41, suggesting a conformational nature of the epitope. This is the first report of a gp41-specific cross-reactive HIV-1-neutralizing human antibody that does not have detectable reactivity to autoantigens. Its novel conserved conformational epitope on gp41 could be helpful in the design of vaccine immunogens and as a target for therapeutics. C1 [Zhang, Mei-Yun; Vu, Bang K.; Dimitrov, Dimiter S.] NCI, CCRNP, CCR, NIH, Frederick, MD 21702 USA. [Zhang, Mei-Yun] NCI, SAIC Frederick Inc, Frederick, MD 21701 USA. [Choudhary, Anil; Quinnan, Gerald; Broder, Christopher C.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Lu, Hong; Jiang, Shibo] New York Blood Ctr, Lindsley F Kimball Res Inst, New York, NY 10021 USA. [Humbert, Michael; Ong, Helena; Ruprecht, Ruth M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Humbert, Michael; Ruprecht, Ruth M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Alam, Munir; Montefiori, David C.; Haynes, Barton F.] Duke Univ, Med Ctr, Durham, NC USA. [Mascola, John R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Zhang, MY (reprint author), NCI, CCRNP, CCR, NIH, Bldg 469,Rm 131,POB B,Miller Dr, Frederick, MD 21702 USA. EM zhangm@ncifcrf.gov; dimitrov@ncifcrf.gov RI Jiang, Shibo/L-4500-2014 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400]; NIAID NIH HHS [P01 AI048280, AI46221, AI47434, AI48280, R01 AI046221, R21 AI046221, R37 AI034266, R37 AI34266] NR 52 TC 34 Z9 36 U1 1 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2008 VL 82 IS 14 BP 6869 EP 6879 DI 10.1128/JVI.00033-08 PG 11 WC Virology SC Virology GA 324UQ UT WOS:000257545300009 PM 18480433 ER PT J AU Goncalvez, AP Chien, CH Tubthong, K Gorshkova, I Roll, C Donau, O Schuck, P Yoksan, S Wang, SD Purcell, RH Lai, CJ AF Goncalvez, Ana P. Chien, Cheng-Hsin Tubthong, Kamolchanok Gorshkova, Inna Roll, Carrie Donau, Olivia Schuck, Peter Yoksan, Sutee Wang, Sy-Dar Purcell, Robert H. Lai, Ching-Juh TI Humanized monoclonal antibodies derived from chimpanzee Fabs protect against Japanese encephalitis virus in vitro and in vivo SO JOURNAL OF VIROLOGY LA English DT Article ID WEST-NILE-VIRUS; YELLOW-FEVER VIRUS; IMMUNOGLOBULIN G1 ANTIBODY; ENVELOPE PROTEIN; DENGUE-VIRUS; DOMAIN-III; REDUCED NEUROINVASIVENESS; INCREASED IMMUNOGENICITY; NEUTRALIZING ANTIBODIES; MEDIATED NEUTRALIZATION AB Japanese encephalitis virus (JEV)-specific Fab antibodies were recovered by repertoire cloning from chimpanzees initially immunized with inactivated JE-VAX and then boosted with attenuated JEV SA14-14-2. From a panel of 11 Fabs recovered by different panning strategies, three highly potent neutralizing antibodies, termed Fabs A3, B2, and E3, which recognized spatially separated regions on the virion, were identified. These antibodies reacted with epitopes in different domains: the major determinant for Fab A3 was Lys(179) (domain 1), that for Fab B2 was Ile(132) (domain II), and that for Fab E3 was Gly(302) (domain III) in the envelope protein, suggesting that these antibodies neutralize the virus by different mechanisms. Potent neutralizing antibodies reacted with a low number of binding sites available on the virion. These three Fabs and derived humanized monoclonal antibodies (MAbs) exhibited high neutralizing activities against a broad spectrum of JEV genotype strains. Demonstration of antibody-mediated protection of JEV infection in vivo is provided using the mouse encephalitis model. MAb B2 was most potent, with a 50% protective dose (ED50) of 0.84 mu g, followed by MAb A3 (ED50 of 5.8 mu g) and then MAb E3 (ED50 of 24.7 mu g) for a 4-week-old mouse. Administration of 200 mu g/mouse of MAb B2 1 day after otherwise lethal JEV infection protected 50% of mice and significantly prolonged the average survival time compared to that of mice in the unprotected group, suggesting a therapeutic potential for use of MAb 132 in humans. C1 [Goncalvez, Ana P.; Roll, Carrie; Lai, Ching-Juh] Natl Inst Biomed Imaging & Bioengn, Mol Viral Biol Sect, NIH, Bethesda, MD 20892 USA. [Purcell, Robert H.] Natl Inst Biomed Imaging & Bioengn, Hepatitis Viruses Sect, NIH, Bethesda, MD 20892 USA. [Gorshkova, Inna; Schuck, Peter] Natl Inst Biomed Imaging & Bioengn, Infect Dis Lab, Natl Inst Allergy & Infect Dis & Protein Biophys, NIH, Bethesda, MD 20892 USA. [Tubthong, Kamolchanok; Yoksan, Sutee] Mahidol Univ, Inst Sci & Technol Res & Dev, Nakhon Pathom, Thailand. [Wang, Sy-Dar] Adimmune Corp, Taichung, Taiwan. RP Goncalvez, AP (reprint author), NIAID, Infect Dis Lab, Mol Virl Biol Sect, 50 S Dr MSC 8005, Bethesda, MD 20892 USA. EM agoncalvez@niaid.nih.gov; clai@niaid.nih.gov OI Schuck, Peter/0000-0002-8859-6966 FU Intramural NIH HHS NR 66 TC 44 Z9 48 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 JUL PY 2008 VL 82 IS 14 BP 7009 EP 7021 DI 10.1128/JVI.00291-08 PG 13 WC Virology SC Virology GA 324UQ UT WOS:000257545300022 PM 18480437 ER PT J AU Li, KJ Zhang, SJ Kronqvist, M Wallin, M Ekstrom, M Derse, D Garoff, H AF Li, Kejun Zhang, Shujing Kronqvist, Malin Wallin, Michael Ekstrom, Maria Derse, David Garoff, Henrik TI Intersubunit disulfide isomerization controls membrane fusion of human T-cell leukemia virus Env SO JOURNAL OF VIROLOGY LA English DT Article ID COMPLETE NUCLEOTIDE-SEQUENCE; RETROVIRUS ENVELOPE PROTEIN; RECEPTOR-BINDING DOMAIN; INFLUENZA HEMAGGLUTININ; SEMLIKI FOREST; TRANSMEMBRANE GLYCOPROTEIN; EXPRESSION VECTORS; TYPE-1 INFECTION; CWLC MOTIF; LOW PH AB Human T-cell leukemia virus (HTLV-1) Env carries a typical disulfide isomerization motif, C225XXC, in the C-terminal domain SU. Here we have tested whether this motif is used for isomerization of the intersubunit disulfide of Env and whether this rearrangement is required for membrane fusion. We introduced the C225A and C228A mutations into Env and found that the former but not the latter mutant matured into covalently linked SU-TM complexes in transfected cells. Next, we constructed a secreted Env ectodomain and showed that it underwent incubation-dependent intersubunit disulfide isomerization on target cells. However, the rearrangement was blocked by the C225A mutation, suggesting that C-255 carried the isomerization-active thiol. Still, it was possible to reduce the intersubunit disulfide of the native C225A ectodomain mutant with dithiothreitol (DTT). The importance of the CXXC-mediated disulfide isomerization for infection was studied using murine leukemia virus vectors pseudotyped with wild-type or C225A HTLV-1 Env. We found that the mutant Env blocked infection, but this could be rescued with DTT. The fusion activity was tested in a fusion-from-with in assay using a coculture of rat XC target and transfected BHK-21 effector cells. We found that the mutation blocked polykaryon formation, but this could be reversed with DTT. Similar DTT-reversible inhibition of infection and fusion was observed when a membrane-impermeable alkylator was present during the infection/fusion incubation. We conclude that the fusion activity of HTLV-1 Env is controlled by an SU CXXC-mediated isomerization of the intersubunit disulfide. Thus, this extends the applicability of the isomerization model from gammaretroviruses to deltaretroviruses. C1 [Li, Kejun; Zhang, Shujing; Kronqvist, Malin; Wallin, Michael; Ekstrom, Maria; Garoff, Henrik] Karolinska Inst, Dept Biosci & Nutr, S-14157 Huddinge, Sweden. [Derse, David] NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA. RP Garoff, H (reprint author), Karolinska Inst, Dept Biosci & Nutr, S-14157 Huddinge, Sweden. EM henrik.garoff@cbt.ki.se NR 52 TC 29 Z9 29 U1 4 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2008 VL 82 IS 14 BP 7135 EP 7143 DI 10.1128/JVI.00448-08 PG 9 WC Virology SC Virology GA 324UQ UT WOS:000257545300032 PM 18480461 ER PT J AU Cunningham, MW Brown, MA Shindle, DB Terrell, SP Hayes, KA Ferree, BC McBride, RT Blankenship, EL Jansen, D Citino, SB Roelke, ME Kiltie, RA Troyer, JL O'Brien, SJ AF Cunningham, Mark W. Brown, Meredith A. Shindle, David B. Terrell, Scott P. Hayes, Kathleen A. Ferree, Bambi C. McBride, R. T. Blankenship, Emmett L. Jansen, Deborah Citino, Scott B. Roelke, Melody E. Kiltie, Richard A. Troyer, Jennifer L. O'Brien, Stephen J. TI Epizootiology and management of feline leukemia virus in the Florida puma SO JOURNAL OF WILDLIFE DISEASES LA English DT Article DE feline leukemia virus; florida panther; infectious disease; Puma concolor coryi; retrovirus; vaccination ID IMMUNODEFICIENCY VIRUS; EXPERIMENTAL-INFECTION; CATS; FELV; VACCINATION; WILDCATS; PANTHERS; PREVALENCE; RETROVIRUS; CONCOLOR AB Feline leukemia virus (FeLv) was not detected in Florida pumas (Puma concolor coryi) in almost 20 yr of surveillance; however, the finding of two FeLV antigen-positive pumas during the 2002-2003 capture season led to an investigation of FeLV in the population. Between January 1990 and April 2007, the proportion of pumas testing FeLV antibody positive increased, with antibody-positive pumas concentrated in the northern portion of puma range. Five 131 (4%) pumas sampled between July 2000 and April 2007 were viremic, with all cases clustered in Okaloacoochee Slough (OKS). Clinical signs and clinical pathology at capture were absent or included lymphadenopathy, moderate-to-severe anemia, and lymphopenia. All viremic pumas died; causes of death were septicemia (n=2), intraspecific aggression (n=2), and anemia/dehydration (n=1). Outcome after FeLV exposure in pumas was similar to that in domestic cats, with evidence of regressive, latent, and persistent infections. Management of the epizootic included vaccination were concentrated in OKS and in a band between OKS and the remainder of the puma population. There have been no new cases since July 2004; however, the potential for reintroduction of the virus remains. C1 [Cunningham, Mark W.; Shindle, David B.; Ferree, Bambi C.; Kiltie, Richard A.] Florida Fish & Wildlife Conservat Commiss, Gainesville, FL 32601 USA. [Brown, Meredith A.; O'Brien, Stephen J.] NCI, Lab Genom Divers, Frederick, MD 21702 USA. [Terrell, Scott P.] Disneys Anim Kingdom, Bay Lake, FL 32830 USA. [Hayes, Kathleen A.] Ohio State Univ, Ctr Retrovirus Res, Columbus, OH 43210 USA. [McBride, R. T.] Ranchers Supply Inc, Alpine, TX 79830 USA. [Blankenship, Emmett L.; Jansen, Deborah] Natl Pk Serv, Big Cypress Natl Preserve, Ochopee, FL 34141 USA. [Citino, Scott B.] White Oak Conservat Ctr, Yulee, FL 32097 USA. [Roelke, Melody E.; Troyer, Jennifer L.] SAIC Frederick, Lab Genom Divers, Frederick, MD 21702 USA. RP Cunningham, MW (reprint author), Florida Fish & Wildlife Conservat Commiss, 1105 SW Williston Rd, Gainesville, FL 32601 USA. EM mark.cunningham@myfwc.com RI Troyer, Jennifer/B-8415-2012; OI Hayes-Ozello, Kathleen/0000-0002-8838-0727 FU FWC; Florida Panther Research and Management Trust; NCI; National Institutes of Health (NIH) [N01-CO-12400]; NIH; Center for Cancer Research; SeaWorld and Busch Gardens Conservation Fund FX We are deeply indebted to FWC, NPS, and US Fish and Wildlife Service biologists and veterinarians who assisted in fieldwork and collected samples over the past 30 yr. Faculty at UF-CVM provided diagnostic and editorial support and included D. Forrester, J. Levy, M. Sunquist, R. Alleman, C. Crawford, C. Buergelt, and B. Homer. We very much appreciate the diagnostic support of S. Hanswn and W. Hardy, Jr., and the technical assistance of W. Johnson and A. Roca. This project was funded in part by FWC through the Federal Endangered Species Project E-1 and the Florida Panther Research and Management Trust Fund and with federal funds from the NCI, National Institutes of Health (NIH), under contract N01-CO-12400. This Research was supported in part by the Intramural Research Program of the NIH, NCI, Center for Cancer Research. Funding was also provided by the SeaWorld and Busch Gardens Conservation Fund. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. NR 48 TC 22 Z9 22 U1 2 U2 20 PU WILDLIFE DISEASE ASSOC, INC PI LAWRENCE PA 810 EAST 10TH ST, LAWRENCE, KS 66044-8897 USA SN 0090-3558 J9 J WILDLIFE DIS JI J. Wildl. Dis. PD JUL PY 2008 VL 44 IS 3 BP 537 EP 552 PG 16 WC Veterinary Sciences SC Veterinary Sciences GA 340TT UT WOS:000258668600001 PM 18689639 ER PT J AU Campa, MI Bradshaw, CP Eckenrode, J Zielinski, DS AF Campa, Mary I. Bradshaw, Catherine P. Eckenrode, John Zielinski, David S. TI Patterns of problem behavior in relation to thriving and precocious behavior in late adolescence SO JOURNAL OF YOUTH AND ADOLESCENCE LA English DT Article DE problem behavior trajectories; precocious behavior; thriving behavior ID LIFE-COURSE-PERSISTENT; LIMITED ANTISOCIAL PATHWAYS; NURSE HOME VISITATION; PHYSICAL AGGRESSION; EMERGING ADULTHOOD; CONDUCT PROBLEMS; EARLY-ONSET; FOLLOW-UP; TRAJECTORIES; CHILDHOOD AB Several studies have indicated that an early onset of delinquent and problem behaviors is associated with a greater risk of subsequent behavioral and mental health problems. This study builds on that literature by examining histories of behavior problems in relation to indicators of thriving and precocious behavior during late adolescence. Using longitudinal data from 289 high-risk adolescents, participants were classified according to their problem behavior histories at ages 15 and 19. Findings indicated that although some adolescents experienced decline over time in their overt behavior problems, those youth showed fewer indicators of thriving when compared to adolescents with no history of behavior problems. Youth with an earlier onset of behavior problems also evinced an increased risk for precocious behavior. Gender differences and implications for prevention through youth development programming are discussed. C1 [Bradshaw, Catherine P.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA. [Zielinski, David S.] NIMH, Bethesda, MD 20892 USA. [Campa, Mary I.; Eckenrode, John] Cornell Univ, Family Life Dev Ctr, Ithaca, NY 14850 USA. [Campa, Mary I.; Eckenrode, John] Cornell Univ, Dept Human Dev, Ithaca, NY 14850 USA. RP Campa, MI (reprint author), Cornell Univ, Family Life Dev Ctr, Ithaca, NY 14850 USA. EM mic8@cornell.edu NR 68 TC 4 Z9 5 U1 3 U2 3 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0047-2891 J9 J YOUTH ADOLESCENCE JI J. Youth Adolesc. PD JUL PY 2008 VL 37 IS 6 BP 627 EP 640 DI 10.1007/s10964-007-9235-x PG 14 WC Psychology, Developmental SC Psychology GA 300ZN UT WOS:000255864500001 ER PT J AU Cappola, AR Maggio, M Ferrucci, L AF Cappola, Anne R. Maggio, Marcello Ferrucci, Luigi TI Is research on hormones and aging finished? No! just started! SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Editorial Material ID WOMENS-HEALTH; GROWTH-HORMONE; ELDERLY-MEN; OLDER WOMEN; DEHYDROEPIANDROSTERONE-SULFATE; POSTMENOPAUSAL WOMEN; TESTOSTERONE; MORTALITY; REPLACEMENT; THERAPY C1 [Cappola, Anne R.] Univ Penn, Sch Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA. [Cappola, Anne R.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Maggio, Marcello; Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21224 USA. RP Cappola, AR (reprint author), Univ Penn, Sch Med, Div Endocrinol Diabet & Metab, 764 CRB,415 Curie Blvd, Philadelphia, PA 19104 USA. EM acappola@mail.med.upenn.edu FU Intramural NIH HHS [Z01 AG000015-49] NR 21 TC 3 Z9 4 U1 1 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JUL PY 2008 VL 63 IS 7 BP 696 EP 697 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 336UE UT WOS:000258389300006 PM 18693223 ER PT J AU Ruggiero, C Metter, EJ Melenovsky, V Cherubini, A Najjar, SS Ble, A Senin, U Longo, DL Ferrucci, L AF Ruggiero, Carmelinda Metter, E. Jeffrey Melenovsky, Vojtech Cherubini, Antonio Najjar, Samer S. Ble, Alessandro Senin, Umberto Longo, Dan L. Ferrucci, Luigi TI High basal metabolic rate is a risk factor for mortality: The Baltimore Longitudinal Study of Aging SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE basal metabolic rate; metabolism; mortality; longevity; theory of aging; aging ID CALORIC RESTRICTION; PHYSICAL-ACTIVITIES; LIFE-SPAN; LONGEVITY; AGE; HUMANS; LONG; BIOMARKERS; MEN AB Background. Despite longstanding controversies from animal studies on the relationship between basal metabolic rate (BMR) and longevity, whether BMR is a risk factor for mortality has never been tested in humans. We evaluate the longitudinal changes in BMR and the relationship between BMR and mortality in the Baltimore Longitudinal Study of Aging (BLSA) participants. Methods. BMR and medical information were collected at the study entry and approximately every 2 years in 1227 participants (972 men) over a 40-year follow-up. BMR, expressed as kcal/m(2)/h, was estimated from the basal O(2) consumption and CO(2) production measured by open-circuit method. Data on all-cause and specific-cause mortality were also obtained. Result. BMR declined with age at a rate that accelerated at older ages. Independent of age. participants who died had a higher BMR compared to those who survived. BMR was a significant risk factor for mortality independent of secular trends in mortality and other well-recognized risk factors for mortality, such as age, body mass index, smoking, white blood cell count, and diabetes. BMR was nonlinearly associated with mortality. The lowest mortality rate was found in the BMR range 31.3-33.9 kcal/m(2)/h. Participants with BMR in the range 33.9-36.4 kcal/m(2)/h and above the threshold of 36.4 kcal/m(2)/h experienced 28% (hazard ratio: 1.28; 95% confidence interval, 1.02-1.61) and 53% (hazard ratio: 1.53; 95% confidence interval, 1.19-1.96) higher mortality risk compared to participants with BMR 31.3-33.9 kcal/m2/h. Conclusion. We confirm previous findings of an age-related decline of BMR. In our study, a blunted age-related decline in BMR was associated with higher mortality, suggesting that such condition reflects poor health status. C1 [Ruggiero, Carmelinda; Metter, E. Jeffrey; Ble, Alessandro; Longo, Dan L.; Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA. [Melenovsky, Vojtech] Inst Clin & Expt Med IKEM, Dept Cardiol, Prague, Czech Republic. [Najjar, Samer S.] NIA, NIH, Human Cardiovasc Studies Unit, Lab Cardiovasc Sci, Baltimore, MD 21225 USA. [Ruggiero, Carmelinda; Cherubini, Antonio; Senin, Umberto] Univ Perugia, Sch Med, Dept Clin & Expt Med, Inst Gerontol & Geriatr, I-06100 Perugia, Italy. RP Ruggiero, C (reprint author), NIA, NIH, Harbor Hosp, 5th Floor,3001 S Hanover St, Baltimore, MD 21225 USA. EM ruggieroc07@hotmail.it OI Cherubini, Antonio/0000-0003-0261-9897 FU Intramural NIH HHS [Z01 AG000015-49] NR 38 TC 46 Z9 46 U1 3 U2 11 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JUL PY 2008 VL 63 IS 7 BP 698 EP 706 PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 336UE UT WOS:000258389300007 PM 18693224 ER PT J AU Padilha, DMP Hilgert, JB Hugo, FN Bos, AJG Ferrucci, L AF Pereira Padilha, Dalva Maria Hilgert, Juliana Balbinot Hugo, Fernando Neves Bos, Angelo Jose Goncalves Ferrucci, Luigi TI Number of teeth and mortality risk in the Baltimore Longitudinal Study of Aging SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE aged; mortality; cohort studies; tooth loss ID QUALITY-OF-LIFE; SERUM INFLAMMATORY MARKERS; CORONARY-HEART-DISEASE; ORAL-HEALTH; TOOTH LOSS; PERIODONTAL-DISEASE; ELDERLY-PEOPLE; GENERAL HEALTH; POPULATION; ASSOCIATION AB Background. Findings from several studies suggested an association between oral health and several health outcomes including cardiovascular disease, aspiration pneumonia, malnutrition, poor quality of life, and mortality. Using data from the Baltimore Longitudinal Study of Aging (BLSA), we tested the hypothesis that number of teeth is indicative of mortality risk independent of other confounders. Methods. Dentists conducted a standardized oral examination that included tooth count, tooth with coronal and cervical caries count, and gingival and periodontal index. Blood tests used in the analysis included fasting glucose, oral glucose tolerance test, serum low-density lipoprotein (LDL), high-density lipoprotein (HDL) cholesterol, triglycerides, and white blood cell counts. Physical activity, skin fold thickness, body mass index and chronic diseases were also evaluated. Results. Of the 500 BLSA participants evaluated, 198 died an average of 130 (+/- 75) months postdental evaluation, and 302 survivors were followed for a mean of 185 (+/- 90) months. Based on multivariate Cox regression models, being edentulous or having than 20 teeth was independently associated with mortality. Conclusion. The results of this study support the notion that number of teeth is a significant and independent risk indicator for early mortality. These findings suggest that the improvement of oral health may have a positive impact on general health and may delay mortality. C1 [Pereira Padilha, Dalva Maria; Hugo, Fernando Neves] Univ Fed Rio Grande do Sul, Sch Dent, Community Oral Hlth Dept, BR-90035003 Porto Alegre, RS, Brazil. [Hilgert, Juliana Balbinot] Univ Luterana Brasil, Postgrad Program Community Hlth, Canoas, RS, Brazil. [Hilgert, Juliana Balbinot] Univ Luterana Brasil, Postgrad Program Dent, Canoas, RS, Brazil. [Bos, Angelo Jose Goncalves; Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA. RP Padilha, DMP (reprint author), Univ Fed Rio Grande do Sul, Sch Dent, Community Oral Hlth Dept, R Ramiro Barcelos 2492, BR-90035003 Porto Alegre, RS, Brazil. EM dalvapadilha@via-rs.net FU Intramural NIH HHS [Z01 AG000015-49] NR 42 TC 38 Z9 40 U1 2 U2 9 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JUL PY 2008 VL 63 IS 7 BP 739 EP 744 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 336UE UT WOS:000258389300013 PM 18693229 ER PT J AU Dear, JW Yuen, PST AF Dear, J. W. Yuen, P. S. T. TI Setting the stage for acute-on-chronic kidney injury SO KIDNEY INTERNATIONAL LA English DT Editorial Material ID DISEASE AB Acute-on-chronic kidney disease will be familiar to many nephrologists. Hsu et al. quantify the risk of acute-on-chronic disease across the stages of preexisting chronic kidney disease. Their study demonstrates the valuable insights that large epidemiological studies can bring to the field of acute kidney injury. C1 [Yuen, P. S. T.] NIDDKD, Renal Diagnost & Therapeut Unit, NIH, Bethesda, MD 20892 USA. [Dear, J. W.] Univ Edinburgh, Ctr Cardiovasc Sci, Queens Med Res Inst, Edinburgh, Midlothian, Scotland. RP Yuen, PST (reprint author), NIDDKD, Renal Diagnost & Therapeut Unit, NIH, 10 Ctr Dr,Room 3N108, Bethesda, MD 20892 USA. EM py@nih.gov RI Yuen, Peter/B-1954-2008 OI Yuen, Peter/0000-0001-9557-3909 FU Intramural NIH HHS [Z99 DK999999] NR 10 TC 5 Z9 9 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JUL PY 2008 VL 74 IS 1 BP 7 EP 9 DI 10.1038/ki.2008.126 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 314DJ UT WOS:000256788900003 PM 18560361 ER PT J AU Gipson, C Hott, MA Brown, P AF Gipson, Chester Hott, Mack A. Brown, Patricia TI A word fro USDA, FDA and OLAW SO LAB ANIMAL LA English DT Editorial Material C1 [Gipson, Chester] USDA, APHIS, AC, Washington, DC 20250 USA. [Brown, Patricia] NIH, OER, OD, HHS, Bethesda, MD 20892 USA. RP Gipson, C (reprint author), USDA, APHIS, AC, Washington, DC 20250 USA. NR 2 TC 4 Z9 4 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD JUL PY 2008 VL 37 IS 7 BP 295 EP 295 DI 10.1038/laban0708-295 PG 1 WC Veterinary Sciences SC Veterinary Sciences GA 320NR UT WOS:000257242300005 PM 18568005 ER PT J AU Bedri, A Gudetta, B Isehak, A Kumbi, S Lulseged, S Mengistu, Y Bhore, AV Bhosale, R Varadhrajan, V Gupte, N Sastry, J Suryavanshi, N Tripathy, S Mmiro, F Mubiru, M Onyango, C Taylor, A Musoke, P Nakabiito, C Abashawl, A Adamu, R Antelman, G Bollinger, RC Bright, P Chaudhary, MA Coberly, J Guay, L Fowler, MG Gupta, A Hassen, E Jackson, JB Moulton, LH Nayak, U Omer, SB Propper, L Ram, M Rexroad, V Ruff, AJ Shankar, A Zwerski, S AF Bedri, Abubaker Gudetta, Berhanu Isehak, Abdulhamid Kumbi, Solomon Lulseged, Sileshi Mengistu, Yohannes Bhore, Arvind V. Bhosale, Ramesh Varadhrajan, Venkat Gupte, Nikhil Sastry, Jayagowri Suryavanshi, Nishi Tripathy, Srikanth Mmiro, Francis Mubiru, Michael Onyango, Carolyne Taylor, Adrian Musoke, Philippa Nakabiito, Clemensia Abashawl, Aida Adamu, Rahel Antelman, Gretchen Bollinger, Robert C. Bright, Patricia Chaudhary, Mohammad A. Coberly, Jacqueline Guay, Laura Fowler, Mary Glenn Gupta, Amita Hassen, Elham Jackson, J. Brooks Moulton, Lawrence H. Nayak, Uma Omer, Saad B. Propper, Lidia Ram, Malathi Rexroad, Vivian Ruff, Andrea J. Shankar, Anita Zwerski, Sheryl CA Six Week Extended Dose Nevirapine TI Extended-dose nevirapine to 6 weeks of age for infants to prevent HIV transmission via breastfeeding in Ethiopia, India, and Uganda: an analysis of three randomised controlled trials SO LANCET LA English DT Article ID MOTHER-TO-CHILD; ANTIRETROVIRAL THERAPY; CLINICAL-TRIAL; SINGLE; ZIDOVUDINE; INTRAPARTUM; LAMIVUDINE; PROPHYLAXIS; RESISTANCE; INFECTION AB Background UNICEF/WHO recommends that infants born to HIVinfected mothers who do not have access to acceptable, feasible, affordable, sustainable, and safe replacement feeding should be exclusively breastfed for at least 6 months. The aim of three trials in Ethiopia, India, and Uganda was to assess whether daily nevirapine given to breastfed infants through 6 weeks of age can decrease HIV transmission via breastfeeding. Methods HIV-infected women breastfeeding their infants were eligible for participation. Participants were randomly assigned to receive either single-dose nevirapine (nevirapine 200 mg to women in labour and nevirapine 2 mg/kg to newborns after birth) or 6 week extended-dose nevirapine (nevirapine 200 mg to women in labour and nevirapine 2 mg/kg to newborn babies after birth plus nevirapine 5 mg daily from days 8-42 for the infant). The randomisation sequences were generated by computer at a central data coordinating Centre. The primary endpoint was HIV infection at 6 months of age in infants who were HIV PCR negative at birth. Analyses were by modified intention to treat, excluding infants with missing specimens and those with indeterminate or confirmed HIV infection at birth. These studies are registered with ClinicalTrials.gov, numbers NCT00074399, NCT00061321, and NCT00639938. Findings 2024 liveborn infants randomised in the study had at least one specimen tested before 6 months of age (1047 infants in the single-dose group and 977 infants in the extended-dose group). The modified intention-to-treat population included 986 infants in the single-dose group and 901 in the extended-dose group. At 6 months, 87 children in the single-dose group and 62 in the extended-dose group were infected with HIV (relative risk 0.80, 95% CI 0 . 58.1. 10; p=0. 16). At 6 weeks of age, 54 children in the single-dose group and 25 in the extended-dose group were HIV positive (0.54, 0 . 34-0.85; p=0.009). 393 infants in the single-dose group and 346 in the extended-dose group experienced grade 3 or 4 serious adverse events during the study (p=0. 54). Interpretation Although a 6-week regimen of daily nevirapine might be associated with a reduction in the risk of HIV transmission at 6 weeks of age, the lack of a significant reduction in the primary endpoint-risk of HIV transmission at 6 months-suggests that a longer course of daily infant nevirapine to prevent HIV transmission via breast milk might be more effective where access to affordable and safe replacement feeding is not yet available and where the risks of replacement feeding are high. Funding US National Institutes of Health; US National Institute of Allergy and Infectious Diseases; Fogarty International Center. C1 [Abashawl, Aida; Adamu, Rahel; Antelman, Gretchen; Bollinger, Robert C.; Bright, Patricia; Chaudhary, Mohammad A.; Coberly, Jacqueline; Guay, Laura; Fowler, Mary Glenn; Gupta, Amita; Hassen, Elham; Jackson, J. Brooks; Moulton, Lawrence H.; Nayak, Uma; Omer, Saad B.; Propper, Lidia; Ram, Malathi; Rexroad, Vivian; Ruff, Andrea J.; Shankar, Anita] Johns Hopkins Univ, Sch Med, Johns Hopkins Ctr Clin Global Hlth Educ, Baltimore, MD 21286 USA. [Zwerski, Sheryl] NIAID, Div Aids, NIH, Bethesda, MD USA. [Bedri, Abubaker; Gudetta, Berhanu; Isehak, Abdulhamid; Kumbi, Solomon; Lulseged, Sileshi; Mengistu, Yohannes] Univ Addis Ababa, Addis Ababa, Ethiopia. [Bhore, Arvind V.; Bhosale, Ramesh; Varadhrajan, Venkat] BJ Med Coll, Pune, Maharashtra, India. [Gupte, Nikhil; Sastry, Jayagowri; Suryavanshi, Nishi] Pune MIT, Pune, Maharashtra, India. [Tripathy, Srikanth] Natl AIDS Res Inst, Pune, Maharashtra, India. [Mmiro, Francis; Mubiru, Michael; Onyango, Carolyne; Taylor, Adrian] Makerere Univ, Johns Hopkins Univ Res Collaborat, Kampala, Uganda. [Nakabiito, Clemensia] Makerere Univ, Minist Hlth, Kampala, Uganda. RP Bollinger, RC (reprint author), Johns Hopkins Univ, Sch Med, Johns Hopkins Ctr Clin Global Hlth Educ, Phipps 540,600 N Wolfe St, Baltimore, MD 21286 USA. EM rcb@jhmi.edu RI Omer, Saad/K-1182-2012; OI Omer, Saad/0000-0002-5383-3474; Moulton, Lawrence/0000-0001-7041-7387 NR 29 TC 161 Z9 164 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD JUL-AUG PY 2008 VL 372 IS 9635 BP 300 EP 313 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 331WH UT WOS:000258042800031 ER PT J AU Freedman, ND Leitzmann, MF Hollenbeck, AR Schatzkin, A Abnet, CC AF Freedman, Neal D. Leitzmann, Michael F. Hollenbeck, Albert R. Schatzkin, Arthur Abnet, Christian C. TI Cigarette smoking and subsequent risk of lung cancer in men and women: analysis of a prospective cohort study SO LANCET ONCOLOGY LA English DT Article ID ENVIRONMENTAL TOBACCO-SMOKE; HISTOLOGIC TYPE; GENDER-DIFFERENCES; US POPULATION; UNITED-STATES; RATES; NONSMOKERS; HEALTH; TRENDS; ADENOCARCINOMA AB Background Whether women are more susceptible than men to lung cancer caused by cigarette smoking has been controversial. To address this question, we aimed to compare incidence rates of lung cancer by stratum of smoking use in men and women of the National Institutes of Health (NIH)-AARP cohort. Methods Participants in the NIH-AARP Diet and Health study responded to a postal questionnaire between Oct 13, 1995, and May 6, 1996, and were followed up until Dec 31, 2003. The questionnaire asked participants about their past and current smoking status, demographics, alcohol intake, tobacco smoking, physical activity, and included a food-frequency questionnaire of 124 items. Incident lung cancers were identified by linkage to individual state cancer registries. We present age-standardised incidence rates for cancer and multivariate hazard ratios (HRs) adjusted for potential confounders, with 95% CIs. This study conforms to the STROBE guidelines. Findings 279214 men and 184623 women from eight states in the USA aged 50-71 years at study baseline were included in this analysis. During follow-up, lung cancers occurred in 4097 men and 2237 women. Incidence rates were 20.3 (95% Cl 16.3-24.3) per 100000 person-years in men who had never smoked (99 cancers) and 25.3 (21.3-29.3) in women who had never smoked (152 cancers); for this group, the adjusted HR for lung cancer was 1.3 (1.0-1.8) for women compared with men. Smoking was associated with increased risk of lung cancer in men and women. The incidence rate of current smokers who smoked more than two packs per day was 1259.2 (1035.0-1483.3) in men and 1308.9 (924.2-1693.6) in women. In current smokers, in a model adjusted for typical smoking dose, the HR was 0.9 (0.8-0.9) for women compared with men. For former smokers, in a model adjusted for years of cessation and typical smoking dose, the HR was 0.9 (0.9-1.0) for women compared with men. Incidence rates of adenocarcinoma, small-cell carcinoma, and undifferentiated tumours were similar in men and women; incidence rates of squamous tumours in men were about twice that in women. Interpretation Our findings suggest that women are not more susceptible than men to the carcinogenic effects of cigarette smoking in the lung. In smokers, incidence rates tended to be higher in men than women with comparable smoking histories, but differences were modest; smoking was strongly associated with lung cancer risk in both men and women. Future studies should confirm whether incidence rates are indeed higher in women who have never smoked than in men who have never smoked. C1 [Freedman, Neal D.; Leitzmann, Michael F.; Schatzkin, Arthur; Abnet, Christian C.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD 20852 USA. [Freedman, Neal D.] NCI, Canc Prevent Fellowship Program, Off Director, NIH,DHHS, Rockville, MD 20852 USA. [Hollenbeck, Albert R.] AARP, Washington, DC USA. RP Freedman, ND (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 6120 Execut Blvd,MSC 7232, Rockville, MD 20852 USA. EM freedmanne@mail.nih.gov RI Abnet, Christian/C-4111-2015; Freedman, Neal/B-9741-2015 OI Abnet, Christian/0000-0002-3008-7843; Freedman, Neal/0000-0003-0074-1098 FU Intramural NIH HHS [Z99 CA999999] NR 40 TC 108 Z9 112 U1 1 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD JUL PY 2008 VL 9 IS 7 BP 649 EP 656 DI 10.1016/51470-2045(08)70154-2 PG 8 WC Oncology SC Oncology GA 324OH UT WOS:000257527400015 PM 18556244 ER PT J AU Shah, SS Lee, JY Verkhoturov, S Tuleuova, N Schweikert, EA Ramanculov, E Revzin, A AF Shah, Sunny S. Lee, Ji Youn Verkhoturov, Stanislav Tuleuova, Nazgul Schweikert, Emile A. Ramanculov, Erlan Revzin, Andalexander TI Exercising spatiotemporal control of cell attachment with optically transparent microelectrodes SO LANGMUIR LA English DT Article ID SELF-ASSEMBLED MONOLAYERS; POLY(ETHYLENE GLYCOL) PHOTOLITHOGRAPHY; ELECTROCHEMICAL DESORPTION; MAMMALIAN-CELLS; CLUSTER IMPACTS; OXIDE SURFACES; ION EMISSION; COCULTURES; ALKYLTRICHLOROSILANES; HEPATOCYTES AB This paper describes a novel approach of controlling cell-surface interactions through an electrochemical "switching" of biointerfacial properties of optically transparent microelectrodes. The indium tin oxide (ITO) microelectrodes, fabricated on glass substrates, were modified with poly(ethylene glycol) (PEG) silane to make glass and ITO regions resistant to protein and cell adhesion. Cyclic voltammetry, with potassium ferricyanide serving as a redox reporter molecule, was used to monitor electron transfer across the electrolyte-ITO interface. PEG silane modification of ITO correlated with diminished electron transfer, judged by the disappearance of ferricyanide redox activity. Importantly, application of reductive potential (-1.4 V vs Ag/AgCl reference) corresponded with reappearance of typical ferricyanide redox peaks, thus pointing to desorption of an insulating PEG silane layer. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) characterization of the silanized ITO surfaces after electrical stimulation indicated complete removal of the silane layer. Significantly, electrical stimulation allowed to "switch" chosen electrodes from nonfouling to protein-adhesive while leaving other ITO and glass regions protected by a nonfouling PEG silane layer. The spatial and temporal control of biointerfacial properties afforded by our approach was utilized to micropattern proteins and cells and to construct micropatterned co-cultures. In the future, control of the biointerfacial properties afforded by this novel approach may allow the organization of multiple cell types into precise geometric configurations in order to create better in vitro mimics of cellular complexity of the native tissues. C1 [Shah, Sunny S.; Lee, Ji Youn; Tuleuova, Nazgul; Revzin, Andalexander] Univ Calif Davis, Dept Biomed Engn, Davis, CA 95616 USA. [Verkhoturov, Stanislav; Schweikert, Emile A.] Texas A&M Univ, Dept Chem, College Stn, TX 77843 USA. [Tuleuova, Nazgul; Ramanculov, Erlan] Natl Biotechnol Ctr, Astana, Kazakhstan. RP Revzin, A (reprint author), Univ Calif Davis, Dept Biomed Engn, Davis, CA 95616 USA. EM arevzin@ucdavis.edu RI Schweikert, Emile/B-7385-2015 OI Schweikert, Emile/0000-0003-3964-7998 NR 38 TC 32 Z9 32 U1 3 U2 14 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0743-7463 J9 LANGMUIR JI Langmuir PD JUL 1 PY 2008 VL 24 IS 13 BP 6837 EP 6844 DI 10.1021/la800231e PG 8 WC Chemistry, Multidisciplinary; Chemistry, Physical; Materials Science, Multidisciplinary SC Chemistry; Materials Science GA 318OI UT WOS:000257101100061 ER PT J AU Ko, RM Kim, HG Wolff, L Klug, CA AF Ko, Rose M. Kim, Hyung-Gyoon Wolff, Linda Klug, Christopher A. TI Roles of p15(Ink4b) and p16(Ink4a) in myeloid differentiation and RUNX1-ETO-associated acute myeloid leukemia SO LEUKEMIA RESEARCH LA English DT Article DE RUNX1-ETO; acute myeloid leukemia; p(15Ink4b); p16(Ink4a); hematopoiesis ID ACUTE MYELOGENOUS LEUKEMIA; T(8/21) FUSION PROTEIN; CELL-CYCLE; TUMOR-SUPPRESSOR; GRANULOCYTIC DIFFERENTIATION; HEMATOPOIETIC STEM; GENE-EXPRESSION; GROWTH ARREST; MURINE MODEL; C/EBP-ALPHA AB Inactivation of p15(Ink4b) expression by promoter hypermethylation occurs in up to 80% of acute myeloid leukemia (AML) cases and is particularly common in the FAB-M2 subtype of AML, which is characterized by the presence of the RUNX1-ETO translocation in 40% of cases. To establish whether the loss of p15(Ink4b) contributes to AML progression in association with RUNXI1-ETO, we have expressed the RUNX1-ETO fusion protein from a retroviral vector in hematopoietic progenitor cells isolated from wild-type, p15(Ink4b) or p16(Ink4a) knockout bone marrow. Analysis of lethally irradiated recipient mice reconstituted with RUNX1-ETO-expressing cells showed that neither p15(Ink4b) or p16(Ink4a) loss significantly accelerated disease progression over the time period of one year post-transplantation. Loss of p15(Ink4b) alone resulted in increased myeloid progenitor cell frequencies in bone marrow by 10-month post-transplant and a 19-fold increase in the frequency of Lin(-)c-Kit(+)Sca-1(+) (LKS) cells that was not associated with expansion of long-term reconstituting HSC. These results strongly suggest that p(15Ink4b) loss must be accompanied by additional oncogenic changes for RUNX1-ETO-associated AML to develop. (c) 2007 Elsevier Ltd. All rights reserved. C1 [Ko, Rose M.; Klug, Christopher A.] Univ Alabama, Dept Biochem & Mol Genet, Birmingham, AL 35294 USA. [Kim, Hyung-Gyoon; Klug, Christopher A.] Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. [Wolff, Linda] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Klug, CA (reprint author), Univ Alabama, Dept Biochem & Mol Genet, 1825 Univ Ave,Shelby Room 510, Birmingham, AL 35294 USA. EM chrisk@uab.edu FU NCI NIH HHS [R01 CA096798-05, R01 CA096798, R01CA087549, R01 CA087549, R01CA096798] NR 40 TC 3 Z9 4 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD JUL PY 2008 VL 32 IS 7 BP 1101 EP 1111 DI 10.1016/j.leukres.2007.10.012 PG 11 WC Oncology; Hematology SC Oncology; Hematology GA 300WM UT WOS:000255856000014 PM 18037485 ER PT J AU Teufel, A Strand, S Maass, T Kanzler, S Zhao, YG Westphal, H Galle, P AF Teufel, Andreas Strand, Susanne Maass, Thorsten Kanzler, Stephan Zhao, Yangu Westphal, Heiner Galle, Peter TI LIVER SPECIFIC LDB1 DELETION RESULTS IN ENHANCED LIVER CANCER DEVELOPMENT SO LIVER TRANSPLANTATION LA English DT Meeting Abstract CT Joint International Congress of the ILTS, ELITA, AND LICAGE CY JUL 09-12, 2008 CL Paris, FRANCE SP ILTS, ELITA, LICAGE C1 [Teufel, Andreas; Strand, Susanne; Maass, Thorsten; Kanzler, Stephan; Galle, Peter] Johannes Gutenberg Univ Mainz, Dept Med 1, D-6500 Mainz, Germany. [Zhao, Yangu; Westphal, Heiner] NICHD, Mammalian Genet Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1527-6465 J9 LIVER TRANSPLANT JI Liver Transplant. PD JUL PY 2008 VL 14 IS 7 BP S131 EP S132 PG 2 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 418JO UT WOS:000264144700230 ER PT J AU Lin, AP Bennett, E Wisk, LE Gharib, M Fraser, SE Wen, H AF Lin, Alexander P. Bennett, Eric Wisk, Lauren E. Gharib, Morteza Fraser, Scott E. Wen, Han TI Circumferential strain in the wall of the common carotid artery: Comparing displacement-encoded and cine MRI in volunteers SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article ID IN-VIVO; VULNERABLE PLAQUE; INTRAVASCULAR ULTRASOUND; STIMULATED ECHOES; HUMAN HEART; STIFFNESS; ATHEROSCLEROSIS; STRESS; DENSE; RISK AB The walls of conduit arteries undergo cyclic stretching from the periodic fluctuation of arterial pressure. Atherosclerotic lesions have been shown to localize to regions of excessive stretching of the arterial wall. We employed a displacement encoding with stimulated echoes (DENSE) sequence to image the motion of the common carotid artery wall and map the two-dimensional (2D) circumferential strain. The sequence utilizes a fully-balanced steady-state free-precession (SSFP) readout with 0.60 mm in-plane resolution. Preliminary results in volunteers at 1.5T (N = 4) and 3.OT (N = 17) are compared to measurements of the lumen circumference from cine images. The agreement between the two independent measurements at both field strengths (P <= 0.001) supports the use of DENSE as a means to map the pulsatile strain in the carotid artery wall. C1 [Lin, Alexander P.; Gharib, Morteza; Fraser, Scott E.] CALTECH, Pasadena, CA 91125 USA. [Bennett, Eric; Wen, Han] NHLBI, NIH, Bethesda, MD 20892 USA. [Wisk, Lauren E.] Univ Calif Los Angeles, Los Angeles, CA USA. RP Lin, AP (reprint author), CALTECH, M-C 114-96, Pasadena, CA 91125 USA. EM alexlin@caltech.edu RI Wisk, Lauren/C-4529-2015; Wen, Han/G-3081-2010 OI Wen, Han/0000-0001-6844-2997 FU Intramural NIH HHS [ZIA HL004606-13] NR 35 TC 23 Z9 24 U1 0 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD JUL PY 2008 VL 60 IS 1 BP 8 EP 13 DI 10.1002/mrm.21621 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 320XE UT WOS:000257267700002 PM 18581403 ER PT J AU Kuklina, EV Whiteman, MK Hillis, SD Jamieson, DJ Meikle, SF Posner, SF Marchbanks, PA AF Kuklina, Elena V. Whiteman, Maura K. Hillis, Susan D. Jamieson, Denise J. Meikle, Susan F. Posner, Samuel F. Marchbanks, Polly A. TI An enhanced method for identifying obstetric deliveries: Implications for estimating maternal morbidity SO MATERNAL AND CHILD HEALTH JOURNAL LA English DT Article; Proceedings Paper CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA DE obstetric deliveries; obstetric labor complications; international classification of diseases; health care surveys ID PREGNANCY-RELATED MORTALITY; UNITED-STATES; ACCURACY; CLASSIFICATION; MAGNITUDE; DIAGNOSES AB Objectives The accuracy of maternal morbidity estimates from hospital discharge data may be influenced by incomplete identification of deliveries. In maternal/infant health studies, obstetric deliveries are often identified only by the maternal outcome of delivery code (International Classification of Diseases code = V27). We developed an enhanced delivery identification method based on additional delivery-related codes and compared the performance of the enhanced method with the V27 method in identifying estimates of deliveries as well as estimates of maternal morbidity. Methods The enhanced and standard V27 methods for identifying deliveries were applied to data from the 1998-2004 Healthcare Cost and Utilization Project Nationwide Inpatient Sample, an annual nationwide representative survey of U.S. hospitalizations. Odds ratios (ORs) and 95% confidence intervals (CIs) from logistic regression were used to examine predictors of deliveries not identified using the V27 method. Results The enhanced method identified 958,868 (3.4%) more deliveries than the 27,128,539 identified using the V27 code alone. Severe complications including major puerperal infections (OR = 3.1, 95% CI 2.8-3.4), hysterectomy (OR = 6.0, 95% CI 5.3-6.8), sepsis (OR = 11.9, 95% CI 10.3-13.6) and respiratory distress syndrome (OR = 16.6, 95% CI 14.4-19.2) were strongly associated with deliveries not identified by the V27 method. Nationwide prevalence rates of severe maternal complications were underestimated with the V27 method compared to the enhanced method, ranging from 9% underestimation for major puerperal infections to 40% underestimation for respiratory distress syndrome. Conclusion Deliveries with severe obstetric complications may be more likely to be missed using the V27 code. Researchers should be aware that selecting deliveries from hospital stay records by V27 codes alone may affect the accuracy of their findings. C1 [Kuklina, Elena V.] Quantell Inc, Ctr Dis Control & Prevent, Atlanta, GA 30341 USA. [Kuklina, Elena V.] Quantell Inc, Taneytown, MD USA. [Whiteman, Maura K.; Hillis, Susan D.; Jamieson, Denise J.; Posner, Samuel F.; Marchbanks, Polly A.] Ctr Dis Control & Prevent, Div Reprod Hlth, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. [Posner, Samuel F.] NICHHD, NIH, Bethesda, MD 20892 USA. RP Kuklina, EV (reprint author), Quantell Inc, Ctr Dis Control & Prevent, 4770 Buford Highway NE,Mailstop K-34, Atlanta, GA 30341 USA. EM ekuklina@cdc.gov OI Posner, Samuel/0000-0003-1574-585X NR 25 TC 110 Z9 110 U1 0 U2 2 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1092-7875 J9 MATERN CHILD HLTH J JI Matern. Child Health J. PD JUL PY 2008 VL 12 IS 4 BP 469 EP 477 DI 10.1007/s10995-007-0256-6 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 332OL UT WOS:000258092200007 PM 17690963 ER PT J AU Wilson, DM Bohr, VA McKinnon, PJ AF Wilson, David M., III Bohr, Vilhelm A. McKinnon, Peter J. TI DNA damage, DNA repair, ageing and age-related disease - Preface SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Editorial Material DE DNA damage; repair; ageing ID LONGEVITY; CANCER C1 [Wilson, David M., III; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, IRP, Baltimore, MD 21224 USA. [McKinnon, Peter J.] St Jude Childrens Hosp, Dept Genet & Tumor Cell Biol, Memphis, TN 38105 USA. RP Wilson, DM (reprint author), NIA, Lab Mol Gerontol, NIH, IRP, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM wilsonda@grc.nia.nih.gov FU Intramural NIH HHS [Z01 AG000743-06, Z99 AG999999]; NINDS NIH HHS [R01 NS037956, R01 NS037956-11] NR 26 TC 29 Z9 29 U1 1 U2 7 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 JUL-AUG PY 2008 VL 129 IS 7-8 BP 349 EP 352 DI 10.1016/j.mad.2008.02.013 PG 4 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 328RS UT WOS:000257816100001 PM 18420253 ER PT J AU Hsieh, P Yamane, K AF Hsieh, Peggy Yamane, Kazuhiko TI DNA mismatch repair: Molecular mechanism, cancer, and ageing SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Review DE mismatch repair; HNPCC; ageing; genome instability; MutS; MutL ID NONPOLYPOSIS COLORECTAL-CANCER; ESCHERICHIA-COLI-MUTS; SACCHAROMYCES-CEREVISIAE MSH2-MSH6; CELL NUCLEAR ANTIGEN; BASE EXCISION-REPAIR; BETA-SLIDING-CLAMP; MICROSATELLITE INSTABILITY; IN-VIVO; ATPASE ACTIVITY; TUMOR-CELLS AB DNA mismatch repair (MMR) proteins are ubiquitous players in a diverse array of important cellular functions. In its role in post-replication repair, MMR safeguards the genome correcting base mispairs arising as a result of replication errors. Loss of MMR results in greatly increased rates of spontaneous mutation in organisms ranging from bacteria to humans. Mutations in MMR genes cause hereditary nonpolyposis colorectal cancer, and loss of MMR is associated with a significant fraction of sporadic cancers. Given its prominence in mutation avoidance and its ability to target a range of DNA lesions, MMR has been under investigation in studies of ageing mechanisms. This review summarizes what is known about the molecular details of the MMR pathway and the role of MMR proteins in cancer susceptibility and ageing. Published by Elsevier Ireland Ltd. C1 [Hsieh, Peggy; Yamane, Kazuhiko] NIDDKD, Genet & Biochem Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Hsieh, P (reprint author), NIDDKD, Genet & Biochem Branch, Natl Inst Hlth, 5 Mem Dr MSC 0538,Bldg 5,Room 324, Bethesda, MD 20892 USA. EM Ph52x@nih.gov FU Intramural NIH HHS [Z01 DK052030-01] NR 240 TC 187 Z9 194 U1 2 U2 51 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 JUL-AUG PY 2008 VL 129 IS 7-8 BP 391 EP 407 DI 10.1016/j.mad.2008.02.012 PG 17 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 328RS UT WOS:000257816100005 PM 18406444 ER PT J AU Stevnsner, T Muftuoglu, M Aamann, MD Bohr, VA AF Stevnsner, Tinna Muftuoglu, Meltem Aamann, Maria Diget Bohr, Vilhelm A. TI The role of Cockayne Syndrome group B (CSB) protein in base excision repair and aging SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Review DE Cockayne Syndrome; oxidative damage; base excision repair; aging ID RNA-POLYMERASE-II; COUPLING FACTOR CSB/ERCC6; INDUCED DNA-DAMAGE; OXIDATIVE STRESS; GENE-PRODUCT; PREFERENTIAL REPAIR; TRANSCRIBED STRAND; INDUCED APOPTOSIS; MAMMALIAN-CELLS; HELICASE DOMAIN AB Cockayne Syndrome (CS) is a rare human genetic disorder characterized by progressive multisystem degeneration and segmental premature aging. The CS complementation group B (CSB) protein is engaged in transcription coupled and global nucleotide excision repair, base excision repair and general transcription. However, the precise molecular function of the CSB protein is still unclear. In the current review we discuss the involvement of CSB in some of these processes, with focus on the role of CSB in repair of oxidative damage, as deficiencies in the repair of these lesions may be an important aspect of the premature aging phenotype of CS. (C) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Stevnsner, Tinna; Aamann, Maria Diget] Univ Aarhus, Dept Mol Biol, Danish Ctr Mol Gerontol, DK-8000 Aarhus C, Denmark. [Muftuoglu, Meltem; Aamann, Maria Diget; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. RP Stevnsner, T (reprint author), Univ Aarhus, Dept Mol Biol, Danish Ctr Mol Gerontol, CF Mollers Alle,Bldg 1130, DK-8000 Aarhus C, Denmark. EM tvs@mb.au.dk FU Intramural NIH HHS [Z01 AG000726-15, Z01 AG000727-15] NR 85 TC 69 Z9 72 U1 0 U2 6 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 JUL-AUG PY 2008 VL 129 IS 7-8 BP 441 EP 448 DI 10.1016/j.mad.2008.04.009 PG 8 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 328RS UT WOS:000257816100009 PM 18541289 ER PT J AU Sabatino, SA Coates, RJ Uhler, RJ Breen, N Tangka, F Shaw, KM AF Sabatino, Susan A. Coates, Ralph J. Uhler, Robert J. Breen, Nancy Tangka, Florence Shaw, Kate M. TI Disparities in mammography use among US women aged 40-64 years, by race, ethnicity, income, and health insurance status, 1993 and 2005 SO MEDICAL CARE LA English DT Article; Proceedings Paper CT AcademyHealth Annual Research Meeting CY JUN 03-05, 2007 CL Orlando, FL SP AcademyHealth DE mammography; disparities; screening ID CANCER SCREENING PRACTICES; EARLY-DETECTION PROGRAM; UNITED-STATES; BREAST-CANCER; NATIONAL BREAST; MEDICAL-CARE; PERFORMANCE; VALIDITY; RECALL AB Objective: To examine current disparities in mammography use, and changes in disparities over time by race, ethnicity, income, insurance, and combinations of these characteristics. Research Design: Comparison of cross-sectional surveys of mammography use using the 1993 and 2005 National Health Interview Survey. Subjects: Women aged 40-64 (1993, n = 4167; 2005, n = 7434). Measures: Mammogram within prior 2 years. Results: In 2005, uninsured women reported the lowest mammography use (38.3%). Though screening increased 6.9 percentage points among low-income, uninsured women, the overall disparity between insured and uninsured women did not change significantly between 1993 and 2005. Screening seems to have declined among middle-income, uninsured women, increasing the gap compared with middle-income, insured women. The lower mammography use in 1993 among American Indian/Alaska Native compared with white women was not present in 2005; however, lower use among Asian compared with white women emerged in 2005. We found no differences between African American and white women. Hispanic women were less likely than non-Hispanic women to report screening in 2005 (58.1% vs. 69.0%). Conclusions: Although mammography use increased for some groups between 1993 and 2005, low-income, uninsured women continued to have the lowest screening rates in 2005 and the disparity for this group was not reduced. The gap in screening use for middle-income, uninsured women increased, resulting from possible declines in mammography even for uninsured women not in poverty. Asian women became less likely to receive screening in 2005. Continuing efforts are needed to eliminate disparities. Increased efforts are especially needed to address the large persistent disparity for uninsured women, including middle-income uninsured women. C1 [Sabatino, Susan A.; Coates, Ralph J.; Uhler, Robert J.; Tangka, Florence; Shaw, Kate M.] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30341 USA. [Breen, Nancy] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Sabatino, SA (reprint author), Ctr Dis Control & Prevent, Div Canc Prevent & Control, Natl Ctr Chron Dis Prevent & Hlth Promot, 4770 Buford Highway Mailstop K-53, Atlanta, GA 30341 USA. EM ssabatino@cdc.gov NR 37 TC 82 Z9 83 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD JUL PY 2008 VL 46 IS 7 BP 692 EP 700 DI 10.1097/MLR.0b013e31817893b1 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 320WJ UT WOS:000257265600008 PM 18580388 ER PT J AU Miller, FG Pearson, SD AF Miller, Franklin G. Pearson, Steven D. TI Coverage with evidence development - Ethical issues and policy implications SO MEDICAL CARE LA English DT Article DE health insurance; coverage; Medicare; clinical research; coercion ID MEDICARE COVERAGE; CLINICAL-RESEARCH; TECHNOLOGIES; REGISTRY; CONSENT AB Coverage with evidence development (CED) is an evolving method of providing provisional access to novel medical interventions while generating the evidence needed to determine whether unconditional coverage is warranted. In this article we review the policy rationale for CED and present a normative analysis that addresses ethical concerns and policy implications. C1 [Miller, Franklin G.; Pearson, Steven D.] NIH, Dept Bioeth, Bethesda, MD 20892 USA. RP Miller, FG (reprint author), NIH, Dept Bioeth, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM fmiller@nih.gov NR 24 TC 27 Z9 27 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD JUL PY 2008 VL 46 IS 7 BP 746 EP 751 DI 10.1097/MLR.0b013e3181789453 PG 6 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 320WJ UT WOS:000257265600015 PM 18580395 ER PT J AU Utian, WH Archer, DF Bachmann, GA Gallaher, JC Grodstein, F Heiman, JR Henderson, VW Hodis, HN Karas, RH Lobo, RA Manson, JE Reid, RL Schmidt, PJ Stuenkel, CA AF Utian, Wulf H. Archer, David F. Bachmann, Gloria A. Gallaher, J. Christopher Grodstein, Francine Heiman, Julia R. Henderson, Victor W. Hodis, Howard N. Karas, Richard H. Lobo, Rogerio A. Manson, JoAnn E. Reid, Robert L. Schmidt, Peter J. Stuenkel, Cynthia A. CA The Board Trustees NAMS TI Estrogen and progestogen use in postmenopausal women: July 2008 position statement of The North American Menopause Society SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Review DE menopause; perimenopause; estrogen; progestogen; hormone therapy; hormone replacement therapy; vasomotor symptoms; vaginal atrophy; sexual function; urinary health; quality of life; osteoporosis; coronary heart disease; venous thromboembolism; stroke; total mortality; diabetes mellitus; endometrial cancer; breast cancer; mood; depression; dementia; cognitive decline; premature menopause; premature ovarian failure; bioidentical hormones; postmenopause; Women's Health Initiative; NAMS ID HORMONE-REPLACEMENT THERAPY; CONJUGATED EQUINE ESTROGENS; RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-LIFE; DOSE TRANSDERMAL ESTRADIOL; BREAST-CANCER RISK; PLACEBO-CONTROLLED TRIAL; CORONARY-HEART-DISEASE; BONE-MINERAL DENSITY; HEALTH INITIATIVE MEMORY AB Objective: To update for both clinicians and the lay public the evidence-based position statement published by The North American Menopause Society (NAMS) in March 2007 regarding its recommendations for menopausal hormone therapy (HT) for postmenopausal women, with consideration for the therapeutic benefit-risk ratio at various times through menopause and beyond. Design: An Advisory Panel of clinicians and researchers expert in the field of women's health was enlisted to review the March 2007 NAMS position statement, evaluate new evidence through an evidence-based analysis, and reach consensus on recommendations. The Panel's recommendations were reviewed and approved by the NAMS Board of Trustees as an official NAMS position statement. The document was provided to other interested organizations to seek their endorsement. Results: Current evidence supports a consensus regarding the role of HT in postmenopausal women, when potential therapeutic benefits and risks around the time of menopause are considered. This paper lists all these areas along with explanatory comments. Conclusions that vary from the 2007 position statement are highlighted. Addenda include a discussion of risk concepts, a new component not included in the 2007 paper, and a recommended list of areas for future HT research. A suggested reading list of key references is also provided. Conclusions: Recent data support the initiation of HT around the time of menopause to treat menopause-related symptoms; to treat or reduce the risk of certain disorders, such as osteoporosis or fractures in select postmenopausal women; or both. The benefit-risk ratio for menopausal HT is favorable close to menopause but decreases with aging and with time since menopause in previously untreated women. C1 [Utian, Wulf H.] Cleveland Clin, Womens Hlth Inst, Cleveland, OH 44106 USA. [Utian, Wulf H.] Case Western Reserve Univ, Sch Med, Cleveland, OH USA. [Utian, Wulf H.] N Amer Menopause Soc, Cleveland, OH USA. [Archer, David F.] Eastern Virginia Med Sch, Conrad Clin Res Ctr, Norfolk, VA 23501 USA. [Bachmann, Gloria A.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Womens Hlth Inst, New Brunswick, NJ USA. [Bachmann, Gloria A.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Obstet Gynecol & Reprod Sci, New Brunswick, NJ USA. [Gallaher, J. Christopher] Creighton Univ, Med Ctr, Omaha, NE USA. [Grodstein, Francine] Harvard Univ, Brigham & Womens Hosp, Channing Lab, Sch Med, Boston, MA 02115 USA. [Heiman, Julia R.] Indiana Univ, Kinsey Inst Res Sex Gender & Reprod, Bloomington, IN USA. [Henderson, Victor W.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Hodis, Howard N.] Univ So Calif, Keck Sch Med, Div Cardiovasc Med, Atherosclerosis Res Unit, Los Angeles, CA 90033 USA. [Karas, Richard H.] Tufts Univ, Sch Med, Tufts New England Med Ctr, Womens Heart Ctr, Boston, MA 02111 USA. [Karas, Richard H.] Tufts Univ, Sch Med, Dept Med, Tufts New England Med Ctr, Boston, MA 02111 USA. [Karas, Richard H.] Tufts Univ, Sch Med, Mol Cardiol Res Inst, Tufts New England Med Ctr, Boston, MA 02111 USA. [Lobo, Rogerio A.] Columbia Univ, Coll Phys & Surg, New York, NY USA. [Manson, JoAnn E.] Harvard Univ, Sch Med, Boston, MA USA. [Manson, JoAnn E.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Manson, JoAnn E.] Brigham & Womens Hosp, Connors Ctr Womens Hlth & Gender Biol, Boston, MA 02115 USA. [Reid, Robert L.] Queens Univ, Div Reprod Endocrinol & Infertil, Kingston, ON, Canada. [Schmidt, Peter J.] NIMH, Behav Endocrinol Branch, Bethesda, MD 20892 USA. [Stuenkel, Cynthia A.] Univ Calif San Diego, La Jolla, CA 92093 USA. RP Utian, WH (reprint author), POB 94527, Cleveland, OH 44101 USA. EM info@menopause.org NR 198 TC 81 Z9 90 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 EI 1530-0374 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD JUL-AUG PY 2008 VL 15 IS 4 BP 584 EP 602 DI 10.1097/gme.0b013e31817b076a PN 1 PG 19 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 324ER UT WOS:000257501000004 ER PT J AU Allison, MA Manson, JE Langer, RD Carr, JJ Rossouw, JE Pettinger, MB Phillips, L Cochrane, BB Eaton, CB Greenland, P Hendrix, S Hsia, J Hunt, JR Jackson, RD Johnson, KC Kuller, LH Robinson, J AF Allison, Matthew A. Manson, JoAnn E. Langer, Robert D. Carr, J. Jeffrey Rossouw, Jacques E. Pettinger, Mary B. Phillips, Lawrence Cochrane, Barbara B. Eaton, Charles B. Greenland, Philip Hendrix, Susan Hsia, Judith Hunt, Julie R. Jackson, Rebecca D. Johnson, Karen C. Kuller, Lewis H. Robinson, Jennifer CA Women's Hlth Initiative Women's Hl TI Oophorectomy, hormone therapy, and subclinical coronary artery disease in women with hysterectomy: the Women's Health Initiative coronary artery calcium study SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE calcium; coronary; oophorectomy; hormone therapy; women; coronary artery disease; atherosclerosis ID ELECTRON-BEAM TOMOGRAPHY; SYSTEMIC CALCIFIED ATHEROSCLEROSIS; RANDOMIZED CONTROLLED-TRIAL; AMERICAN-HEART-ASSOCIATION; COMPUTED-TOMOGRAPHY; POSTMENOPAUSAL WOMEN; REPLACEMENT THERAPY; PROGNOSTIC VALUE; FOLLOW-UP; UNILATERAL OOPHORECTOMY AB Objective. Surgical menopause has been associated with an increased risk of coronary heart disease events. In this study, we aimed to determine the associations between coronary artery calcium (CAC) and hysterectomy, oophorectomy, and hormone therapy use with a focus on the duration of menopause for which there was no hormone therapy use. Design: In a substudy of the Women's Health Initiative placebo-controlled trial of conjugated equine estrogens (0.625 rng/d), we measured CAC by computed tomography 1.3 years after the trial was stopped. Participants included 1,064 women with previous hysterectomy, aged 50 to 59 years at baseline. The mean trial period was 7.4 years. Imaging was performed at a mean of 1.3 years after the trial was stopped. Results: Mean age was 55.1 years at randomization and 64.8 years at CAC measurement. In the overall cohort, there were no significant associations between bilateral oophorectomy, years since hysterectomy, years since hysterectomy without taking hormone therapy (HT), years since bilateral oophorectomy, and years of HT use before Women's Health Initiative enrollment and the presence of CAC. However, there was a significant interaction between bilateral oophorectomy and prerandomization HT use for the presence of any CAC (P = 0.05). When multivariable analyses were restricted to women who reported no previous HT use, those with bilateral oophorectomy had an odds ratio of 2.0 (95% CI: 1.2-3.4) for any CAC compared with women with no history of oophorectomy, whereas among women with unilateral or partial oophorectorny, the odds of any CAC was 1.7 (95% CI: 1.0-2.8). Among women with bilateral oophorectomy, HT use within 5 years of oophorectomy was associated with a lower prevalence of CAC. Conclusions: Among women with previous hysterectomy, subclinical coronary artery disease was more prevalent among those with oophorectorny and no prerandomization HT use, independent of traditional cardiovascular disease risk factors. The results suggest that factors related to oophorectomy and the absence of estrogen treatment in oophorectomized women may be related to coronary heart disease. C1 [Allison, Matthew A.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Manson, JoAnn E.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. [Langer, Robert D.] Geisinger Hlth Syst, Danville, PA USA. [Carr, J. Jeffrey] Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. [Rossouw, Jacques E.] NHLBI, Bethesda, MD 20892 USA. [Pettinger, Mary B.; Hunt, Julie R.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Phillips, Lawrence] Emory Univ, Atlanta, GA 30322 USA. [Cochrane, Barbara B.] Univ Washington, Seattle, WA 98195 USA. [Eaton, Charles B.] Brown Univ, Providence, RI 02912 USA. [Greenland, Philip] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Hendrix, Susan] Wayne State Univ, Detroit, MI USA. [Hsia, Judith] George Washington Univ, Washington, DC USA. [Jackson, Rebecca D.] Ohio State Univ, Columbus, OH 43210 USA. [Johnson, Karen C.] Univ Tennessee, Hlth Sci Ctr, Memphis, TN USA. [Kuller, Lewis H.] Univ Pittsburgh, Pittsburgh, PA USA. [Robinson, Jennifer] Univ Iowa, Iowa City, IA USA. RP Allison, MA (reprint author), 8950 Villa La Jolla Dr,Suite B-122, La Jolla, CA 92093 USA. EM mallison@ucsd.edu RI Carr, John/A-1938-2012; OI Carr, John/0000-0002-4398-8237; Allison, Matthew/0000-0003-0777-8272 FU WHI NIH HHS [N01 WH022110, N01 WH022110-024, N01 WH032120] NR 52 TC 33 Z9 35 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD JUL-AUG PY 2008 VL 15 IS 4 BP 639 EP 647 DI 10.1097/gme.0b013e31816d5b1c PN 1 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 324ER UT WOS:000257501000009 PM 18458645 ER PT J AU Loprinzi, CL Barton, DL Sloan, JA Novotny, PJ Dakhil, SR Verdirame, JD Knutson, WH Kelaghan, J Christensen, B AF Loprinzi, Charles L. Barton, Debra L. Sloan, Jeff A. Novotny, Paul J. Dakhil, Shaker R. Verdirame, Joseph D. Knutson, Wilma H. Kelaghan, Joseph Christensen, Brad TI Mayo Clinic and North Central Cancer Treatment Group hot flash studies: a 20-year experience SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE hot flashes; hot flushes; breast cancer ID RANDOMIZED CONTROLLED-TRIAL; HORMONE REPLACEMENT THERAPY; ESTROGEN PLUS PROGESTIN; BREAST-CANCER; PILOT EVALUATION; BLACK COHOSH; DEPOMEDROXYPROGESTERONE ACETATE; TRANSDERMAL CLONIDINE; POSTMENOPAUSAL WOMEN; DOUBLE-BLIND AB Objective: This project was designed to provide an overview of hot flash studies conducted over the past two decades at the Mayo Clinic and in the North Central Cancer Treatment Group. Design: Prospective clinical trials performed by these investigators are illustrated, described, and discussed. Results: Ten randomized, controlled (eight placebo controlled), double-blind clinical trials were conducted involving a total of 1,581 women and three placebo-controlled, double-blind clinical trials involving a total of 329 men were conducted. In addition, 14 pilot trials, having involved more than 325 participants to date, were conducted. Conclusions: Data from the pilot trials have given direction for substances that ought to be further explored in more definitive studies. In men, randomized studies demonstrate that hot flashes are markedly decreased by low doses of megestrol acetate, moderately decreased by gabapentin, but not substantially decreased by clonidine. Results from the randomized trials in women demonstrate that hot flashes are markedly decreased by relatively low doses of progestational agents (megestrol acetate and medroxyprogesterone acetate), moderately decreased by venlafaxine, mildly to moderately decreased by fluoxetine, mildly decreased by clonidine, but not substantially decreased by vitamin E, a soy phytoestrogen product, or black cohosh. Last, the data investigated in these studies support the hypothesis that, for the treatment of hot flashes in women, the results of therapeutic maneuvers are similar regardless of whether the patient has a history of breast cancer and/or is taking tamoxifen. C1 [Loprinzi, Charles L.; Barton, Debra L.; Christensen, Brad] Mayo Clin, Dept Oncol, Rochester, MN 55905 USA. [Sloan, Jeff A.; Novotny, Paul J.] Mayo Clin, Canc Ctr Stat, Rochester, MN 55905 USA. [Dakhil, Shaker R.] Wichita Community Clin Oncol Program, Wichita, KS USA. [Verdirame, Joseph D.] Alegent Hlth Immanuel Med Ctr, Omaha, NE USA. [Knutson, Wilma H.] Duluth Clin, Duluth, MN USA. [Kelaghan, Joseph] NCI, Community Oncol & Prevent Trials Res Grp, Bethesda, MD 20892 USA. RP Loprinzi, CL (reprint author), Mayo Clin, Dept Oncol, 200 1st St SW, Rochester, MN 55905 USA. EM cloprinzi@mayo.edu NR 44 TC 30 Z9 31 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD JUL-AUG PY 2008 VL 15 IS 4 BP 655 EP 660 DI 10.1097/gme.0b013e3181679150 PN 1 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 324ER UT WOS:000257501000011 PM 18427355 ER PT J AU Rebois, RV Robitaille, M Petrin, D Zylbergold, P Trieu, P Hebert, TE AF Rebois, R. Victor Robitaille, Melanie Petrin, Darlaine Zylbergold, Peter Trieu, Phan Hebert, Terence E. TI Combining protein complementation assays with resonance energy transfer to detect multipartner protein complexes in living cells SO METHODS LA English DT Article DE bioluminescence resonance energy transfer; fluorescence resonance energy transfer; protein complementation assay; protein-protein interaction; G protein signalling complexes; bimolecular fluorescence complementation ID GREEN-FLUORESCENT PROTEIN; CARDIAC MUSCARINIC RECEPTORS; FORM STABLE COMPLEXES; ADENYLYL-CYCLASE; IN-VIVO; SIGNALING COMPLEXES; COUPLED RECEPTORS; TRANSFER BRET; VISUALIZATION; COOPERATIVITY AB A variety of fluorescent proteins with different spectral properties have been created by mutating green fluorescent protein. When these proteins are split in two, neither fragment is fluorescent per se, nor can a fluorescent protein be reconstituted by co-expressing the complementary N- and C-terminal fragments. However, when these fragments are genetically fused to proteins that associate with each other in cellulo, the N- and C-terminal fragments of the fluorescent protein are brought together and can reconstitute a fluorescent protein. A similar protein complementation assay (PCA) can be performed with two complementary fragments of various luciferase isoforms. This makes these assays useful tools for detecting the association of two proteins in living cells. Bioluminescence resonance energy transfer (BRET) or fluorescence resonance energy transfer (FRET) occurs when energy from, respectively, a luminescent or fluorescent donor protein is non-radiatively transferred to a fluorescent acceptor protein. This transfer of energy can only occur if the proteins are within 100 angstrom of each other. Thus, BRET and FRET are also useful tools for detecting the association of two proteins in living cells. By combining different protein fragment complementation assays (PCA) with BRET or FRET it is possible to demonstrate that three or more proteins are simultaneous parts of the same protein complex in living cells. As an example of the utility of this approach, we show that as many as four different proteins are simultaneously associated as part of a G protein-coupled receptor signalling complex. (c) 2008 Elsevier Inc. All rights reserved. C1 [Robitaille, Melanie; Petrin, Darlaine; Zylbergold, Peter; Trieu, Phan; Hebert, Terence E.] McGill Univ, Dept Pharmacol & Therapeut, Montreal, PQ H3G 1Y6, Canada. [Rebois, R. Victor] Natl Inst Deafness & Other Commun Disorders, Bethesda, MD 20892 USA. [Rebois, R. Victor] Natl Inst Neurol Disorders & Stroke, Bethesda, MD 20892 USA. [Robitaille, Melanie] Univ Montreal, Dept Biochim, Montreal, PQ H3C 3J7, Canada. RP Hebert, TE (reprint author), McGill Univ, Dept Pharmacol & Therapeut, Room 1303 McIntyre Med Sci Bldg,3655 Promenade Si, Montreal, PQ H3G 1Y6, Canada. EM terence.hebert@mcgill.ca FU NIH; National Institute of Deafness; National Institute of Neurological Disorders and Stroke; Canadian Institutes of Health Research; Heart and Stroke Foundation of Quebec; CIHR Team in GPCR Allosteric Regulation (CTiGAR); Chercheur National of the Fonds de la Recherche en Sante du Quebec; Fonds de la Recherche en Sante du Quebec FX This work was supported in part by the Intramural Research Program of the NIH, National Institute of Deafness and Other Communication Disorders and the National Institute of Neurological Disorders and Stroke, R.V.R., and by grants from the Canadian Institutes of Health Research and the Heart and Stroke Foundation of Quebec to T.E.H. This work was also supported by the CIHR Team in GPCR Allosteric Regulation (CTiGAR). T.E.H. is a Chercheur National of the Fonds de la Recherche en Sante du Quebec. M.R. holds a doctoral award from the Fonds de la Recherche en Sante du Quebec. NR 32 TC 28 Z9 32 U1 1 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 J9 METHODS JI Methods PD JUL PY 2008 VL 45 IS 3 BP 214 EP 218 DI 10.1016/j.ymeth.2008.06.006 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 339YV UT WOS:000258614100006 PM 18586102 ER PT J AU Grebe, KM Yewdell, JW Bennink, JR AF Grebe, Kristie M. Yewdell, Jonathan W. Bennink, Jack R. TI Heterosubtypic immunity to influenza A virus: where do we stand? SO MICROBES AND INFECTION LA English DT Article DE Influenza A virus; Heterosubtypic immunity; Antibodies; T cells ID CYTOTOXIC T-CELLS; TOXIC LYMPHOCYTES-T; LETHAL INFLUENZA; HETEROTYPIC IMMUNITY; MATRIX PROTEIN-2; M2 PROTEIN; B-CELL; EXTRACELLULAR DOMAIN; CROSS-PROTECTION; INFECTED-CELLS AB Influenza A virus (IAV) strains are denoted by the subtype of their hemagglutinin (HA) and neuraminidase (NA) virion surface proteins. Major changes in HA subtype among strains circulating in humans are reffered to as "antigenic shift". Antigenic shift can occur by two means: direct transmission of a zoonotic strain to humans or through reshuffling of the segmented genome in cells co-infected with animal and human strains. The lack of circulating anti-HA antibodies in human populations to a novel IAV results in extremely high frequency of illness and the potential for severe morbidity and mortality on a world-wide basis: the dreaded pandemic. Such pandemics could be partially controlled by developing a vaccine that generated effective heterosubtypic immunity (HSI) based on immune recognition of IAV antigens conserved across all viral strains. While it has long been known that T cells exhibit such broad cross-reactive specificity that could provide effective HSI, recent influenza and speculate aon the potential for this approach to contribute to public health. Published by Elsevier Masson SAS. C1 [Grebe, Kristie M.; Yewdell, Jonathan W.; Bennink, Jack R.] NIAID, Viral Immunol & Cellular Biol Sect, Viral Dis Lab, NIH,DHHS, Bethesda, MD 20892 USA. RP Bennink, JR (reprint author), NIAID, Viral Immunol & Cellular Biol Sect, Viral Dis Lab, NIH,DHHS, 33 North Dr, Bethesda, MD 20892 USA. EM jbennink@nih.gov RI yewdell, jyewdell@nih.gov/A-1702-2012 FU NIAID; Division of Intramural Research; NTH; DHHS FX This research was supported by the NIAID, Division of Intramural Research, NTH, DHHS. We wish to thank Suzanne Epstein for a critical reading of the manuscript. NR 75 TC 109 Z9 113 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD JUL PY 2008 VL 10 IS 9 SI SI BP 1024 EP 1029 DI 10.1016/j.micinf.2008.07.002 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 372FU UT WOS:000260888300015 PM 18662798 ER PT J AU Xue, HH Jing, XF Bollenbacher-Reilley, J Zhao, DM Haring, JS Yang, BL Liu, CY Bishop, GA Harty, JT Leonard, WJ AF Xue, Hai-Hui Jing, Xuefang Bollenbacher-Reilley, Julie Zhao, Dong-Mei Haring, Jodie S. Yang, Baoli Liu, Chengyu Bishop, Gail A. Harty, John T. Leonard, Warren J. TI Targeting the GA binding protein beta 1L isoform does not perturb lymphocyte development and function SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSCRIPTION FACTOR GABP; T-CELLS; GENE-TRANSCRIPTION; RECEPTOR-ALPHA; NEUROMUSCULAR-JUNCTION; SYNAPTIC EXPRESSION; ETS PROTEINS; SUBUNIT GENE; PAX-5 BSAP; ACTIVATION AB GA binding protein (GASP) is a ubiquitously expressed Ets family transcription factor that consists of two subunits, GABP alpha and GABP beta. GABP alpha binds to DNA, and GABP beta heterodimerizes with GABP alpha and possesses the ability to transactivate target genes. Our previous studies using GABP alpha-deficient mice revealed that GABPa is required for the development of both T and B cells. Two splice variants of GABP beta are generated from the Gabpbl locus and differ in their carboxy-terminal lengths and sequences. The longer isoform (GABP beta 1L) can homodimerize and thus form alpha(2)beta(2), tetramers depending on the gene context, whereas the shorter isoform (GABP beta 1S) cannot. In this study, we generated mice that are deficient in GABP beta 1L but that retain the expression of GABP beta 1S. Surprisingly, GABP beta 1L(-1-) mice had normal T- and B-cell development, and mature T and B cells showed normal responses to various stimuli. In contrast, targeting both GABP beta 1L and GABP beta 1S resulted in early embryonic lethality. Because of its incapability of forming homodimers, GABP beta 1S has been suspected to have a dominant negative role in regulating GABP target genes. Our findings argue against such a possibility and rather suggest that GABP beta 1S has a critical role in maintaining the transcriptional activity of the GABP alpha/beta complex. C1 [Xue, Hai-Hui; Jing, Xuefang; Zhao, Dong-Mei; Haring, Jodie S.; Bishop, Gail A.; Harty, John T.] Univ Iowa, Dept Microbiol, Carver Coll Med, Iowa City, IA 52246 USA. [Yang, Baoli] Univ Iowa, Dept Obstet & Gynecol, Carver Coll Med, Iowa City, IA 52246 USA. [Bishop, Gail A.; Harty, John T.] Univ Iowa, Interdisciplinary Grad Program Immunol, Carver Coll Med, Iowa City, IA 52246 USA. [Bollenbacher-Reilley, Julie; Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. [Liu, Chengyu] NHLBI, Transgen Core Facil, NIH, Bethesda, MD 20892 USA. RP Xue, HH (reprint author), Univ Iowa, Dept Microbiol, Carver Coll Med, 51 Newton Rd,BSB 3-710, Iowa City, IA 52246 USA. EM hai-hui-xue@uiowa.edu FU Intramural NIH HHS NR 41 TC 6 Z9 6 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 2008 VL 28 IS 13 BP 4300 EP 4309 DI 10.1128/MCB.01855-07 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 318NS UT WOS:000257099400008 PM 18426908 ER PT J AU Frew, IJ Minola, A Georgiev, S Hitz, M Moch, H Richard, S Vortmeyer, AO Krek, W AF Frew, Ian J. Minola, Andrea Georgiev, Strahil Hitz, Manuela Moch, Holger Richard, Stephane Vortmeyer, Alexander O. Krek, Wilhelm TI Combined Vhlh and Pten mutation causes genital tract cystadenoma and squamous metaplasia SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HIPPEL-LINDAU-DISEASE; TUMOR-SUPPRESSOR; EPIDIDYMAL CYSTADENOMAS; PROGNOSTIC-SIGNIFICANCE; TARGETED INACTIVATION; PAPILLARY CYSTADENOMA; GENE-EXPRESSION; CELL CARCINOMA; NOTCH; P63 AB Patients with von Hippel-Lindau (VHL) disease develop tumors in a range of tissues, but existing mouse models of Vhlh mutation have failed to reproduce these lesions. Epididymal cystadenomas arise frequently in VHL patients, but VHL mutation alone is believed to be insufficient for tumor formation, implying a requirement for cooperating mutations in epididymal pathogenesis. Here we show that epididymal cystadenomas from VHL patients frequently also lack expression of the PTEN tumor suppressor and display activation of phosphatidylinositol 3-kinase (PI3K) pathway signaling. Strikingly, while conditional inactivation of either Vhlh or Pten in epithelia of the mouse genital tract fails to produce a tumor phenotype, their combined deletion causes benign genital tract tumors with regions of squamous metaplasia and cystadenoma. The latter are histologically identical to lesions found in VHL patients. Importantly, these lesions are characterized by expansion of basal stem cells, high levels of expression and activity of HIF1 alpha and HIF2 alpha, and dysregulation of PI3K signaling. Our studies suggest a model for cooperative tumor suppression in which inactivation of PTEN facilitates epididymal cystadenoma genesis initiated by loss of VHL. C1 [Frew, Ian J.; Minola, Andrea; Georgiev, Strahil; Hitz, Manuela; Krek, Wilhelm] Swiss Fed Inst Technol, Inst Cell Biol, CH-8093 Zurich, Switzerland. [Moch, Holger] Univ Zurich Hosp, Inst Surg Pathol, Dept Pathol, CH-8091 Zurich, Switzerland. [Richard, Stephane] Fac Med Paris Sud, Genet Oncol EPHE, Villejuif, France. [Richard, Stephane] CNRS, FRE 2939, Inst Cancerol Gustave Roussy, Villejuif, France. [Vortmeyer, Alexander O.] Natl Inst Hlth, NINDS, Surg Neurol Branch, Bethesda, MD USA. RP Krek, W (reprint author), Swiss Fed Inst Technol, Inst Cell Biol, CH-8093 Zurich, Switzerland. EM wilhelm.krek@cell.biol.ethz.ch OI Frew, Ian/0000-0003-2735-5509 NR 52 TC 27 Z9 27 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 2008 VL 28 IS 14 BP 4536 EP 4548 DI 10.1128/MCB.02132-07 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 325UI UT WOS:000257613400008 PM 18474617 ER PT J AU Kuwano, Y Kim, HH Abdelmohsen, K Pullmann, R Martindale, JL Yang, XL Gorospe, M AF Kuwano, Yuki Kim, Hyeon Ho Abdelmohsen, Kotb Pullmann, Rudolf, Jr. Martindale, Jennifer L. Yang, Xiaoling Gorospe, Myriam TI MKP-1 mRNA stabilization and translational control by RNA-Binding proteins HuR and NF90 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID AU-RICH ELEMENT; MAP KINASE PHOSPHATASE-1; IMMEDIATE-EARLY GENE; NUCLEAR EXPORT; P38 MAPK; IN-VIVO; EXPRESSION; STRESS; TURNOVER; PHOSPHORYLATION AB The mitogen-activated protein (MAP) kinase phosphatase 1 (MKP-1) plays a major role in dephosphorylating and thereby inactivating the MAP kinases extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38. Here, we examine the posttranscriptional events underlying the robust MKP-1 induction by oxidants in HeLa cells. H2O2 treatment potently stabilized the MKP-1 mRNA and increased the association of MKP-1 mRNA with the translation machinery. Four RNA-binding proteins (RNA-BPs) that influence mRNA turnover and/or translation (HuR, NF90, TIAR, and TIA-1) were found to bind to biotinylated transcripts spanning the MKP-1 AU-rich 3' untranslated region. By using ribonucleoprotein immunoprecipitation analysis, we showed that H2O2 treatment increased the association of MKP-1 mRNA with HuR and NF90 and decreased its association with the translational repressors TIAR and TIA-1. HuR or NF90 silencing significantly diminished the H2O2-stimulated MKP-1 mRNA stability; HuR silencing also markedly decreased MKP-1 translation. In turn, lowering MKP-1 expression in HuR-silenced cultures resulted in substantially elevated phosphorylation of JNK and p38 after H2O2 treatment. Collectively, MKP-1 upregulation by oxidative stress is potently influenced by increased mRNA stability and translation, mediated at least in part by the RNA-BPs HuR and NF90. C1 [Kuwano, Yuki; Kim, Hyeon Ho; Abdelmohsen, Kotb; Pullmann, Rudolf, Jr.; Martindale, Jennifer L.; Yang, Xiaoling; Gorospe, Myriam] NIA, Cellular & Mol Biol Lab, Intramural Res Program, NIH, Baltimore, MD 21228 USA. RP Gorospe, M (reprint author), NIA IRP, LCMB, NIH, Box 12,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM myriam-gorospe@nih.gov OI abdelmohsen, Kotb/0000-0001-6240-5810 FU Intramural NIH HHS NR 62 TC 130 Z9 132 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 JUL PY 2008 VL 28 IS 14 BP 4562 EP 4575 DI 10.1128/MCB.00165-08 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 325UI UT WOS:000257613400010 PM 18490444 ER PT J AU Guigon, CJ Zhao, L Lu, CX Willingham, MC Cheng, SY AF Guigon, Celine J. Zhao, Li Lu, Changxue Willingham, Mark C. Cheng, Sheue-yann TI Regulation of beta-catenin by a novel nongenomic action of thyroid hormone beta receptor SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSCRIPTIONAL ACTIVITY; MOUSE MODEL; FUNCTIONAL INTERACTION; SIGNALING PATHWAY; ACTIVATION; CARCINOMA; CANCER; GAMMA; GENE; MUTATION AB We previously created a knock-in mutant mouse harboring a dominantly negative mutant thyroid hormone receptor beta (TR beta(PV/PV) mouse) that spontaneously develops a follicular thyroid carcinoma similar to human thyroid cancer. We found that beta-catenin, which plays a critical role in oncogenesis, was highly elevated in thyroid tumors of TR beta(PV/PV) mice. We sought to understand the molecular basis underlying aberrant accumulation of beta-catenin by mutations of TR beta in vivo. Cell-based studies showed that thyroid hormone (T3) induced the degradation of beta-catenin in cells expressing TR beta via proteasomal pathways. In contrast, no T3-induced degradation occurred in cells expressing the mutant receptor (TR beta PV). In vitro binding studies and cell-based analyses revealed that beta-catenin physically associated with unliganded TR beta or TR beta PV. However, in the presence of T3, beta-catenin was dissociated from TR beta-beta-catenin complexes but not from TR beta PV beta-catenin complexes. beta-Catenin signaling was repressed by T3 in TR beta-expressing cells through decreasing beta-catenin-mediated transcription activity and target gene expression, whereas sustained beta-catenin signaling was observed in TR beta PV-expressing cells. The stabilization of beta-catenin, via association with a mutated TR beta, represents a novel activating mechanism of the oncogenic protein beta-catenin that could contribute to thyroid carcinogenesis in TR beta(PV/PV) mice. C1 [Guigon, Celine J.; Zhao, Li; Lu, Changxue; Cheng, Sheue-yann] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Willingham, Mark C.] Wake Forest Univ, Dept Pathol, Winston Salem, NC 27109 USA. RP Cheng, SY (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Room 5128, Bethesda, MD 20892 USA. EM chengs@mail.nih.gov FU Intramural NIH HHS NR 40 TC 46 Z9 48 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 2008 VL 28 IS 14 BP 4598 EP 4608 DI 10.1128/MCB.02192-07 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 325UI UT WOS:000257613400013 PM 18474620 ER PT J AU Araya, R Kudo, M Kawano, M Ishii, K Hashikawa, T Iwasato, T Itohara, S Terasaki, T Oohira, A Mishina, Y Yamada, M AF Araya, Runa Kudo, Moeko Kawano, Masako Ishii, Katsuyoshi Hashikawa, Tsutomu Iwasato, Takuji Itohara, Shigeyoshi Terasaki, Tetsuya Oohira, Atsuhiko Mishina, Yuji Yamada, Masahisa TI BMP signaling through BMPRIA in astrocytes is essential for proper cerebral angiogenesis and formation of the blood-brain-barrier SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article ID BONE MORPHOGENETIC PROTEINS; ENDOTHELIAL GROWTH-FACTOR; DORSAL TELENCEPHALIC MIDLINE; CENTRAL-NERVOUS-SYSTEM; DOPAMINERGIC-NEURONS; RETINAL VASCULATURE; CHONDROITIN SULFATE; LINEAGE COMMITMENT; NEURITE OUTGROWTH; PROGENITOR CELLS AB Bone morphogenetic protein (BMP) signaling is involved in differentiation of neural precursor cells into astrocytes, but its contribution to angiogenesis is not well characterized. This study examines the role of BMP signaling through BMP type IA receptor (BMPRIA) in early neural development using a conditional knockout mouse model, in which Bmpr1a is selectively disrupted in telencephalic neural stem cells. The conditional mutant mice show a significant increase in the number of cerebral blood vessels and the level of vascular endothelial growth factor (VEGF) is significantly upregulated in the mutant astrocytes. The mutant mice also show leakage of immunoglobulin around cerebral microvessels in neonatal mice, suggesting a defect in formation of the blood-brain-barrier. In addition, astrocytic endfeet fail to encircle cortical blood vessels in the mutant mice. These results suggest that BMPRIA signaling in astrocytes regulates the expression of VEGF for proper cerebrovascular angiogenesis and has a role on in the formation of the blood-brain-barrier. (C) 2008 Elsevier Inc. All Fights reserved. C1 [Mishina, Yuji] NIEHS, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. [Araya, Runa; Kudo, Moeko; Yamada, Masahisa] RIKEN, Brain Sci Inst, Yamada Res Unit, Wako, Saitama 3510198, Japan. [Kawano, Masako] RIKEN, Brain Sci Inst, Lab Cell Culture Dev, Wako, Saitama 3510198, Japan. [Ishii, Katsuyoshi; Hashikawa, Tsutomu] RIKEN, Brain Sci Inst, Lab Neural Architecture, Wako, Saitama 3510198, Japan. [Iwasato, Takuji; Itohara, Shigeyoshi] RIKEN, Brain Sci Inst, Lab Behav Genet, Wako, Saitama 3510198, Japan. [Terasaki, Tetsuya] Tohoku Univ, Dept Mol Biopharm & Genet, Sendai, Miyagi 9808578, Japan. [Oohira, Atsuhiko] Aichi Human Serv Ctr, Inst Dev Res, Dept Perinatol, Aichi 4800392, Japan. RP Mishina, Y (reprint author), NIEHS, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. EM mishina@niehs.nih.gov; masahisa@brain.riken.jp RI Itohara, Shigeyoshi/I-8769-2012; Terasaki, Tetsuya/K-6730-2012 OI Itohara, Shigeyoshi/0000-0002-2410-9989; Terasaki, Tetsuya/0000-0002-6332-7575 FU Intramural NIH HHS [Z01 ES071003-10]; NIEHS NIH HHS [ES071003-10, Z01 ES071003] NR 85 TC 18 Z9 18 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell. Neurosci. PD JUL PY 2008 VL 38 IS 3 BP 417 EP 430 DI 10.1016/j.mcn.2008.04.003 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 324XS UT WOS:000257553300011 PM 18501628 ER PT J AU Nakagome, S Pecon-Slattery, J Masuda, R AF Nakagome, Shigeki Pecon-Slattery, Jill Masuda, Ryuichi TI Unequal rates of Y chromosome gene divergence during speciation of the family Ursidae SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE Ursidae; sex-linked genes; male-biased dispersal; female philopatry; matriarchal structure ID MALE-DRIVEN EVOLUTION; BEARS URSUS-ARCTOS; EFFECTIVE POPULATION-SIZE; SEX-BIASED DISPERSAL; MITOCHONDRIAL GENES; MOLECULAR EVOLUTION; NATAL DISPERSAL; DNA-SEQUENCES; PHYLOGEOGRAPHY; CARNIVORES AB Evolution of the bear family Ursidae is well investigated in terms of morphological, paleontological, and genetic features. However, several phylogenetic ambiguities occur within the subfamily Ursinae (the family Ursidae excluding the giant panda and spectacled bear), which may correlate with behavioral traits of female philopatry and male-biased dispersal which form the basis of the observed matriarchal population structure in these species. In the process of bear evolution, we investigate the premise that such behavioral traits may be reflected in patterns of variation among genes with different modes of inheritance: matrilineal mitochondrial DNA (mtDNA), patrilineal Y chromosome, biparentally inherited autosomes, and the X chromosome. In the present study, we sequenced 3 Y-linked genes (3,453 bp) and 4 X-linked genes (4,960 bp) and reanalyzed previously published sequences from autosome genes (2,347 bp) in ursid species to investigate differences in evolutionary rates associated with patterns of inheritance. The results describe topological incongruence between sex-linked genes and autosome genes and between nuclear DNA and mtDNA. In more ancestral branches within the bear phylogeny, Y-linked genes evolved faster than autosome and X-linked genes, consistent with expectations based on male-driven evolution. However, this pattern changes among branches leading to each species within the lineage of Ursinae whereby the evolutionary rates of Y-linked genes have fewer than expected substitutions. This inconsistency between more recent nodes of the bear phylogeny with more ancestral nodes may reflect the influences of sex-biased dispersal as well as molecular evolutionary characteristics of the Y chromosome, and stochastic events in species natural history, and phylogeography unique to ursine bears. C1 [Nakagome, Shigeki; Masuda, Ryuichi] Hokkaido Univ, Grad Sch Sci, Div Biol Sci, Sapporo, Hokkaido, Japan. [Pecon-Slattery, Jill] NCI, Lab Genom Divers, Frederick, MD 21701 USA. [Masuda, Ryuichi] Hokkaido Univ, Dept Genome Dynam, Sapporo, Hokkaido, Japan. RP Nakagome, S (reprint author), Univ Tokyo, Grad Sch Frontier Sci, Dept Integrated Biol, Kashiwa, Chiba, Japan. EM masudary@ees.hokudai.ac.jp RI MASUDA, RYUICHI/G-5223-2012; OI Nakagome, Shigeki/0000-0001-9613-975X NR 57 TC 21 Z9 23 U1 3 U2 39 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0737-4038 EI 1537-1719 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD JUL PY 2008 VL 25 IS 7 BP 1344 EP 1356 DI 10.1093/molbev/msn086 PG 13 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 316VZ UT WOS:000256979100010 PM 18400788 ER PT J AU Ramsden, C Melo, FL Figueiredo, LM Holmes, EC Zanotto, PMA AF Ramsden, Cadhla Melo, Fernando L. Figueiredo, Luiz. M. Holmes, Edward C. Zanotto, Paolo M. A. CA VGDN Consortium TI High rates of molecular evolution in hantaviruses SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE hantavirus; nucleotide substitution; molecular evolution; substitution rates ID PULMONARY SYNDROME; GENETIC DIVERSITY; VIRUS EVOLUTION; NORTH-AMERICA; RNA VIRUSES; INFECTION; MICE; TRANSMISSION; SUBSTITUTION; POPULATIONS AB Hantaviruses are rodent-borne Bunyaviruses that infect the Arvicolinae, Murinae, and Sigmodontinae subfamilies of Muridae. The rate of molecular evolution in the hantaviruses has been previously estimated at approximately 10(-7) nucleotide substitutions per site, per year (substitutions/site/year), based on the assumption of codivergence and hence shared divergence times with their rodent hosts. If substantiated, this would make the hantaviruses among the slowest evolving of all RNA viruses. However, as hantaviruses replicate with an RNA-dependent RNA polymerase, with error rates in the region of one mutation per genome replication, this low rate of nucleotide substitution is anomalous. Here, we use a Bayesian coalescent approach to estimate the rate of nucleotide substitution from serially sampled gene sequence data for hantaviruses known to infect each of the 3 rodent subfamilies: Araraquara virus ( Sigmodontinae), Dobrava virus ( Murinae), Puumala virus ( Arvicolinae), and Tula virus ( Arvicolinae). Our results reveal that hantaviruses exhibit shortterm substitution rates of 10(-2) to 10(-4) substitutions/site/year and so are within the range exhibited by other RNA viruses. The disparity between this substitution rate and that estimated assuming rodent-hantavirus codivergence suggests that the codivergence hypothesis may need to be reevaluated. C1 [Ramsden, Cadhla; Holmes, Edward C.] Penn State Univ, Ctr Infect Dis Dynam, Dept Biol, University Pk, PA 16802 USA. [Melo, Fernando L.; Zanotto, Paolo M. A.] Univ Sao Paulo, Inst Biomed Sci, LEMB, Sao Paulo, Brazil. [Figueiredo, Luiz. M.] Univ Sao Paulo, Sch Med, BR-14049 Ribeirao Preto, SP, Brazil. [Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Ramsden, C (reprint author), Penn State Univ, Ctr Infect Dis Dynam, Dept Biol, University Pk, PA 16802 USA. EM pzanotto@usp.br RI Braconi, Carla/B-3320-2014; Moro de Sousa, Ricardo Luiz/F-9084-2016; OI Braconi, Carla/0000-0002-5370-8980; Holmes, Edward/0000-0001-9596-3552 NR 28 TC 56 Z9 56 U1 2 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0737-4038 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD JUL PY 2008 VL 25 IS 7 BP 1488 EP 1492 DI 10.1093/molbev/msn093 PG 5 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 316VZ UT WOS:000256979100024 PM 18417484 ER PT J AU Lee, D Zhao, XH Yim, YI Eisenberg, E Greene, LE AF Lee, Dong-won Zhao, Xiaohong Yim, Yang-In Eisenberg, Evan Greene, Lois E. TI Essential role of cyclin-G-associated kinase (auxilin-2) in developing and mature mice SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID CLATHRIN-COATED VESICLES; MEDIATED ENDOCYTOSIS; BARRIER FUNCTION; GOLGI-APPARATUS; MULTIPLE ROLES; IN-VIVO; CELLS; RECRUITMENT; EXCHANGE; ADAPTER AB Hsc70 with its cochaperone, either auxilin or GAK, not only uncoats clathrin-coated vesicles but also acts as a chaperone during clathrin-mediated endocytosis. However, because synaptojanin is also involved in uncoating, it is not clear whether GAK is an essential gene. To answer this question, GAK conditional knockout mice were generated and then mated to mice expressing Cre recombinase under the control of the nestin, albumin, or keratin-14 promoters, all of which turn on during embryonic development. Deletion of GAK from brain, liver, or skin dramatically altered the histology of these tissues, causing the mice to die shortly after birth. Furthermore, by expressing a tamoxifen-inducible promoter to express Cre recombinase we showed that deletion of GAK caused lethality in adult mice. Mouse embryonic fibroblasts in which the GAK was disrupted showed a lack of clathrin-coated pits and a complete block in clathrin-mediated endocytosis. We conclude that GAK deletion blocks development and causes lethality in adult animals by disrupting clathrin-mediated endocytosis. C1 [Lee, Dong-won; Zhao, Xiaohong; Yim, Yang-In; Eisenberg, Evan; Greene, Lois E.] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Greene, LE (reprint author), NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. EM greenel@helix.nih.gov NR 39 TC 24 Z9 25 U1 0 U2 4 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD JUL PY 2008 VL 19 IS 7 BP 2766 EP 2776 DI 10.1091/mbc.E07-11-1115 PG 11 WC Cell Biology SC Cell Biology GA 347RH UT WOS:000259158200008 PM 18434600 ER PT J AU Barr, VA Bernot, KM Srikanth, S Gwack, Y Balagopalan, L Regan, CK Helman, DJ Sommers, CL Oh-hora, M Rao, A Samelson, LE AF Barr, Valarie A. Bernot, Kelsie M. Srikanth, Sonal Gwack, Yousang Balagopalan, Lakshmi Regan, Carole K. Helman, Daniel J. Sommers, Connie L. Oh-hora, Masatsugu Rao, Anjana Samelson, Lawrence E. TI Dynamic movement of the calcium sensor STIM1 and the calcium channel Orai1 in activated T-cells: Puncta and distal caps SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID OPERATED CA2+ ENTRY; STROMAL INTERACTION MOLECULE-1; PLASMA-MEMBRANE; IMMUNOLOGICAL SYNAPSE; ENDOPLASMIC-RETICULUM; CRAC CHANNEL; ANTIGEN RECEPTOR; SIGNAL-TRANSDUCTION; LYMPHOCYTE-ACTIVATION; INTRACELLULAR CALCIUM AB The proteins STIM1 and Orai1 are the long sought components of the store-operated channels required in T-cell activation. However, little is known about the interaction of these proteins in T-cells after engagement of the T-cell receptor. We found that T-cell receptor engagement caused STIM1 and Orai1 to colocalize in puncta near the site of stimulation and accumulate in a dense structure on the opposite side of the T-cell. FRET measurements showed a close interaction between STIM1 and Orai1 both in the puncta and in the dense cap-like structure. The formation of cap-like structures did not entail rearrangement of the entire endoplasmic reticulum. Cap formation depended on TCR engagement and tyrosine phosphorylation, but not on channel activity or Ca2+ influx. These caps were very dynamic in T-cells activated by contact with superantigen pulsed B-cells and could move from the distal pole to an existing or a newly forming immunological synapse. One function of this cap may be to provide preassembled Ca2+ channel components to existing and newly forming immunological synapses. C1 [Barr, Valarie A.; Bernot, Kelsie M.; Balagopalan, Lakshmi; Regan, Carole K.; Helman, Daniel J.; Sommers, Connie L.; Samelson, Lawrence E.] NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA. [Srikanth, Sonal; Gwack, Yousang; Oh-hora, Masatsugu; Rao, Anjana] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Srikanth, Sonal; Gwack, Yousang; Oh-hora, Masatsugu; Rao, Anjana] Immune Dis Inst, Boston, MA 02115 USA. RP Samelson, LE (reprint author), NCI, Cellular & Mol Biol Lab, Bldg 37, Bethesda, MD 20892 USA. EM samelson@helix.nih.gov FU National Institutes of Health (NIH) [AI40127, GM075256]; National Cancer Institute; Center for Cancer Research FX We thank Dr. Alex Braiman for help with FRET calculations, Dr. Mark Philips for the tagged M1 constructs, Dr. Arthur Weiss for the JCam1.6 and Lck reconstituted JCam1.6 cell lines, and Barbara J. Taylor at the FACS CORE Facility. This research was supported by the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute, Center for Cancer Research and by NIH Grants AI40127 and GM075256 to A. R.. NR 77 TC 76 Z9 76 U1 1 U2 4 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD JUL PY 2008 VL 19 IS 7 BP 2802 EP 2817 DI 10.1091/mbc.E08-02-0146 PG 16 WC Cell Biology SC Cell Biology GA 347RH UT WOS:000259158200011 PM 18448669 ER PT J AU Oh, YK Lee, HJ Jeong, MH Rhee, M Mo, JW Song, EH Lim, JY Choi, KH Jo, I Park, SI Gao, B Kwon, Y Kim, WH AF Oh, Yeo Kyoung Lee, Hyun Jung Jeong, Mi-Hee Rhee, Marie Mo, Ji-Won Song, Eun Hyeon Lim, Joong-Yeon Choi, Kyung-Hee Jo, Inho Park, Sang Ick Gao, Bin Kwon, Yongil Kim, Won-Ho TI Role of activating transcription factor 3 on TAp73 stability and apoptosis in paclitaxel-treated cervical cancer cells SO MOLECULAR CANCER RESEARCH LA English DT Article ID DNA-DAMAGE; TARGET GENES; P73; P53; PROTEIN; TAXOL; ATF3; MDM2; EXPRESSION; PATHWAY AB Taxol (paclitaxel) is a potent anticancer drug that has been found to be effective against several tumor types, including cervical cancer. However, the exact mechanism underlying the antitumor effects of paclitaxel is poorly understood. Here, paclitaxel induced the apoptosis of cervical cancer HeLa cells and correlated with the enhanced activation of caspase-3 and TAp73, which was strongly inhibited by TAp73 beta small interfering RNA (siRNA). In wild-type activating transcription factor 3 (ATF3)-overexpressed cells, paclitaxel enhanced apoptosis through increased a and 0 isoform expression of TAp73; however, these events were attenuated in cells containing inactive COO H-terminal-deleted ATF3 [ATF3(Delta C)] or ATF3 siRNA. In contrast, paclitaxel-induced ATF3 expression did not change in TAp73 beta-overexpressed or TAp73 beta siRNA-cotransfected cells. Furthermore, paclitaxel-induced ATF3 translocated into the nucleus where TAp73 beta is expressed, but not in ATF3(Delta C) or TAp73 beta siRNA-transfected cells. As confirmed by the GST pull-down assay, ATF3 bound to the DNA-binding domain of p73, resulting in the activation of p2l or Bax transcription, a downstream target of p73. Overexpression of ATF3 prolonged the half-life of TAp73 beta by inhibiting its ubiquitination and thereby enhancing its transactivation and proapoptotic activities. Additionally, ATF3 induced by paclitaxel potentiated the stability of TAp73, not its transcriptional level. Chromatin immunoprecipitation analyses show that TAp73 beta and ATF3 are recruited directly to the p2l and Bax promoter. Collectively, these results reveal that overexpression of ATF3 potentiates paclitaxel-induced apoptosis of HeLa cells, at least in part, by enhancing TAp73 beta's stability and its transcriptional activity. The investigation shows that ATF3 may function as a tumor-inhibiting factor through direct regulatory effects on TAp73 beta, suggesting a functional link between ATF3 and TAp73 beta. C1 [Oh, Yeo Kyoung; Lee, Hyun Jung; Rhee, Marie; Mo, Ji-Won; Song, Eun Hyeon; Lim, Joong-Yeon; Park, Sang Ick; Kim, Won-Ho] NIH, Ctr Biomed Sci, Div Intractable Dis, Seoul 122701, South Korea. [Jeong, Mi-Hee; Choi, Kyung-Hee] Chung Ang Univ, Coll Nat Sci, Dept Biol, Mol Biol Lab, Seoul 156756, South Korea. [Jo, Inho] Ewha Womans Univ, Sch Med, Dept Mol Med, Seoul, South Korea. [Gao, Bin] NIAAA, Lab Physiol Studies, Sect Liver Biol, Bethesda, MD USA. [Kwon, Yongil] Hallym Univ, Kangdong Sacred Heart Hosp, Seoul, South Korea. RP Kim, WH (reprint author), NIH, Ctr Biomed Sci, Div Intractable Dis, 194 Tongillo, Seoul 122701, South Korea. EM jhkwh@nih.go.kr FU Intramural NIH HHS [Z99 AA999999, ZIA AA000368-11, ZIA AA000369-11] NR 47 TC 14 Z9 14 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD JUL PY 2008 VL 6 IS 7 BP 1232 EP 1249 DI 10.1158/1541-7786.MCR-07-0297 PG 18 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 329UK UT WOS:000257895900016 PM 18644986 ER PT J AU Chen, Z Ricker, JL Malhotra, PS Nottingham, L Bagain, L Lee, TL Yeh, NT Van Waes, C AF Chen, Zhong Ricker, Justin L. Malhotra, Pramit S. Nottingham, Liesl Bagain, Lorena Lee, Tin Lap Yeh, Ning T. Van Waes, Carter TI Differential bortezomib sensitivity in head and neck cancer lines corresponds to proteasome, nuclear factor-kappa B and activator protein-1 related mechanisms SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID SQUAMOUS-CELL CARCINOMA; GROWTH-FACTOR RECEPTOR; RANDOMIZED PHASE-II; INHIBITOR PS-341; MULTIPLE-MYELOMA; GENE-EXPRESSION; TUMOR-GROWTH; IN-VIVO; TRANSCRIPTION FACTORS; LEUKEMIA-CELLS AB Head and neck squamous cell carcinomas (HNSCC) exhibit constitutive activation of transcription factors nuclear factor-kappa B (NF-kappa B) and activator protein-1 (AP-1), which are modulated by the proteasome and promote resistance to cell death. HNSCC show variable sensitivity to the proteasome inhibitor bortezomib in vitro as well as in murine xenografts and patient tumors in vivo, and the mechanisms are not well understood. To address this question, the sensitivities of nine HNSCC cell lines to bortezomib were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, and the potential relationship between the sensitivity and bortezomib effects on biological processes was examined in HNSCC lines of differential bortezomib sensitivity. The most sensitive cell line (UM-SCC-11B) underwent cell death at 10(-9) mol/L in vitro and tumor regression at a maximally tolerated dose of bortezomib in a murine xenograft model. The differential sensitivity between UM-SCC-11A and UM-SCC-11B cells corresponded to differences in the extent of suppression of proteasome activity, ubiquitinated protein degradation, and NF-kappa B and AP-1 activation. Lower concentrations of bortezomib transiently increased NF-kappa B and sustained AP-1 activation in UM-SCC-11A cells. AP-1 reporter activity and cell density of UM-SCC-11A were suppressed when bortezomib was combined with c-Jun NH2-terminal kinase and p38 kinase pathways inhibitors. Thus, the differential sensitivities to bortezomib corresponded to dissimilar effects on the proteasome, NF-kappa B and AP-1 activities. Inhibition of c-Jun NH2-terminal kinase and p38 pathways blocked AP-1 activity and enhanced the antitumor effects. These findings revealed molecular mechanisms of bortezomib sensitivity and resistance, which are under development as biomarkers for clinical trials in patients with HNSCC. C1 [Chen, Zhong; Ricker, Justin L.; Nottingham, Liesl; Bagain, Lorena; Lee, Tin Lap; Yeh, Ning T.; Van Waes, Carter] Natl Inst Deafness & Other Commun Disorders, Tumor Biol Sect, Head & Neck Surg Branch, NIH, Bethesda, MD 20892 USA. [Malhotra, Pramit S.] Univ Minnesota Hosp, Dept Otolaryngol Head & Neck Surg, Minneapolis, MN USA. RP Van Waes, C (reprint author), Natl Inst Deafness & Other Commun Disorders, Tumor Biol Sect, Head & Neck Surg Branch, NIH, 10-5D55,MSC-1419, Bethesda, MD 20892 USA. EM vanwaesc@nidcd.nih.gov RI Lee, Tin-Lap/A-7853-2009 OI Lee, Tin-Lap/0000-0002-6654-0988 FU Intramural NIH HHS [Z01 DC000016-14, Z99 DC999999]; NIDCD NIH HHS [Z01 DC000016] NR 53 TC 34 Z9 35 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD JUL PY 2008 VL 7 IS 7 BP 1949 EP 1960 DI 10.1158/1535-7163.MCT-07-2046 PG 12 WC Oncology SC Oncology GA 330SW UT WOS:000257964100022 PM 18645005 ER PT J AU Koll, TT Feis, SS Wright, MH Teniola, MM Richardson, MM Robles, AI Bradsher, J Capala, J Varticovski, L AF Koll, Thuy T. Feis, Steven S. Wright, Mollie H. Teniola, Modupe M. Richardson, Mekel M. Robles, Ana I. Bradsher, John Capala, Jacek Varticovski, Lyuba TI HSP90 inhibitor, DMAG, synergizes with radiation of lung cancer cells by interfering with base excision and ATM-mediated DNA repair SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID IONIZING-RADIATION; MAMMALIAN-CELLS; TUMOR-CELLS; COMET ASSAY; DAMAGE; GELDANAMYCIN; 17-(DIMETHYLAMINOETHYLAMINO)-17-DEMETHOXYGELDANAMYCIN; ENZYMES; 17-DIMETHYLAMINOETHYLAMINO-17-DEMETHOXYGELDANAMYCIN; RADIOSENSITIVITY AB Inhibition of heat shock protein 90 (HSP90) leads to inappropriate processing of proteins involved in cell survival pathways. We found that HSP90 inhibitor, 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (DMAG), is synergistic with radiation for non-small cell lung cancer cell lines, NCI-H460 and A549. To establish the optimal schedule for this combination, cells were radiated before, after, or simultaneously with DMAG, and survival was scored by clonogenic assay. The sequence of DMAG administration was critical for synergy with radiation, and pretreatment for 16 h led to maximal synergy. Similar radiosensitization was observed in isogenic cells in which expression of wild-type p53 was silenced by RNA interference, although p53 loss rendered cells overall less radiosensitive. The mechanistic basis for synergy was studied by Western blotting, cell cycle analysis, alkaline comet assay, and direct measurement of the activities of key base excision repair enzymes. Regardless of schedule of administration, DMAG led to degradation of proteins involved in activation of cell survival pathways after radiation, which did not explain the differences in the schedule of administration observed in clonogenic assays. In addition to previously reported decrease in activation of ATM, pretreatment with DMAG blocked activation of base excision repair machinery and activity of key enzymes, apurinic/apyrimidinic endonuclease, and DNA polymerase-beta. Similarly, pretreatment with specific apurinic/apyrimidinic endonuclease inhibitor, CRT0044876, reproduced the effects of DMAG. Thus, administration of HSP90 inhibitors before radiation is critical for optimizing their use as radiosensitizers. C1 [Koll, Thuy T.; Feis, Steven S.; Wright, Mollie H.; Teniola, Modupe M.; Richardson, Mekel M.; Robles, Ana I.; Bradsher, John; Varticovski, Lyuba] Natl Canc Inst, Ctr Canc Res, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. [Capala, Jacek] Natl Canc Inst, Ctr Canc Res, Radiat Oncol Branch, Bethesda, MD 20892 USA. [Koll, Thuy T.] Creighton Univ, Sch Med, Omaha, NE USA. RP Varticovski, L (reprint author), Natl Canc Inst, Ctr Canc Res, Human Carcinogenesis Lab, 9000 Rockville Pike,37-3060, Bethesda, MD 20892 USA. EM varticol@mail.nih.gov FU Intramural NIH HHS [Z01 BC010658-03, Z99 CA999999] NR 33 TC 51 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 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD JUL PY 2008 VL 7 IS 7 BP 1985 EP 1992 DI 10.1158/1535-7163.MCT-07-2104 PG 8 WC Oncology SC Oncology GA 330SW UT WOS:000257964100025 PM 18645008 ER PT J AU Da Fontoura-Rodrigues, ML Lima-Rosa, CAV Tchaicka, L Valdez, FP Rodrigues, FHG De Paula, RC Gough, MP Johnson, WE Bonatto, SL Eizirik, E AF Da Fontoura-Rodrigues, Manoel L. Lima-Rosa, Carlos Andre V. Tchaicka, Ligia Valdez, Fernanda P. Rodrigues, Flavio H. G. De Paula, Rogerio C. Gough, Michael P. Johnson, Warren E. Bonatto, Sandro L. Eizirik, Eduardo TI Cross-amplification and characterization of 13 tetranucleotide microsatellites in multiple species of Neotropical canids SO MOLECULAR ECOLOGY RESOURCES LA English DT Article DE Canidae; Carnivora; short tandem repeats AB We tested 47 tetranucleotide microsatellite loci developed for the domestic dog in four species of Neotropical canids, aiming to produce a standardized set that could be successfully used even in noninvasive samples across this group. We identified 13 suitable loci, nine of which constitute a standardized set for all species. Considering only the ideal panel of nine loci, the mean expected heterozygosity (averaged across species) per locus ranged from 0.58 to 0.92 (overall mean 0.76), and the maximum probability of identity value was 1.3 x 10(-9). This set of loci has a great potential for application in evolutionary, ecological and conservation studies. C1 [Da Fontoura-Rodrigues, Manoel L.; Lima-Rosa, Carlos Andre V.; Tchaicka, Ligia; Valdez, Fernanda P.; Bonatto, Sandro L.] Pontificia Univ Catolica Rio Grande do Sul, Fac Biociencias, BR-90619900 Porto Alegre, RS, Brazil. [Da Fontoura-Rodrigues, Manoel L.; Lima-Rosa, Carlos Andre V.; Tchaicka, Ligia; Valdez, Fernanda P.] Univ Fed Rio Grande do Sul, Dept Genet, Inst Biociencias, BR-91501970 Porto Alegre, RS, Brazil. [Rodrigues, Flavio H. G.] Univ Fed Minas Gerais, ICB, Dept Biol Geral, BR-31270910 Belo Horizonte, MG, Brazil. [Gough, Michael P.; Johnson, Warren E.; Eizirik, Eduardo] NCI, Lab Genom Divers, Ft Detrick, MD 21702 USA. RP Eizirik, E (reprint author), Pontificia Univ Catolica Rio Grande do Sul, Fac Biociencias, Av Ipiranga 6681,Predio 12, BR-90619900 Porto Alegre, RS, Brazil. EM eduardo.eizirik@pucrs.br RI Bonatto, Sandro/A-1240-2010; Rodrigues, Flavio/E-4924-2012; Eizirik, Eduardo/K-8034-2012; Johnson, Warren/D-4149-2016 OI Bonatto, Sandro/0000-0002-0064-467X; Rodrigues, Flavio/0000-0002-4797-0085; Eizirik, Eduardo/0000-0002-9658-0999; Johnson, Warren/0000-0002-5954-186X NR 9 TC 1 Z9 1 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1471-8278 J9 MOL ECOL RESOUR JI Mol. Ecol. Resour. PD JUL PY 2008 VL 8 IS 4 BP 898 EP 900 DI 10.1111/j.1755-0998.2008.02103.x PG 3 WC Biochemistry & Molecular Biology; Ecology; Evolutionary Biology SC Biochemistry & Molecular Biology; Environmental Sciences & Ecology; Evolutionary Biology GA 324IF UT WOS:000257511600045 PM 21585923 ER PT J AU Zhou, J Oakley, RH Cidlowski, JA AF Zhou, Junguo Oakley, Robert H. Cidlowski, John A. TI DAX-1 (dosage-sensitive sex reversal-adrenal hypoplasia congenita critical region on the X-chromosome, gene 1) selectively inhibits transactivation but not transrepression mediated by the glucocorticoid receptor in a LXXLL-dependent manner SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID HYPOGONADOTROPIC HYPOGONADISM; TRANSCRIPTIONAL COACTIVATOR; DNA-BINDING; EXPRESSION; HORMONE; CELLS; COREPRESSOR; MUTATIONS; DOMAIN; GRIP1 AB The glucocorticoid receptor (GR) mediates virtually all actions of glucocorticoids, and the nature and magnitude of a cell's response to these steroids are determined primarily by hormone concentration and GR signaling capacity. DAX-1 (dosage-sensitive sex reversal-adrenal hypoplasia congenita critical region on the X-chromosome, gene 1) is an orphan nuclear receptor that functions as a corepressor, and deletion or mutation of DAX-1 causes a decrease in glucocorticoid production. However it is unclear whether DAX-1 also alters GR function as a transcription factor. Here, we demonstrate that DAX-1 acts as a novel selective GR modulator. It specifically inhibits ligand-dependent GR transactivation with little effect on GR-mediated transrepression. As demonstrated by coimmunoprecipitation and glutathione-S-transferase pull-down assays, DAX-1 physically interacts with GR, but this interaction does not influence either ligand-induced GR nuclear translocation or subsequent GR association with glucocorticoid-responsive elements. Instead, DAX-1 competes with coactivators such as GR-interacting protein 1 for binding to the receptor. Specifically, suppression of GR transactivation is mediated by the N-terminal half of DAX-1, and in particular the LXXLL motifs. Thus we demonstrate that DAX-1 directly modulates GR signaling in addition to affecting glucocorticoid hormone levels. C1 [Zhou, Junguo; Oakley, Robert H.; Cidlowski, John A.] NIEHS, Mol Endocrinol Grp, Lab Signal Transduct, NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Cidlowski, JA (reprint author), NIEHS, Mol Endocrinol Grp, Lab Signal Transduct, NIH,Dept Hlth & Human Serv, Bldg 101,MD F3-07,111 TW Alexander Dr,Res Triangl, Res Triangle Pk, NC 27709 USA. EM cidlows1@niehs.nih.gov FU Intramural NIH HHS NR 51 TC 15 Z9 16 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD JUL PY 2008 VL 22 IS 7 BP 1521 EP 1534 DI 10.1210/me.2007-0273 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 319DO UT WOS:000257144500002 PM 18417736 ER PT J AU Bonocora, RP Caignan, G Woodrell, C Werner, MH Hinton, DM AF Bonocora, Richard P. Caignan, Gregori Woodrell, Christopher Werner, Milton H. Hinton, Deborah M. TI A basic/hydrophobic cleft of the T4 activator MotA interacts with the C-terminus of E-coli sigma(70) to activate middle gene transcription SO MOLECULAR MICROBIOLOGY LA English DT Article ID BACTERIOPHAGE-T4 ASIA PROTEIN; RNA-POLYMERASE HOLOENZYME; DNA-BINDING DOMAIN; CRYSTAL-STRUCTURE; REGION 4; ANGSTROM RESOLUTION; LAMBDA-CL; SUBUNIT; PROMOTER; IDENTIFICATION AB Transcriptional activation often employs a direct interaction between an activator and RNA polymerase. For activation of its middle genes, bacteriophage T4 appropriates Escherichia coli RNA polymerase through the action of two phage-encoded proteins, MotA and AsiA. Alone, AsiA inhibits transcription from a large class of host promoters by structurally remodelling region 4 of sigma(70), the primary specificity subunit of E. coli RNA polymerase. MotA interacts both with sigma(70) region 4 and with a DNA element present in T4 middle promoters. AsiA-induced remodelling is proposed to make the far C-terminus of sigma(70) region 4 accessible for MotA binding. Here, NMR chemical shift analysis indicates that MotA uses a 'basic/hydrophobic' cleft to interact with the C-terminus of AsiA-remodelled sigma(70), but MotA does not interact with AsiA itself. Mutations within this cleft, at residues K3, K28 and Q76, both impair the interaction of MotA with sigma(70) region 4 and MotA-dependent activation. Furthermore, mutations at these residues greatly decrease phage viability. Most previously described activators that target sigma(70) directly use acidic residues to engage a basic surface of region 4. Our work supports accumulated evidence indicating that 'sigma appropriation' by MotA and AsiA uses a fundamentally different mechanism to activate transcription. C1 [Caignan, Gregori; Woodrell, Christopher; Werner, Milton H.] Rockefeller Univ, Lab Mol Biophys, New York, NY 10021 USA. [Bonocora, Richard P.; Hinton, Deborah M.] Natl Inst Hlth, NIDDK, Mol & Cellular Biol Lab, Gene Express & Regulat Sect, Bethesda, MD USA. RP Werner, MH (reprint author), ATDC Biosci Ctr, 0390,311 Ferst Dr, Atlanta, GA 30332 USA. EM mwerner@celtaxsys.com; dhinton@helix.nih.gov FU Intramural NIH HHS [Z01 DK057802-20]; NIGMS NIH HHS [R01 GM063793, R01 GM063793-04, 5R01GM063793-04] NR 59 TC 13 Z9 13 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD JUL PY 2008 VL 69 IS 2 BP 331 EP 343 DI 10.1111/j.1365-2958.2008.06276.x PG 13 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 325DS UT WOS:000257569200005 PM 18485078 ER PT J AU Simanek, E Patri, AK AF Simanek, Eric Patri, Anil K. TI Biodistribution of nanomedicines SO MOLECULAR PHARMACEUTICS LA English DT Editorial Material C1 [Simanek, Eric] Texas A&M Univ, Dept Chem, College Stn, TX 77843 USA. [Patri, Anil K.] NCI, SAIC Frederick, Nanotechnol Characterizat Lab, Frederick, MD 21701 USA. RP Simanek, E (reprint author), Texas A&M Univ, Dept Chem, College Stn, TX 77843 USA. EM simanek@tamu.edu; patria@mail.nih.gov RI Nanotechnology Characterization Lab, NCL/K-8454-2012 NR 0 TC 1 Z9 1 U1 1 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1543-8384 J9 MOL PHARMACEUT JI Mol. Pharm. PD JUL-AUG PY 2008 VL 5 IS 4 BP 473 EP 473 DI 10.1021/mP800083a PG 1 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 334MQ UT WOS:000258226300001 PM 18672948 ER PT J AU Dobrovolskaia, MA Aggarwal, P Hall, JB McNeil, SE AF Dobrovolskaia, Marina A. Aggarwal, Parag Hall, Jennifer B. McNeil, Scott E. TI Preclinical studies to understand nanoparticle interaction with the immune system and its potential effects on nanoparticle biodistribution SO MOLECULAR PHARMACEUTICS LA English DT Article; Proceedings Paper CT 7th International Symposium on Polymer Therapeutics CY MAY 26-28, 2007 CL Ctr Invest Principe Felipe, Valencia, SPAIN HO Ctr Invest Principe Felipe DE nanoparticles; immunology; biodistribution; preclinical characterization ID RED-BLOOD-CELLS; IN-VIVO; COMPLEMENT ACTIVATION; MACROPHAGE UPTAKE; DRUG-DELIVERY; GENE DELIVERY; DENDRIMERS; PROTEIN; POLOXAMINE-908; VITRO AB Nanoparticles have unique physicochemical properties which make them promising platforms for drug delivery. However, immune cells in the bloodstream (such as monocytes, platelets, leukocytes, and dendritic cells) and in tissues (such as resident phagocytes) have a propensity to engulf and eliminate certain nanoparticles. A nanoparticle's interaction with plasma proteins (opsonins) and blood components (via hemolysis, thrombogenicity and complement activation) may influence uptake and clearance and hence potentially affect distribution and delivery to the intended target sites. Nanoparticle uptake by the immune cells is influenced by many factors. Different nanoparticles have been shown to act on different pathways, while various characteristics/properties also affect which pathway is employed for particle internalization. Nanoparticle protein binding occurs almost instantaneously once the particle enters biological medium, and the physical properties of such a particle-protein complex are often different than those of the formulated particle. These new properties can contribute to different biological responses and change nanoparticle biodistribution. Therefore, in the situation when specific delivery to immune cells is not desired, the ideal nanoparticle platform is the one whose integrity is not disturbed in the complex biological environment, which provides extended circulation in the blood to maximize delivery to the target site, is not toxic to blood cellular components, and is "invisible" to the immune cells which can remove it from circulation. This review discusses the most recent data on nanoparticle interactions with blood components and how particle size and surface charge define their hematocompatibility. This includes properties which determine particle interaction with plasma proteins and uptake by macrophages. We will also provide an overview of in vitro methods useful in identifying interactions with components of the immune system and the potential effects of such interaction on particle distribution to tissues. C1 [Dobrovolskaia, Marina A.; Aggarwal, Parag; Hall, Jennifer B.; McNeil, Scott E.] SAIC Frederick Inc, NCI Frederick, Nanotechnol Characterizat Lab, Adv Technol Program, Frederick, MD 21702 USA. RP Dobrovolskaia, MA (reprint author), SAIC Frederick Inc, NCI Frederick, Nanotechnol Characterizat Lab, Adv Technol Program, 1050 Boyles St,Bldg 469, Frederick, MD 21702 USA. EM marina@mail.nih.gov RI Nanotechnology Characterization Lab, NCL/K-8454-2012 FU NCI NIH HHS [N01-CO-12400, N01 CO012400, N01CO12400] NR 45 TC 433 Z9 440 U1 21 U2 149 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1543-8384 J9 MOL PHARMACEUT JI Mol. Pharm. PD JUL-AUG PY 2008 VL 5 IS 4 BP 487 EP 495 DI 10.1021/mp800032f PG 9 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 334MQ UT WOS:000258226300003 PM 18510338 ER PT J AU Alexis, F Pridgen, E Molnar, LK Farokhzad, OC AF Alexis, Frank Pridgen, Eric Molnar, Linda K. Farokhzad, Omid C. TI Factors affecting the clearance and biodistribution of polymeric nanoparticles SO MOLECULAR PHARMACEUTICS LA English DT Article; Proceedings Paper CT 7th International Symposium on Polymer Therapeutics CY MAY 26-28, 2007 CL Ctr Invest Principe Felipe, Valencia, SPAIN HO Ctr Invest Principe Felipe DE biodistribution; circulation half-life; polymeric nanoparticles ID ADVANCED SOLID TUMORS; PHASE-II TRIAL; IN-VIVO; DRUG-DELIVERY; POLYETHYLENE-GLYCOL; CREMOPHOR-FREE; BREAST-CANCER; GENEXOL-PM; POLYCYANOACRYLATE NANOPARTICLES; FENESTRATED ENDOTHELIUM AB Nanoparticle (NP) drug delivery systems (5-250 nm) have the potential to improve current disease therapies because of their ability to overcome multiple biological barriers and releasing a therapeutic load in the optimal dosage range. Rapid clearance of circulating nanoparticles during systemic delivery is a critical issue for these systems and has made it necessary to understand the factors affecting particle biodistribution and blood circulation half-life. In this review, we discuss the factors which can influence nanoparticle blood residence time and organ specific accumulation. These factors include interactions with biological barriers and tunable nanoparticle parameters, such as composition, size, core properties, surface modifications (pegylation and surface charge), and finally, targeting ligand functionalization. All these factors have been shown to substantially affect the biodistribution and blood circulation half-life of circulating nanoparticles by reducing the level of nonspecific uptake, delaying opsonization, and increasing the extent of tissue specific accumulation. C1 [Alexis, Frank; Farokhzad, Omid C.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Lab Nanomed & Biomat,Dept Anesthesiol, Boston, MA 02115 USA. [Alexis, Frank; Pridgen, Eric; Farokhzad, Omid C.] MIT, Harvard Ctr Canc Nanotechnol Excellence, Cambridge, MA 02139 USA. [Alexis, Frank] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Pridgen, Eric] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Molnar, Linda K.] NCI, NIH, Bethesda, MD 20892 USA. RP Alexis, F (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Lab Nanomed & Biomat,Dept Anesthesiol, 75 Francis St,MRB-505, Boston, MA 02115 USA. EM falexis@zeus.bwh.harvard.edu; ofarokhzad@zeus.bwh.harvard.edu FU NCI NIH HHS [U54 CA119349, CA119349]; NIBIB NIH HHS [EB003647, K08 EB003647] NR 104 TC 1245 Z9 1266 U1 65 U2 485 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1543-8384 J9 MOL PHARMACEUT JI Mol. Pharm. PD JUL-AUG PY 2008 VL 5 IS 4 BP 505 EP 515 DI 10.1021/mp800051m PG 11 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 334MQ UT WOS:000258226300005 PM 18672949 ER PT J AU Boswell, CA Eck, PK Regino, CAS Bernardo, M Wong, KJ Milenic, DE Choyke, PL Brechbiel, MW AF Boswell, C. Andrew Eck, Peter K. Regino, Celeste A. S. Bernardo, Marcelino Wong, Karen J. Milenic, Diane E. Choyke, Peter L. Brechbiel, Martin W. TI Synthesis, characterization, and biological evaluation of integrin alpha(v)beta(3)-targeted PAMAM dendrimers SO MOLECULAR PHARMACEUTICS LA English DT Article; Proceedings Paper CT 7th International Symposium on Polymer Therapeutics CY MAY 26-28, 2007 CL Ctr Invest Principe Felipe, Valencia, SPAIN HO Ctr Invest Principe Felipe DE dendrimer; angiogenesis; alpha(v)beta(3); RGD peptide; multimodal imaging; optical imaging; optical microscopy; flow cytometry; gamma-scintigraphic imaging; MRI ID MRI CONTRAST AGENTS; MAGNETIC-RESONANCE; TUMOR ANGIOGENESIS; PEPTIDE; CONJUGATION; CELLS; MACROMOLECULES; GROWTH; CORES AB Ligand size and valency strongly influence the receptor uptake and clearance of tumor angiogenesis imaging agents. The structures of successful imaging agents exhibit a high degree of variability, encompassing small monovalent arginine-glycine-aspartic acid (RGD)-containing peptides, multivalent RGD-oligomers, and a monoclonal antibody against integrin alpha-v-beta-3 (alpha(v)beta(3)). We have pursued a nanoscale approach to imaging of angiogenesis using rationally designed polyamidoamine (PAMAM) dendrimers covalently adorned with RGD-cyclopeptides. An orthogonal oxime-ligation strategy was applied to chemoselectively effect conjugation of the PAMAM dendrimers with RGD-cyclopeptides for targeting alpha(v)beta(3). Fluorescent dyes for optical imaging and chelates for gadolinium-based magnetic resonance (MR) imaging were subsequently appended to create robust multimodal macromolecular imaging agents. Fluorescence microscopy revealed selective binding of the resulting RGD peptide-bearing dendrimer with empty chelates to alpha(v)beta(3)-expressing cells, but somewhat reduced selectivity was observed following Gd(III) complexation. The expected incomplete saturation of chelates with Gd(III) ions permitted radiometal complexation, and an in vivo tissue distribution of the resulting agent in M21 melanoma tumor-bearing mice showed mostly renal and reticuloendothelial accumulation, with the tumor:blood ratio peaking (3.30 +/- 0.03) at 2 h postinjection. C1 [Boswell, C. Andrew; Milenic, Diane E.; Brechbiel, Martin W.] NCI, NIH, Radiat Oncol Branch, Radioimmune & Inorgan Chem Sect, Bethesda, MD 20892 USA. [Eck, Peter K.; Regino, Celeste A. S.; Bernardo, Marcelino; Wong, Karen J.; Choyke, Peter L.] NCI, NIH, Ctr Canc Res, Mol Imaging Program, Bethesda, MD 20892 USA. [Bernardo, Marcelino] SAIC Frederick Inc, NCI Frederick, Lab Anim Sci Program, Frederick, MD 21702 USA. RP Brechbiel, MW (reprint author), NCI, NIH, Radiat Oncol Branch, Radioimmune & Inorgan Chem Sect, Bldg 10,Room 1B40,10 Ctr Dr, Bethesda, MD 20892 USA. EM martinwb@mail.nih.gov OI Eck, Peter/0000-0003-2371-9774; Boswell, Charles/0000-0002-0426-9846 FU Intramural NIH HHS [Z01 SC006353-25, Z01 SC010051-12]; NCI NIH HHS [N01-CO-12400, N01CO12400] NR 41 TC 97 Z9 102 U1 1 U2 14 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1543-8384 J9 MOL PHARMACEUT JI Mol. Pharm. PD JUL-AUG PY 2008 VL 5 IS 4 BP 527 EP 539 DI 10.1021/mp800022a PG 13 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 334MQ UT WOS:000258226300007 PM 18537262 ER PT J AU VanWert, AL Srimaroeng, C Sweet, DH AF VanWert, Adam L. Srimaroeng, Chutima Sweet, Douglas H. TI Organic anion transporter 3 (Oat3/Slc22a8) interacts with carboxyfluoroquinolones, and deletion increases systemic exposure to ciprofloxacin SO MOLECULAR PHARMACOLOGY LA English DT Article ID ORGANIC ANION TRANSPORTER; RENAL PROXIMAL TUBULES; EPITHELIAL-CELL LINE; CATION TRANSPORTERS; NALIDIXIC-ACID; KNOCKOUT MICE; RAT-KIDNEY; DNA GYRASE; LEVOFLOXACIN; OAT3 AB Carboxyfluoroquinolones, such as ciprofloxacin, are used for the treatment of numerous infectious diseases. Renal secretion is a major determinant of their systemic and urinary concentration, but the specific transporters involved are virtually unknown. In vivo studies implicate the organic anion transporter (OAT) family as a pivotal component of carboxyfluoroquinolone renal secretion. Therefore, this study identified the specific renal basolateral OAT(s) involved, thereby highlighting potential sources of carboxyfluoroquinolone-drug interactions and variable efficacy. Two heterologous expression systems, Xenopus laevis oocytes and cell monolayers, were used to determine the roles of murine and human renal basolateral mOat1/hOAT1 and mOat3/hOAT3. Ciprofloxacin was transported by mOat3 in both systems (K(m) value, 70 +/- 6 mu M) and demonstrated no interaction with mOat1 or hOAT1. Furthermore, ciprofloxacin, norfloxacin, ofloxacin, and gatifloxacin exhibited concentration-dependent inhibition of transport on mOat3 in cells with inhibition constants of 198 +/- 39, 558 +/- 75, 745 +/- 165, and 941 +/- 232 mu M, respectively. Ciprofloxacin and gatifloxacin also inhibited hOAT3. Thereafter, in vivo elimination of ciprofloxacin was assessed in wild-type and Oat3 null mice [Oat3(-/-)]. Oat3(-/-) mice exhibited significantly elevated plasma levels of ciprofloxacin at clinically relevant concentrations (P < 0.05, male mice; P < 0.01, female mice). Oat3(-/-) mice also demonstrated a reduced volume of distribution (27%, P < 0.01, male mice; 14%, P < 0.01, female mice) and increased area under the concentration-time curve (25%, P < 0.05, male mice; 33%, P < 0.01, female mice). Female Oat3(-/-) mice had a 35% (P < 0.01) reduction in total clearance of ciprofloxacin relative to wild type. In addition, putative ciprofloxacin metabolites were significantly elevated in Oat3(-/-) mice. The present findings indicate that polymorphisms of and drug interactions on hOAT3 may influence carboxyfluoroquinolone efficacy, especially in urinary tract infections. C1 [VanWert, Adam L.; Sweet, Douglas H.] Med Univ S Carolina, Dept Pharmaceut & Biomed Sci, Charleston, SC 29425 USA. [Srimaroeng, Chutima] Natl Inst Environm Hlth Sci, Lab Pharmacol & Chem, Res Triangle Pk, NC USA. RP Sweet, DH (reprint author), Med Univ S Carolina, Dept Pharmaceut & Biomed Sci, 280 Calhoun St Room QE218,POB 250140, Charleston, SC 29425 USA. EM sweetd@musc.edu RI Sweet, Douglas/H-7914-2013; OI Sweet, Douglas/0000-0002-8911-9184; Srimaroeng, Chutima/0000-0002-5537-1023 FU NCRR NIH HHS [C0-RR015455, C06 RR015455]; NIDDK NIH HHS [R01 DK067216-04, R01 DK067216, R01-DK067216] NR 44 TC 51 Z9 53 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD JUL PY 2008 VL 74 IS 1 BP 122 EP 131 DI 10.1124/mol.107.042853 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 315OP UT WOS:000256889600013 PM 18381565 ER PT J AU Pezawas, L Meyer-Lindenberg, A Goldman, AL Verchninski, BA Chen, G Kolachana, BS Egan, MF Mattay, VS Hariri, AR Weinberger, DR AF Pezawas, L. Meyer-Lindenberg, A. Goldman, A. L. Verchninski, B. A. Chen, G. Kolachana, B. S. Egan, M. F. Mattay, V. S. Hariri, A. R. Weinberger, D. R. TI Evidence of biologic epistasis between BDNF and SLC6A4 and implications for depression SO MOLECULAR PSYCHIATRY LA English DT Article DE 5-HTTLPR; BDNF; anxiety; depression; neurotrophins; neuroimaging ID SEROTONIN TRANSPORTER GENE; CATECHOL-O-METHYLTRANSFERASE; FACTOR VAL66MET POLYMORPHISM; FAMILY-BASED ASSOCIATION; AFFECTIVE-DISORDERS; PROMOTER POLYMORPHISM; PERSONALITY-TRAITS; MAJOR DEPRESSION; BIPOLAR DISORDER; CEREBRAL-CORTEX AB Complex genetic disorders such as depression likely exhibit epistasis, but neural mechanisms of such gene-gene interactions are incompletely understood. 5-HTTLPR and BDNF VAL66MET, functional polymorphisms of the serotonin (5-HT) transporter (SLC6A4) and brain-derived neurotrophic factor (BDNF) gene, impact on two distinct, but interacting signaling systems, which have been related to depression and to the modulation of neurogenesis and plasticity of circuitries of emotion processing. Recent clinical studies suggest that the BDNF MET allele, which shows abnormal intracellular trafficking and regulated secretion, has a protective effect regarding the development of depression and in mice of social defeat stress. Here we show, using anatomical neuroimaging techniques in a sample of healthy subjects (n = 111), that the BDNF MET allele, which is predicted to have reduced responsivity to 5-HT signaling, protects against 5-HTTLPR S allele-induced effects on a brain circuitry encompassing the amygdala and the subgenual portion of the anterior cingulate (rAC). Our analyses revealed no effect of the 5-HTTLPR S allele on rAC volume in the presence of BDNF MET alleles, whereas a significant volume reduction (P < 0.001) was seen on BDNF VAL/VAL background. Interacting genotype effects were also found in structural connectivity between amygdala and rAC (P = 0.002). These data provide in vivo evidence of biologic epistasis between SLC6A4 and BDNF in the human brain by identifying a neural mechanism linking serotonergic and neurotrophic signaling on the neural systems level, and have implications for personalized treatment planning in depression. C1 [Pezawas, L.; Meyer-Lindenberg, A.; Goldman, A. L.; Verchninski, B. A.; Kolachana, B. S.; Egan, M. F.; Mattay, V. S.; Weinberger, D. R.] NIMH, Cognit & Psychosis Program, Intramural Res Program, Natl Inst Hlth, Bethesda, MD 20892 USA. [Pezawas, L.] Med Univ Vienna, Div Biol Psychiat, Vienna, Austria. [Meyer-Lindenberg, A.] Cent Inst Mental Hlth, Dept Psychiat & Psychotherapy, D-6800 Mannheim, Germany. [Chen, G.] NIMH, NIH, Bethesda, MD 20892 USA. [Hariri, A. R.] Univ Pittsburgh, Sch Med, Dept Psychiat, Western Psychiat Inst & Clin, Pittsburgh, PA USA. RP Weinberger, DR (reprint author), NIMH, Cognit & Psychosis Program, Intramural Res Program, Natl Inst Hlth, Room 4S-235,MSC1379,10 Ctr Dr, Bethesda, MD 20892 USA. EM weinberd@intra.nimh.nih.gov RI Hariri, Ahmad/D-5761-2011; OI Pezawas, Lukas/0000-0002-1329-6352; Meyer-Lindenberg, Andreas/0000-0001-5619-1123 FU Intramural NIH HHS NR 60 TC 137 Z9 142 U1 5 U2 17 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD JUL PY 2008 VL 13 IS 7 BP 709 EP 716 DI 10.1038/mp.2008.32 PG 8 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 314TV UT WOS:000256832700009 PM 18347599 ER PT J AU Cecchinato, V Trindade, CJ Laurence, A Heraud, JM Brenchley, JM Ferrari, MG Zaffiri, L Tryniszewska, E Tsai, WP Vaccari, M Parks, RW Venzon, D Douek, DC O'Shea, JJ Franchini, G AF Cecchinato, V. Trindade, C. J. Laurence, A. Heraud, J. M. Brenchley, J. M. Ferrari, M. G. Zaffiri, L. Tryniszewska, E. Tsai, W. P. Vaccari, M. Parks, R. Washington Venzon, D. Douek, D. C. O'Shea, J. J. Franchini, G. TI Altered balance between Th17 and Th1 cells at mucosal sites predicts AIDS progression in simian immunodeficiency virus-infected macaques SO MUCOSAL IMMUNOLOGY LA English DT Article ID REGULATORY T-CELLS; GROWTH-FACTOR-BETA; OPPORTUNISTIC INFECTIONS; GASTROINTESTINAL-TRACT; PERIPHERAL-BLOOD; SEVERE DEPLETION; LAMINA PROPRIA; SIV INFECTION; HIV-INFECTION; CUTTING EDGE AB Loss of CD4(+) T cells in the gut is necessary but not sufficient to cause AIDS in animal models, raising the possibility that a differential loss of CD4(+) T-cell subtypes may be important. We found that CD4(+) T cells that produce interleukin (IL)-17, a recently identified lineage of effector CD4(+) T-helper cells, are infected by SIVmac251 in vitro and in vivo, and are found at lower frequency at mucosal and systemic sites within a few weeks from infection. In highly viremic animals, Th1 cells predominates over Th17 T cells and the frequency of Th17 cells at mucosal sites is negatively correlated with plasma virus level. Because Th17 cells play a central role in innate and adaptive immune response to extracellular bacteria, our finding may explain the chronic enteropathy in human immunodeficiency virus (HIV) infection. Thus, therapeutic approaches that reconstitute an adequate balance between Th1 and Th17 may be beneficial in the treatment of HIV infection. C1 [Cecchinato, V.; Trindade, C. J.; Heraud, J. M.; Zaffiri, L.; Tryniszewska, E.; Tsai, W. P.; Vaccari, M.; Parks, R. Washington; Franchini, G.] NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA. [Laurence, A.; O'Shea, J. J.] NIAMSD, Mol Immunol & Inflammat Branch, Bethesda, MD 20892 USA. [Brenchley, J. M.] NIAID, Immunopathogenesis Unit, Mol Microbiol Lab, Bethesda, MD USA. [Ferrari, M. G.] Adv BioSci Labs Inc, Kensington, MD USA. [Zaffiri, L.] Univ Roma La Sapienza, Dept Infect & Trop Dis, Rome, Italy. [Tryniszewska, E.] Med Univ Bialystok, Dept Microbiol Diagnost, Bialystok, Poland. [Venzon, D.] NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. [Douek, D. C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, Bethesda, MD 20892 USA. RP Franchini, G (reprint author), NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA. EM franchig@mail.nih.gov RI Laurence, Arian/A-8770-2009; HERAUD, Jean-Michel/O-1464-2013 OI Laurence, Arian/0000-0003-0942-8292; HERAUD, Jean-Michel/0000-0003-1107-0859 FU NIH; National Cancer Institute; Center for Cancer Research FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research.; Thanks to W. Strober, Mucosal Immunity Section, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, for helpful discussion; L. Hudacik, D. Weiss, J. Treece, and R. Pal of Advanced BioScience Laboratories, for study assistance and animal care; and Steven Snodgrass for editorial assistance. NR 50 TC 136 Z9 144 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1933-0219 J9 MUCOSAL IMMUNOL JI Mucosal Immunol. PD JUL PY 2008 VL 1 IS 4 BP 279 EP 288 DI 10.1038/mi.2008.14 PG 10 WC Immunology SC Immunology GA 366HI UT WOS:000260470900005 PM 19079189 ER PT J AU Petkau, J Reingold, SC Held, U Cutter, GR Fleming, TR Hughes, MD Miller, DH McFarland, HF Wolinsky, JS AF Petkau, J. Reingold, S. C. Held, U. Cutter, G. R. Fleming, T. R. Hughes, M. D. Miller, D. H. McFarland, H. F. Wolinsky, J. S. TI Magnetic resonance imaging as a surrogate outcome for multiple sclerosis relapses SO MULTIPLE SCLEROSIS LA English DT Article DE multiple sclerosis; magnetic resonance imaging; gadolinium enhanced lesions; surrogacy; prognosis; correlations ID PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; CLINICAL-TRIALS; END-POINTS; INTERFERON BETA-1B; MRI METRICS; MULTICENTER; DISABILITY; PROGRESSION; MS AB Background Magnetic resonance imaging (MRI) of lesions in the brain may be the best current candidate for a surrogate biological marker of clinical outcomes in relapsing remitting multiple sclerosis (MS), based on its role as an objective indicator of disease pathology. No biological surrogate marker has yet been validated for MS clinical outcomes. Objective The objective of this study was to use a multi-phased study to determine if a valid surrogate relationship could be demonstrated between counts of contrast enhancing lesions (CELs) and occurrence of relapses in MS. Methods We examined correlations for the concurrent and predictive relationship between CELs over 6 months and MS relapses over the same 6 months and an additional 6 months (total: 12 months), using available data on untreated patients from a large clinical trial and natural history database. Results Concurrent and predictive correlations were inadequate to justify continuation of this study to the planned additional phases required to demonstrate a surrogate relationship between CELs and MS relapses. Conclusions Confidence intervals for correlations between CELs and MS relapses exclude the possibility that CELs can be a good surrogate for relapses over the time scales we investigated. Further exploration of surrogacy between MRI measures and MS clinical outcomes may require improved datasets, the development of MRI techniques that couple better to clinical disease, and the ability to test a wide range of imaging-and clinically-based hypotheses for surrogacy. C1 [Wolinsky, J. S.] Univ Texas Hlth Sci Ctr Houston, Dept Neurol, Houston, TX 77030 USA. [Petkau, J.] Univ British Columbia, Dept Stat, Vancouver, BC V6T 1W5, Canada. [Reingold, S. C.] Sci & Clin Review Associates LLC, New York, NY USA. [Reingold, S. C.] Natl Multiple Sclerosis Soc, New York, NY USA. [Held, U.] Univ Zurich Hosp, Horton Ctr Patient Oriented Res, CH-8091 Zurich, Switzerland. [Cutter, G. R.] Univ Alabama, Dept Biostat, Birmingham, AL 35294 USA. [Fleming, T. R.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Hughes, M. D.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Miller, D. H.] Inst Neurol, NMR Res Unit, London WC1N 3BG, England. [McFarland, H. F.] Natl Inst Neurol Disorders & Stroke, Natl Inst Hlth, Neuroimmunol Branch, Bethesda, MD USA. RP Wolinsky, JS (reprint author), Univ Texas Hlth Sci Ctr Houston, Dept Neurol, 6431 Fannin St,Suite 7-044, Houston, TX 77030 USA. EM jerry.s.wolinsky@uth.tmc.edu RI Held, Ulrike /D-3666-2013; OI Held, Ulrike/0000-0003-3105-5840 FU Multiple Sclerosis Society [748]; NIAID NIH HHS [R01 AI029168, R37 AI029168-19] NR 25 TC 27 Z9 27 U1 0 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 J9 MULT SCLER JI Mult. Scler. PD JUL PY 2008 VL 14 IS 6 BP 770 EP 778 DI 10.1177/1352458507088104 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 334WN UT WOS:000258252200008 PM 18535021 ER PT J AU De Flora, S D'Agostini, F Balansky, R Camoirano, A Cartiglia, C Longobardi, M Travaini, G Steele, VE Pesce, C Izzotti, A AF De Flora, Silvio D'Agostini, Francesco Balansky, Roumen Camoirano, Anna Cartiglia, Cristina Longobardi, Mariagrazia Travaini, Giorgia Steele, Vernon E. Pesce, Carlo Izzotti, Alberto TI High susceptibility of neonatal mice to molecular, biochemical and cytogenetic alterations induced by environmental cigarette smoke and light SO MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH LA English DT Article; Proceedings Paper CT 5th International Conference on Environmental Mutagens in Human Populations CY MAY 20-24, 2007 CL Antalya, TURKEY DE environmental cigarette smoke; mainstream cigarette smoke; UV-containing light; carcinogenicity; intermediate biomarkers; genotoxicity; neonatal mice ID CHEMOPREVENTIVE AGENTS; RESPIRATORY-TRACT; N-ACETYLCYSTEINE; LUNG-TUMORS; MOUSE LUNG; POTENT CARCINOGENICITY; GENE-EXPRESSION; HALOGEN LAMPS; HAIRLESS MICE; EXPOSED RATS AB Our recent studies have shown that both cigarette smoke and UV-containing light, which are the most widespread and ubiquitous mutagens and carcinogens in the world, cause systemic genotoxic damage in hairless mice. Further studies were designed with the aim of evaluating the induction of genotoxic and carcinogenic effects in Swiss albino mice exposed to smoke and/or light since birth. We observed that a 4-month whole-body exposure of mice to mainstream cigarette smoke, starting at birth, caused an early and potent carcinogenic response in the lung and other organs. Our further experiments showed that exposure of mice to environmental cigarette smoke, during the first 5 weeks of life, resulted in a variety of significant alterations of intermediate biomarkers, including cytogenetic damage in bone marrow and peripheral blood, formation of lipid peroxidation products, increase of bulky DNA adduct levels, induction of oxidative DNA damage, and overexpression of OGG1 gene in lung, stimulation of apoptosis, hyperproliferation and loss of Fhit protein in pulmonary alveolar macrophages and/or bronchial epithelial cells, and early histopathological alterations in the respiratory tract. Moreover, exposure of mice to UV-containing light, mimicking solar irradiation, significantly enhanced oxidative DNA damage and bulky DNA adduct levels in lung, and synergized with smoke in inducing molecular alterations in the respiratory tract. The baseline OGG1 expression in lung was particularly high at birth and decreased in post-weanling mice. Oxidative DNA damage and other investigated end-points exhibited differential patterns in post-weanling mice and adult mice. The findings of these studies provide a mechanistic clue to the general concept that the neonatal period and early stages of life are critical in affecting susceptibility to carcinogens. (C) 2007 Elsevier B.V. All rights reserved. C1 [De Flora, Silvio; D'Agostini, Francesco; Balansky, Roumen; Camoirano, Anna; Cartiglia, Cristina; Longobardi, Mariagrazia; Travaini, Giorgia; Izzotti, Alberto] Univ Genoa, Dept Hlth Sci, I-16132 Genoa, Italy. [Balansky, Roumen] Natl Oncol Ctr, Sofia 1756, Bulgaria. [Steele, Vernon E.] Natl Canc Inst, Rockville, MD 20892 USA. [Pesce, Carlo] Univ Genoa, Dept Biophys Med & Odontostomatol Sci & Technol, I-16132 Genoa, Italy. RP De Flora, S (reprint author), Univ Genoa, Dept Hlth Sci, Via Pastore 1, I-16132 Genoa, Italy. EM sdf@unige.it OI izzotti, alberto/0000-0002-8588-0347 FU NCI NIH HHS [N01-CN53301] NR 41 TC 22 Z9 22 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5742 J9 MUTAT RES-REV MUTAT JI Mutat. Res.-Rev. Mutat. Res. PD JUL-AUG PY 2008 VL 659 IS 1-2 BP 137 EP 146 DI 10.1016/j.mrrev.2007.11.004 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 342VF UT WOS:000258811000017 PM 18155953 ER PT J AU Chorley, BN Wang, X Campbell, MR Pittman, GS Noureddine, MA Bell, DA AF Chorley, Brian N. Wang, Xuting Campbell, Michelle R. Pittman, Gary S. Noureddine, Maher A. Bell, Douglas A. TI Discovery and verification of functional single nucleotide polymorphisms in regulatory genomic regions: Current and developing technologies SO MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH LA English DT Article; Proceedings Paper CT 5th International Conference on Environmental Mutagens in Human Populations CY MAY 20-24, 2007 CL Antalya, TURKEY DE polymorphism; SNPs; gene regulation; functional genomics; microsphere assay ID SURFACE-PLASMON RESONANCE; PROTEIN-DNA INTERACTIONS; HUMAN GENE-EXPRESSION; FACTOR-BINDING-SITES; IMAGING MEASUREMENTS; RESPONSE ELEMENTS; GOLD SURFACES; IN-VIVO; CHROMATIN IMMUNOPRECIPITATION; HYBRIDIZATION ADSORPTION AB The most common form of genetic variation, single nucleotide polymorphisms or SNPs, can affect the way an individual responds to the environment and modify disease risk. Although most of the millions of SNPs have little or no effect on gene regulation and protein activity, there are many circumstances where base changes can have deleterious effects. Non-synonymous SNPs that result in amino acid changes in proteins have been studied because of their obvious impact on protein activity. It is well known that SNPs within regulatory regions of the genome can result in disregulation of gene transcription. However, the impact of SNPs located in putative regulatory regions, or rSNPs, is harder to predict for two primary reasons. First, the mechanistic roles of non-coding genomic sequence remain poorly defined. Second, experimental validation of the functional consequences of rSNPs is often slow and laborious. In this review, we summarize traditional and novel methodologies for candidate rSNPs selection, in particular in silico techniques that aid in candidate rSNP selection. Additionally we will discuss molecular biological techniques that assess the impact of rSNPs on binding of regulatory machinery, as well as functional consequences on transcription. Standard techniques such as EMSA and luciferase reporter constructs are still widely used to assess effects of rSNPs on binding and gene transcription; however, these protocols are often bottlenecks in the discovery process. Therefore, we highlight novel and developing high-throughput protocols that promise to aid in shortening the process of rSNP validation. Given the large amount of genomic information generated from a multitude of re-sequencing and genome-wide SNP array efforts, future focus should be to develop validation techniques that will allow greater understanding of the impact these polymorphisms have on human health and disease. Published by Elsevier B.V. C1 [Chorley, Brian N.; Wang, Xuting; Campbell, Michelle R.; Pittman, Gary S.; Noureddine, Maher A.; Bell, Douglas A.] Natl Inst Environm Hlth Sci, Environm Genom Sect, Mol Genet Lab, Natl Inst Hlth, Res Triangle Pk, NC 27709 USA. RP Bell, DA (reprint author), C3-03,POB 12233, Res Triangle Pk, NC 27709 USA. EM bell1@niehs.nih.gov OI Wang, Xuting/0000-0001-6781-8008 FU Intramural NIH HHS [Z01 ES100475-06] NR 109 TC 89 Z9 96 U1 4 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5742 J9 MUTAT RES-REV MUTAT JI Mutat. Res.-Rev. Mutat. Res. PD JUL-AUG PY 2008 VL 659 IS 1-2 BP 147 EP 157 DI 10.1016/j.mrrev.2008.05.001 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 342VF UT WOS:000258811000018 PM 18565787 ER PT J AU Wolff, J Larsen, PR AF Wolff, Jan Larsen, P. Reed TI Dr Joseph Edward Rall SO NATURE CLINICAL PRACTICE ENDOCRINOLOGY & METABOLISM LA English DT Biographical-Item C1 [Wolff, Jan] NIDDK, Endocrine Biochem Sect, Lab Biochem & Genet, Bethesda, MD 20892 USA. RP Wolff, J (reprint author), NIDDK, Endocrine Biochem Sect, Lab Biochem & Genet, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1745-8366 J9 NAT CLIN PRACT ENDOC JI Nat. Clin. Pract. Endocrinol. Metab. PD JUL PY 2008 VL 4 IS 7 BP 359 EP 359 DI 10.1038/ncpendmet0871 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 315YX UT WOS:000256917200001 PM 18568042 ER PT J AU Crandall, JP Knowler, WC Kahn, SE Marrero, D Florez, JC Bray, GA Haffner, SM Hoskin, M Nathan, DM AF Crandall, Jill P. Knowler, William C. Kahn, Steven E. Marrero, David Florez, Jose C. Bray, George A. Haffner, Steven M. Hoskin, Mary Nathan, David M. CA Diabet Prevention Program Res Grp TI The prevention of type 2 diabetes SO NATURE CLINICAL PRACTICE ENDOCRINOLOGY & METABOLISM LA English DT Review DE impaired glucose tolerance; prediabetes; prevention; type 2 diabetes ID IMPAIRED GLUCOSE-TOLERANCE; LIFE-STYLE INTERVENTION; RANDOMIZED CONTROLLED-TRIAL; BETA-CELL FUNCTION; 10-YEAR FOLLOW-UP; COST-EFFECTIVENESS; HIGH-RISK; INSULIN-RESISTANCE; FASTING GLUCOSE; CARDIOVASCULAR-DISEASE AB Type 2 diabetes mellitus (T2DM) affects more than 7% of adults in the Us and leads to substantial personal and economic burden. In prediabetic states insulin secretion and action-potential targets of preventive interventions-are impaired. In trials lifestyle modification (i.e. weight loss and exercise) has proven effective in preventing incident T2DM in high-risk groups, although weight loss has the greatest effect. Various medications (e.g. metformin, thiazolidinediones and acarbose) can also prevent or delay T2DM. Whether diabetes-prevention strategies also ultimately prevent the development of diabetic vascular complications is unknown, but cardiovascular risk factors are favorably affected. Preventive strategies that can be implemented in routine clinical settings have been developed and evaluated. Widespread application has, however, been limited by local financial considerations, even though cost-effectiveness might be achieved at the population level. C1 [Crandall, Jill P.] Albert Einstein Coll Med, Diabet Res Ctr, Bronx, NY 10461 USA. [Hoskin, Mary] NIDDK, Diabet Epidemiol & Clin Res Sect, Diabet Prevent Program Outcomes Study, Phoenix, AZ USA. [Kahn, Steven E.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Marrero, David] Indiana Univ, Bloomington, IN 47405 USA. [Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res & Diabet Unit, Boston, MA 02114 USA. [Bray, George A.] Louisiana State Univ, Baton Rouge, LA 70803 USA. [Haffner, Steven M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Haffner, Steven M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Clin Epidemiol, San Antonio, TX 78229 USA. [Nathan, David M.] Harvard Univ, Sch Med, Ctr Diabet, Boston, MA USA. [Nathan, David M.] Harvard Univ, Sch Med, Gen Clin Res Ctr, Boston, MA USA. RP Crandall, JP (reprint author), Albert Einstein Coll Med, Diabet Res Ctr, 1300 Morris Pk Ave, Bronx, NY 10461 USA. EM crandall@aecom.yu.edu OI Kahn, Steven/0000-0001-7307-9002 FU Intramural NIH HHS [Z01 DK069000-42]; NIDDK NIH HHS [U01 DK048489, U01 DK048489-06] NR 99 TC 101 Z9 103 U1 1 U2 20 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1745-8366 J9 NAT CLIN PRACT ENDOC JI Nat. Clin. Pract. Endocrinol. Metab. PD JUL PY 2008 VL 4 IS 7 BP 382 EP 393 DI 10.1038/ncpendmet0843 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 315YX UT WOS:000256917200010 PM 18493227 ER PT J AU Bagrov, AY Shapiro, JI AF Bagrov, Alexei Y. Shapiro, Joseph I. TI Endogenous digitalis: pathophysiologic roles and therapeutic applications SO NATURE CLINICAL PRACTICE NEPHROLOGY LA English DT Review DE end-stage renal disease; endogenous cardiotonic steroids; hypertension; Na+/K+-ATPase; natriuretic hormone ID OUABAIN-LIKE COMPOUND; DIGOXIN-LIKE IMMUNOREACTIVITY; PLASMALEMMAL NA/K-ATPASE; CONGESTIVE-HEART-FAILURE; HIGH-SALT INTAKE; DAHL-S RATS; EXPERIMENTAL UREMIC CARDIOMYOPATHY; BLOOD-PRESSURE REGULATION; SODIUM-PUMP INHIBITORS; VOLUME-EXPANDED DOGS AB Endogenous digitalis-like factors, also called cardiotonic steroids, have been thought for nearly half a century to have important roles in health and disease. The endogenous cardiotonic steroids ouabain and marinobufagenin have been identified in humans, and an effector mechanism has been delineated by which these hormones signal through the sodium/ potassium-transporting ATPase. These findings have increased interest in this field substantially. Although cardiotonic steroids were first considered important in the regulation of renal sodium transport and arterial pressure, subsequent work has implicated these hormones in the control of cell growth, apoptosis and fibrosis, among other processes. This Review focuses on the role of endogenous cardiotonic steroids in the pathophysiology of essential hypertension, congestive heart failure, end-stage renal disease and pre-eclampsia. We also discuss potential therapeutic strategies that have emerged as a result of the increased understanding of the regulation and actions of cardiotonic steroids. C1 [Bagrov, Alexei Y.] NIH, NIA, Intramural Res Program, Cardiovasc Sci Lab,Hypertens Unit, Baltimore, MD 21224 USA. [Shapiro, Joseph I.] Univ Toledo, Coll Med, Dept Med, Toledo, OH 43606 USA. RP Bagrov, AY (reprint author), NIH, NIA, Intramural Res Program, Cardiovasc Sci Lab,Hypertens Unit, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM bagrova@mail.nih.gov FU Intramural NIH HHS [Z01 AG000609-15] NR 171 TC 59 Z9 61 U1 0 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1745-8323 J9 NAT CLIN PRACT NEPHR JI Nat. Clin. Pract. Nephrol. PD JUL PY 2008 VL 4 IS 7 BP 378 EP 392 DI 10.1038/ncpneph0848 PG 15 WC Urology & Nephrology SC Urology & Nephrology GA 320XT UT WOS:000257269200010 PM 18542120 ER PT J AU Noth, U Steinert, AF Tuan, RS AF Noeth, Ulrich Steinert, Andre F. Tuan, Rocky S. TI Technology Insight: adult mesenchymal stem cells for osteoarthritis therapy SO NATURE CLINICAL PRACTICE RHEUMATOLOGY LA English DT Review DE articular cartilage; biomaterial scaffold; gene delivery; osteoarthritis; mesenchymal stem cell ID AUTOLOGOUS CHONDROCYTE IMPLANTATION; GENE-THERAPY; ARTICULAR-CARTILAGE; BONE-MARROW; CHONDROGENIC DIFFERENTIATION; OSTEOCHONDRAL DEFECTS; JOINT DISEASES; STROMAL CELLS; KNEE; REPAIR AB Despite the high prevalence and morbidity of osteoarthritis (OA), an effective treatment for this disease is currently lacking. Restoration of the diseased articular cartilage in patients with OA is, therefore, a challenge of considerable appeal to researchers and clinicians. Techniques that cause multipotent adult mesenchymal stem cells (MSCs) to differentiate into cells of the chondrogenic lineage have led to a variety of experimental strategies to investigate whether MSCs instead of chondrocytes can be used for the regeneration and maintenance of articular cartilage. MSC-based strategies should provide practical advantages for the patient with OA. These strategies include use of MSCs as progenitor cells to engineer cartilage implants that can be used to repair chondral and osteochondral lesions, or as trophic producers of bioactive factors to initiate endogenous regenerative activities in the OA joint. Targeted gene therapy might further enhance these activities of MSCs. Delivery of MSCs might be attained by direct intra-articular injection or by graft of engineered constructs derived from cell-seeded scaffolds; this latter approach could provide a three dimensional construct with mechanical properties that are congruous with the weight-bearing function of the joint. Promising experimental and clinical data are beginning to emerge in support of the use of MSCs for regenerative applications. C1 [Tuan, Rocky S.] NIAMSD, Cartilage Biol & Orthoped Branch, NIH, Bethesda, MD 20892 USA. [Noeth, Ulrich] Univ Wurzburg, Orthoped Ctr Musculoskeletal Res, Div Tissue Engn, Wurzburg, Germany. RP Tuan, RS (reprint author), NIAMSD, Cartilage Biol & Orthoped Branch, NIH, Bldg 50,Room 1523,50 S Dr MSC 8022, Bethesda, MD 20892 USA. EM tuanr@mail.nih.gov RI Steinert, Prof. Dr. , Andre/P-4559-2015 OI Steinert, Prof. Dr. , Andre/0000-0002-4397-8434 FU Intramural NIH HHS NR 63 TC 123 Z9 129 U1 1 U2 25 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1745-8382 J9 NAT CLIN PRACT RHEUM JI Nat. Clin. Pract. Rheumatol. PD JUL PY 2008 VL 4 IS 7 BP 371 EP 380 DI 10.1038/ncprheum0816 PG 10 WC Rheumatology; Social Issues SC Rheumatology; Social Issues GA 320XP UT WOS:000257268800013 PM 18477997 ER PT J AU Allikmets, R Dean, M AF Allikmets, Rando Dean, Michael TI Bringing age-related macular degeneration into focus SO NATURE GENETICS LA English DT Editorial Material ID COMPLEMENT FACTOR-H; GENE; SUSCEPTIBILITY; POLYMORPHISM; VARIANT; HTRA1; INCREASES; RISK C1 [Allikmets, Rando] Columbia Univ, Dept Ophthalmol & Pathol, New York, NY 10032 USA. [Dean, Michael] Natl Canc Inst, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD 21702 USA. [Allikmets, Rando] Columbia Univ, Dept Cell Biol, New York, NY 10032 USA. RP Allikmets, R (reprint author), Columbia Univ, Dept Ophthalmol & Pathol, New York, NY 10032 USA. EM rla22@columbia.edu RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 NR 15 TC 20 Z9 21 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JUL PY 2008 VL 40 IS 7 BP 820 EP 821 DI 10.1038/ng0708-820 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 319MA UT WOS:000257166500012 PM 18583975 ER PT J AU Sulem, P Gudbjartsson, DF Stacey, SN Helgason, A Rafnar, T Jakobsdottir, M Steinberg, S Gudjonsson, SA Palsson, A Thorleifsson, G Palsson, S Sigurgeirsson, B Thorisdottir, K Ragnarsson, R Benediktsdottir, KR Aben, KK Vermeulen, SH Goldstein, AM Tucker, MA Kiemeney, LA Olafsson, JH Gulcher, J Kong, A Thorsteinsdottir, U Stefansson, K AF Sulem, Patrick Gudbjartsson, Daniel F. Stacey, Simon N. Helgason, Agnar Rafnar, Thorunn Jakobsdottir, Margret Steinberg, Stacy Gudjonsson, Sigurjon A. Palsson, Arnar Thorleifsson, Gudmar Palsson, Snaebjoern Sigurgeirsson, Bardur Thorisdottir, Kristin Ragnarsson, Rafn Benediktsdottir, Kristrun R. Aben, Katja K. Vermeulen, Sita H. Goldstein, Alisa M. Tucker, Margaret A. Kiemeney, Lambertus A. Olafsson, Jon H. Gulcher, Jeffrey Kong, Augustine Thorsteinsdottir, Unnur Stefansson, Kari TI Two newly identified genetic determinants of pigmentation in Europeans SO NATURE GENETICS LA English DT Article ID TYRP1 GENE; POLYMORPHISM; AGOUTI; SKIN; POPULATION; SEQUENCE; ALBINISM; MELANOMA; HUMANS AB We present results from a genome-wide association study for variants associated with human pigmentation characteristics among 5,130 Icelanders, with follow-up analyses in 2,116 Icelanders and 1,214 Dutch individuals. Two coding variants in TPCN2 are associated with hair color, and a variant at the ASIP locus shows strong association with skin sensitivity to sun, freckling and red hair, phenotypic characteristics similar to those affected by well-known mutations in MC1R. C1 [Sulem, Patrick; Gudbjartsson, Daniel F.; Stacey, Simon N.; Helgason, Agnar; Rafnar, Thorunn; Jakobsdottir, Margret; Steinberg, Stacy; Gudjonsson, Sigurjon A.; Palsson, Arnar; Thorleifsson, Gudmar; Palsson, Snaebjoern; Gulcher, Jeffrey; Kong, Augustine; Thorsteinsdottir, Unnur; Stefansson, Kari] deCODE genet, IS-101 Reykjavik, Iceland. [Sigurgeirsson, Bardur; Thorisdottir, Kristin; Benediktsdottir, Kristrun R.; Olafsson, Jon H.] Landspitali Univ Hosp, Dept Dermatol, IS-101 Reykjavik, Iceland. [Sigurgeirsson, Bardur; Benediktsdottir, Kristrun R.; Olafsson, Jon H.] Landspitali Univ Hosp, Dept Pathol, IS-101 Reykjavik, Iceland. [Thorisdottir, Kristin; Ragnarsson, Rafn] Landspitali Univ Hosp, Dept Plast Surg, IS-101 Reykjavik, Iceland. [Aben, Katja K.; Kiemeney, Lambertus A.] Ctr Comprehens Canc, NL-6501 BG Nijmegen, Netherlands. [Aben, Katja K.; Vermeulen, Sita H.; Kiemeney, Lambertus A.] Radboud Univ Nijmegen, Dept Epidemiol & Biostat, NL-6500 HB Nijmegen, Netherlands. [Goldstein, Alisa M.; Tucker, Margaret A.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Services, Bethesda, MD 20892 USA. [Kiemeney, Lambertus A.] Radboud Univ Nijmegen, Dept Urol, NL-6500 HB Nijmegen, Netherlands. RP Gudbjartsson, DF (reprint author), deCODE genet, Sturlugata 8, IS-101 Reykjavik, Iceland. EM daniel.gudbjartsson@decode.is; kstefans@decode.is RI Palsson, Snaebjorn/J-9113-2012; Kiemeney, Lambertus/D-3357-2009; Tucker, Margaret/B-4297-2015; Helgason, Agnar/K-1522-2015; Palsson, Arnar/M-2742-2015; Vermeulen, H.H.M./L-4716-2015; Aben, Katja/G-9686-2016; OI Kiemeney, Lambertus/0000-0002-2368-1326; Aben, Katja/0000-0002-0214-2147; Palsson, Arnar/0000-0002-6525-8112; Sigurgeirsson, Bardur/0000-0002-9733-9742; Gudbjartsson, Daniel/0000-0002-5222-9857 FU Intramural NIH HHS NR 14 TC 169 Z9 174 U1 3 U2 25 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JUL PY 2008 VL 40 IS 7 BP 835 EP 837 DI 10.1038/ng.160 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 319MA UT WOS:000257166500016 PM 18488028 ER PT J AU Brown, KM MacGregor, S Montgomery, GW Craig, DW Zhao, ZZ Iyadurai, K Henders, AK Homer, N Campbell, MJ Stark, M Thomas, S Schmid, H Holland, EA Gillanders, EM Duffy, DL Maskiell, JA Jetann, J Ferguson, M Stephan, DA Cust, AE Whiteman, D Green, A Olsson, H Puig, S Ghiorzo, P Hansson, J Demenais, F Goldstein, AM Gruis, NA Elder, DE Bishop, JN Kefford, RF Giles, GG Armstrong, BK Aitken, JF Hopper, JL Martin, NG Trent, JM Mann, GJ Hayward, NK AF Brown, Kevin M. MacGregor, Stuart Montgomery, Grant W. Craig, David W. Zhao, Zhen Zhen Iyadurai, Kelly Henders, Anjali K. Homer, Nils Campbell, Megan J. Stark, Mitchell Thomas, Shane Schmid, Helen Holland, Elizabeth A. Gillanders, Elizabeth M. Duffy, David L. Maskiell, Judith A. Jetann, Jodie Ferguson, Megan Stephan, Dietrich A. Cust, Anne E. Whiteman, David Green, Adele Olsson, Hakan Puig, Susana Ghiorzo, Paola Hansson, Johan Demenais, Florence Goldstein, Alisa M. Gruis, Nelleke A. Elder, David E. Bishop, Julia Newton Kefford, Richard F. Giles, Graham G. Armstrong, Bruce K. Aitken, Joanne F. Hopper, John L. Martin, Nicholas G. Trent, Jeffrey M. Mann, Graham J. Hayward, Nicholas K. TI Common sequence variants on 20q11.22 confer melanoma susceptibility SO NATURE GENETICS LA English DT Article ID GENE; ASSOCIATION; PIGMENTATION; POLYMORPHISM; POPULATION; PHENOTYPE; ARRAYS; ASIP; RISK AB We conducted a genome-wide association pooling study for cutaneous melanoma and performed validation in samples totaling 2,019 cases and 2,105 controls. Using pooling, we identified a new melanoma risk locus on chromosome 20 (rs910873 and rs1885120), with replication in two further samples (combined P < 1 x 10(-15)). The per allele odds ratio was 1.75 (1.53, 2.01), with evidence for stronger association in early-onset cases. C1 [MacGregor, Stuart; Montgomery, Grant W.; Zhao, Zhen Zhen; Henders, Anjali K.; Campbell, Megan J.; Stark, Mitchell; Thomas, Shane; Duffy, David L.; Whiteman, David; Green, Adele; Martin, Nicholas G.; Hayward, Nicholas K.] Queensland Inst Med Res, Populat Studies & Genet Div, Brisbane, Qld 4029, Australia. [Brown, Kevin M.] Translat Genom Res Inst, Integrated Canc Genom Div, Phoenix, AZ 85028 USA. [Craig, David W.; Stephan, Dietrich A.] Translat Genom Res Inst, Neurogenom Div, Phoenix, AZ 85028 USA. [Homer, Nils] Univ Calif Los Angeles, Los Angeles, CA 90095 USA. [Schmid, Helen; Holland, Elizabeth A.; Kefford, Richard F.; Mann, Graham J.] Univ Sydney, Westmead Millennium Inst, Sydney Melanoma Unit, Westmead, NSW 2145, Australia. [Schmid, Helen; Holland, Elizabeth A.; Kefford, Richard F.; Mann, Graham J.] Univ Sydney, Westmead Inst Canc Res, Westmead, NSW 2145, Australia. [Gillanders, Elizabeth M.] NHGRI, Inherited Dis Res Branch, Natl Inst Hlth, Baltimore, MD 21224 USA. [Maskiell, Judith A.; Cust, Anne E.; Hopper, John L.] Univ Melbourne, Sch Populat Hlth, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic 3052, Australia. [Jetann, Jodie; Ferguson, Megan; Aitken, Joanne F.] Canc Council Queensland, Viertel Ctr Res Canc Control, Brisbane, Qld 4004, Australia. [Olsson, Hakan] Univ Hosp, Lund Canc Ctr, Dept Oncol, SE-22185 Lund, Sweden. [Puig, Susana] Univ Barcelona, Hosp Clin, Inst Invest Biomed August P & Sune, Dermatol Dept,Melanoma Unit, E-08036 Barcelona, Spain. [Ghiorzo, Paola] Univ Genoa, Dept Oncol Biol & Genet, I-16132 Genoa, Italy. [Hansson, Johan] Karolinska Inst, Dept Oncol Pathol, S-17176 Stockholm, Sweden. [Hansson, Johan] Karolinska Univ Hosp, S-17176 Stockholm, Sweden. [Demenais, Florence] Fdn Jean Dausset CEPH, INSERM, U794, F-75010 Paris, France. [Goldstein, Alisa M.] NCI, Div Canc Epidemiol & Genet, Genet Epidemiol Branch, Bethesda, MD 20892 USA. [Gruis, Nelleke A.] Leiden Univ, Med Ctr, Dept Dermatol, NL-2333 AL Leiden, Netherlands. [Elder, David E.] Univ Pennsylvania, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Bishop, Julia Newton] Univ Leeds, Leeds Inst Mol Med, Epidemiol & Biostat Sect, Leeds LS9 7TF, W Yorkshire, England. [Giles, Graham G.] Canc Council Victoria, Canc Epidemiol Ctr, Carlton, Vic 3053, Australia. [Armstrong, Bruce K.] Univ Sydney, Sch Publ Hlth, Sydney, NSW 2006, Australia. [Trent, Jeffrey M.] Translat Genom Res Inst, Genet Basis Human Dis Div, Phoenix, AZ 85028 USA. RP MacGregor, S (reprint author), Queensland Inst Med Res, Populat Studies & Genet Div, Brisbane, Qld 4029, Australia. EM stuart.macgregor@qimr.edu.au RI Aitken, Joanne/C-5289-2009; Macgregor, Stuart/C-6442-2009; Stark, Mitchell/E-3542-2010; Mann, Graham/G-4758-2014; Demenais, Florence/G-3298-2013; hayward, nicholas/C-1367-2015; Armstrong, Bruce/K-9464-2015; Montgomery, Grant/B-7148-2008; Duffy, David/B-7392-2013; Whiteman, David/P-2728-2014; Green, Adele/P-2736-2014; OI Puig, Susana/0000-0003-1337-9745; Giles, Graham/0000-0003-4946-9099; Martin, Nicholas/0000-0003-4069-8020; Macgregor, Stuart/0000-0001-6731-8142; Stark, Mitchell/0000-0002-4510-2161; Mann, Graham/0000-0003-1301-405X; Demenais, Florence/0000-0001-8361-0936; hayward, nicholas/0000-0003-4760-1033; Armstrong, Bruce/0000-0001-8940-7525; Montgomery, Grant/0000-0002-4140-8139; Duffy, David/0000-0001-7227-632X; Whiteman, David/0000-0003-2563-9559; Green, Adele/0000-0002-2753-4841; Gruis, Nelleke/0000-0002-5210-9150 FU NCI NIH HHS [CA083115, CA109544, CA83115, CA88363, R01 CA083115, R01 CA083115-08, R01 CA088363, R01 CA088363-07, R01 CA109544]; NHLBI NIH HHS [HL086528, U01 HL086528] NR 11 TC 136 Z9 139 U1 1 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JUL PY 2008 VL 40 IS 7 BP 838 EP 840 DI 10.1038/ng.163 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 319MA UT WOS:000257166500017 PM 18488026 ER PT J AU Gudbjartsson, DF Sulem, P Stacey, SN Goldstein, AM Rafnar, T Sigurgeirsson, B Benediktsdottir, KR Thorisdottir, K Ragnarsson, R Sveinsdottir, SG Magnusson, V Lindblom, A Kostulas, K Botella-Estrada, R Soriano, V Juberias, P Grasa, M Saez, B Andres, R Scherer, D Rudnai, P Gurzau, E Koppova, K Kiemeney, LA Jakobsdottir, M Steinberg, S Helgason, A Gretarsdottir, S Tucker, MA Mayordomo, JI Nagore, E Kumar, R Hansson, J Olafsson, JH Gulcher, J Kong, A Thorsteinsdottir, U Stefansson, K AF Gudbjartsson, Daniel F. Sulem, Patrick Stacey, Simon N. Goldstein, Alisa M. Rafnar, Thorunn Sigurgeirsson, Bardur Benediktsdottir, Kristrun R. Thorisdottir, Kristin Ragnarsson, Rafn Sveinsdottir, Steinunn G. Magnusson, Veronica Lindblom, Annika Kostulas, Konstantinos Botella-Estrada, Rafael Soriano, Virtudes Juberias, Pablo Grasa, Matilde Saez, Berta Andres, Raquel Scherer, Dominique Rudnai, Peter Gurzau, Eugene Koppova, Kvetoslava Kiemeney, Lambertus A. Jakobsdottir, Margret Steinberg, Stacy Helgason, Agnar Gretarsdottir, Solveig Tucker, Margaret A. Mayordomo, Jose I. Nagore, Eduardo Kumar, Rajiv Hansson, Johan Olafsson, Jon H. Gulcher, Jeffrey Kong, Augustine Thorsteinsdottir, Unnur Stefansson, Kari TI ASIP and TYR pigmentation variants associate with cutaneous melanoma and basal cell carcinoma SO NATURE GENETICS LA English DT Article ID MELANOCORTIN-1 RECEPTOR MC1R; NONMELANOMA SKIN-CANCER; RISK-FACTORS; GENE VARIANTS; CONFERS RISK; EYE-COLOR; POLYMORPHISM; AGOUTI; HAIR; SUSCEPTIBILITY AB Fair color increases risk of cutaneous melanoma (CM) and basal cell carcinoma (BCC). Recent genome-wide association studies have identified variants affecting hair, eye and skin pigmentation in Europeans. Here, we assess the effect of these variants on risk of CM and BCC in European populations comprising 2,121 individuals with CM, 2,163 individuals with BCC and over 40,000 controls. A haplotype near ASIP, known to affect a similar spectrum of pigmentation traits as MC1R variants, conferred significant risk of CM (odds ratio (OR) 1.45, P = 1.2 x 10(-9)) and BCC (OR = 1.33, P = 1.2 x 10(-6)). The variant in TYR encoding the R402Q amino acid substitution, previously shown to affect eye color and tanning response, conferred risk of CM (OR = 1.21, P = 2.8 x 10(-7)) and BCC (OR = 1.14, P = 6.1 x 10(-4)). An eye color variant in TYRP1 was associated with risk of CM (OR = 1.15, P = 4.6 x 10(-4)). The association of all three variants is robust with respect to adjustment for the effect of pigmentation. C1 [Gudbjartsson, Daniel F.; Sulem, Patrick; Stacey, Simon N.; Rafnar, Thorunn; Jakobsdottir, Margret; Steinberg, Stacy; Helgason, Agnar; Gretarsdottir, Solveig; Gulcher, Jeffrey; Kong, Augustine; Thorsteinsdottir, Unnur; Stefansson, Kari] deCODE Genet, IS-101 Reykjavik, Iceland. [Goldstein, Alisa M.; Tucker, Margaret A.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Services, Bethesda, MD 20892 USA. [Sigurgeirsson, Bardur; Benediktsdottir, Kristrun R.; Thorisdottir, Kristin; Olafsson, Jon H.] Landspitali Univ Hosp, Dept Dermatol, IS-101 Reykjavik, Iceland. [Sigurgeirsson, Bardur; Benediktsdottir, Kristrun R.; Thorisdottir, Kristin; Olafsson, Jon H.] Landspitali Univ Hosp, Dept Pathol, IS-101 Reykjavik, Iceland. [Benediktsdottir, Kristrun R.; Thorisdottir, Kristin] Landspitali Univ Hosp, Dept Plast Surg, IS-101 Reykjavik, Iceland. [Sveinsdottir, Steinunn G.] Clin Res Ctr, IS-110 Reykjavik, Iceland. [Magnusson, Veronica] Karolinska Univ Hosp Solna, Karolinska Inst, Canc Ctr Karolinska, Dept Oncol Pathol, S-17176 Stockholm, Sweden. [Lindblom, Annika] Karolinska Inst, Dept Mol Med, S-17176 Stockholm, Sweden. [Kostulas, Konstantinos] Karolinska Univ Hosp, Karolinska Inst, Dept Neurol, S-14186 Huddinge, Sweden. [Botella-Estrada, Rafael] Inst Valenciano Oncol, Dept Dermatol, Valencia 46009, Spain. [Soriano, Virtudes; Nagore, Eduardo] Inst Valenciano Oncol, Dept Oncol, Valencia 46009, Spain. [Juberias, Pablo; Grasa, Matilde] Univ Hosp, Div Dermatol, Zaragoza 50009, Spain. [Saez, Berta] Hlth Sci Inst, Zaragoza 50009, Spain. [Andres, Raquel; Mayordomo, Jose I.] Hlth Sci Inst, Div Med Oncol, Zaragoza 50009, Spain. [Scherer, Dominique; Kumar, Rajiv] German Canc Res Ctr, Div Mol Genet Epidemiol, D-69120 Heidelberg, Germany. [Rudnai, Peter] Natl Inst Environm Hlth, H-1450 Budapest, Hungary. [Gurzau, Eugene] Ctr Environm Hlth, RO Cluj Napoca, Romania. [Koppova, Kvetoslava] State Hlth Inst, SK-97576 Banska Bystr, Slovakia. [Kiemeney, Lambertus A.] Ctr Comprehens Canc, NL-6501 BG Nijmegen, Netherlands. [Kiemeney, Lambertus A.] Radboud Univ Nijmegen, Nijmegen Med Ctr, Dept Epidemiol & Biostat, NL-6500 HB Nijmegen, Netherlands. [Kiemeney, Lambertus A.] Radboud Univ Nijmegen, Nijmegen Med Ctr, Dept Urol, NL-6500 HB Nijmegen, Netherlands. RP Gudbjartsson, DF (reprint author), deCODE Genet, Sturlugata 8, IS-101 Reykjavik, Iceland. EM daniel.gudbjartsson@decode.is; kstefans@decode.is RI Mayordomo, Jose/K-3453-2013; Kiemeney, Lambertus/D-3357-2009; Tucker, Margaret/B-4297-2015; Helgason, Agnar/K-1522-2015; Hoiom, Veronica/F-4153-2012; OI Kiemeney, Lambertus/0000-0002-2368-1326; Kumar, Rajiv/0000-0002-6093-0395; Sigurgeirsson, Bardur/0000-0002-9733-9742; Gudbjartsson, Daniel/0000-0002-5222-9857 FU Intramural NIH HHS; NCI NIH HHS [N02-CP-91026] NR 30 TC 196 Z9 199 U1 0 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JUL PY 2008 VL 40 IS 7 BP 886 EP 891 DI 10.1038/ng.161 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 319MA UT WOS:000257166500024 PM 18488027 ER PT J AU Wang, ZB Zang, CZ Rosenfeld, JA Schones, DE Barski, A Cuddapah, S Cui, KR Roh, TY Peng, WQ Zhang, MQ Zhao, KJ AF Wang, Zhibin Zang, Chongzhi Rosenfeld, Jeffrey A. Schones, Dustin E. Barski, Artem Cuddapah, Suresh Cui, Kairong Roh, Tae-Young Peng, Weiqun Zhang, Michael Q. Zhao, Keji TI Combinatorial patterns of histone acetylations and methylations in the human genome SO NATURE GENETICS LA English DT Article ID CHROMATIN DOMAINS; GENE-EXPRESSION; T-CELLS; TRANSCRIPTION; ENHANCERS; LANGUAGE; COMPLEX; CODE AB Histones are characterized by numerous posttranslational modifications that influence gene transcription(1,2). However, because of the lack of global distribution data in higher eukaryotic systems(3), the extent to which gene-specific combinatorial patterns of histone modifications exist remains to be determined. Here, we report the patterns derived from the analysis of 39 histone modifications in human CD4(+) T cells. Our data indicate that a large number of patterns are associated with promoters and enhancers. In particular, we identify a common modification module consisting of 17 modifications detected at 3,286 promoters. These modifications tend to colocalize in the genome and correlate with each other at an individual nucleosome level. Genes associated with this module tend to have higher expression, and addition of more modifications to this module is associated with further increased expression. Our data suggest that these histone modifications may act cooperatively to prepare chromatin for transcriptional activation. C1 [Wang, Zhibin; Schones, Dustin E.; Barski, Artem; Cuddapah, Suresh; Cui, Kairong; Roh, Tae-Young; Zhao, Keji] NHLBI, Lab Mol Immunol, US NIH, Bethesda, MD 20892 USA. [Zang, Chongzhi] George Washington Univ, Dept Phys, Washington, DC 20052 USA. [Rosenfeld, Jeffrey A.; Zhang, Michael Q.] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. NYU, Dept Biol, New York, NY 10003 USA. RP Zhao, KJ (reprint author), NHLBI, Lab Mol Immunol, US NIH, Bethesda, MD 20892 USA. EM zhaok@nhlbi.nih.gov RI Zang, Chongzhi/D-1445-2011; OI Barski, Artem/0000-0002-1861-5316 FU Intramural NIH HHS [Z01 HL005801-05]; NHGRI NIH HHS [R01 HG001696, HG001696, R01 HG001696-05] NR 30 TC 1080 Z9 1100 U1 11 U2 82 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JUL PY 2008 VL 40 IS 7 BP 897 EP 903 DI 10.1038/ng.154 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 319MA UT WOS:000257166500026 PM 18552846 ER PT J AU She, XW Cheng, Z Zollner, S Church, DM Eichler, EE AF She, Xinwei Cheng, Ze Zoellner, Sebastian Church, Deanna M. Eichler, Evan E. TI Mouse segmental duplication and copy number variation SO NATURE GENETICS LA English DT Article ID HUMAN GENOME; STRUCTURAL VARIATION; ARRAY CGH; EVOLUTION; CHROMOSOME; EXPANSION; SELECTION; HOTSPOTS; STRAINS; SYNTENY AB Detailed analyses of the clone-based genome assembly reveal that the recent duplication content of mouse (4.94%) is now comparable to that of human (5.5%), in contrast to previous estimates from the whole-genome shotgun sequence assembly. However, the architecture of mouse and human genomes differs markedly: most mouse duplications are organized into discrete clusters of tandem duplications that show depletion of genes and transcripts and enrichment of long interspersed nuclear element (LINE) and long terminal repeat (LTR) retroposons. We assessed copy number variation of the C57BL/6J duplicated regions within 15 mouse strains previously used for genetic association studies, sequencing and the Mouse Phenome Project. We determined that over 60% of these base pairs are polymorphic among the strains (on average, there was 20 Mb of copy-number-variable DNA between different mouse strains). Our data suggest that different mouse strains show comparable, if not greater, copy number polymorphism when compared to human; however, such variation is more locally restricted. We show large and complex patterns of interstrain copy number variation restricted to large gene families associated with spermatogenesis, pregnancy, viviparity, pheromone signaling and immune response. C1 [She, Xinwei; Cheng, Ze; Eichler, Evan E.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Zoellner, Sebastian] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Zoellner, Sebastian] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Church, Deanna M.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. [Eichler, Evan E.] Howard Hughes Med Inst, Seattle, WA 98195 USA. RP Eichler, EE (reprint author), Univ Washington, Dept Genome Sci, 1705 NE Pacific St, Seattle, WA 98195 USA. EM eee@gs.washington.edu FU Howard Hughes Medical Institute; NHGRI NIH HHS [HG002385, R01 HG002385, R01 HG002385-07] NR 30 TC 146 Z9 148 U1 1 U2 13 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JUL PY 2008 VL 40 IS 7 BP 909 EP 914 DI 10.1038/ng.172 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 319MA UT WOS:000257166500028 PM 18500340 ER PT J AU Schubert, C Rotimi, C AF Schubert, Charlotte Rotimi, Charles TI Straight talk with ... Charles Rotimi SO NATURE MEDICINE LA English DT Editorial Material C1 [Rotimi, Charles] NIH, Intramural Ctr Genom & Hlth Disparities, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 HG999999] NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JUL PY 2008 VL 14 IS 7 BP 704 EP 705 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 323NL UT WOS:000257452700011 PM 18607362 ER PT J AU Beuming, T Kniazeff, J Bergmann, ML Shi, L Gracia, L Raniszewska, K Newman, AH Javitch, JA Weinstein, H Gether, U Loland, CJ AF Beuming, Thijs Kniazeff, Julie Bergmann, Marianne L. Shi, Lei Gracia, Luis Raniszewska, Klaudia Newman, Amy Hauck Javitch, Jonathan A. Weinstein, Harel Gether, Ulrik Loland, Claus J. TI The binding sites for cocaine and dopamine in the dopamine transporter overlap SO NATURE NEUROSCIENCE LA English DT Article ID TRANSMEMBRANE DOMAIN-I; HUMAN SEROTONIN TRANSPORTERS; NEUROTRANSMITTER TRANSPORTERS; SUBSTRATE TRANSPORT; BACTERIAL HOMOLOG; UPTAKE INHIBITORS; RECOGNITION; MODEL; ACID; IDENTIFICATION AB Cocaine is a widely abused substance with psychostimulant effects that are attributed to inhibition of the dopamine transporter (DAT). We present molecular models for DAT binding of cocaine and cocaine analogs constructed from the high-resolution structure of the bacterial transporter homolog LeuT. Our models suggest that the binding site for cocaine and cocaine analogs is deeply buried between transmembrane segments 1, 3, 6 and 8, and overlaps with the binding sites for the substrates dopamine and amphetamine, as well as for benztropine-like DAT inhibitors. We validated our models by detailed mutagenesis and by trapping the radiolabeled cocaine analog [(3)H] CFT in the transporter, either by cross-linking engineered cysteines or with an engineered Zn(2+)-binding site that was situated extracellularly to the predicted common binding pocket. Our data demonstrate the molecular basis for the competitive inhibition of dopamine transport by cocaine. C1 [Kniazeff, Julie; Bergmann, Marianne L.; Raniszewska, Klaudia; Gether, Ulrik; Loland, Claus J.] Univ Copenhagen, Panum Inst 18 6, Fac Hlth Sci, Dept Neurosci & Pharmacol,Mol Neuropharmacol Grp, DK-2200 Copenhagen, Denmark. [Beuming, Thijs; Shi, Lei; Gracia, Luis; Weinstein, Harel] Cornell Univ, Weill Med Coll, Dept Physiol & Biophys, New York, NY 10021 USA. [Shi, Lei; Weinstein, Harel] Cornell Univ, Weill Med Coll, Inst Computat Biomed, New York, NY 10021 USA. [Newman, Amy Hauck] Natl Inst Drug Abuse, Med Chem Sect, Medicat Discovery Res Branch,NIH, Intramural Res Program,Dept Hlth & Human Servs, Baltimore, MD 21224 USA. [Javitch, Jonathan A.] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY 10023 USA. [Javitch, Jonathan A.] Columbia Univ, Coll Phys & Surg, Dept Pharmacol, New York, NY 10023 USA. [Javitch, Jonathan A.] Columbia Univ, Coll Phys & Surg, Ctr Mol Recognit, New York, NY 10023 USA. RP Gether, U (reprint author), Univ Copenhagen, Panum Inst 18 6, Fac Hlth Sci, Dept Neurosci & Pharmacol,Mol Neuropharmacol Grp, Blegdamsvej 3, DK-2200 Copenhagen, Denmark. EM gether@sund.ku.dk RI Loland, Claus/E-5975-2014; OI Loland, Claus/0000-0002-1773-1446; Gether, Ulrik/0000-0002-0020-3807 FU Intramural NIH HHS [Z01 DA000389-12]; NIDA NIH HHS [DA 22413, K05 DA022413, P01 DA012408, P01 DA12408] NR 47 TC 171 Z9 172 U1 1 U2 28 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD JUL PY 2008 VL 11 IS 7 BP 780 EP 789 DI 10.1038/nn.2146 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 318KD UT WOS:000257089400015 PM 18568020 ER PT J AU Chernomordik, LV Kozlov, MM AF Chernomordik, Leonid V. Kozlov, Michael M. TI Mechanics of membrane fusion SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Review ID MOLECULAR-DYNAMICS SIMULATIONS; INFLUENZA-VIRUS HEMAGGLUTININ; MEDIATED FUSION; LIPID-BILAYERS; VESICLE FUSION; PORE FORMATION; CELL-MEMBRANE; INTERMEDIATE STRUCTURE; PHOSPHOLIPID-VESICLES; BIOLOGICAL-MEMBRANES AB Diverse membrane fusion reactions in biology involve close contact between two lipid bilayers, followed by the local distortion of the individual bilayers and reformation into a single, merged membrane. We consider the structures and energies of the fusion intermediates identified in experimental and theoretical work on protein-free lipid bilayers. On the basis of this analysis, we then discuss the conserved fusion-through-hemifusion pathway of merger between biological membranes and propose that the entire progression, from the close juxtaposition of membrane bilayers to the expansion of a fusion pore, is controlled by protein-generated membrane stresses. C1 [Chernomordik, Leonid V.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Membrane Biol, Lab Cellular & Mol Biophys, Bethesda, MD 20892 USA. [Kozlov, Michael M.] Tel Aviv Univ, Sackler Fac Med, Dept Physiol & Pharmacol, IL-69978 Tel Aviv, Israel. RP Chernomordik, LV (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Membrane Biol, Lab Cellular & Mol Biophys, Bethesda, MD 20892 USA. EM chernoml@mail.nih.gov; michk@post.tau.ac.il FU Intramural NIH HHS [Z01 HD001501-16] NR 122 TC 386 Z9 390 U1 7 U2 137 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1545-9993 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD JUL PY 2008 VL 15 IS 7 BP 675 EP 683 DI 10.1038/nsmb.1455 PG 9 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 322YZ UT WOS:000257412500005 PM 18596814 ER PT J AU Basselin, M Chang, L Chen, M Bell, JM Rapoport, SI AF Basselin, Mireille Chang, Lisa Chen, Mei Bell, Jane M. Rapoport, Stanley I. TI Chronic carbamazepine administration attenuates dopamine D(2)-like receptor-initiated signaling via arachidonic acid in rat brain SO NEUROCHEMICAL RESEARCH LA English DT Article DE bipolar disorder; carbamazepine; phospholipase A(2); D(2)-like receptors; quinpirole; arachidonic acid; prostaglandin E(2); brain imaging ID DNA-BINDING ACTIVITY; BIPOLAR DISORDER; UNANESTHETIZED RATS; CHRONIC LITHIUM; PREFRONTAL CORTEX; FRONTAL-CORTEX; DOCOSAHEXAENOIC ACID; PARKINSONS-DISEASE; PROTEIN EXPRESSION; PHOSPHOLIPASE A(2) AB Observations that dopaminergic antagonists are beneficial in bipolar disorder and that dopaminergic agonists can produce mania suggest that bipolar disorder involves excessive dopaminergic transmission. Thus, mood stabilizers used to treat the disease might act in part by downregulating dopaminergic transmission. In agreement, we reported that dopamine D(2)-like receptor mediated signaling involving arachidonic acid (AA, 20:4n-6) was downregulated in rats chronically treated with lithium. To see whether chronic carbamazepine, another mood stabilizer, did this as well, we injected i.p. saline or the D(2)-like receptor agonist, quinpirole (1 mg/kg), into unanesthetized rats that had been pretreated for 30 days with i.p. carbamazepine (25 mg/kg/day) or vehicle, and used quantitative autoradiography to measure regional brain incorporation coefficients (k*) for AA, markers of signaling. We also measured brain prostaglandin E(2) (PGE(2)), an AA metabolite. In vehicle-treated rats, quinpirole compared with saline significantly increased k* for AA in 35 of 82 brain regions examined, as well as brain PGE(2) concentration. Affected regions belong to dopaminergic circuits and have high D(2)-like receptor densities. Chronic carbamazepine pretreatment prevented the quinpirole-induced increments in k* and in PGE(2). These findings are consistent with the hypothesis that effective mood stabilizers generally downregulate brain AA signaling via D(2)-like receptors, and that this signaling is upregulated in bipolar disorder. C1 [Basselin, Mireille; Chang, Lisa; Chen, Mei; Bell, Jane M.; Rapoport, Stanley I.] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. RP Basselin, M (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Bldg 9,Room 1S126, Bethesda, MD 20892 USA. EM mirvasln@mail.nih.gov FU Intramural NIH HHS [Z01 AG000134-25, ] NR 56 TC 16 Z9 16 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD JUL PY 2008 VL 33 IS 7 BP 1373 EP 1383 DI 10.1007/s11064-008-9595-y PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 307MF UT WOS:000256322300025 PM 18302021 ER PT J AU Brewer, M Changi, F Antonellis, A Fischbeck, K Polly, P Nicholson, G Kennerson, M AF Brewer, Megan Changi, Febriani Antonellis, Anthony Fischbeck, Kurt Polly, Patsie Nicholson, Garth Kennerson, Marina TI Evidence of a founder haplotype refines the X-linked Charcot-Marie-Tooth (CMTX3) locus to a 2.5 Mb region SO NEUROGENETICS LA English DT Article DE X-linked Charcot-Marie-Tooth disease; founder effect; linkage analysis ID DISEASE; NEUROPATHY; MUTATIONS; HETEROGENEITY; FAMILIES; MOTOR; GENE AB X-linked Charcot-Marie-Tooth (CMTX) disease is a common inherited degenerative disorder of the peripheral nerve. Previously, our laboratory identified a large New Zealand/United Kingdom (NZ/UK) family mapping to the CMTX3 locus (Xq26.3-27.1). We have now identified a second large, Australian X-linked CMT family that links to the CMTX3 locus. This new family has the same phenotype as our previously described CMTX3 family, with slightly milder disease in males than CMTX1 and asymptomatic carrier females. This study also includes the re-analysis of one of the original US pedigrees reporting the CMTX3 locus. The large Australian family shared the complete disease haplotype with our original NZ/UK family, while the American family shared only the distal portion of the disease haplotype. Comparison of the frequency of the CMTX3 haplotype to the normal population showed strong statistical evidence (p<0.0001) indicating that the smaller shared haplotype is identical by descent. This suggests that the new CMTX3 family, our previously reported family, and the original American CMTX3 family have a common ancestor, and the disease in these families is caused by a founder mutation. The ancestral recombination observed in the American family refines the CMTX3 interval to a 2.5 Mb region between DXS984 and DXS8106. In this region, 11 out of the 15 annotated genes have been excluded for pathogenic mutations. C1 [Brewer, Megan; Changi, Febriani; Nicholson, Garth; Kennerson, Marina] ANZAC Res Inst, Northcott Neurosci Lab, Concord, NSW 2139, Australia. [Nicholson, Garth; Kennerson, Marina] Concord Hosp, Mol Med Lab, Concord, NSW, Australia. [Brewer, Megan; Nicholson, Garth; Kennerson, Marina] Univ Sydney, Fac Med, Camperdown, NSW, Australia. [Antonellis, Anthony] NIH, Genome Technol Branch, Bethesda, MD 20892 USA. [Fischbeck, Kurt] NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. [Polly, Patsie] ANZAC Res Inst, Canc Pharmacol Unit, Concord, NSW, Australia. [Polly, Patsie] Univ New S Wales, Fac Med, Sch Med Sci, Dept Pathol, Kensington, NSW 2033, Australia. RP Brewer, M (reprint author), ANZAC Res Inst, Northcott Neurosci Lab, Concord, NSW 2139, Australia. EM mbrewer@med.usyd.edu.au FU Intramural NIH HHS; NINDS NIH HHS [R00 NS060983, R01 NS073748] NR 14 TC 5 Z9 5 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1364-6745 J9 NEUROGENETICS JI Neurogenetics PD JUL PY 2008 VL 9 IS 3 BP 191 EP 195 DI 10.1007/s10048-008-0126-4 PG 5 WC Genetics & Heredity; Clinical Neurology SC Genetics & Heredity; Neurosciences & Neurology GA 320EJ UT WOS:000257216200005 PM 18458969 ER PT J AU Terry, G Liow, JS Chernet, E Zoghbi, SS Phebus, L Felder, CC Tauscher, J Schaus, JM Pike, VW Halldin, C Innis, RB AF Terry, Garth Liow, Jeih-San Chernet, Eyassu Zoghbi, Sami S. Phebus, Lee Felder, Christian C. Tauscher, Johannes Schaus, John M. Pike, Victor W. Halldin, Christer Innis, Robert B. TI Positron emission tomography imaging using an inverse agonist radioligand to assess cannabinoid CB(1) receptors in rodents SO NEUROIMAGE LA English DT Article ID P-GLYCOPROTEIN; SR 141716A; PHARMACOLOGICAL-ACTIVITY; ENDOCANNABINOID SYSTEM; BRAIN; BINDING; ANANDAMIDE; ANTAGONISM; MICE; TRANSPORTER AB [(11)C] MePPEP is an inverse agonist and a radioligand developed to image cannabinoid CB(1) receptors with positron emission tomography (PET). It provides reversible, high specific signal in monkey brain. We assessed [(11)C] MePPEP in rodent brain with regard to receptor selectivity, susceptibility to transport by P-glycoprotein (P-gp), sensitivity to displacement by agonists, and accumulation of radiometabolites. We used CB(1) receptor knockout mice and P-gp knockout mice to assess receptor selectivity and sensitivity to efflux transport, respectively. Using serial measurements of PET brain activity and plasma concentrations of [(11)C] MePPEP, we estimated CB(1) receptor density in rat brain as distribution volume. CB(1) knockout mice showed only nonspecific brain uptake, and [(11)C] MePPEP was not a substrate for P-gp. Direct acting agonists anandamide (10 mg/ kg), methanandamide (10 mg/ kg), CP 55,940 (1 mg/ kg), and indirect agonist URB597 (0.3 and 0.6 mg/ kg) failed to displace [(11)C] MePPEP, while the inverse agonist rimonabant (3 and 10 mg/ kg) displaced >65% of [(11)C] MePPEP. Radiometabolites represented similar to 13% of total radioactivity in brain between 30 and 120 min. [(11)C] MePPEP was selective for the CB(1) receptor, was not a substrate for P-gp, and was more potently displaced by inverse agonists than agonists. The low potency of agonists suggests either a large receptor reserve or non-overlapping binding sites for agonists and inverse agonists. Radiometabolites of [(11)C] MePPEP in brain caused distribution volume to be overestimated by similar to 13%. Published by Elsevier Inc. C1 [Terry, Garth; Liow, Jeih-San; Zoghbi, Sami S.; Pike, Victor W.; Innis, Robert B.] NIMH, NIH, Mol Imaging Branch, Bethesda, MD 20892 USA. [Chernet, Eyassu; Phebus, Lee; Felder, Christian C.; Tauscher, Johannes; Schaus, John M.] Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. [Terry, Garth; Halldin, Christer] Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, Stockholm, Sweden. RP Innis, RB (reprint author), NIMH, NIH, Mol Imaging Branch, 31 Ctr Dr,Room B2-B37,MSC 2035, Bethesda, MD 20892 USA. EM robert.innis@nih.gov RI Tauscher, Johannes/M-5976-2016 FU Intramural NIH HHS [Z01 MH002795-06]; NIMH NIH HHS [Z01 MH002795] NR 33 TC 31 Z9 31 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUL PY 2008 VL 41 IS 3 BP 690 EP 698 DI 10.1016/j.neuroimage.2008.03.004 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 306TW UT WOS:000256271700005 PM 18456516 ER PT J AU Pierson, ME Andersson, J Nyberg, S McCarthy, DJ Finnema, SJ Varnas, K Takano, A Karlsson, P Gulyas, B Medd, AM Lee, CM Powell, ME Heys, JR Potts, W Seneca, N Mrzljak, L Farde, L Halldin, C AF Pierson, M. Edward Andersson, Jan Nyberg, Svante McCarthy, Dennis J. Finnema, Sjoerd J. Varnas, Katarina Takano, Akihiro Karlsson, Per Gulyas, Balazs Medd, Amy M. Lee, Chi-Ming Powell, Mark E. Heys, J. Richard Potts, William Seneca, Nicholas Mrzljak, Ladislav Farde, Lars Halldin, Christer TI [(11)C]AZ10419369: A selective 5-HT(1B) receptor radioligand suitable for positron emission tomography (PET). Characterization in the primate brain SO NEUROIMAGE LA English DT Article ID D2-DOPAMINE RECEPTORS; AGGRESSIVE-BEHAVIOR; MAJOR DEPRESSION; C-11 RACLOPRIDE; BINDING-SITES; RAT-BRAIN; ANTAGONIST; AR-A000002; SEROTONIN; RELEASE AB The 5-HT(1B) receptor has been implicated in several psychiatric disorders and is a potential pharmacological target in the treatment of depression. Here we report the synthesis of a novel PET radioligand, [(11)C]AZ10419369 (5-methyl-8-(4-methyl-piperazin-1-yl)-4-oxo-4H-chromene-2-carboxylic acid (4-morpholin-4-yl-phenyl)-amide), for in vivo visualization of 5-HT1B receptors in the brains of macaques and humans subjects. [(11)C]AZ10419369 was prepared by N-methylation of (8-(1-piperazinyl)5- methylchrom-2-en-4-one-2-(4-morpholinophenyl) carboxamide, using carbon-11 methyl triflate. Regional brain uptake patterns of [(11)C]AZ10419369 were characterized by PET measurements in two macaques and a preliminary study in two human subjects. In addition, AZ10419369 was prepared in tritium labeled form for in vitro autoradiography studies in macaque brain tissue sections. The radiochemical purity of [(11)C]AZ10419369 was >99% and specific radioactivity was >3600 Ci/ mmol. After iv injection of [(11)C]AZ10419369, 3-4% was in brain after 7.5 min. The regional brain distribution of radioactivity was similar in humans and macaques showing the highest uptake of radioactivity in the occipital cortex and the basal ganglia, in accord with autoradiographic studies performed using [(3)H]AZ10419369. Uptake was moderate in the temporal and frontal cortical regions, lower in the thalamus and lowest in the cerebellum. In macaques pre-treated with the selective 5-HT(1B) receptor antagonist, AR-A000002, binding was reduced in a dose-dependent manner, consistent with specific binding to 5-HT(1B) receptors. These data support [11C] AZ10419369 as a suitable radioligand for labeling 5-HT(1B) receptors in the primate brain. This radioligand may be useful in future studies evaluating drug-induced receptor occupancy and measurement of brain 5-HT1B receptor levels in patients with psychiatric disorders. (C) 2008 Published by Elsevier Inc. C1 [Pierson, M. Edward; McCarthy, Dennis J.; Medd, Amy M.; Lee, Chi-Ming; Powell, Mark E.; Heys, J. Richard; Potts, William; Mrzljak, Ladislav] AstraZeneca Pharmaceut CNS Discovery, Wilmington, DE 19850 USA. [Andersson, Jan; Finnema, Sjoerd J.; Varnas, Katarina; Takano, Akihiro; Karlsson, Per; Gulyas, Balazs; Seneca, Nicholas; Farde, Lars; Halldin, Christer] Karolinska Univ Hosp, Psychiat Sect, Dept Clin Neurosci, Karolinska Inst, S-17176 Stockholm, Sweden. [Nyberg, Svante] AstraZeneca Pharmaceut Clin Neurosci, Sodertalje, Sweden. [Seneca, Nicholas] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. [Farde, Lars] CNSPain Discovery, Sodertalje, Sweden. RP Pierson, ME (reprint author), AstraZeneca Pharmaceut CNS Discovery, 1800 Concord Pike,POB 15437, Wilmington, DE 19850 USA. EM edward.pierson@astrazeneca.com; Christer.Halldin@ki.se RI Andersson, Jan/C-4093-2013; Gulyas, Balazs/F-9508-2015 NR 42 TC 43 Z9 43 U1 2 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUL PY 2008 VL 41 IS 3 BP 1075 EP 1085 DI 10.1016/j.neuroimage.2008.02.063 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 306TW UT WOS:000256271700034 PM 18434202 ER PT J AU Singleton, A Morris, H AF Singleton, Andrew Morris, Huw TI Association, expression, pathobiology - Is too much tau in PD a blueprint for genetic association? SO NEUROLOGY LA English DT Editorial Material ID DISEASE; HAPLOTYPE C1 [Singleton, Andrew] NIA, NIH, Neurogenet Lab, Bethesda, MD 20892 USA. [Morris, Huw] Cardiff Univ, Sch Med, Univ Wales Hosp, Cardiff, Wales. RP Singleton, A (reprint author), NIA, NIH, Neurogenet Lab, Bethesda, MD 20892 USA. EM singleta@mail.nih.gov RI Morris, Huw/B-8527-2008; Singleton, Andrew/C-3010-2009; turton, miranda/F-4682-2011 OI Morris, Huw/0000-0002-5473-3774; NR 9 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUL 1 PY 2008 VL 71 IS 1 BP 11 EP 12 DI 10.1212/01.wnl.0000316388.84840.1f PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 321FH UT WOS:000257289600003 PM 18591501 ER PT J AU Roiser, JP Levy, J Fromm, SJ Wang, HY Hasler, G Sahakian, BJ Drevets, WC AF Roiser, Jonathan P. Levy, Jamey Fromm, Stephen J. Wang, Hongye Hasler, Gregor Sahakian, Barbara J. Drevets, Wayne C. TI The effect of acute tryptophan depletion on the neural correlates of emotional processing in healthy volunteers SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE serotonin; acute tryptophan depletion; functional magnetic resonance imaging; emotion; affective go/no-go test; caudate ID MEDIAL PREFRONTAL CORTEX; MAJOR DEPRESSIVE DISORDER; INDUCED DOPAMINE RELEASE; EVENT-RELATED FMRI; RECEPTOR SUBTYPES; UNMEDICATED PATIENTS; NUCLEUS-ACCUMBENS; CINGULATE CORTEX; DECISION-MAKING; MOOD AB The processing of affective material is known to be modulated by serotonin (5-HT), but few studies have used neurophysiological measures to characterize the effect of changes in 5-HT on neural responses to emotional stimuli. We used functional magnetic resonance imaging to investigate the effect of acute tryptophan depletion, which reduces central 5-HT synthesis, on neural responses to emotionally valenced verbal stimuli. Though no participants experienced significant mood change, emotional information processing was substantially modified following 5-HT depletion. A behavioral bias toward positive stimuli was attenuated following depletion, which was accompanied by increased hemodynamic responses during the processing of emotional words in several subcortical structures. Inter-individual differences in tryptophan depletion-elicited anxiety correlated positively with the caudate bias toward negative stimuli. These data suggest that 5-HT may play an important role in mediating automatic negative attentional biases in major depression, as well as resilience against negative distracting stimuli in never-depressed individuals. C1 [Roiser, Jonathan P.] Inst Neurol, Dept Imaging Neurosci, London WC1N 3BG, England. [Roiser, Jonathan P.; Levy, Jamey; Fromm, Stephen J.; Wang, Hongye; Hasler, Gregor; Drevets, Wayne C.] NIMH, Sect Neuroimaging Mood & Anxiety Disorders, NIH, Bethesda, MD 20892 USA. [Sahakian, Barbara J.] Univ Cambridge, Addenbrookes Hosp, Dept Psychiat, Cambridge CB2 2QQ, England. RP Roiser, JP (reprint author), Inst Neurol, Dept Imaging Neurosci, Room 807,Queen Sq House, London WC1N 3BG, England. EM j.roiser@ion.ucl.ac.uk RI Roiser, Jonathan/A-1791-2010; Hasler, Gregor/E-4845-2012; OI Hasler, Gregor/0000-0002-8311-0138; Levy, Jamey/0000-0002-7434-7213 FU Intramural NIH HHS [Z01 MH002817-05]; Medical Research Council [G0001354] NR 63 TC 42 Z9 43 U1 3 U2 13 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JUL PY 2008 VL 33 IS 8 BP 1992 EP 2006 DI 10.1038/sj.npp.1301581 PG 15 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 312SU UT WOS:000256691900020 PM 17882232 ER PT J AU Zhong, XJ Pedersen, LC Kunkel, TA AF Zhong, Xuejun Pedersen, Lars C. Kunkel, Thomas A. TI Characterization of a replicative DNA polymerase mutant with reduced fidelity and increased translesion synthesis capacity SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ACTIVE-SITE; SACCHAROMYCES-CEREVISIAE; MOTIF-A; DELTA; ALPHA; EPSILON; RESIDUE; ERRORS; ETA; BACTERIOPHAGE-RB69 AB Changing a highly conserved amino acid in motif A of any of the four yeast family B DNA polymerases, DNA polymerase alpha, delta, epsilon or zeta, results in yeast strains with elevated mutation rates. In order to better understand this phenotype, we have performed structure function studies of homologous mutants of RB69 DNA polymerase (RB69 pol), a structural model for family B members. When Leu415 in RB69 pol is replaced with phenylalanine or glycine, the mutant polymerases retain high-catalytic efficiency for correct nucleotide incorporation, yet have increased error rates due to increased misinsertion, increased mismatch extension and inefficient proofreading. The Leu415Phe mutant also has increased dNTP insertion efficiency opposite a template 8-oxoG and opposite an abasic site. The 2.5 angstrom crystal structure of a ternary complex of RB69 L415F pol with a correctly base-paired incoming dTTP reveals that the phenylalanine ring is accommodated within a cavity seen in the wild-type enzyme, without steric clash or major change in active site geometry, consistent with retention of high-catalytic efficiency for correct incorporation. In addition, slight structural differences were observed that could be relevant to the reduced fidelity of L415F RB69 pol. C1 [Zhong, Xuejun; Kunkel, Thomas A.] NIEHS, NIH, DHHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. [Pedersen, Lars C.; Kunkel, Thomas A.] NIEHS, NIH, DHHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. RP Kunkel, TA (reprint author), NIEHS, NIH, DHHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. EM kunkel@niehs.nih.gov FU Intramural NIH HHS; NIEHS NIH HHS [Z01 ES065070] NR 34 TC 18 Z9 19 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL PY 2008 VL 36 IS 12 BP 3892 EP 3904 DI 10.1093/nar/gkn312 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 325HA UT WOS:000257578600003 PM 18503083 ER PT J AU Gaynutdinov, TI Neumann, RD Panyutin, IG AF Gaynutdinov, Timur I. Neumann, Ronald D. Panyutin, Igor G. TI Structural polymorphism of intramolecular quadruplex of human telomeric DNA: effect of cations, quadruplex-binding drugs and flanking sequences SO NUCLEIC ACIDS RESEARCH LA English DT Article ID K+ SOLUTION; POTASSIUM SOLUTION; HUMAN-CHROMOSOMES; PORPHYRIN; PARALLEL; REPEAT; TELOMESTATIN; COMPLEXES; TRIPLEX; FORMS AB G-quadruplex structures formed in the telomeric DNA are thought to play a role in the telomere function. Drugs that stabilize the G-quadruplexes were shown to have anticancer effects. The structures formed by the basic telomeric quadruplex-forming unit G(3)(TTAG(3))(3) were the subject of multiple studies. Here, we employ (125)I-radioprobing, a method based on analysis of the distribution of DNA breaks after decay of (125)I incorporated into one of the nucleotides, to determine the fold of the telomeric DNA in the presence of TMPyP4 and telomestatin, G-quadruplex-binding ligands and putative anticancer drugs. We show that d[G(3)(TTAG(3))(3) (125)I-CT] adopts basket conformation in the presence of NaCl and that addition of either of the drugs does not change this conformation of the quadruplex. In KCl, the d[G(3)(TTAG(3))(3) (125)I-CT] is most likely present as a mixture of two or more conformations, but addition of the drugs stabilize the basket conformation. We also show that d[G(3)(TTAG(3))(3) (125)I-CT] with a 5'-flanking sequence folds into (3+1) type 2 conformation in KCl, while in NaCl it adopts a novel (3+1) basket conformation with a diagonal central loop. The results demonstrate the structural flexibility of the human telomeric DNA; and show how cations, quadruplex-binding drugs and flanking sequences can affect the conformation of the telomeric quadruplex. C1 [Gaynutdinov, Timur I.; Neumann, Ronald D.; Panyutin, Igor G.] NIH, Warren G Magnuson Clin Ctr, Dept Nucl Med, Bethesda, MD 20892 USA. RP Panyutin, IG (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Nucl Med, Bethesda, MD 20892 USA. EM igorp@helix.nih.gov FU Intramural NIH HHS [NIH0012037052]; PHS HHS [NIH0012037052] NR 45 TC 49 Z9 49 U1 4 U2 17 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL PY 2008 VL 36 IS 12 BP 4079 EP 4087 DI 10.1093/nar/gkn351 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 325HA UT WOS:000257578600020 PM 18535007 ER PT J AU Dexheimer, TS Kozekova, A Rizzo, CJ Stone, MP Pommier, Y AF Dexheimer, Thomas S. Kozekova, Albena Rizzo, Carmelo J. Stone, Michael P. Pommier, Yves TI The modulation of topoisomerase I-mediated DNA cleavage and the induction of DNA-topoisomerase I crosslinks by crotonaldehyde-derived DNA adducts SO NUCLEIC ACIDS RESEARCH LA English DT Article ID 1,N-2-PROPANODEOXYGUANOSINE ADDUCTS; CHEMICAL CARCINOGENESIS; DEOXYGUANOSINE ADDUCTS; N-NITROSOPYRROLIDINE; 5'-CPG-3' SEQUENCE; HUMAN TISSUES; MINOR-GROOVE; ACETALDEHYDE; ACROLEIN; CAMPTOTHECIN AB Crotonaldehyde is a representative alpha, beta-unsaturated aldehyde endowed of mutagenic and carcinogenic properties related to its propensity to react with DNA. Cyclic crotonaldehyde-derived deoxyguanosine (CrA-PdG) adducts can undergo ring opening in duplex DNA to yield a highly reactive aldehydic moiety. Here, we demonstrate that site-specifically modified DNA oligonucleotides containing a single CrA-PdG adduct can form crosslinks with topoisomerase I (Top1), both directly and indirectly. Direct covalent complex formation between the CrA-PdG adduct and Top1 is detectable after reduction with sodium cyanoborohydride, which is consistent with the formation of a Schiff base between Top1 and the ring open aldehyde form of the adduct. In addition, we show that the CrA-PdG adduct alters the cleavage and religation activities of Top1. It suppresses Top1 cleavage complexes at the adduct site and induces both reversible and irreversible cleavage complexes adjacent to the CrA-PdG adduct. The formation of stable DNA-Top1 crosslinks and the induction of Top1 cleavage complexes by CrA-PdG are mutually exclusive. Lastly, we found that crotonaldehyde induces the formation of DNA Top1 complexes in mammalian cells, which suggests a potential relationship between formation of DNA Top1 crosslinks and the mutagenic and carcinogenic properties of crotonaldehyde. C1 [Dexheimer, Thomas S.; Pommier, Yves] NCI, NIH, Ctr Canc Res, Mol Pharmacol Lab, Bethesda, MD 20892 USA. [Kozekova, Albena; Rizzo, Carmelo J.; Stone, Michael P.] Vanderbilt Univ, Dept Chem, Ctr Mol Toxicol, Nashville, TN 37235 USA. RP Pommier, Y (reprint author), NCI, NIH, Ctr Canc Res, Mol Pharmacol Lab, Bethesda, MD 20892 USA. EM pommier@nih.gov FU Intramural NIH HHS; NIEHS NIH HHS [ES05355, P01 ES005355, P30 ES000267, ES00267] NR 46 TC 17 Z9 17 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL PY 2008 VL 36 IS 12 BP 4128 EP 4136 DI 10.1093/nar/gkn334 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 325HA UT WOS:000257578600025 PM 18550580 ER PT J AU Lia, G Semsey, S Lewis, DEA Adhya, S Bensimon, D Dunlap, D Finzi, L AF Lia, Giuseppe Semsey, Szabolcs Lewis, Dale E. A. Adhya, Sankar Bensimon, David Dunlap, David Finzi, Laura TI The antiparallel loops in gal DNA SO NUCLEIC ACIDS RESEARCH LA English DT Article ID TRANSCRIPTION ACTIVATOR PROTEIN; INTERFERON-BETA ENHANCEOSOME; SUPERCOILED DNA; RNA-POLYMERASE; LAC REPRESSOR; FUNCTIONAL SUBUNIT; SINGLE-MOLECULE; COMPLEX; BINDING; LAMBDA AB Interactions between proteins bound to distant sites along a DNA molecule require bending and twisting deformations in the intervening DNA. In certain systems, the sterically allowed proteinDNA and proteinprotein interactions are hypothesized to produce loops with distinct geometries that may also be thermodynamically and biologically distinct. For example, theoretical models of Gal repressor/HU-mediated DNA-looping suggest that the antiparallel DNA loops, A1 and A2, are thermodynamically quite different. They are also biologically different, since in experiments using DNA molecules engineered to form only one of the two loops, the A2 loop failed to repress in vitro transcription. Surprisingly, single molecule measurements show that both loop trajectories form and that they appear to be quite similar energetically and kinetically. C1 [Finzi, Laura] Emory Univ, Dept Phys, Atlanta, GA 30322 USA. [Lia, Giuseppe] Harvard Univ, Dept Chem, Cambridge, MA 02138 USA. [Semsey, Szabolcs] Eotvos Lorand Univ, Dept Genet, H-1117 Budapest, Hungary. [Lewis, Dale E. A.; Adhya, Sankar] Mol Biol Lab, NIH, Bethesda, MD USA. [Bensimon, David] Ecole Normale Super, Lab Phys Stat, F-75231 Paris, France. [Dunlap, David] Emory Univ, Dept Cell Biol, Atlanta, GA 30322 USA. RP Finzi, L (reprint author), Emory Univ, Dept Phys, Atlanta, GA 30322 USA. EM lfinzi@emory.edu RI Semsey, Szabolcs/L-6329-2013; Bensimon, David/E-7768-2015; OI Bensimon, David/0000-0003-1971-9907; Semsey, Szabolcs/0000-0002-4522-5495 FU Intramural NIH HHS; NCI NIH HHS [Z01 BC010017] NR 42 TC 15 Z9 15 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL PY 2008 VL 36 IS 12 BP 4204 EP 4210 DI 10.1093/nar/gkn389 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 325HA UT WOS:000257578600032 PM 18573800 ER PT J AU Gotea, V Ovcharenko, I AF Gotea, Valer Ovcharenko, Ivan TI DiRE: identifying distant regulatory elements of co-expressed genes SO NUCLEIC ACIDS RESEARCH LA English DT Article ID FACTOR-BINDING SITES; CONSERVED NONCODING SEQUENCES; HUMAN GENOME; DROSOPHILA-MELANOGASTER; COREGULATED GENES; EXPRESSION DATA; MODULES; IDENTIFICATION; MOUSE; ENHANCERS AB Regulation of gene expression in eukaryotic genomes is established through a complex cooperative activity of proximal promoters and distant regulatory elements (REs) such as enhancers, repressors and silencers. We have developed a web server named DiRE, based on the Enhancer Identification (EI) method, for predicting distant regulatory elements in higher eukaryotic genomes, namely for determining their chromosomal location and functional characteristics. The server uses gene co-expression data, comparative genomics and profiles of transcription factor binding sites (TFBSs) to determine TFBS-association signatures that can be used for discriminating specific regulatory functions. DiREs unique feature is its ability to detect REs outside of proximal promoter regions, as it takes advantage of the full gene locus to conduct the search. DiRE can predict common REs for any set of input genes for which the user has prior knowledge of co-expression, co-function or other biologically meaningful grouping. The server predicts function-specific REs consisting of clusters of specifically-associated TFBSs and it also scores the association of individual transcription factors (TFs) with the biological function shared by the group of input genes. Its integration with the Array2BIO server allows users to start their analysis with raw microarray expression data. The DiRE web server is freely available at http://dire.dcode.org. C1 [Gotea, Valer; Ovcharenko, Ivan] Natl Ctr Biotechnol Informat, Natl Lib Med, Natl Inst Hlth, Bethesda, MD 20894 USA. RP Ovcharenko, I (reprint author), Natl Ctr Biotechnol Informat, Natl Lib Med, Natl Inst Hlth, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM ovcharei@ncbi.nlm.nih.gov OI Gotea, Valer/0000-0001-7857-3309 FU Intramural NIH HHS NR 53 TC 63 Z9 68 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL PY 2008 VL 36 SU S BP W133 EP W139 DI 10.1093/nar/gkn300 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 333GZ UT WOS:000258142300026 PM 18487623 ER PT J AU Johnson, M Zaretskaya, I Raytselis, Y Merezhuk, Y McGinnis, S Madden, TL AF Johnson, Mark Zaretskaya, Irena Raytselis, Yan Merezhuk, Yuri McGinnis, Scott Madden, Thomas L. TI NCBIBLAST: a better web interface SO NUCLEIC ACIDS RESEARCH LA English DT Article ID SUBSTITUTION MATRICES; SEQUENCE-ANALYSIS; BLAST AB Basic Local Alignment Search Tool (BLAST) is a sequence similarity search program. The public interface of BLAST, http://www.ncbi.nlm.nih.gov/ blast, at the NCBI website has recently been reengineered to improve usability and performance. Key new features include simplified search forms, improved navigation, a list of recent BLAST results, saved search strategies and a documentation directory. Here, we describe the BLAST web application's new features, explain design decisions and outline plans for future improvement. C1 [Johnson, Mark; Zaretskaya, Irena; Raytselis, Yan; Merezhuk, Yuri; McGinnis, Scott; Madden, Thomas L.] Natl Ctr Biotechnol Informat, Natl Inst Hlth, Natl Lib Med, Bethesda, MD 20894 USA. RP Madden, TL (reprint author), Natl Ctr Biotechnol Informat, Natl Inst Hlth, Natl Lib Med, Bldg 38A,8600 Rockvill Pike, Bethesda, MD 20894 USA. EM madden@ncbi.nlm.nih.gov NR 8 TC 555 Z9 569 U1 8 U2 45 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL PY 2008 VL 36 SU S BP W5 EP W9 DI 10.1093/nar/gkn201 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 333GZ UT WOS:000258142300003 PM 18440982 ER PT J AU Mashiach, E Schneidman-Duhovny, D Andrusier, N Nussinov, R Wolfson, HJ AF Mashiach, Efrat Schneidman-Duhovny, Dina Andrusier, Nelly Nussinov, Ruth Wolfson, Haim J. TI FireDock: a web server for fast interaction refinement in molecular docking SO NUCLEIC ACIDS RESEARCH LA English DT Article ID PROTEIN-PROTEIN DOCKING; FLEXIBLE SIDE-CHAINS; ALGORITHM; DISCRIMINATION; OPTIMIZATION; PREDICTION; CLUSPRO AB Structural details of proteinprotein interactions are invaluable for understanding and deciphering biological mechanisms. Computational docking methods aim to predict the structure of a proteinprotein complex given the structures of its single components. Protein flexibility and the absence of robust scoring functions pose a great challenge in the docking field. Due to these difficulties most of the docking methods involve a two-tier approach: coarse global search for feasible orientations that treats proteins as rigid bodies, followed by an accurate refinement stage that aims to introduce flexibility into the process. The FireDock web server, presented here, is the first web server for flexible refinement and scoring of proteinprotein docking solutions. It includes optimization of side-chain conformations and rigid-body orientation and allows a high-throughput refinement. The server provides a user-friendly interface and a 3D visualization of the results. A docking protocol consisting of a global search by PatchDock and a refinement by FireDock was extensively tested. The protocol was successful in refining and scoring docking solution candidates for cases taken from docking benchmarks. We provide an option for using this protocol by automatic redirection of PatchDock candidate solutions to the FireDock web server for refinement. The FireDock web server is available at http://bioinfo3d.cs.tau.ac.il/FireDock/. C1 [Mashiach, Efrat; Schneidman-Duhovny, Dina; Andrusier, Nelly; Wolfson, Haim J.] Tel Aviv Univ, Raymond & Beverly Sackler Fac Exact Sci, Sch Comp Sci, IL-69978 Tel Aviv, Israel. [Nussinov, Ruth] SAIC Frederick Inc, NCI, Ctr Canc Res Nanobiol Program, Basic Res Program, Frederick, MD 21702 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Fac Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel. RP Wolfson, HJ (reprint author), Tel Aviv Univ, Raymond & Beverly Sackler Fac Exact Sci, Sch Comp Sci, IL-69978 Tel Aviv, Israel. EM wolfson@post.tau.ac.il RI Wolfson, Haim/A-1837-2011 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400]; NIAID NIH HHS [1UC1AI067231, UC1 AI067231] NR 37 TC 152 Z9 154 U1 0 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL PY 2008 VL 36 SU S BP W229 EP W232 DI 10.1093/nar/gkn186 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 333GZ UT WOS:000258142300043 PM 18424796 ER PT J AU Schneidman-Duhovny, D Dror, O Inbar, Y Nussinov, R Wolfson, HJ AF Schneidman-Duhovny, Dina Dror, Oranit Inbar, Yuval Nussinov, Ruth Wolfson, Haim J. TI PharmaGist: a webserver for ligand-based pharmacophore detection SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DRUG DESIGN; IDENTIFICATION; SUPERPOSITION; MOLECULES; ALIGNMENT; CATALYST; GALAHAD; SETS; 3D AB Predicting molecular interactions is a major goal in rational drug design. Pharmacophore, which is the spatial arrangement of features that is essential for a molecule to interact with a specific target receptor, is an important model for achieving this goal. We present a freely available web server, named PharmaGist, for pharmacophore detection. The employed method is ligand based. Namely, it does not require the structure of the target receptor. Instead, the input is a set of structures of drug-like molecules that are known to bind to the receptor. The output consists of candidate pharmacophores that are computed by multiple flexible alignment of the input ligands. The method handles the flexibility of the input ligands explicitly and in deterministic manner within the alignment process. PharmaGist is also highly efficient, where a typical run with up to 32 drug-like molecules takes seconds to a few minutes on a stardard PC. Another important characteristic is the capability of detecting pharmacophores shared by different subsets of input molecules. This capability is a key advantage when the ligands belong to different binding modes or when the input contains outliers. The webserver has a user-friendly interface available at http://bioinfo3d.cs.tau.ac.il/PharmaGist. C1 [Schneidman-Duhovny, Dina; Dror, Oranit; Inbar, Yuval; Wolfson, Haim J.] Tel Aviv Univ, Raymond & Beverly Sackler Fac Exact Sci, Sch Comp Sci, IL-69978 Tel Aviv, Israel. [Nussinov, Ruth] Tel Aviv Univ, Sackler Fac Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. [Nussinov, Ruth] NCI, SAIC Frederick, Ctr Canc Res, Basic Res Program,Nanobiol Program, Frederick, MD 21702 USA. RP Schneidman-Duhovny, D (reprint author), Tel Aviv Univ, Raymond & Beverly Sackler Fac Exact Sci, Sch Comp Sci, IL-69978 Tel Aviv, Israel. EM duhovka@tau.ac.il RI Wolfson, Haim/A-1837-2011 FU Intramural NIH HHS; NCI NIH HHS [N01CO12400, N01-CO-12400]; NIAID NIH HHS [1UC1AI067231, UC1 AI067231] NR 28 TC 49 Z9 51 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL PY 2008 VL 36 SU S BP W223 EP W228 DI 10.1093/nar/gkn187 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 333GZ UT WOS:000258142300042 PM 18424800 ER PT J AU Shulman-Peleg, A Shatsky, M Nussinov, R Wolfson, HJ AF Shulman-Peleg, Alexandra Shatsky, Maxim Nussinov, Ruth Wolfson, Haim J. TI MultiBind and MAPPIS: webservers for multiple alignment of protein 3D-binding sites and their interactions SO NUCLEIC ACIDS RESEARCH LA English DT Article ID RECOGNITION SITES; DATA SET; INTERFACES; PATTERNS; CONSERVATION; COMPLEXES AB Analysis of protein-ligand complexes and recognition of spatially conserved physico-chemical properties is important for the prediction of binding and function. Here, we present two webservers for multiple alignment and recognition of binding patterns shared by a set of protein structures. The first webserver, MultiBind (http://bioinfo3d.cs.tau.ac.il/MultiBind), performs multiple alignment of protein binding sites. It recognizes the common spatial chemical binding patterns even in the absence of similarity of the sequences or the folds of the compared proteins. The input to the MultiBind server is a set of protein-binding sites defined by interactions with small molecules. The output is a detailed list of the shared physico- chemical binding site properties. The second webserver, MAPPIS (http://bioinfo3d.cs.tau.ac.il/MAPPIS), aims to analyze protein-protein interactions. It performs multiple alignment of protein-protein interfaces (PPIs), which are regions of interaction between two protein molecules. MAPPIS recognizes the spatially conserved physico- chemical interactions, which often involve energetically important hot-spot residues that are crucial for protein-protein associations. The input to the MAPPIS server is a set of protein-protein complexes. The output is a detailed list of the shared interaction properties of the interfaces. C1 [Shulman-Peleg, Alexandra; Wolfson, Haim J.] Tel Aviv Univ, Raymond & Beverly Sackler Fac Exact Sci, Sch Comp Sci, IL-69978 Tel Aviv, Israel. [Nussinov, Ruth] Tel Aviv Univ, Sackler Fac Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. [Shatsky, Maxim] Berkeley Natl Lab, Phys Biosci Div, Berkeley, CA USA. [Nussinov, Ruth] SAIC Frederick Inc, NCI, Lab Expt & Computat Biol, Basic Res Program, Frederick, MD 21702 USA. RP Shulman-Peleg, A (reprint author), Tel Aviv Univ, Raymond & Beverly Sackler Fac Exact Sci, Sch Comp Sci, IL-69978 Tel Aviv, Israel. EM wolfson@post.tau.ac.il RI Wolfson, Haim/A-1837-2011 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400]; NIAID NIH HHS [1UC1AI067231, UC1 AI067231] NR 30 TC 51 Z9 52 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL PY 2008 VL 36 SU S BP W260 EP W264 DI 10.1093/nar/gkn185 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 333GZ UT WOS:000258142300049 PM 18467424 ER PT J AU Sullivan, RT Morehouse, CB Thomas, JW AF Sullivan, Robert T. Morehouse, Caroline B. Thomas, James W. CA Nisc Comparative Sequencing Progra TI Uprobe 2008: an online resource for universal overgo hybridization-based probe retrieval and design SO NUCLEIC ACIDS RESEARCH LA English DT Article ID UCSC GENOME BROWSER; EVOLUTIONARY; SEQUENCE; REGIONS AB Cross-species sequence comparisons are a prominent method for analyzing genomic DNA and an ever increasing number of species are being selected for whole-genome sequencing. Targeted comparative genomic sequencing is a complementary approach to whole-genome shotgun sequencing and can produce high-quality sequence assemblies of orthologous chromosomal regions of interest from multiple species. Genomic libraries necessary to support targeted mapping and sequencing projects are available for more than 90 vertebrates. An essential step for utilizing these and other genomic libraries for targeted mapping and sequencing is the development of the hybridization-based probes, which are necessary to screen a genomic library of interest. The Uprobe website (http://uprobe.genetics.emory.edu) provides a public online resource for identifying or designing universal overgo-hybridization probes from conserved sequences that can be used to efficiently screen one or more genomic libraries from a designated group of species. Currently, Uprobe provides the ability to search or design probes for use in broad groups of species, including mammals and reptiles, as well as more specific clades, including marsupials, carnivores, rodents and nonhuman primates. In addition, Uprobe has the capability to design custom probes from multiple-species sequence alignments provided by the user, thus providing a general tool for targeted comparative physical mapping. C1 [Sullivan, Robert T.; Morehouse, Caroline B.; Thomas, James W.] Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA 30322 USA. [Nisc Comparative Sequencing Progra] Natl Inst Hlth Intramural Sequencing Ctr, Natl Human Genome Res Inst, Natl Inst Hlth, Bethesda, MD 20892 USA. [Nisc Comparative Sequencing Progra] Genome Technol Branch, Bethesda, MD 20892 USA. RP Thomas, JW (reprint author), Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA 30322 USA. EM jthomas@genetics.emory.edu FU Intramural NIH HHS; NCRR NIH HHS [R24 RR022239, R24RR022239] NR 14 TC 4 Z9 4 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL PY 2008 VL 36 SU S BP W149 EP W153 DI 10.1093/nar/gkn293 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 333GZ UT WOS:000258142300029 PM 18515352 ER PT J AU Hochman, N Houri-Haddad, Y Koblinski, J Wahl, L Roniger, M Bar-Sinai, A Weiss, EI Hochman, J AF Hochman, Nira Houri-Haddad, Yael Koblinski, Jennifer Wahl, Larry Roniger, Maayan Bar-Sinai, Allan Weiss, Ervin I. Hochman, Jacob TI Cranberry juice constituents impair lymphoma growth and augment the generation of antilymphoma antibodies in syngeneic mice SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID FRUIT VACCINIUM-MACROCARPON; FIMBRIATED ESCHERICHIA-COLI; IN-VITRO ANTICANCER; TUMOR-CELL LINES; ANTIOXIDANT ACTIVITIES; MALIGNANT-LYMPHOMA; INHIBIT ADHERENCE; EXTRACT; EXPRESSION; BIOFILM AB In addition to its nutritional value, cranberry juice has been effective in treating urinary tract infections. Various reports have also demonstrated its potential for inhibiting in vitro growth of transformed cell lines. Here we show that a fraction [nondialyzable material (NDM) of a molecular weight range 12,000-30,000 (NDM 12-30K)] derived from cranberry juice impairs in vitro growth and invasion through extracellular matrix of Rev-2-T-6 murine lymphoma cells. Furthermore, intraperitoneal injection of this fraction at nontoxic doses both inhibits the growth of Rev-2-T-6 tumors in vivo and enhances the generation of antilymphoma antibodies. These findings demonstrate the in vivo efficacy of cranberry components against malignant lymphoma in immune competent hosts. C1 [Roniger, Maayan; Bar-Sinai, Allan; Hochman, Jacob] Hebrew Univ Jerusalem, Alexander Silberman Inst Life Sci, Dept Cell & Anim Biol, IL-91904 Jerusalem, Israel. [Hochman, Nira; Houri-Haddad, Yael; Weiss, Ervin I.] Hebrew Univ Hadassah Jerusalem, Fac Med Dent, Dept Prosthodont, Jerusalem, Israel. [Koblinski, Jennifer] Northwestern Univ, Feinberg Sch Med, Dept Pathol, Chicago, IL USA. [Wahl, Larry] Natl Inst Dent & Craniofacial Res, Immunopathol Sect, NIH, Bethesda, MD USA. RP Hochman, J (reprint author), Hebrew Univ Jerusalem, Alexander Silberman Inst Life Sci, Dept Cell & Anim Biol, IL-91904 Jerusalem, Israel. EM hochman@vms.huji.ac.il NR 31 TC 10 Z9 10 U1 0 U2 1 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0163-5581 EI 1532-7914 J9 NUTR CANCER JI Nutr. Cancer PD JUL-AUG PY 2008 VL 60 IS 4 BP 511 EP 517 DI 10.1080/01635580801956493 PG 7 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 331BW UT WOS:000257988700010 PM 18584485 ER PT J AU Nunez, NP Perkins, SN Smith, NCP Berrigan, D Berendes, DM Varticovski, L Barrett, JC Hursting, SD AF Nunez, Nomeli P. Perkins, Susan N. Smith, Nicole C. P. Berrigan, David Berendes, David M. Varticovski, Lyuba Barrett, J. Carl Hursting, Stephen D. TI Obesity accelerates mouse mammary tumor growth in the absence of ovarian hormones SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID BONE-MINERAL DENSITY; FACTOR-I LEVELS; BREAST-CANCER; CALORIC RESTRICTION; ENERGY RESTRICTION; INSULIN-RESISTANCE; BODY-COMPOSITION; TRANSGENIC MICE; MECHANISMS; RISK AB Obesity increases incidence and mortality of breast cancer in postmenopausal women. Mechanisms underlying this association are poorly understood. Suitable animal models are needed to elucidate potential mechanisms for this association. To determine the effects of obesity on mammary tumor growth, nonovariectomized and ovariectomized C57BL/6 mice of various body weights (lean, overweight, and obese) were implanted subcutaneously with mammary tumor cells from syngeneic Wnt-1 transgenic mice. In mice, the lean phenotype was associated with reduced Wnt-1 tumor growth regardless of ovarian hormone status. Ovariectomy delayed Wnt-1 tumor growth consistent with the known hormone responsiveness of these tumors. However, obesity accelerated tumor growth in ovariectomized but not in nonovariectomized animals. Diet-induced obesity in a syngeneic mouse model of breast cancer enhanced tumor growth, specifically in the absence of ovarian hormones. These results support epidemiological evidence that obesity is associated with increased breast cancer incidence and mortality in postmenopausal but not premenopausal women. In contrast, maintaining a lean body weight phenotype was associated with reduced Wnt-1 tumor growth regardless of ovarian hormone status. C1 [Nunez, Nomeli P.; Perkins, Susan N.; Smith, Nicole C. P.; Berendes, David M.; Barrett, J. Carl; Hursting, Stephen D.] NCI, Lab Biosyst & Canc, NIH, Bethesda, MD 20892 USA. [Nunez, Nomeli P.; Perkins, Susan N.; Hursting, Stephen D.] NCI, Canc Prevent Fellowship Program, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. [Nunez, Nomeli P.; Perkins, Susan N.; Smith, Nicole C. P.; Hursting, Stephen D.] Univ Texas Austin, Dept Human Ecol, Div Nutr Sci, Austin, TX 78712 USA. [Smith, Nicole C. P.] NCI, Basic Res Program, SAIC Frederick Inc, Frederick, MD USA. [Berrigan, David] NCI, Appl Res Program, Div Canc Control & Populat Sci, NIH, Bethesda, MD USA. [Varticovski, Lyuba] NCI, Human Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD USA. [Barrett, J. Carl] Novartis Inst Biomed Res, Cambridge, MA USA. RP Hursting, SD (reprint author), NCI, Lab Biosyst & Canc, NIH, Bethesda, MD 20892 USA. EM shursting@mail.utexas.edu RI Biguzzi, Felipe/E-4724-2015 FU Intramural NIH HHS NR 47 TC 55 Z9 56 U1 1 U2 2 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 0163-5581 J9 NUTR CANCER JI Nutr. Cancer PD JUL-AUG PY 2008 VL 60 IS 4 BP 534 EP 541 DI 10.1080/01635580801966195 PG 8 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 331BW UT WOS:000257988700013 PM 18584488 ER PT J AU Elahi, D Egan, JM Shannon, RP Meneilly, GS Khatri, A Habener, JF Andersen, DK AF Elahi, Dariush Egan, Josephine M. Shannon, Richard P. Meneilly, Graydon S. Khatri, Ashok Habener, Joel F. Andersen, Dana K. TI GLP-1 (9-36) amide, cleavage product of GLP-1 (7-36) amide, is a glucoregulatory peptide SO OBESITY LA English DT Article ID GLUCAGON-LIKE PEPTIDE-1; DEPENDENT INSULINOTROPIC POLYPEPTIDE; METFORMIN-TREATED PATIENTS; TYPE-2 DIABETES-MELLITUS; MEDIATED GLUCOSE-UPTAKE; BETA-CELL FUNCTION; IN-VIVO; METABOLITE; SECRETION; RECEPTOR AB Objective: Glucagon-like peptide-1 (GLP-1) (7-36) amide is a glucoregulatory hormone with insulinotropic and insulinomimetic actions. We determined whether the insulinomimetic effects of GLP-1 are mediated through its principal metabolite, GLP-1 (9-36) amide (GLP-1m). Methods and Procedures: Glucose turnover during two, 2-h, euglycemic clamps was measured in 12 lean and 12 obese (BMI 25 or 30 kg/m(2)) male and female subject volunteers with normal oral glucose tolerance test. Saline or GLP-1m were infused from 0 to 60 min in each study. Additionally, seven lean and six obese subjects underwent a third clamp in which the GLP-1 receptor (GLP-1R) antagonist, exendin (9-39) amide was infused from -60 to 60 min with GLP-1m from 0 to 60 min. Results: No glucose infusion was required in lean subjects to sustain euglycemia ( glucose clamp) during saline or GLP-1m infusions. However, in obese subjects glucose infusion was necessary during GLP-1m infusion alone in order to compensate for a marked (>50%) inhibition of hepatic glucose production (HGP). Plasma insulin levels remained constant in lean subjects but rose significantly in obese subjects after termination of the peptide infusions. During GLP-1R blockade, infusion of glucose was immediately required upon starting GLP-1m infusions in all subjects due to a more dramatic reduction in HGP, as well as a delpayed and modest insulinotropic response. Discussion: We conclude that GLP-1m potently inhibits HGP and is a weak insulinotropic agent. These properties are particularly apparent and pronounced in obese but only become apparent in lean subjects during GLP-1 (7-36) receptor blockade. These previously unrecognized antidiabetogenic actions of GLP-1m may have therapeutic usefulness. C1 [Elahi, Dariush; Andersen, Dana K.] Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21205 USA. [Elahi, Dariush; Khatri, Ashok; Habener, Joel F.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Elahi, Dariush; Khatri, Ashok; Habener, Joel F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Egan, Josephine M.] NIA, Clin Invest Lab, Diabet Sect, Baltimore, MD 21224 USA. [Shannon, Richard P.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Meneilly, Graydon S.] Univ British Columbia, Dept Med, Sch Med, Vancouver, BC, Canada. RP Elahi, D (reprint author), Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21205 USA. EM delahi1@jhmi.edu FU Intramural NIH HHS; NIA NIH HHS [AG 00599, AG 623175, P01 AG000599]; NIDDK NIH HHS [DK 30834] NR 51 TC 51 Z9 58 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD JUL PY 2008 VL 16 IS 7 BP 1501 EP 1509 DI 10.1038/oby.2008.229 PG 9 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 321RX UT WOS:000257325300005 PM 18421270 ER PT J AU Chang, S Masse, LC Moser, RP Dodd, KW Arganaraz, F Fuemmler, BF Jemal, A AF Chang, Shine Masse, Louise C. Moser, Richard P. Dodd, Kevin W. Arganaraz, Facundo Fuemmler, Bernard F. Jemal, Ahmedin TI State ranks of incident cancer burden due to overweight and obesity in the united states, 2003 SO OBESITY LA English DT Article ID RENAL-CELL CARCINOMA; BODY-MASS INDEX; POSTMENOPAUSAL BREAST-CANCER; RISK-FACTORS; PROSTATE-CANCER; PHYSICAL-ACTIVITY; COLON-CANCER; ENDOMETRIAL CANCER; COLORECTAL-CANCER; WEIGHT-GAIN AB Objective: Given links between obesity and cancer, we estimated incident cancer burden due to overweight and obesity at the state level in the United States. Methods and Procedures: Using state rankings by per capita burden of incident cancer cases diagnosed in 2003 that were related to overweight and obesity, we examined the frequency with which states ranked in the highest and lowest quintiles of weight-related burden for cancers of the postmenopausal breast, endometrium, kidney, colon, and prostate. In this study, data from the Behavioral Risk Factor Surveillance System (BRFSS), US Census, US Mortality Public Use Data Tapes, and National Cancer Institute Surveillance, Epidemiology, and End Results ( SEER) Program were used. Results: Western states had the lowest weight-related cancer burden for both sexes. Iowa, South Dakota, and West Virginia had the highest burden for all three types of male cancers. West Virginia is the only state that ranked in the quintile of highest weight-related burden for all four cancers considered in women. Discussion: For certain cancers, including endometrial, postmenopausal breast, and colon cancers, states with high burdens clustered in geographic regions, warranting further inquiry. Although state ranks for the total cancer burden and the prevalence of overweight and obesity correlated with state ranks for weight-related incident cancer burden, they often served poorly as its proxy. Such a finding cautions against simply targeting states with high overweight and obesity or high total burdens of cancers for which overweight and obesity are risk factors, as this approach may not reach areas of unrecognized burden. C1 [Masse, Louise C.; Arganaraz, Facundo; Fuemmler, Bernard F.] NCI, Hlth Promot Res Branch, Div Canc Control & Populat Sci, US Dept HHS,NIH, Bethesda, MD 20892 USA. [Moser, Richard P.] NCI, Off Associate Director, Behav Res Program, Div Canc Control & Populat Sci,US Dept HHS,NIH, Bethesda, MD 20892 USA. [Dodd, Kevin W.] NCI, Biometry Res Branch, Canc Prevent Div, US Dept HHS,NIH, Bethesda, MD 20892 USA. [Jemal, Ahmedin] Amer Canc Soc, Epidemiol & Surveillance Res Dept, Atlanta, GA 30329 USA. [Chang, Shine; Arganaraz, Facundo; Fuemmler, Bernard F.] NCI, Off Prevent Oncol, Canc Prevent Div, US Dept HHS,NIH, Bethesda, MD 20892 USA. RP Chang, S (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. EM ShineChang@MDAnderson.org NR 63 TC 9 Z9 9 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD JUL PY 2008 VL 16 IS 7 BP 1636 EP 1650 DI 10.1038/oby.2008.228 PG 15 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 321RX UT WOS:000257325300025 PM 18421271 ER PT J AU Brubaker, L Nygaard, I Richter, HE Visco, A Weber, AM Cundiff, GW Fine, P Ghetti, C Brown, MB AF Brubaker, Linda Nygaard, Ingrid Richter, Holly E. Visco, Anthony Weber, Anne M. Cundiff, Geoffrey W. Fine, Paul Ghetti, Chiara Brown, Morton B. CA Pelvic Floor Disorders Network TI Two-year outcomes after sacrocolpopexy with and without burch to prevent stress urinary incontinence SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID PELVIC ORGAN PROLAPSE; QUALITY-OF-LIFE; VAGINAL VAULT PROLAPSE; SACRAL COLPOPEXY; ABDOMINAL SACROCOLPOPEXY; FLOOR DISORDERS; SEXUAL FUNCTION; WOMEN; COLPOSUSPENSION; POSTERIOR AB OBJECTIVES: To report anatomic and functional outcomes 2 years after sacrocolpopexy in stress-continent women with or without prophylactic Burch colposuspension. METHODS: In the Colpopexy and Urinary Reduction Efforts (CARE) trial, stress-continent women undergoing sacrocolpopexy were randomized to receive or not receive a Burch colposuspension. Outcomes included urinary symptoms, other pelvic symptoms, and pelvic support. Standardized pelvic organ prolapse quantificationexaminations and validated outcome measures including the Pelvic Floor Distress Inventory and the Pelvic Floor Impact Questionnaire were completed before surgery and at several postoperative intervals, including at 2 years. RESULTS: This analysis is based on 302 of 322 randomized participants. Most were Caucasian (94%), with a mean age of 62 +/- 10 years (mean +/- standard deviation). Two years after surgery, 32.0% and 45.2% of women in the Burch and control groups, respectively, met the stress incontinence endpoint (presence of symptoms or positive cough stress test or interval treatment for stress incontinence, P=.026). The apex was well supported (point C within 2 cm of total vaginal length) in 95% of women, and this was not affected by concomitant Burch (P=.18). There was a trend toward fewer urgency symptoms in the Burch group (32.0% versus 44.5% no Burch, P=.085). Twenty participants experienced mesh or suture erosions. CONCLUSION: The early advantage of prophylactic Burch colposuspension for stress incontinence that was seen at 3 months remains at 2 years. Apical anatomic success rates are high and not affected by concomitant Burch. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov, ClinicalTrials.gov, NCT00065845. C1 [Brubaker, Linda] Loyola Univ, Stritch Sch Med, Dept Obstet & Gynecol, Maywood, IL 60153 USA. Loyola Univ, Stritch Sch Med, Dept Urol, Maywood, IL 60153 USA. Univ Utah, Sch Med, Dept Obstet & Gynecol, Salt Lake City, UT 84132 USA. Univ Alabama, Sch Med, Dept Obstet & Gynecol, Birmingham, AL USA. Univ N Carolina, Sch Med, Dept Obstet & Gynecol, Chapel Hill, NC USA. NICHHD, Contracept & Reprod Hlth Branch, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Gynecol & Obstet, Baltimore, MD 21205 USA. Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA. Univ Pittsburgh, Dept Obstet & Gynecol, Pittsburgh, PA USA. Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. RP Brubaker, L (reprint author), Loyola Univ, Stritch Sch Med, Dept Obstet & Gynecol, 2160 S 1st Ave, Maywood, IL 60153 USA. EM Lbrubaker@lumc.edu FU NICHD NIH HHS [U10 HD 41268, U10 HD 41267, U10 HD 41261, U10 HD041248, U10 HD 41263, U01 HD 41249, U10 HD041261, U10 HD041250, U10 HD041250-06, U01 HD041249, U10 HD 41250, U10 HD041263, U10 HD 41248, U10 HD041269, U10 HD041268, U10 HD041267, U10 HD 41269] NR 17 TC 96 Z9 98 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD JUL PY 2008 VL 112 IS 1 BP 49 EP 55 DI 10.1097/AOG.0b013e3181778d2a PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 321BQ UT WOS:000257279600010 PM 18591307 ER PT J AU Reddy, UM Filly, RA Copel, JA AF Reddy, Uma M. Filly, Roy A. Copel, Joshua A. TI Prenatal Imaging - Ultrasonography and magnetic resonance imaging SO OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material ID PLACENTA-ACCRETA; OBSTETRIC ULTRASONOGRAPHY; 2ND-TRIMESTER ULTRASOUND; SURGICAL CORRELATION; CONTROLLED TRIAL; DOWNS-SYNDROME; 2ND TRIMESTER; MR PROCEDURES; LIMB VOLUME; FETAL AB The Eunice Kennedy Shriver National Institute of Child Health and Human Development held a workshop on September 18-19, 2006, to summarize the available evidence on the role and performance of current fetal imaging technology and to establish a research agenda. Ultrasonography is the imaging modality of choice for pregnancy evaluation due to its relatively low cost, real-time capability, safety, and operator comfort and experience. First-trimester ultrasonography extends the available window for fetal observation and raises the possibility of performing an early anatomic survey. Three-dimensional ultrasonography has the potential to expand the clinical application of ultrasonography by permitting local acquisition of volumes and remote review and interpretation at specialized centers. New advances allow performance of fetal magnetic resonance imaging (MRI) without maternal or fetal sedation, with improved characterization and prediction of prognosis of certain fetal central nervous system anomalies such as ventriculomegaly when compared with ultrasonography. Fewer data exist on the usefulness of fetal MRI for non-central nervous system anomalies. C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Yale Univ, Sch Med, New Haven, CT USA. RP Reddy, UM (reprint author), 6100 Execut Blvd,Room 4B03F, Bethesda, MD 20892 USA. EM reddyu@mail.nih.gov FU Intramural NIH HHS [Z99 HD999999] NR 54 TC 35 Z9 39 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD JUL PY 2008 VL 112 IS 1 BP 145 EP 157 DI 10.1097/01.AOG.0000318871.95090.d9 PG 13 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 321BQ UT WOS:000257279600023 PM 18591320 ER PT J AU Imanguli, MM Alevizos, I Brown, R Pavletic, SZ Atkinson, JC AF Imanguli, M. M. Alevizos, I. Brown, R. Pavletic, S. Z. Atkinson, J. C. TI Oral graft-versus-host disease SO ORAL DISEASES LA English DT Review DE graft-versus host disease; xerostomia; salivary gland disease; hematopoietic stem cell transplant ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; REGULATORY T-CELLS; CONSENSUS DEVELOPMENT PROJECT; MINOR SALIVARY-GLANDS; WORKING GROUP-REPORT; CHIMERIC MONOCLONAL-ANTIBODY; SJOGREN-LIKE SYNDROME; CENTRAL MEMORY CELLS; TERM-FOLLOW-UP AB OBJECTIVE: Graft-versus-host disease (GVHD) is a leading cause of morbidity and mortality in patients receiving hematopoietic cell transplant. It is estimated that 40-70% of engrafted patients surviving the initial transplant eventually develop chronic GVHD (cGVHD), which can persist for months to years and require long-term management from multiple disciplines. This review describes the oral component of this transplant complication. DESIGN: The search related to GVHD patho-biology, salivary gland disease after hematopoietic cell transplant and treatments for oral GVHD encompassed literature from 1966 through 2008. Searches were limited to the MEDLINE/PubMed database and English language literature in peer-reviewed journals. RESULTS: Our understanding of the patho-biology of oral cGVHD is based on studies of other affected tissues. It is difficult to determine the prevalence and incidence of salivary gland disease after transplant because there is no universally accepted case definition. In general, clinical trials for treatment of oral cGVHD have been too small to make strong recommendations for use in clinical practice. CONCLUSIONS: Larger well-designed clinical studies are needed to understand the patho-biology of oral cGVHD and determine best treatments for this disease. C1 [Imanguli, M. M.; Pavletic, S. Z.] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Alevizos, I.] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, Bethesda, MD USA. [Brown, R.] Howard Univ, Coll Dent, Dept Oral Diagnost Serv, Washington, DC 20059 USA. [Atkinson, J. C.] Natl Inst Dent & Craniofacial Res, Clin Trials Program, Div Extramural Res, Bethesda, MD USA. RP Atkinson, JC (reprint author), 6701 Democracy Blvd,Rm 634,MSC 4878, Bethesda, MD 20892 USA. EM jatkinso@mail.nih.gov FU Intramural NIH HHS [Z99 DE999999] NR 132 TC 42 Z9 44 U1 1 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1354-523X EI 1601-0825 J9 ORAL DIS JI Oral Dis. PD JUL PY 2008 VL 14 IS 5 BP 396 EP 412 DI 10.1111/j.1601-0825.2008.01448.x PG 17 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 314XV UT WOS:000256843400003 PM 18593456 ER PT J AU Atkinson, JC Harvey, KE Domingo, DL Trujillo, MI Guadagnini, JP Gollins, S Giri, N Hart, TC Alter, BP AF Atkinson, J. C. Harvey, K. E. Domingo, D. L. Trujillo, M. I. Guadagnini, J-P Gollins, S. Giri, N. Hart, T. C. Alter, B. P. TI Oral and dental phenotype of dyskeratosis congenita SO ORAL DISEASES LA English DT Article DE dyskeratosis congenita; leukoplakia; tooth development; DKC1; TERC; TERT ID PERMANENT TEETH; MARROW FAILURE; TELOMERASE; DISEASE; MUTATIONS; TERT AB Dyskeratosis congenita (DC) is an inherited bone marrow failure syndrome that is characterized by lacey reticular hyperpigmentation of the skin, dystrophic nails, mucous membrane leukoplakia and pancytopenia. Diagnosis may be delayed until clinical signs are apparent. Severe pancytopenia frequently causes early mortality of DC patients, who have an increased risk of developing oropharyngeal squamous cell carcinoma. Several case reports have described oral changes in DC, which include oral leukoplakia, increased dental caries, hypodontia, thin enamel structure, aggressive periodontitis, intraoral brown pigmentation, tooth loss, taurodontism and blunted roots. We determined the prevalence of these previously reported findings in a cohort of 17 patients with DC and 23 family members. The most common oral changes in DC patients were oral leukoplakia (65% of the entire DC population), decreased root/crown ratio (75% with sufficient tooth development) and mild taurodontism (57% with sufficient tooth development). From the clinical perspective, a diagnosis of DC or other inherited bone marrow failure syndrome should be considered in young persons with oral leukoplakia, particularly those with no history of smoking. Multiple permanent teeth with decreased root/crown ratios further suggest DC. C1 [Atkinson, J. C.; Harvey, K. E.; Domingo, D. L.; Trujillo, M. I.; Guadagnini, J-P; Gollins, S.; Giri, N.; Hart, T. C.] Natl Inst Dent & Craniofacial Res, Clin Res Ctr, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. [Giri, N.; Alter, B. P.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. RP Atkinson, JC (reprint author), Natl Inst Dent & Craniofacial Res, Clin Res Ctr, Dept Hlth & Human Serv, NIH, 45 Ctr Dr,Room 4AS25L,MSC 6401, Bethesda, MD 20892 USA. EM jatkinso@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 28 TC 16 Z9 16 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1354-523X J9 ORAL DIS JI Oral Dis. PD JUL PY 2008 VL 14 IS 5 BP 419 EP 427 DI 10.1111/j.1601-0825.2007.01394.x PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 314XV UT WOS:000256843400005 PM 18938267 ER PT J AU Zeliadt, SB Ramsey, SD Potosky, AL Arora, NK Blough, DK Oakley-Girvan, I Hamilton, AS Van den Eeden, SK Penson, DF AF Zeliadt, Steven B. Ramsey, Scott D. Potosky, Arnold L. Arora, Neeraj K. Blough, David K. Oakley-Girvan, Ingrid Hamilton, Ann S. Van den Eeden, Stephen K. Penson, David F. TI Association of Pre-Existing Symptoms with Treatment Decisions among Newly Diagnosed Prostate Cancer Patients SO PATIENT-PATIENT CENTERED OUTCOMES RESEARCH LA English DT Article AB Background: The choice between surgical and non-surgical treatment options is a fundamental decision for men with local-stage prostate cancer because of differences in risks of genitourinary adverse effects among available treatments. Objectives: We assessed whether pre-existing genitourinary symptoms at the time of diagnosis influenced men's preferences for surgery over other management options. Methods: We recruited 593 patients with newly diagnosed local-stage prostate cancer prior to initiating treatment from an integrated healthcare system, an academic urology center, and community urology clinics. We used logistic regression to compare whether men had a preference for non-surgical options or only preferred surgery. Results: Nearly 60% of participants indicated that they were considering nonsurgical options. Age and clinical characteristics but not pre-existing genito-urinary symptoms influenced the decision between surgical or non-surgical options. A total of 62% of men reported adverse effects as a main factor in their treatment decision. Men with more aggressive tumor types were less likely to consider adverse effects; however, men who reported poor ability to have an erection were more likely to consider adverse effects in their treatment decision (p < 0.001). Conclusion: Sexual dysfunction at time of diagnosis, but not other genitourinary symptoms, is associated with men considering treatment-related adverse effects when considering surgery versus other options. Men who are not experiencing sexual dysfunction at diagnosis may discount the risks of adverse effects in the decision-making process. C1 [Zeliadt, Steven B.; Ramsey, Scott D.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Potosky, Arnold L.] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA. [Arora, Neeraj K.] NCI, Bethesda, MD 20892 USA. [Blough, David K.] Univ Washington, Seattle, WA 98195 USA. [Oakley-Girvan, Ingrid] No Calif Canc Ctr, Fremont, CA USA. [Hamilton, Ann S.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Van den Eeden, Stephen K.] Kaiser Permanente, Oakland, CA USA. [Penson, David F.] Univ So Calif, Norris Canc Ctr, Los Angeles, CA USA. RP Ramsey, SD (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1100 Fairview Ave N,Box 19024,M3-B232, Seattle, WA 98109 USA. EM sramsey@fhcrc.org FU National Cancer Institute [N01-PC-35142, N01-PC-35139, N01-PC-35136, HHSN261200700321P]; Fred Hutchinson Cancer Research Center; State of Washington FX Work on this manuscript was supported by the National Cancer Institute contracts N01-PC-35142, N01-PC-35139, N01-PC-35136, and HHSN261200700321P. Case ascertainment for the focus group research was supported by the Cancer Surveillance System of the Fred Hutchinson Cancer Research Center, which is funded by contract no. N01-PC-35142 from the Surveillance, Epidemiology and End Results (SEER) Program of the National Cancer Institute with additional support from the Fred Hutchinson Cancer Research Center and the State of Washington. The recruitment efforts in the Pacific Northwest region were made possible by independent urologists in community clinics throughout Washington (Centralia, Edmonds, Everett, Olympia, Port Angeles, Tacoma, Silverdale, Spokane) and Portland, OR. NR 35 TC 5 Z9 5 U1 0 U2 0 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1178-1653 J9 PATIENT JI Patient PD JUL 1 PY 2008 VL 1 IS 3 BP 189 EP 200 DI 10.2165/1312067-200801030-00006 PG 12 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA V18JI UT WOS:000208000700006 PM 20119493 ER PT J AU Smith, MA Morton, CL Phelps, DA Kolb, EA Lock, R Carol, H Reynolds, CP Maris, JM Keir, ST Wu, JR Houghton, PJ AF Smith, Malcolm A. Morton, Christopher L. Phelps, Doris A. Kolb, E. Anders Lock, Richard Carol, Hernan Reynolds, C. Patrick Maris, John M. Keir, Stephen T. Wu, Jianrong Houghton, Peter J. TI Stage 1 testing and pharmacodynamic evaluation of the HSP90 inhibitor alvespimycin (17-DMAG, KOS-1022) by the pediatric preclinical testing program SO PEDIATRIC BLOOD & CANCER LA English DT Article DE alvespimycin; developmental therapeutics; preclinical testing ID PHASE-I TRIAL; CELL-LINES; CHAPERONE HEAT-SHOCK-PROTEIN-90; ANTITUMOR EFFICACY; TYROSINE KINASE; CANCER MODELS; 17-(DIMETHYLAMINOETHYLAMINO)-17-DEMETHOXYGELDANAMYCIN; PHARMACOKINETICS; TARGET; VIVO AB Background. Alvespimycin (17-DMAG, KOS-1022), a potent small-molecule inhibitor of the protein chaperone Hsp90, is being developed as an anticancer agent because of the multiple Hsp90 client proteins involved in cancer cell growth and survival. Procedures. Alvespimycin was tested against the in vitro panel of the Pediatric Preclinical Testing Program (PPTP) at concentrations from 1 nM to 10 mu M and was tested against the PPTP's in vivo tumor panels by intraperitoneal administration using a 50 mg/kg BID twice weekly x 6 weeks dose and schedule. Hsp70 induction in tumor and liver tissue was used as a pharmacodynamic measure of Hsp90 inhibition and stress response induction. Results. Alvespimycin had a median IC50 of 68 nM against the PPTP's in vitro panel, with a trend for lower IC50 values for the rhabdomyosarcoma panel (median IC50 32 nM) and for higher IC50 values for the neuroblastoma panel (median IC50 380 nM). Using the time to event activity measure, alvespimycin had intermediate or high activity against 4 of 28 evaluable solid tumor xenografts, including 3 of 4 alveolar rhabdomyosarcoma xenografts (one with a partial response). Hsp70 induction was observed in tumor tissue from both responding and non-responding xenografts. Conclusions. Alvespimycin demonstrated little in vivo antitumor activity against most of the PPTP's preclinical models. The greatest drug effect was observed for the alveolar rhabdomyosarcoma xenografts in the rhabdomyosarcoma panel. Hsp70 induction was observed in responding and non-responding xenografts, suggesting that tumor-specific events subsequent to HSP90 inhibition are primary determinants of antitumor activity. C1 [Morton, Christopher L.; Phelps, Doris A.; Wu, Jianrong; Houghton, Peter J.] St Jude Childrens Hosp, Dept Mol Pharmacol, Memphis, TN 38105 USA. [Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. [Kolb, E. Anders] Childrens Hosp Montefiore, Bronx, NY USA. [Lock, Richard; Carol, Hernan] Childrens Canc Inst Australia Med Res, Randwick, NSW, Australia. [Reynolds, C. Patrick] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Maris, John M.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Philadelphia, PA 19104 USA. [Maris, John M.] Abramson Family Canc Res Inst, Philadelphia, PA USA. [Keir, Stephen T.] Duke Univ, Med Ctr, Durham, NC USA. RP Houghton, PJ (reprint author), St Jude Childrens Hosp, Dept Mol Pharmacol, 332 N Lauderdale St, Memphis, TN 38105 USA. EM peter.houghton@stjude.org RI Houghton, Peter/E-3265-2011; Carol, Hernan/F-5750-2013; Lock, Richard/G-4253-2013; OI Carol, Hernan/0000-0002-9443-8032; Reynolds, C. Patrick/0000-0002-2827-8536 FU NCI NIH HHS [CA21765, N01 CM042216, N01-CM-42216, CA108786] NR 40 TC 21 Z9 21 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD JUL PY 2008 VL 51 IS 1 BP 34 EP 41 DI 10.1002/pbc.21508 PG 8 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 300IF UT WOS:000255816800008 PM 18260120 ER PT J AU Maris, JM Courtright, J Houghton, PJ Morton, CL Kolb, EA Lock, R Tajbakhsh, M Reynolds, CP Keir, ST Wu, JR Smith, MA AF Maris, John M. Courtright, Joshua Houghton, Peter J. Morton, Christopher L. Kolb, E. Anders Lock, Richard Tajbakhsh, Mayamin Reynolds, C. Patrick Keir, Stephen T. Wu, Jianrong Smith, Malcolm A. TI Initial testing (stage 1) of sunitinib by the pediatric preclinical testing program SO PEDIATRIC BLOOD & CANCER LA English DT Article DE developmental therapeutics; preclinical testing; sunitinib ID ACUTE LYMPHOBLASTIC-LEUKEMIA; ENDOTHELIAL GROWTH-FACTOR; RENAL-CELL CARCINOMA; GASTROINTESTINAL STROMAL TUMOR; TYROSINE KINASE INHIBITOR; IN-VIVO; IMATINIB MESYLATE; SOLID TUMORS; HUMAN NEUROBLASTOMA; CANCER MODELS AB Background. Sunitinib is an orally bioavailable, multi-targeted tyrosine kinase inhibitor with selectivity for PDGF receptors, VEGF receptors, FLT3, and KIT. Procedures. Sunitinib was tested at concentrations ranging from 0.1 nM to 1.0 mu M against 23 cell lines from the PPTP in vitro panel. We also compared sunitinib (53.5 mg/kg) or vehicle administered for 28 clays by oral gavage in 46 murine xenograft models representing 9 distinct pediatric cancer histologies. Results. The leukemia cell line, Kasumi-1 (gain-of-function KIT(Asn822Lys) mutation) was the only line with an in vitro response to sunitinib (IC(50) 75.7 nM). Sunitinib significantly prolonged EFS in 19 of 35 (54%) of the solid tumor, and in 3 of 8 (38%) of the ALL xenografts analyzed. Using the PPTP time to event measure of efficacy, sunitinib had intermediate (13) and high (1) levels of activity against 14 of 34 evaluable solid tumor xenografts, including 4 of 6 rhabdomyosarcoma, 4 of 5 Ewing turner, and 2 of 3 rhabdoid tumor xenografts. Following cessation of treatment for the 14 solid tumor xenografts without tumor events by day 28, tumor growth rate increased in most. The only regression noted to sunitinib in the solid tumor panels was a complete response in a rhabdoid tumor xenograft. Conclusions. Sunitinib demonstrated significant tumor growth inhibition against most of the PPTP's solid tumor panels, but little activity against the neuroblastoma and ALL panel. Antitumor activity was manifested primarily as tumor growth delay, consistent with an anti-angiogenic effect for sunitinib against many of the pediatric preclinical models evaluated. C1 [Maris, John M.; Courtright, Joshua] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Philadelphia, PA 19104 USA. [Maris, John M.; Courtright, Joshua] Abramson Family Canc Res Inst, Philadelphia, PA USA. [Houghton, Peter J.; Morton, Christopher L.; Wu, Jianrong] St Jude Childrens Hosp, Memphis, TN 38105 USA. [Kolb, E. Anders] Childrens Hosp Montefiore, Bronx, NY USA. [Lock, Richard; Tajbakhsh, Mayamin] Childrens Canc Inst Australia Med Res, Randwick, NSW, Australia. [Reynolds, C. Patrick] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Keir, Stephen T.] Duke Univ, Med Ctr, Durham, NC USA. [Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Maris, JM (reprint author), Univ Penn, Childrens Hosp Philadelphia, Sch Med, Philadelphia, PA 19104 USA. EM maris@chop.edu RI Houghton, Peter/E-3265-2011; Lock, Richard/G-4253-2013; OI Reynolds, C. Patrick/0000-0002-2827-8536 FU NCI NIH HHS [CA108786, CA21765, N01-CM-42216, P30 CA021765] NR 37 TC 52 Z9 56 U1 1 U2 2 PU WILEY PERIODICALS, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD JUL PY 2008 VL 51 IS 1 BP 42 EP 48 DI 10.1002/pbc.21535 PG 7 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 300IF UT WOS:000255816800009 PM 18293383 ER PT J AU Read, JS AF Read, Jennifer S. TI Prevention of mother-to-child transmission of HIV through breast milk SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Editorial Material DE HIV; breast milk (human milk) ID HUMAN-IMMUNODEFICIENCY-VIRUS; POSTNATAL TRANSMISSION; UNITED-STATES; TRIAL C1 NICHHD, NIH, Pediat Adolescent & Maternal AIDS Branch, Bethesda, MD 20892 USA. RP Read, JS (reprint author), NICHHD, NIH, Pediat Adolescent & Maternal AIDS Branch, Bethesda, MD 20892 USA. NR 16 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD JUL PY 2008 VL 27 IS 7 BP 649 EP 650 DI 10.1097/INF.0b013e318180b4b7 PG 2 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 319PR UT WOS:000257176600014 PM 18596474 ER PT J AU Anderson, LA Li, Y Graubard, BI Whitby, D Mbisa, G Tan, S Goedert, JJ Engels, EA AF Anderson, Lesley A. Li, Yan Graubard, Barry I. Whitby, Denise Mbisa, Georgina Tan, Sylvia Goedert, James J. Engels, Eric A. TI Human herpesvirus 8 seroprevalence among children and adolescents in the United States SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE human herpesvirus 8; HHV-8; Kaposi sarcoma-associated herpes virus; KSHV; children; adolescents; US; asthma; hay fever; socioeconomic status; familial clustering ID RISK-FACTORS; INFECTION; TRANSMISSION AB We measured human herpesvirus-8 antibodies (K8.1 and orf73 enzyme immunoassays) in 4166 children, aged 6-17 years, in a U.S. cross-sectional survey. Forty-six were K8.1 seropositive (weighted seroprevalence: 1.1%) and 20 were orf73 seropositive (weighted seroprevalence 0.4%). K8.1 seropositivity was associated with asthma (odds ratio: 6.3; 95% confidence interval: 2.4-16.9) and hay fever (3.5; 1.1-11.0), and there were borderline associations with measures of crowding and low socioeconomic status. C1 [Anderson, Lesley A.; Goedert, James J.; Engels, Eric A.] NCI, Div Canc Epidemiol & Genet, Infect & Immunoepidemiol Branch, Bethesda, MD 20892 USA. [Anderson, Lesley A.] NCI, NIH, Canc Prevent Fellowship Program, Off Prevent Oncol,Div Canc Prevent, Bethesda, MD 20892 USA. [Graubard, Barry I.] NCI, Div Canc Epidemiol & Genet, Biostat Branch, Bethesda, MD 20892 USA. [Whitby, Denise] NCI, SAIC Frederick, Viral Epidemiol Sect, AIDS Vaccine Program, Frederick, MD USA. [Tan, Sylvia] RTI Int, Rockville, MD USA. RP Engels, EA (reprint author), NCI, Div Canc Epidemiol & Genet, Infect & Immunoepidemiol Branch, 6120 Execut Blvd,EPS 7076, Bethesda, MD 20892 USA. EM engelse@mail.nih.gov OI Anderson, Lesley/0000-0002-1000-3649 FU Intramural NIH HHS NR 9 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD JUL PY 2008 VL 27 IS 7 BP 661 EP 664 DI 10.1097/INF.0b013e3181691740 PG 4 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 319PR UT WOS:000257176600021 PM 18536622 ER PT J AU Chantry, CJ Hughes, MD Alvero, C Cervia, JS Meyer, WA Hodge, J Borum, P Moye, J AF Chantry, Caroline J. Hughes, Michael D. Alvero, Carmelita Cervia, Joseph S. Meyer, William A., III Hodge, Janice Borum, Peggy Moye, Jack, Jr. CA PACTG 1010 Team TI Lipid and glucose alterations in HIV-Infected children beginning or changing antiretroviral therapy SO PEDIATRICS LA English DT Article DE children; cholesterol glucose; HIV; insulin; insulin resistance; triglycerides; apolipoprotein; viral load; immune reconstitution; insulin like growth factor-1; insulin like growth factor binding protein ID GROWTH-HORMONE; LIPODYSTROPHY SYNDROME; PROTEASE INHIBITORS; METABOLIC-CHANGES; RISK-FACTORS; INSULIN-RESISTANCE; BODY-COMPOSITION; SERUM-LIPIDS; HYPERLIPIDEMIA; COHORT AB OBJECTIVE. The objective of this study was to describe lipid profiles and glucose homeostasis in HIV- positive children after initiating or changing antiretroviral therapy and their associations with viral, immune, antiretroviral therapy, and growth factor parameters. METHODS. Ninety- seven prepubertal HIV- positive children aged 1 month to < 13 years were observed for 48 weeks after beginning or changing antiretroviral therapy. Fasting lipid panels, serum glucose, insulin, insulin- like growth factor-1 and binding proteins-1 and -3 , plasma viral load, and CD4% were measured. Each child was matched on age, gender, and race/ ethnicity to children from the National Health and Nutrition Examination Survey, used to give z scores for each child's lipid values. Multivariate regression was used to evaluate the association of changes in z scores over 48 weeks with suppression of HIV-1 RNA, change in CD4% and growth factors, and antiretroviral therapy, adjusted for entry z score, CD4%, log(10) HIV-1 RNA, Centers for Disease Control and Prevention category, and total fat and cholesterol dietary intake. RESULTS. Lipid, apolipoprotein, and insulin levels all increased significantly by 48 weeks. Multivariate analysis of changes demonstrated that increased HDL and decreased total- HDL cholesterol ratio were associated with CD4% increase and with insulin- like growth factor-1, which increased to normal (versus remained stable or became low) over 48 weeks. Total cholesterol levels increased among children who achieved HIV-1 RNA of < 400 copies per mL. Antiretroviral therapy regimens that included both a protease inhibitor and a non-nucleoside reverse transcriptase inhibitor were associated with greater increases in total- HDL cholesterol ratio than regimens that contained a protease inhibitor or a non - nucleoside reverse transcriptase inhibitor but not both. CONCLUSIONS. In these HIV-positive children with predominantly mild- to- moderate disease, initiation or change in antiretroviral therapy was associated with significant increases in multiple lipid measures and insulin resistance. Favorable lipid changes were associated with CD4% increases, suggesting a protective effect of immune reconstitution on atherosclerosis, and with increased insulin- like growth factor-1 levels, supporting the theory that reduced growth hormone resistance may be a mechanism by which lipid profiles are improved. Finally, antiretroviral therapy regimens that contain both a non - nucleoside reverse transcriptase inhibitor and a protease inhibitor are associated with worse lipid profiles than regimens that contain 1 but not both of these drug classes. C1 [Chantry, Caroline J.] Univ Calif Davis, Med Ctr, Dept Pediat, Sacramento, CA 95817 USA. [Hughes, Michael D.; Alvero, Carmelita] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. [Cervia, Joseph S.] Albert Einstein Coll Med, Dept Internal Med, Bronx, NY 10467 USA. [Cervia, Joseph S.] Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10467 USA. [Hodge, Janice] Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA. [Meyer, William A., III] Quest Diagnost, Baltimore, MD USA. [Borum, Peggy] Univ Florida, Dept Food Sci & Human Nutr, Gainesville, FL 32611 USA. [Borum, Peggy] Univ Florida, Dept Pediat, Gainesville, FL USA. [Moye, Jack, Jr.] NICHHD, NIH, Bethesda, MD 20892 USA. RP Chantry, CJ (reprint author), Univ Calif Davis, Med Ctr, Dept Pediat, 2516 Stocklon Blvd, Sacramento, CA 95817 USA. EM caroline.chantry@ucdmc.ucdavis.edu OI moye, john/0000-0001-9976-8586 FU NIAID NIH HHS [U01 AI068632-03] NR 37 TC 28 Z9 28 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 JUL PY 2008 VL 122 IS 1 BP E129 EP E138 DI 10.1542/peds.2007-2467 PG 10 WC Pediatrics SC Pediatrics GA 320YN UT WOS:000257271200077 PM 18519448 ER PT J AU Hjuler, T Wohlfahrt, J Kaltoft, MS Koch, A Biggar, RJ Melbye, M AF Hjuler, Thomas Wohlfahrt, Jan Kaltoft, Margit Staum Koch, Anders Biggar, Robert John Melbye, Mads TI Risks of invasive pneumococcal disease in children with underlying chronic diseases SO PEDIATRICS LA English DT Article DE pneumococcal infections; epidemiology; comorbidity; invasive procedures; disease susceptibility; case-control studies ID STREPTOCOCCUS-PNEUMONIAE INFECTIONS; BACTERIAL-MENINGITIS; COCHLEAR IMPLANTS; POPULATION; EPIDEMIOLOGY; SEROTYPES; CARRIAGE; REGISTRY; ADULTS AB OBJECTIVE. The risk of invasive pneumococcal disease is increased among children with some chronic diseases. The objective of this study was to quantify the risk of invasive pneumococcal disease in a wide range of chronic diseases. PATIENTS AND METHODS. Cases of invasive pneumococcal disease among children (aged 0-17 years) were identified from 1977 through 2005 by using a national surveillance program in Denmark. Rate ratios were assessed in a case-control study by using 10 age- and gender-matched controls per case. Chronic diseases were defined a priori. RESULTS. Among 1655 children with invasive pneumococcal disease, 19% had a history of chronic disease, according to our definition, versus 5% of controls. An increased risk of invasive pneumococcal disease was observed for children followed > 30 days after initial hospital contact for a chronic disease, but it was also increased in children with >= 5 hospital contacts for any other reason. Children with a history of cancer, chronic renal disease, splenectomy, and transplantation were particularly susceptible to invasive pneumococcal disease. Adjusted for number of hospital contacts, the risk for children with other types of chronic disease was 1.4-fold more than for those with hospital contacts for any reason. CONCLUSIONS. Cancer, chronic renal diseases, splenectomy, and transplantation were strongly associated with an increased risk of invasive pneumococcal disease in children. For children with other chronic diseases, their excess risk seemed to be attributable mostly to frail children having repeated hospital contact rather than their underlying condition. C1 [Kaltoft, Margit Staum] Statens Serum Inst, Dept Bacteriol Mycol & Parasitol, DK-2300 Copenhagen, Denmark. [Hjuler, Thomas; Wohlfahrt, Jan; Koch, Anders; Biggar, Robert John; Melbye, Mads] Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark. [Biggar, Robert John] Natl Canc Inst, Viral Epidemiol Branch, Div Epidemiol & Genet, Bethesda, MD USA. RP Hjuler, T (reprint author), Statens Serum Inst, Dept Epidemiol Res, 5 Artillerivej, DK-2300 Copenhagen, Denmark. EM tta@ssi.dk OI Koch, Anders/0000-0001-9205-1048 NR 33 TC 34 Z9 36 U1 0 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUL PY 2008 VL 122 IS 1 BP E26 EP E32 DI 10.1542/peds.2007-1510 PG 7 WC Pediatrics SC Pediatrics GA 320YN UT WOS:000257271200064 PM 18595971 ER PT J AU Levine, TP Liu, J Das, A Lester, B Lagasse, L Shankaran, S Bada, HS Bauer, CR Higgins, R AF Levine, Todd P. Liu, Jing Das, Abhik Lester, Barry Lagasse, Linda Shankaran, Seetha Bada, Henrietta S. Bauer, Charles R. Higgins, Rosemary TI Effects of prenatal cocaine exposure on special education in school-aged children SO PEDIATRICS LA English DT Article DE prenatal exposure; cocaine; education; schools ID MATERNAL LIFE-STYLE; EARLY LANGUAGE-DEVELOPMENT; IN-UTERO; SOCIOECONOMIC-STATUS; DRUG EXPOSURE; BIRTH-WEIGHT; FOLLOW-UP; PREGNANCY; BEHAVIOR; OUTCOMES AB OBJECTIVE. The objective of this study was to evaluate the effects of prenatal cocaine exposure on special education at age 7 with adjustment for covariates. METHODS. As part of the prospective, longitudinal, multisite study of children with prenatal cocaine exposure (Maternal Lifestyle Study), school records were reviewed for 943 children at 7 years to determine involvement in special education outcomes: (1) individualized education plan; (2) special education conditions; (3) support services; (4) special education classes; and (5) speech and language services. Logistic regression was used to examine the effect of prenatal cocaine exposure on these outcomes with environmental, maternal, and infant medical variables as covariates, as well as with and without low child IQ. RESULTS. Complete data for each analysis model were available for 737 to 916 children. When controlling for covariates including low child IQ, prenatal cocaine exposure had a significant effect on individualized education plan. When low child IQ was not included in the model, prenatal cocaine exposure had a significant effect on support services. Male gender, low birth weight, white race, and low child IQ also predicted individualized education plan. Low birth weight and low child IQ were significant in all models. White race was also significant in speech and language services. Other covariate effects were model specific. When included in the models, low child IQ accounted for more of the variance and changed the significance of other covariates. CONCLUSIONS. Prenatal cocaine exposure increased the likelihood of receiving an individualized education plan and support services, with adjustment for covariates. Low birth weight and low child IQ increased the likelihood of all outcomes. The finding that white children were more likely to get an individualized education plan and speech and language services could indicate a greater advantage in getting educational resources for this population. C1 [Levine, Todd P.; Liu, Jing; Lester, Barry; Lagasse, Linda] Brown Univ, Dept Pediat, Warren Alpert Med Sch, Providence, RI 02912 USA. [Das, Abhik] Res Triangle Inst Int, Res Triangle Pk, NC USA. [Shankaran, Seetha] Wayne State Univ, Sch Med, Dept Pediat, Detroit, MI 48201 USA. [Bada, Henrietta S.] Univ Kentucky, Coll Med, Dept Pediat, Lexington, KY USA. [Bauer, Charles R.] Univ Miami, Sch Med, Dept Pediat, Miami, FL USA. [Higgins, Rosemary] NICHHD, Bethesda, MD 20892 USA. RP Levine, TP (reprint author), Brown Ctr Study Children Risk, 101 Dudley St, Providence, RI 02905 USA. EM TLevine@wihri.org FU NICHD NIH HHS [U10 HD021385, N01-HD-2-3159, U01 HD 36790, U01 HD036790, U01 HD036790-08, U10 HD 21385, U10 HD 21397, U10 HD 21415, U10 HD 27904, U10 HD021397, U10 HD027904]; NIDA NIH HHS [U10 DA024117, U10 DA024117-01, U10 DA024118-01, U10 DA024119, U10 DA024119-01, U10 DA024128-06]; NIMH NIH HHS [T32 MH019927, T32MH19927] NR 61 TC 17 Z9 18 U1 4 U2 5 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUL PY 2008 VL 122 IS 1 BP E83 EP E91 DI 10.1542/peds.2007-2826 PG 9 WC Pediatrics SC Pediatrics GA 320YN UT WOS:000257271200071 PM 18541617 ER PT J AU Nanda, S Uhl, G AF Nanda, Shreeya Uhl, George TI Interview - Dr.George Uhl SO PHARMACOGENOMICS LA English DT Editorial Material C1 [Uhl, George] Natl Inst Drug Abuse, Intramural Res Program, Mol Neurobiol Res Branch, NIH, Baltimore, MD 21224 USA. EM GUHL@intra.nida.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1462-2416 J9 PHARMACOGENOMICS JI Pharmacogenomics PD JUL PY 2008 VL 9 IS 7 BP 813 EP 817 DI 10.2217/14622416.9.7.813 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 329NT UT WOS:000257875000007 ER PT J AU Enoch, MA AF Enoch, Mary-Anne TI The role of GABA(A) receptors in the development of alcoholism SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Review DE GABA; ethanol; neurosteroids; benzodiazepines; tolerance; withdrawal; reward; VTA; stress; anxiety; genes; GABRA2 ID GAMMA-AMINOBUTYRIC-ACID; CHRONIC INTERMITTENT ETHANOL; VENTRAL TEGMENTAL AREA; ANTISOCIAL PERSONALITY-DISORDER; SUBUNIT MESSENGER-RNA; GATED ION CHANNELS; PROTEIN-KINASE-C; NEUROACTIVE STEROIDS; LINKAGE DISEQUILIBRIUM; NICOTINIC RECEPTORS AB Alcoholism is a common, heritable, chronic relapsing disorder. GABA(A) receptors undergo allosteric modulation by ethanol, anesthetics, benzodiazepines and neurosteroids and have been implicated in the acute as well as the chronic effects of ethanol including tolerance, dependence and withdrawal. Medications targeting GABA(A) receptors ameliorate the symptoms of acute withdrawal. Ethanol induces plasticity in GABA(A) receptors: tolerance is associated with generally decreased GABA(A) receptor activation and differentially altered subunit expression. The dopamine (DA) mesolimbic reward pathway originating in the ventral tegmental area (VTA), and interacting stress circuitry play an important role in the development of addiction. VTA GABAergic interneurons are the primary inhibitory regulators of DA neurons and a subset of VTA GABA(A) receptors may be implicated in the switch from heavy drinking to dependence. GABA(A) receptors modulate anxiety and response to stress; important elements of sustained drinking and relapse. The GABA(A) receptor subunit genes clustered on chromosome 4 are highly expressed in the reward pathway. Several recent studies have provided strong evidence that one of these genes, GABRA2, is implicated in alcoholism in humans. The influence of the interaction between ethanol and GABA(A) receptors in the reward pathway on the development of alcoholism together with genetic and epigenetic vulnerabilities will be explored in this review. Published by Elsevier Inc. C1 NIAAA, Neurogenet Lab, NIH, DICBR, Bethesda, MD 20892 USA. RP Enoch, MA (reprint author), NIAAA, Neurogenet Lab, NIH, DICBR, 5625 Fishers Lane,Room 3S32,MSC 9412, Bethesda, MD 20892 USA. EM maenoch@niaaa.nih.gov FU Intramural NIH HHS [Z01 AA000305-04] NR 158 TC 106 Z9 106 U1 1 U2 17 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD JUL PY 2008 VL 90 IS 1 BP 95 EP 104 DI 10.1016/j.pbb.2008.03.007 PG 10 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 320VD UT WOS:000257262300012 PM 18440057 ER PT J AU Figg, WD Chau, CH Okita, R Preusch, P Tracy, TS McLeod, H Reed, M Pieper, J Knoell, D Miller, K Speedie, M Blouin, R Kroboth, P Koda-Kimble, MA Taylor, P Cohen, J Giacomini, K AF Figg, William D. Chau, Cindy H. Okita, Richard Preusch, Peter Tracy, Timothy S. McLeod, Howard Reed, Michael Pieper, John Knoell, Daren Miller, Ken Speedie, Marilyn Blouin, Robert Kroboth, Patricia Koda-Kimble, Mary Anne Taylor, Palmer Cohen, Jordan Giacomini, Kathy TI Pharm.D. pathways to biomedical research: The National Institutes of Health special conference on pharmacy research SO PHARMACOTHERAPY LA English DT Article DE pharmacy; National Institutes of Health grants; NIH; research; education; training; doctor of pharmacy; Pharm.D.; pharmaceutical scientist; mentoring AB To address the shortage of research-trained pharmaceutical scientists (or doctor of pharmacy [Pharm.D.] scientists), a 2-day pharmacy research conference titled "Pharm.D. Pathways to Biomedical Research" was convened on December 13-14, 2006, at the National Institutes of Health (NIH) campus (Bethesda, MD). The workshop included invited speakers and participants from academia, industry, and government. Forty-two pharmacy schools were represented, including deans and clinical pharmaceutical scientists with current NIH funding. In addition, several pharmacy professional organizations were represented-American Association of Colleges of Pharmacy, American College of Clinical Pharmacy, American Society of Health-System Pharmacists, and the Accreditation Council on Pharmaceutical Education. The workshop was divided into three sessions followed by breakout discussion groups: the first session focused on presentations by leading pharmaceutical scientists who described their path to success; the second session examined the NIH grant system, particularly as it relates to training opportunities in biomedical research and funding mechanisms; and the third session addressed biomedical research education and training from the perspective of scientific societies and academia. We summarize the discussions and findings from the workshop and highlight some important considerations for the future of research in the pharmacy community This report also puts forth recommendations for educating future pharmaceutical scientists. C1 [Figg, William D.; Chau, Cindy H.] NCI, Bethesda, MD 20892 USA. [Okita, Richard; Preusch, Peter] Natl Inst Gen Med Sci, Bethesda, MD USA. [Tracy, Timothy S.; Speedie, Marilyn] Univ Minnesota, Coll Pharm, Minneapolis, MN 55455 USA. [McLeod, Howard; Blouin, Robert] Univ N Carolina, Sch Pharm, Chapel Hill, NC USA. [Reed, Michael] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Pieper, John] Univ New Mexico, Coll Pharm, Albuquerque, NM 87131 USA. [Knoell, Daren] Ohio State Univ, Columbus, OH 43210 USA. [Miller, Ken] Amer Assoc Coll Pharm, Alexandria, VA USA. [Kroboth, Patricia] Univ Pittsburgh, Sch Pharm, Pittsburgh, PA USA. [Koda-Kimble, Mary Anne; Giacomini, Kathy] Univ Calif San Francisco, Sch Pharm, San Francisco, CA 94143 USA. [Taylor, Palmer] Univ Calif San Diego, Sch Pharm, San Diego, CA 92103 USA. [Cohen, Jordan] Univ Iowa, Coll Pharm, Iowa City, IA 52242 USA. RP Figg, WD (reprint author), Bldg 10,Room 5A01,9000 Rockville Pike, Bethesda, MD 20892 USA. EM wdfigg@hefix.nih.gov RI Figg Sr, William/M-2411-2016 NR 5 TC 7 Z9 7 U1 0 U2 2 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 JUL PY 2008 VL 28 IS 7 BP 821 EP 833 DI 10.1592/phco.28.7.821 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 316OH UT WOS:000256959000002 PM 18576897 ER PT J AU Hosui, A Hennighausen, L AF Hosui, Atsushi Hennighausen, Lothar TI Genomic dissection of the cytokine-controlled STAT5 signaling network in liver SO PHYSIOLOGICAL GENOMICS LA English DT Review DE signal transducers and activators of transcription; knockout; metabolism ID GROWTH-FACTOR-I; POSTNATAL BODY GROWTH; ACUTE-PHASE RESPONSE; GENE-EXPRESSION; INTERFERON-GAMMA; CELL-GROWTH; HEPATOCELLULAR-CARCINOMA; UP-REGULATION; IFN-GAMMA; STAT5A(-/-)5B(-/-) MICE AB Hosui A, Hennighausen L. Genomic dissection of the cytokine-controlled STAT5 signaling network in liver. Physiol Genomics 34: 135-143, 2008. First published May 6, 2008; doi:10.1152/physiolgenomics.00048.2008.-Growth hormone (GH) controls the physiology and pathophysiology of the liver, and its signals are conducted by two members of the family of signal transducers and activators of transcription, STAT5A and STAT5B. Mice in which the Stat5a/b locus has been inactivated specifically in hepatocytes display GH resistance, the sex-specific expression of genes associated with liver metabolism and the cytochrome P-450 system is lost, and they develop hepatosteatosis. Several groups have shown by global gene expression profiling that a cadre of STAT5A/B target genes identify genetic cascades induced by GH and other cytokines. Evidence is accumulating that in the absence of STAT5A/B GH aberrantly activates STAT1 and STAT3 and their downstream target genes and thereby offers a partial explanation of some of the physiological alterations observed in Stat5a/b-null mice and human patients. We hypothesize that phenotypic changes observed in the absence of STAT5A/B are due to two distinct molecular consequences: first, the failure of STAT5A/B target genes to be activated by GH and second, the rerouting of GH signaling to other members of the STAT family. Rerouting of GH signaling to STAT1 and STAT3 might partially compensate for the loss of STAT5A/B, but it certainly activates biological programs distinct from STAT5A/B. Here we discuss the extent to which studies on global gene expression profiling have fostered a better understanding of the biology behind cytokine-STAT5A/B networks in hepatocytes. We also explore whether this wealth of information on gene activity can be used to further understand the roles of cytokines in liver disease. C1 [Hosui, Atsushi; Hennighausen, Lothar] NIDDK, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. [Hosui, Atsushi] Osaka Univ, Dept Gastroenterol & Hepatol, Grad Sch Med, Osaka, Japan. RP Hennighausen, L (reprint author), NIDDK, Lab Genet & Physiol, NIH, 8 Ctr Dr,Rm 101, Bethesda, MD 20892 USA. EM hosui@medone.med.osaka-u.ac.jp; lotharh@mail.nih.gov FU National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases FX This work was supported by the intramural program of the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases. NR 99 TC 17 Z9 18 U1 1 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD JUL PY 2008 VL 34 IS 2 BP 135 EP 143 DI 10.1152/physiolgenomics.00048.2008 PG 9 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 433MQ UT WOS:000265208400001 PM 18460640 ER PT J AU Deng, S Wang, Y Inui, T Chen, SN Farnsworth, NR Cho, S Franzblau, SG Pauli, GF AF Deng, Shixin Wang, Yuehon Inui, Taichi Chen, Shao-Nong Farnsworth, Norman R. Cho, Sanghyun Franzblau, Scott G. Pauli, Guido F. TI Anti-TB polyynes from the roots of Angelica sinensis SO PHYTOTHERAPY RESEARCH LA English DT Article DE Angelica sinensis; botanicals; dong quai; dang gui; polyynes; anti-TB activity; tuberculosis ID POLYACETYLENES; FALCARINDIOL AB Following chemotaxonomic evidence, the PE and CHC13 extracts of the roots of the botanical Angelica sinensis (Oliv.) Diels (Dang Gui) were investigated for in vitro anti-TB activity, in parallel to studying their serotonergic and GABAergic potential. The activities were confirmed to overlap chemically with the neurotropic active principles present in medium lipophilic fractions. Phytochemical investigations led to the isolation of five polyynes: falcarindiol (1), 9Z,17-octadecadiene-12,14-diyne-1,11,16-trioi,l-acetate (2), oplopandiol (3), beptadeca-l-ene-9,10-epoxy-4,6-diyne-3,8-dioI (4) and the new polyyne 8-hydroxy-l-methoxy-(Z)-9-heptadecene4,6-diyn-3-one (5), as characterized by spectroscopic techniques including 1D, 2D NMR and HR-MS. All compounds were tested against two pathogenic strains of Mycobacterium tuberculosis (H37Rv and Erdman) in vitro in a microplate Alamar Blue assay (MABA). The most potent anti-TB constituents were 1 and 2, exhibiting MIC values of 1.4-26.7 gg/mL; 3 showed moderate MICs (49.5 and 50.2 gg/mL, respectively) while 4 and 5 were weakly active (MIC > 60 gg/mL). Notably, none of the five compounds exhibited significant cytotoxicity against Vero cells. These findings not only reveal a new potential area of therapeutic value for A. sinensis, but also underline the role of polyynes as anti-TB active principles in ethnobotanical preparations, and as lead compounds. Copyright (c) 2008 John Wiley & Sons, Ltd. C1 [Deng, Shixin; Inui, Taichi; Chen, Shao-Nong; Farnsworth, Norman R.; Pauli, Guido F.] Univ Illinois, Coll Pharm, Dept Med Chem & Pharmacognosy, Chicago, IL 60612 USA. [Deng, Shixin; Chen, Shao-Nong; Farnsworth, Norman R.; Pauli, Guido F.] Univ Illinois, Coll Pharm, NIH, Ctr Bot Dietary Supplements Res, Chicago, IL 60612 USA. [Deng, Shixin; Chen, Shao-Nong; Farnsworth, Norman R.; Pauli, Guido F.] Univ Illinois, Coll Pharm, Program Collaborat Res Pharmaceut Sci, Chicago, IL 60612 USA. [Wang, Yuehon; Inui, Taichi; Cho, Sanghyun; Franzblau, Scott G.; Pauli, Guido F.] Univ Illinois, Coll Pharm, Inst TB Res, Chicago, IL 60612 USA. RP Pauli, GF (reprint author), Univ Illinois, Coll Pharm, Dept Med Chem & Pharmacognosy, 833 S Wood St, Chicago, IL 60612 USA. EM gfp@uic.edu OI Deng, Shixin/0000-0002-3947-7629; Pauli, Guido/0000-0003-1022-4326; Franzblau, Scott/0000-0002-8698-0243 FU NCCIH NIH HHS [P50 AT000155, P50 AT000155-09, P50 AT00155] NR 15 TC 28 Z9 29 U1 1 U2 10 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0951-418X J9 PHYTOTHER RES JI Phytother. Res. PD JUL PY 2008 VL 22 IS 7 BP 878 EP 882 DI 10.1002/ptr.2303 PG 5 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 332AO UT WOS:000258054200005 PM 18567055 ER PT J AU Waterman, C Smith, R Der, MA Beutler, J AF Waterman, C. Smith, R. Der, Marderosian A. Beutler, J. TI Bioassay-guided isolation of African ethnobotanical anthelmintics SO PLANTA MEDICA LA English DT Meeting Abstract CT 7th Joint Meeting of the Association-Francophone-pour-l'Enselgnement-et-la-Recherche-en-Pharmacog nosie/American-Society-of-Pharmacognosy/Society-for-Medicinal-Plant-Rese arch/Phytochem-Society-of-Europe/Societa-Italiana-di-Fitochimica CY AUG 03-08, 2008 CL Athens, GREECE SP Assoc Francophone Enseignement Rech Pharmacognosie, Amer Soc Pharmacognosy, Soc Medicinal Plant Res, Phytochem Soc Europe, Soc Italiana Fitochim ID CAENORHABDITIS-ELEGANS C1 [Waterman, C.; Smith, R.; Der, Marderosian A.] Univ Sci Philadelphia, Philadelphia, PA 19104 USA. [Beutler, J.] Natl Canc Inst, Frederick, MD 21702 USA. RI Beutler, John/B-1141-2009 OI Beutler, John/0000-0002-4646-1924 NR 8 TC 0 Z9 0 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0032-0943 J9 PLANTA MED JI Planta Med. PD JUL PY 2008 VL 74 IS 9 BP 1086 EP 1086 PG 1 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 334ZY UT WOS:000258261801099 ER PT J AU Ta, HP Maciuk, A Vautier, S Milane, A Welti, S Champy, P Wainer, IW Fernandez, C Figadere, B AF Ta, H. P. Maciuk, A. Vautier, S. Milane, A. Welti, S. Champy, P. Wainer, I. W. Fernandez, C. Figadere, B. TI High-resolution bioguided screening of Ganoderma capense for P-GP modulating activity SO PLANTA MEDICA LA English DT Meeting Abstract CT 7th Joint Meeting of the Association-Francophone-pour-l'Enselgnement-et-la-Recherche-en-Pharmacog nosie/American-Society-of-Pharmacognosy/Society-for-Medicinal-Plant-Rese arch/Phytochem-Society-of-Europe/Societa-Italiana-di-Fitochimica CY AUG 03-08, 2008 CL Athens, GREECE SP Assoc Francophone Enseignement Rech Pharmacognosie, Amer Soc Pharmacognosy, Soc Medicinal Plant Res, Phytochem Soc Europe, Soc Italiana Fitochim C1 [Ta, H. P.; Maciuk, A.; Champy, P.; Figadere, B.] Univ Paris 11, Lab Pharmacognosy, F-92296 Chatenay Malabry, France. [Vautier, S.; Milane, A.; Fernandez, C.] Univ Paris 11, Lab Clin Pharm, F-92296 Chatenay Malabry, France. [Welti, S.] Univ Lille 2, Fac Pharm, Lab Bot, F-59800 Lille, France. [Wainer, I. W.] NIA, NIH, Clin Invest Lab, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0032-0943 J9 PLANTA MED JI Planta Med. PD JUL PY 2008 VL 74 IS 9 BP 1106 EP 1107 PG 2 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 334ZY UT WOS:000258261801178 ER PT J AU Kapadia, GJ Udiak, E Ma, Y Ito, Y AF Kapadia, G. J. Udiak, E. Ma, Y. Ito, Y. TI Alkaloid profile of leaves of horticultural cultivar of Catharanthus roseus SO PLANTA MEDICA LA English DT Meeting Abstract CT 7th Joint Meeting of the Association-Francophone-pour-l'Enselgnement-et-la-Recherche-en-Pharmacog nosie/American-Society-of-Pharmacognosy/Society-for-Medicinal-Plant-Rese arch/Phytochem-Society-of-Europe/Societa-Italiana-di-Fitochimica CY AUG 03-08, 2008 CL Athens, GREECE SP Assoc Francophone Enseignement Rech Pharmacognosie, Amer Soc Pharmacognosy, Soc Medicinal Plant Res, Phytochem Soc Europe, Soc Italiana Fitochim C1 [Kapadia, G. J.; Udiak, E.; Ito, Y.] NHLBI, Bioseparat Technol Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA. [Kapadia, G. J.; Udiak, E.] Howard Univ, Sch Pharm, Dept Pharmaceut Sci, Washington, DC 20059 USA. [Ma, Y.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0032-0943 J9 PLANTA MED JI Planta Med. PD JUL PY 2008 VL 74 IS 9 BP 1124 EP 1124 PG 1 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 334ZY UT WOS:000258261801248 ER PT J AU Baccarelli, A Giacomini, SM Corbetta, C Landi, MT Bonzini, M Consonni, D Grillo, P Patterson, DG Pesatori, AC Bertazzi, PA AF Baccarelli, Andrea Giacomini, Sara M. Corbetta, Carlo Landi, Maria Teresa Bonzini, Matteo Consonni, Dario Grillo, Paolo Patterson, Donald G., Jr. Pesatori, Angela C. Bertazzi, Pier Alberto TI Neonatal thyroid function in seveso 25 years after maternal exposure to dioxin SO PLOS MEDICINE LA English DT Article ID OPERATION RANCH HAND; ARYL-HYDROCARBON RECEPTOR; IN-UTERO EXPOSURE; POLYCHLORINATED-BIPHENYLS; HORMONE STATUS; FOLLOW-UP; CHLORINATED DIOXINS; POSTNATAL EXPOSURE; IODINE DEFICIENCY; 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN AB Background Neonatal hypothyroidism has been associated in animal models with maternal exposure to several environmental contaminants; however, evidence for such an association in humans is inconsistent. We evaluated whether maternal exposure to 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a persistent and widespread toxic environmental contaminant, is associated with modified neonatal thyroid function in a large, highly exposed population in Seveso, Italy. Methods and Findings Between 1994 and 2005, in individuals exposed to TCDD after the 1976 Seveso accident we conducted: (i) a residence- based population study on 1,014 children born to the 1,772 women of reproductive age in the most contaminated zones (A, very high contamination; B, high contamination), and 1,772 age- matched women from the surrounding noncontaminated area (reference); (ii) a biomarker study on 51 mother - child pairs for whom recent maternal plasma dioxin measurements were available. Neonatal blood thyroid- stimulating hormone (b-TSH) was measured on all children. We performed crude and multivariate analyses adjusting for gender, birth weight, birth order, maternal age, hospital, and type of delivery. Mean neonatal b- TSH was 0.98 mu U/ml (95% confidence interval [ CI] 0.90 - 1.08) in the reference area (n 533), 1.35 lU/ ml ( 95% CI 1.22 - 1.49) in zone B (n = 425), and 1.66 mu U/ ml (95% CI 1.19 - 2.31) in zone A (n = 56) (p < 0.001). The proportion of children with b- TSH. 5 mu U/ ml was 2.8% in the reference area, 4.9% in zone B, and 16.1% in zone A (p < 0.001). Neonatal b- TSH was correlated with current maternal plasma TCDD (n = 51, beta = 0.47, p < 0.001) and plasma toxic equivalents of coplanar dioxin- like compounds (n = 51, b = 0.45, p = 0.005). Conclusions Our data indicate that environmental contaminants such as dioxins have a long-lasting capability to modify neonatal thyroid function after the initial exposure. C1 [Baccarelli, Andrea] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Baccarelli, Andrea; Giacomini, Sara M.; Bonzini, Matteo; Consonni, Dario; Grillo, Paolo; Pesatori, Angela C.; Bertazzi, Pier Alberto] Univ Milan, Clin Lavoro L Devoto, Dept Environm & Occupat Hlth, Milan, Italy. [Baccarelli, Andrea; Giacomini, Sara M.; Bonzini, Matteo; Consonni, Dario; Grillo, Paolo; Pesatori, Angela C.; Bertazzi, Pier Alberto] Osped Maggiore Policlin, Regina Elena Fdn, IRCCS, Dept Prevent Med, Milan, Italy. [Corbetta, Carlo] V Buzzi Childrens Hosp, Neonatal Screening Lab, Milan, Italy. [Landi, Maria Teresa] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Natl Inst Health,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Patterson, Donald G., Jr.] EnviroSolut Consulting, Jasper, GA USA. RP Baccarelli, A (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM abaccare@hsph.harvard.edu RI Bonzini, Matteo/K-7540-2016; bertazzi, pietro alberto/D-5039-2017; OI Bonzini, Matteo/0000-0002-6405-7554; bertazzi, pietro alberto/0000-0003-3475-2449; Baccarelli, Andrea/0000-0002-3436-0640; pesatori, angela/0000-0002-0261-3252 NR 52 TC 49 Z9 50 U1 0 U2 5 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 JUL PY 2008 VL 5 IS 7 BP 1133 EP 1142 AR e161 DI 10.1371/journal.pmed.0050161 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 330VI UT WOS:000257970500019 PM 18666825 ER PT J AU Fogli, M Mavilio, D Brunetta, E Varchetta, S Ata, K Roby, G Kovacs, C Follmann, D Pende, D Ward, J Barker, E Marcenaro, E Moretta, A Fauci, AS AF Fogli, Manuela Mavilio, Domenico Brunetta, Enrico Varchetta, Stefania Ata, Khaled Roby, Gregg Kovacs, Colin Follmann, Dean Pende, Daniela Ward, Jeffrey Barker, Edward Marcenaro, Emanuela Moretta, Alessandro Fauci, Anthony S. TI Lysis of endogenously infected CD4+T cell blasts by rIL-2 activated autologous natural killer cells from HIV-infected viremic individuals SO PLOS PATHOGENS LA English DT Article ID CD4(+) T-CELLS; CLASS-I; ANTIRETROVIRAL THERAPY; MEDIATED CYTOTOXICITY; DOWN-REGULATION; NK CELLS; HLA-C; EXPRESSION; IMMUNODEFICIENCY; VIRUS AB Understanding the cellular mechanisms that ensure an appropriate innate immune response against viral pathogens is an important challenge of biomedical research. In vitro studies have shown that natural killer (NK) cells purified from healthy donors can kill heterologous cell lines or autologous CD4+ T cell blasts exogenously infected with several strains of HIV-1. However, it is not known whether the deleterious effects of high HIV-1 viremia interferes with the NK cell-mediated cytolysis of autologous, endogenously HIV-1-infected CD4+ T cells. Here, we stimulate primary CD4+ T cells, purified ex vivo from HIV-1-infected viremic patients, with PHA and rIL2 (with or without rIL-7). This experimental procedure allows for the significant expansion and isolation of endogenously infected CD4+ T cell blasts detected by intracellular staining of p24 HIV-1 core antigen. We show that, subsequent to the selective down-modulation of MHC class-I (MHC-I) molecules, HIV-1-infected p24(pos) blasts become partially susceptible to lysis by rIL-2-activated NK cells, while uninfected p24(neg) blasts are spared from killing. This NK cell-mediated killing occurs mainly through the NKG2D activation pathway. However, the degree of NK cell cytolytic activity against autologous, endogenously HIV-1-infected CD4+ T cell blasts that down-modulate HLA-A and-B alleles and against heterologous MHC-I-neg cell lines is particularly low. This phenomenon is associated with the defective surface expression and engagement of natural cytotoxicity receptors (NCRs) and with the high frequency of the anergic CD56(neg)/CD16(pos) subsets of highly dysfunctional NK cells from HIV-1-infected viremic patients. Collectively, our data demonstrate that the chronic viral replication of HIV-1 in infected individuals results in several phenotypic and functional aberrancies that interfere with the NK cell-mediated killing of autologous p24(pos) blasts derived from primary T cells. C1 [Fogli, Manuela; Mavilio, Domenico; Brunetta, Enrico; Varchetta, Stefania; Ata, Khaled; Roby, Gregg; Fauci, Anthony S.] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Mavilio, Domenico; Brunetta, Enrico; Varchetta, Stefania] Ist Clin Humanitas, Expt Immunol Lab, Milan, Italy. [Varchetta, Stefania] Univ Pavia, I-27100 Pavia, Italy. [Kovacs, Colin] Univ Toronto, Dept Med, Toronto, ON, Canada. [Follmann, Dean] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. [Pende, Daniela] Ist Nazl Ric Canc, I-16132 Genoa, Italy. [Ward, Jeffrey] SUNY Upstate Med Univ, Dept Microbiol & Immunol, Syracuse, NY USA. [Barker, Edward] Rush Univ, Med Ctr, Dept Immunol & Microbiol, Chicago, IL 60612 USA. [Marcenaro, Emanuela; Moretta, Alessandro] Univ Genoa, Dipartimento Med Sperimentale, Genoa, Italy. RP Mavilio, D (reprint author), NIAID, Immunoregulat Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM dmavilio@niaid.nih.gov RI Pende, Daniela/J-7429-2016; OI Pende, Daniela/0000-0003-1565-451X; Varchetta, Stefania/0000-0002-0289-2896; Mavilio, Domenico/0000-0001-6147-0952 FU NIAID; NIH FX This research was supported by the intramural Research Program of NIAID, NIH. NR 37 TC 52 Z9 53 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD JUL PY 2008 VL 4 IS 7 AR e1000101 DI 10.1371/journal.ppat.1000101 PG 13 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 356MT UT WOS:000259783000007 PM 18617991 ER PT J AU Kozmik, Z Ruzickova, J Jonasova, K Matsumoto, Y Vopalensky, P Kozmikova, I Strnad, H Kawamura, S Piatigorsky, J Paces, V Vlcek, C AF Kozmik, Zbynek Ruzickova, Jana Jonasova, Kristyna Matsumoto, Yoshifumi Vopalensky, Pavel Kozmikova, Iryna Strnad, Hynek Kawamura, Shoji Piatigorsky, Joram Paces, Vaclav Vlcek, Cestmir TI Assembly of the cnidarian camera-type eye from vertebrate-like components SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE evolution; gene; opsin; photoreceptor; cnidaria ID TRANSCRIPTIONAL REGULATION; TRIPEDALIA-CYSTOPHORA; FINE-STRUCTURE; BOX JELLYFISH; NEURAL CREST; EYELESS GENE; EVOLUTION; CUBOMEDUSAN; DROSOPHILA; MITF AB Animal eyes are morphologically diverse. Their assembly, however, always relies on the same basic principle, i.e., photoreceptors located in the vicinity of dark shielding pigment. Cnidaria as the likely sister group to the Bilateria are the earliest branching phylum with a well developed visual system. Here, we show that camera-type eyes of the cubozoan jellyfish, Tripedalia cystophora, use genetic building blocks typical of vertebrate eyes, namely, a ciliary phototransduction cascade and melanogenic pathway. Our findings indicative of parallelism provide an insight into eye evolution. Combined, the available data favor the possibility that vertebrate and cubozoan eyes arose by independent recruitment of orthologous genes during evolution. C1 [Kozmik, Zbynek; Ruzickova, Jana; Jonasova, Kristyna; Vopalensky, Pavel; Kozmikova, Iryna; Strnad, Hynek; Paces, Vaclav; Vlcek, Cestmir] Acad Sci Czech Republic, Inst Mol Genet, Prague 14220 4, Czech Republic. [Matsumoto, Yoshifumi; Kawamura, Shoji] Univ Tokyo, Grad Sch Frontier Sci, Chiba 2778562, Japan. [Piatigorsky, Joram] NEI, NIH, Bethesda, MD 20892 USA. RP Kozmik, Z (reprint author), Acad Sci Czech Republic, Inst Mol Genet, Videnska 1083, Prague 14220 4, Czech Republic. EM kozmik@img.cas.cz; joramp@nei.nih.gov; vlcek@img.cas.cz RI Kozmikova, Iryna/G-3591-2014; Kozmik, Zbynek/G-3581-2014; Kozmik, Zbynek/I-8807-2014; Vlcek, Cestmir/I-8820-2014; Strnad, Hynek/B-7361-2008; OI Strnad, Hynek/0000-0002-0141-8340; Vopalensky, Pavel/0000-0002-6171-1557 FU Intramural NIH HHS NR 44 TC 60 Z9 60 U1 6 U2 21 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 1 PY 2008 VL 105 IS 26 BP 8989 EP 8993 DI 10.1073/pnas.0800388105 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 322DC UT WOS:000257354400035 PM 18577593 ER PT J AU Kalueff, AV LaPorte, JL Murphy, DL Sufka, K AF Kalueff, Allan V. LaPorte, Justin L. Murphy, Dennis L. Sufka, Kenneth TI Hybridizing behavioral models: A possible solution to some problems in neurophenotyping research? SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY LA English DT Review DE behavioral phenotyping; experimental models; high-throughput testing; research strategies; single and multiple domains ID OBSESSIVE-COMPULSIVE DISORDER; SEPARATION-STRESS PARADIGM; RECEPTOR KNOCKOUT MICE; ELEVATED PLUS-MAZE; CHRONIC ANTIDEPRESSANT TREATMENT; ANXIETY-RELATED BEHAVIOR; ONE-TRIAL TEST; MUTANT MICE; SEROTONIN TRANSPORTER; FOOD-RESTRICTION AB The use of batteries of single-domain tests for neurophenotyping research is a common strategy to achieve higher data density and explore different behavioral domains. This approach, however, is accompanied by several methodological challenges, briefly discussed here. As an alternative, this paper advocates the wider use of extensive "hybrid" protocols that assess multiple domains in parallel, or logically/logistically combine experimental paradigms, in a way that disproportionately maximizes the number of tested phenotypes per experimental manipulation. Several examples of this approach are given in this paper, demonstrating the potential to reduce time, cost and subject requirements for the experiments. Offering behavioral analyses that are lacking in the standard single-domain tests, such "hybrid" models enable innovative modeling of neuropsychiatric disorders by more thorough and broader investigation of complex phenotypical characteristics. Published by Elsevier Inc. C1 [Kalueff, Allan V.; LaPorte, Justin L.; Murphy, Dennis L.] NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. [Sufka, Kenneth] Univ Mississippi, Dept Psychol, Oxford, MS USA. RP Kalueff, AV (reprint author), NIMH, Clin Sci Lab, NIH, Bldg 10,Room 3D41,10 Ctr Dr,MSC 1264, Bethesda, MD 20892 USA. EM kalueva@mail.nih.gov FU Intramural NIH HHS NR 94 TC 19 Z9 19 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-5846 EI 1878-4216 J9 PROG NEURO-PSYCHOPH JI Prog. Neuro-Psychopharmacol. Biol. Psychiatry PD JUL 1 PY 2008 VL 32 IS 5 BP 1172 EP 1178 DI 10.1016/j.pnpbp.2007.12.010 PG 7 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 334HP UT WOS:000258213200008 PM 18222590 ER PT J AU Pierce, BL Plymate, S Ostrander, EA Stanford, JL AF Pierce, Brandon L. Plymate, Stephen Ostrander, Elaine A. Stanford, Janet L. TI Diabetes mellitus and prostate cancer risk SO PROSTATE LA English DT Article DE diabetes; prostate cancer; odds ratio; aggressive prostate cancer ID UNITED-STATES; US MEN; HEALTH; METAANALYSIS; HISTORY AB BACKGROUND. Epidemiological evidence suggests that diabetes mellitus (DM) is associated with a decrease in risk for prostate cancer (PCa). The objective of this study was to examine the association between PCa risk and several characteristics of DM (duration, age at diagnosis, treatment) in data from two population-based, case-control studies of PCa. METHODS. PCa cases (n =1,752), and controls (n =1,644) were residents of King County, Washington identified using the Surveillance, Epidemiology, and End Results Seattle-Puget Sound cancer registry and random digit dialing, respectively. The majority of PCa patients had localized stage disease (78%). Using self-reported on DM, logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (95% CI) for associations between DM characteristics and PCa risk. RESULTS. After adjustment for confounding factors, DM status was not significantly associated with PCa risk (OR = 0.98; 95% CI = 0.76-1.27). However, early-onset DM (diagnosed before age 30) showed a significant inverse association with PCa risk (OR = 0.27; 95% CI = 0.07-0.97). Time since DM diagnosis (median = 6 years) and DM treatment types (i.e., diet changes, oral medications, and insulin) did :not show significant associations with PCa risk. CONCLUSIONS. These data suggest that DM is not associated with PCa risk; however, early-onset DM, possibly reflecting insulin dependent DM (type 1), may be an important component of the previously reported inverse association between DM on PCa risk, but these findings are based on a small number of observations and require further investigation. C1 [Pierce, Brandon L.; Stanford, Janet L.] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Pierce, Brandon L.] Univ Washington, Inst Publ Hlth Genet, Seattle, WA 98195 USA. [Plymate, Stephen] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. [Ostrander, Elaine A.] Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. [Ostrander, Elaine A.] GRECC VAPSHCS, Seattle, WA 98195 USA. [Stanford, Janet L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Stanford, JL (reprint author), Fred Hutchinson Canc Res Ctr, Program Epidemiol, Div Publ Hlth Sci, 1100 Fairview Ave N,M4-B874, Seattle, WA 98109 USA. EM jstanfor@fhcrc.org OI Pierce, Brandon/0000-0002-7829-952X; Ostrander, Elaine/0000-0001-6075-9738 FU Intramural NIH HHS; NCI NIH HHS [CA56678, CA92579, N01-PC35142, R01 CA056678, R01 CA092579, R25-CA94880] NR 21 TC 32 Z9 33 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-4137 J9 PROSTATE JI Prostate PD JUL 1 PY 2008 VL 68 IS 10 BP 1126 EP 1132 DI 10.1002/pros.20777 PG 7 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 319ID UT WOS:000257156400010 PM 18459104 ER PT J AU Miklossy, G Tozser, J Kadas, J Ishima, R Louis, JM Bagossi, P AF Miklossy, Gabriella Tozser, Jozsef Kadas, Janos Ishima, Rieko Louis, John M. Bagossi, Peter TI Novel macromolecular inhibitors of human immunodeficiency virus-1 protease SO PROTEIN ENGINEERING DESIGN & SELECTION LA English DT Article DE dimerization; human immunodeficiency virus-1 protease; macromolecular inhibitor; NMR; trans-dominant effect ID WILD-TYPE VIRUS; HIV-1 PROTEASE; DIMERIZATION INHIBITORS; TYPE-1 PROTEASE; GENE-EXPRESSION; GAG MUTANTS; TAT MUTANT; REPLICATION; RESISTANCE; PRECURSOR AB An intracellularly expressed defective human immunodeficiency virus type-1 (HIV-1) protease (PR) monomer could function as a dominant-negative inhibitor of the enzyme that requires dimerization for activity. Based on in silico studies, two mutant PRs harboring hydrophilic mutations, capable of forming favorable inter- and intra-subunit interactions, were selected: PRRE containing Asp25Arg and Gly49Glu mutations, and PRRER containing an additional Ile50Arg mutation. The mutants were expressed and tested by PR assays, nuclear magnetic resonance (NMR) and cell culture experiments. The mutant PRs showed dose-dependent inhibition of the wild-type PR in a fluorescent microtiter plate PR assay. Furthermore, both mutants were retained by hexahistidine-tagged wild-type HIV-1 PR immobilized on nickel-chelate affinity resin. For the first time, heterodimerization between wild-type and dominant-negative mutant PRs were also demonstrated by NMR spectroscopy. H-1-N-15 Heteronuclear Single Quantum Coherence NMR spectra showed that although PRRE has a high tendency to aggregate, PRRER exists mainly as a folded monomer at 25-35 mu M concentration, but in the presence of wild-type PR in a ratio of 1:1, heterodimerization occurs with both mutants. While the recombinant virus containing the PR(RE)sequence showed only very low level of expression, expression of the viral proteins of the virus with the PRRER sequence was comparable with that of the wild-type. In cell culture experiments, infectivity of viral particles containing PRRER protein was reduced by 82%, at mutant to wild-type infective DNA ratio of 2:1. C1 [Miklossy, Gabriella; Tozser, Jozsef; Kadas, Janos; Bagossi, Peter] Univ Debrecen, Dept Biochem & Mol Biol, Res Ctr Mol Med, Med & Hlth Sci Ctr, H-4012 Debrecen, Hungary. [Ishima, Rieko] Univ Pittsburgh, Dept Biol Struct, Sch Med, Pittsburgh, PA 15260 USA. [Louis, John M.] NIDDK, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Bagossi, P (reprint author), Univ Debrecen, Dept Biochem & Mol Biol, Res Ctr Mol Med, Med & Hlth Sci Ctr, POB 6, H-4012 Debrecen, Hungary. EM peter@indi.biochem.dote.hu RI Tozser, Jozsef/A-7840-2008; OI Tozser, Jozsef/0000-0003-0274-0056; Tozser, Jozsef/0000-0001-5076-8729 FU Intramural NIH HHS [Z99 DK999999] NR 50 TC 4 Z9 4 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1741-0126 EI 1741-0134 J9 PROTEIN ENG DES SEL JI Protein Eng. Des. Sel. PD JUL PY 2008 VL 21 IS 7 BP 453 EP 461 DI 10.1093/protein/gzn022 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 316WB UT WOS:000256979300005 PM 18480092 ER PT J AU Hortin, GL Sviridov, D AF Hortin, Glen L. Sviridov, Denis TI Analysis of molecular forms of albumin in urine SO PROTEOMICS CLINICAL APPLICATIONS LA English DT Review DE albuminuria; kidney disease; urinary albumin; urinary peptidomics; urinary proteomics ID CHROMATOGRAPHY-MASS-SPECTROMETRY; DEPENDENT DIABETES-MELLITUS; LIQUID-CHROMATOGRAPHY; 2-DIMENSIONAL ELECTROPHORESIS; GLOMERULAR-DISEASES; PROTEOME; PLASMA; NEPHROPATHY; PROTEINS; FRAGMENTS AB Albumin is not only one of the most abundant urinary protein components and one of the most widely used clinical markers for kidney disease, it also is a significant source of molecular complexity of the urinary proteome and peptidome. Urine contains multiple fragments and modified forms of albumin. Analysis of molecular forms of albumin in urine is of fundamental importance for understanding clinical assays for albumin quantification, specimen stability, and proteomic and peptidomic analysis of urine. C1 [Hortin, Glen L.; Sviridov, Denis] NIH, Dept Lab Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Hortin, GL (reprint author), NIH, Dept Lab Med, Warren G Magnuson Clin Ctr, Bldg 10,Room 2C-407, Bethesda, MD 20892 USA. EM ghortin@mail.cc.nih.gov NR 46 TC 9 Z9 11 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1862-8346 J9 PROTEOM CLIN APPL JI Proteom. Clin. Appl. PD JUL PY 2008 VL 2 IS 7-8 BP 950 EP 955 DI 10.1002/prca.200780145 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 332NB UT WOS:000258088600002 PM 21136896 ER PT J AU Qin, M Smith, CB AF Qin, Mei Smith, Carolyn Beebe TI Unaltered hormonal response to stress in a mouse model of fragile X syndrome SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE corticosterone; adrenocorticotrophic hormone; circadian rhythm; fragile X; restraint; elevated plus-maze ID FMR1 KNOCKOUT MOUSE; MENTAL-RETARDATION; MICE; PHENOTYPE; CORTISOL; ANXIETY AB Reports in the clinical literature and studies of fmr1 knockout mice have led to the hypothesis that, in addition to mental retardation, fragile X syndrome is characterized by a dysregulation of hypothalamic-pituitary-adrenal axis function. We have systematically examined this hypothesis by studying the effects of stress on adrenocorticotrophic hormone and corticosterone levels in adult, mate fmr1 knockout mice. Initially we determined the circadian rhythms of the plasma hormone levels in both wild-type and fmr1 knockout mice and established the optimal time to impose the stress. We found no genotypic differences in the circadian rhythms of either hormone. We studied two types of stressors, immobilization and spatial novelty; spatial novelty was 5 min in an elevated plus-maze. We varied the duration of immobilization and followed the time course of recovery of hormones to their pre-stress levels. Despite the lower anxiety exhibited by fmr1 knockout mice in the elevated plus-maze, hormonal responses to and recovery from this spatial novelty were similar in both genotypes. Further, we found no genotypic differences in hormonal responses to immobilization stress. The results of our study indicate that, in FVB/NJ mice, the hormonal response to and recovery from acute stress is unaltered by the lack of fragile X mental retardation protein. Published by Elsevier Ltd. C1 [Qin, Mei; Smith, Carolyn Beebe] NIMH, United States Publ Hlth, Dept Hlth & Human Serv, Sect Neuroadaptat & Prot Metab,NIH, Bethesda, MD 20892 USA. RP Smith, CB (reprint author), NIMH, United States Publ Hlth, Dept Hlth & Human Serv, Sect Neuroadaptat & Prot Metab,NIH, Bldg 10 2D54,10 Ctr Dr, Bethesda, MD 20892 USA. EM beebec@intra.nimh.nih.gov FU Intramural NIH HHS [Z01 MH000889-28] NR 22 TC 18 Z9 19 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD JUL PY 2008 VL 33 IS 6 BP 883 EP 889 DI 10.1016/j.psyneuen.2008.03.010 PG 7 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 336HZ UT WOS:000258356200018 PM 18479837 ER PT J AU Terracciano, A Lockenhoff, CE Zonderman, AB Ferrucci, L Costa, PT AF Terracciano, Antonio Lockenhoff, Coerinna E. Zonderman, Alan B. Ferrucci, Luigi Costa, Paul T., Jr. TI Personality predictors of longevity: Activity, emotional stability, and conscientiousness SO PSYCHOSOMATIC MEDICINE LA English DT Article DE neuroticism; health; mortality; longevity; smoking; obesity ID CORONARY-HEART-DISEASE; ALL-CAUSE MORTALITY; 5-FACTOR MODEL; PATIENT ADHERENCE; PHYSICAL-ACTIVITY; HEALTH BEHAVIORS; NEUROTICISM; TRAITS; DEPRESSION; LIFE AB To examine the association between personality traits and longevity. Methods: Using the Guilford-Zimmerman Temperament Survey, personality traits were assessed in 2359 participants (38% women; age = 17 to 98 years, mean = 50 years) from the Baltimore Longitudinal Study of Aging, starting in 1958. Over the duration of the study, 943 (40%) participants died, on average 18 years after their personality assessment. The association of each trait with longevity was examined by Cox regression controlling for demographic variables. Results: In preliminary analyses among the deceased, those who scored I standard deviation (SD) above the mean on General Activity (a facet of Extraversion), Emotional Stability (low Neuroticism), or Conscientiousness lived on average 2 to 3 years longer than those scoring 1 SD below the mean. Survival analyses on the full sample confirmed the association of General Activity, Emotional Stability, and Conscientiousness with lower risk of death, such that every 1-SD increase was related to about 13%, 15%, and 27% risk reduction, respectively. The association of personality traits with longevity was largely independent from the influence of smoking and obesity. Personality predictors of longevity did not differ by sex, except for Ascendance (a facet of Extraversion). Emotional Stability was a significant predictor when the analyses were limited to deaths due to cardiovascular disease, with comparable effect sizes for General Activity and Conscientiousness. Conclusions: In a large sample of generally healthy individuals followed for almost five decades, longevity was associated with being conscientious, emotionally stable, and active. C1 [Terracciano, Antonio] NIA, Lab Personal & Cognit, NIH, DHHS, Baltimore, MD 21224 USA. RP Terracciano, A (reprint author), NIA, Lab Personal & Cognit, NIH, DHHS, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM TerraccianoA@mail.nih.gov RI terracciano, antonio/B-1884-2008; Vollrath, Margarete/G-1297-2011; OI Loeckenhoff, Corinna/0000-0003-1605-1323; Costa, Paul/0000-0003-4375-1712; Zonderman, Alan B/0000-0002-6523-4778 FU Intramural NIH HHS [Z01 AG000184-19, Z99 AG999999, ZIA AG000183-22, ZIA AG000183-23, ZIA AG000197-03, ZIA AG000197-04] NR 69 TC 104 Z9 107 U1 3 U2 30 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD JUL-AUG PY 2008 VL 70 IS 6 BP 621 EP 627 DI 10.1097/PSY.0b013e31817b9371 PG 7 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 328VU UT WOS:000257827100001 PM 18596250 ER PT J AU Tyburski, JB Patterson, AD Krausz, KW Slavik, J Fornace, AJ Gonzalez, FJ Idle, JR AF Tyburski, John B. Patterson, Andrew D. Krausz, Kristopher W. Slavik, Josef Fornace, Albert J., Jr. Gonzalez, Frank J. Idle, Jeffrey R. TI Radiation metabolomics. 1. Identification of minimally invasive urine biomarkers for gamma-radiation exposure in mice SO RADIATION RESEARCH LA English DT Article ID IONIZING-RADIATION; EXPRESSION PROFILES; DIURNAL-VARIATION; SYSTEMS BIOLOGY; THYMINE GLYCOL; DNA-DAMAGE; RAT URINE; EXCRETION; METABOLISM; INJURY AB Gamma-radiation exposure has both short- and long-term adverse health effects. The threat of modern terrorism places human populations at risk for radiological exposures, yet current medical countermeasures to radiation exposure are limited. Here we describe metabolomics for gamma-radiation biodosimetry in a mouse model. Mice were gamma-irradiated at doses of 0, 3 and 8 Gy (2.57 Gy/min), and urine samples collected over the first 24 h after exposure were analyzed by ultra-performance liquid chromatography-time-of-flight mass spectrometry (UPLC-TOFMS). Multivariate data were analyzed by orthogonal partial least squares (OPLS). Both 3- and 8-Gy exposures yielded distinct urine metabolomic phenotypes. The top 22 ions for 3 and 8 Gy were analyzed further, including tandem mass spectrometric comparison with authentic standards, revealing that N-hexanoylglycine and beta-thymidine are urinary biomarkers of exposure to 3 and 8 Gy, 3-hydroxy-2-methylbenzoic acid 3-O-sulfate is elevated in urine of mice exposed to 3 but not 8 Gy, and taurine is elevated after 8 but not 3 Gy. Gene Expression Dynamics Inspector (GEDI) self-organizing maps showed clear dose-response relationships for subsets of the urine metabolome. This approach is useful for identifying mice exposed to gamma radiation and for developing metabolomic strategies for noninvasive radiation biodosimetry in humans. (C) 2008 by Radiation Research Society. C1 [Slavik, Josef; Idle, Jeffrey R.] Univ Bern, Inst Clin Pharmacol, CH-3010 Bern, Switzerland. [Tyburski, John B.; Patterson, Andrew D.; Krausz, Kristopher W.; Slavik, Josef; Gonzalez, Frank J.] Natl Canc Inst, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA. [Tyburski, John B.] Natl Canc Inst, Canc Prevent Fellowship Program, Off Prevent Oncol, Bethesda, MD 20892 USA. [Fornace, Albert J., Jr.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. RP Idle, JR (reprint author), Univ Bern, Inst Clin Pharmacol, Murtenstr 35, CH-3010 Bern, Switzerland. EM jidle@ikp.unibe.ch RI Fornace, Albert/A-7407-2008; Patterson, Andrew/G-3852-2012; OI Fornace, Albert/0000-0001-9695-085X; Patterson, Andrew/0000-0003-2073-0070; Idle, Jeff/0000-0002-6143-1520 FU Intramural NIH HHS [Z99 CA999999]; NIAID NIH HHS [U19 AI067773, U19 AI067773-02] NR 49 TC 89 Z9 96 U1 1 U2 13 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD JUL PY 2008 VL 170 IS 1 BP 1 EP 14 DI 10.1667/RR1265.1 PG 14 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 321IN UT WOS:000257298100001 PM 18582157 ER PT J AU Ferrucci, L Giallauria, F Guralnik, JM AF Ferrucci, Luigi Giallauria, Francesco Guralnik, Jack M. TI Epidemiology of Aging SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article DE Aging; Epidemiology; Demographics; Mortality; Disability; Risk factors ID SEVERE WALKING DISABILITY; SKELETAL-MUSCLE STRENGTH; ALL-CAUSE MORTALITY; ALZHEIMERS-DISEASE; PHYSICAL PERFORMANCE; WOMENS HEALTH; RISK-FACTORS; OLDER WOMEN; EXTREME LONGEVITY; LIFE-SPAN AB Over the past century, truly remarkable changes have been observed in the health of older persons throughout the world, and these changes have strongly impacted society. The growth of the older population has resulted mostly from a general increase in the overall population size but is also strongly influenced by major declines in leading causes of mortality. These demographic transformations reverberate in society, increasing medical care and social needs, which are expected to increase steeply in the years to come. Based on demographic and epidemiologic perspectives, these changes were already detectable decades before and should have prompted radical changes in the structure and function of our system of health and social protection at that time. We come to this enormous challenge unprepared. C1 [Ferrucci, Luigi; Giallauria, Francesco] Harbor Hosp, NIA, NIH, Clin Res Branch,Longitudinal Studies Sect, Baltimore, MD 21225 USA. [Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. RP Ferrucci, L (reprint author), Harbor Hosp, NIA, NIH, Clin Res Branch,Longitudinal Studies Sect, 3001 S Hanover St, Baltimore, MD 21225 USA. EM ferruccilu@grc.nia.nih.gov RI Giallauria, Francesco/B-5681-2013 OI Giallauria, Francesco/0000-0003-4119-9397 FU NIA NIH HHS [Z01 AG000015-50] NR 65 TC 33 Z9 36 U1 1 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD JUL PY 2008 VL 46 IS 4 BP 643 EP + DI 10.1016/j.rcl.2008.07.005 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 366BU UT WOS:000260455900002 PM 18922285 ER PT J AU Griego, FY Bogen, KT Price, PS Weed, DL AF Griego, Furnie Y. Bogen, Kenneth T. Price, Paul S. Weed, Douglas L. TI Exposure, epidemiology and human cancer incidence of naphthalene SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE naphthalene; exposure; epidemiology; cancer incidence; exposure sources; consumer products; industrial products; pesticidal products; cigarettes; long-term average exposure concentrations AB This report provides a summary of deliberations conducted under the charge for members of Module B participating in the Naphthalene State-of-the-Science Symposium (NS3), Monterey, CA, October 9-12, 2006. The panel's charge was to derive consensus estimates of human exposure to naphthalene under various conditions, cancer incidence plausibly associated with these exposures, and identify quintessential research that could significantly reduce or eliminate material uncertainties to inform human cancer risk assessment. Relying in large part on a commissioned paper [Price, P.S., Jayjock, M.A., 2008. Available data on naphthalene exposures: strengths and limitations, in this issue], exposure levels were estimated for background (0.0001-0.003 mu g/m(3)), ambient air (0.001-1.0 mu g/m(3)), vehicles (0.003-3.0 mu g/m(3)), residences (0.1-10 mu g/m(3)), mothball use (on-label: 1-100 mu g/m(3); off label: 10-100 mu g/m(3)), and occupational (low: 3-100 mu g/m(3); high: 30-1,000 mu g/m(3)). There have been few published reports of human cancer associated with naphthalene exposure. Several research projects are suggested that could reduce uncertainty in our understanding of human exposure. Using best scientific judgment, it is reasonably certain that the largest non-occupational exposures to naphthalene are indoor/residential exposures, particularly in households that use naphthalene-based products such as mothballs. However, even the highest of these exposures is likely to fall one or more orders of magnitude below moderate or high-level occupational exposure levels experienced by the few known cohorts exposed occupationally to naphthalene alone or as part of chemical mixtures such as jet fuel. (C) 2008 Elsevier Inc. All rights reserved. C1 [Griego, Furnie Y.; Price, Paul S.] Independent Consultant, Windermere, FL USA. [Weed, Douglas L.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. RP Griego, FY (reprint author), Independent Consultant, Windermere, FL USA. EM fumie@stanfordalumni.org NR 10 TC 19 Z9 19 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD JUL PY 2008 VL 51 IS 2 SU 1 BP S22 EP S26 DI 10.1016/j.yrtph.2008.02.003 PG 5 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 320RW UT WOS:000257253700004 PM 18423820 ER PT J AU North, DW Abdo, KM Benson, JM Dahl, AR Morris, JB Renne, R Witschi, H AF North, D. Warner Abdo, Kamal M. Benson, Janet M. Dahl, Alan R. Morris, John B. Renne, Roger Witschi, Hanspeter TI A review of whole animal bioassays of the carcinogenic potential of naphthalene SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Review DE naphthalene; animal bioassay; National Toxicology Program (NTP); cancer; carcinogenesis; tumorigenesis; cytotoxicity; maximum tolerated dose (MTD); inhalation studies ID SPRAGUE-DAWLEY RATS; INHALATION EXPOSURE; BUTADIENE DIEPOXIDE; SPECIES-DIFFERENCES; F344 RATS; MICE; 1,3-BUTADIENE; METABOLISM; DISPOSITION; MONOEPOXIDE AB This report provides a summary of deliberations conducted under the charge for members of Module A participating in the Naphthalene State-of-the-Science Symposium (NS3), Monterey, CA, October 9-12, 2006. Whole animal bioassays have been performed by the National Toxicology Program in mice and rats to ascertain the carcinogenic potential of naphthalene by inhalation exposure. A statistically significant increased incidence of pulmonary alveolar/bronchiolar adenoma (a benign lesion), was observed among female mice; an observed increase among the males did not reach statistical significance. No nasal tumors were observed in either sex. A tumorigenic response was observed in both sexes of rats, in males an increased incidence of nasal respiratory epithelium adenoma (a benign rather than malignant lesion) and in females, olfactory epithelial neuroblastoma. Interpretations of these studies vary. On the one hand, evidence of extensive non-neoplastic response in both sexes of both species indicates cytotoxicity occurred at all doses, and strongly suggests that cytotoxicity played a significant role in the tumor responses observed in the target tissues. On the other hand, olfactory epithelial neuroblastoma has rarely been observed in NTP bioassays. This review seeks to develop a consensus understanding of the scientific evidence provided by these studies, taking into account that they have been used as the basis for quantitative human cancer risk assessment, and suggests scientific studies that, if performed, could resolve scientific uncertainties. (C) 2007 Elsevier Inc. All rights reserved. C1 [North, D. Warner] N Works Inc, Belmont, MA USA. [North, D. Warner] Stanford Univ, Dept Management Sci & Engn, Terman Engn Ctr, Stanford, CA 94305 USA. [Abdo, Kamal M.] NIEHS, Natl Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA. [Benson, Janet M.] Lovelace Resp Res Inst, Albuquerque, NM 87108 USA. [Dahl, Alan R.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Morris, John B.] Univ Connecticut, Coll Pharm, Dept Pharmaceut Sci, Storrs, CT 06269 USA. [Renne, Roger] Battelle Pacific NW Labs, Richland, WA 99352 USA. [Witschi, Hanspeter] Univ Calif Davis, Sch Vet Med, Dept Pharmacol & Toxicol, Davis, CA 95616 USA. RP North, DW (reprint author), N Works Inc, 1002 Misty Lane, Belmont, MA USA. EM northworks@mindspring.com NR 33 TC 13 Z9 14 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD JUL PY 2008 VL 51 IS 2 SU 1 BP S6 EP S14 DI 10.1016/j.yrtph.2007.09.022 PG 9 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 320RW UT WOS:000257253700002 PM 18364246 ER PT J AU Wallace, GL Happe, F AF Wallace, Gregory L. Happe, Francesca TI Time perception in autism spectrum disorders SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism; Asperger disorder; Temporal cognition; Duration judgment; Perception; Time perception ID ATTENTION-DEFICIT/HYPERACTIVITY-DISORDER; DEFICIT HYPERACTIVITY DISORDER; ENHANCED DISCRIMINATION; BEHAVIORAL-INHIBITION; CHILDREN; ADHD; MEMORY; SAVANT; ADULTS; REPRODUCTION AB Duration judgment has not been comprehensively examined in autism spectrum disorders (ASD), despite reports of perceptual idiosyncrasies in these individuals. Time estimation, production, and reproduction were tested in 25 individuals with ASD and 25 controls matched group-wise on age and IQ. Individuals with ASD performed comparably to matched controls in time estimation and production, but showed a tendency to outperform controls oil a task of time reproduction, Time perception of large units is intact for children and adolescents with ASD. Time reproduction may represent a cognitive asset in ASD, likely reflecting strengths in eidetic-type imagery in which a pure recording of a stimulus is less affected by top-down modulation. published by Elsevier Ltd. C1 [Wallace, Gregory L.; Happe, Francesca] Kings Coll London, Inst Psychiat, Social Genet & Dev Psychiat Ctr, London WC2R 2LS, England. RP Wallace, GL (reprint author), NIMH, Lab Brain & Cognit, 10 Ctr Dr,Room 4C104,MSC 1366, Bethesda, MD 20892 USA. EM gregwallace@mail.nih.gov RI Happe, Francesca/D-5544-2012; OI Wallace, Gregory/0000-0003-0329-5054 NR 34 TC 24 Z9 24 U1 2 U2 23 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1750-9467 J9 RES AUTISM SPECT DIS JI Res. Autism Spectr. Disord. PD JUL-SEP PY 2008 VL 2 IS 3 BP 447 EP 455 DI 10.1016/j.rasd.2007.09.005 PG 9 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA 408DK UT WOS:000263413900005 ER PT J AU Perez-Escamilla, R Segall-Correa, AM AF Perez-Escamilla, Rafael Segall-Correa, Ana Maria TI Food insecurity measurement and indicators SO REVISTA DE NUTRICAO-BRAZILIAN JOURNAL OF NUTRITION LA English DT Article DE Bias (Epidemiology); Caribbean region; Food insecurity; Latin America ID SECURITY SCALE; VALIDATION; CAMPINAS; BRAZIL; MODULE; TOOL AB The United Nations define food security as "People having at all times, physical, social and economic access to sufficient, safe and nutritious food which meets their dietary needs and food preferences for an active and healthy life." There are five methods that are commonly applied in national surveys that can be used to assess food insecurity. Of these, four are indirect or derivative measures of food insecurity ( United Nations Food and Agriculture Organization method, household expenditure surveys, dietary intake assessment and anthropometry). The only method that represents a fundamental or direct measure of food insecurity is the one based on experience-based food insecurity scales. All the methods complement each other and the method of choice depends on the question being answered and the economic and logistical resources available to collect valid data. All the methods have serious measurement error issues that can be reduced by fully understanding the principles underlying them and the use of highly trained and standardized research field workers. As shown in Brazil, the use of experience-based food insecurity measurement scales for mapping, targeting, and understanding the determinants and consequences of food insecurity is very promising. Thus, we recommend the Latin American and Caribbean Region to work towards the adoption of a single regional module that can be adapted to the local contexts based on qualitative cognitive research followed by quantitative confirmation of the scale's psychometric properties. The Brazilian experience-based food insecurity measurement project is likely to provide useful insights to other countries in the region. C1 [Perez-Escamilla, Rafael] Univ Connecticut, Connecticut NIH EXPORT Ctr Excellence Eliminating, Storrs, CT 06269 USA. [Segall-Correa, Ana Maria] Univ Estadual Campinas, Fac Ciencias Med, Dept Prevent & Social Med, Campinas, SP, Brazil. RP Perez-Escamilla, R (reprint author), Univ Connecticut, Connecticut NIH EXPORT Ctr Excellence Eliminating, Storrs, CT 06269 USA. EM rafael.perez-escamilla@uconn.edu RI Segall-Correa, Ana Maria/K-6689-2012 OI Segall-Correa, Ana Maria/0000-0003-0140-064X NR 21 TC 5 Z9 10 U1 0 U2 5 PU PONTIFICIA UNIVERSIDADE CATOLICA CAMPINAS PI CAMPINAS PA NUCLEO EDITORACAO SBI-CCV, CAMPUS II AV JOHN BOYD DUNLOP S-N PREDIO ONTOLOGIA JD IPAUSSURAMA, CAMPINAS, SP 13060-904, BRAZIL SN 1415-5273 J9 REV NUTR JI Rev. Nutr. PD JUL-AUG PY 2008 VL 21 BP 15 EP 26 PG 12 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 457EW UT WOS:000266912300003 ER PT J AU Segall-Correa, AM Marin-Leon, L Helito, H Perez-Escamilla, R Santos, LMP Paes-Sousa, R AF Segall-Correa, Ana Maria Marin-Leon, Leticia Helito, Hugo Perez-Escamilla, Rafael Pacheco Santos, Leonor Maria Paes-Sousa, Romulo TI Cash transference and food insecurity in Brazil: analysis of national data SO REVISTA DE NUTRICAO-BRAZILIAN JOURNAL OF NUTRITION LA Portuguese DT Article DE Household survey; Proverty; Public policy; Food security AB Objective The 2004 National Household Survey Data was analyzed to test the hypothesis that cash transference from government social programs is associated with household food security. Methods Secondary data were used from the National Household Sample Survey which interviewed residents of 112,716 households. The present analysis included permanent and temporary private households, where food security items were informed by a resident of the household, restricting the collection of data to households with per capita monthly income of up to 1 minimum wage, representing 51.2% of the sample. Three models for estimating the amount of cash transference were developed; model 3 was chosen because it was less likely to overestimate effects. To analyze how cash transference affected the prevalence of food security, only households that received cash transference were included in the analysis, representing 14.2% of the interviewed households. The association between food security and cash transference, controlled for other independent variables, was estimated using a logistic regression model with stepwise method for each of the three income strata. Results The mean per capita cash transference was of R$81.68 per family. Multiple logistic regression showed an increased chance of food security of 8% per each R$10.00 contributed by social programs. Rural residence, male head of household, and Caucasian head of household were factors that also presented a higher chance of food security. Conclusion The hypothesis was confirmed, showing a positive association between cash transfer and household food security, regardless of the effects of other explanatory factors. C1 [Segall-Correa, Ana Maria; Helito, Hugo] Univ Estadual Campinas, Fac Ciencias Med, Dept Prevent & Social Med, Grp Pesquisa Seguranca Alimentar, BR-13084970 Campinas, SP, Brazil. [Perez-Escamilla, Rafael] Univ Connecticut, NIH EXPORT Ctr Excellence Eliminating Hlth Dispar, Storrs, CT USA. [Pacheco Santos, Leonor Maria] Minist Desenvolvimento Social & Combate Fome, Secretaria Avaliacao & Gestao Informacao, Brasilia, DF, Brazil. [Paes-Sousa, Romulo] Pontificia Univ Catolica Minas Gerais, Programa Posgrad Ciencias Sociais, Belo Horizonte, MG, Brazil. RP Segall-Correa, AM (reprint author), Univ Estadual Campinas, Fac Ciencias Med, Dept Prevent & Social Med, Grp Pesquisa Seguranca Alimentar, Caixa Postal 6111,Cidade Univ, BR-13084970 Campinas, SP, Brazil. EM segall@fcm.unicamp.br NR 16 TC 10 Z9 10 U1 0 U2 1 PU PONTIFICIA UNIVERSIDADE CATOLICA CAMPINAS PI CAMPINAS PA NUCLEO EDITORACAO SBI-CCV, CAMPUS II AV JOHN BOYD DUNLOP S-N PREDIO ONTOLOGIA JD IPAUSSURAMA, CAMPINAS, SP 13060-904, BRAZIL SN 1415-5273 J9 REV NUTR JI Rev. Nutr. PD JUL-AUG PY 2008 VL 21 BP 39 EP 51 PG 13 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 457EW UT WOS:000266912300005 ER PT J AU Ricci, EP Herbreteau, CH Decimo, D Schaupp, A Datta, SAK Rein, A Darlix, JL Ohlmann, T AF Ricci, Emiliano P. Herbreteau, Cecile H. Decimo, Didier Schaupp, Andreas Datta, Siddhartha A. K. Rein, Alan Darlix, Jean-Luc Ohlmann, Theophile TI In vitro expression of the HIV-2 genomic RNA is controlled by three distinct internal ribosome entry segments that are regulated by the HIV protease and the Gag polyprotein SO RNA-A PUBLICATION OF THE RNA SOCIETY LA English DT Article DE HIV; translation initiation; Gag; IRES; HIV protease ID IMMUNODEFICIENCY-VIRUS TYPE-1; MESSENGER-RNA; TRANSLATIONAL CONTROL; PROMOTES TRANSLATION; RETICULOCYTE LYSATE; INITIATION-FACTORS; GENE-EXPRESSION; BINDING-PROTEIN; SITE; ENCAPSIDATION AB The HIV-2 genomic RNA serves both as a messenger for protein synthesis and as a genome for viral assembly and particle production. Our previous work has shown that the HIV-2 genomic RNA encodes two additional Gag proteins that are N-terminal truncated isoforms of the p57 Gag polyprotein. In this study, by the use of mono- and bicistronic RNAs we show that translation at the three AUGs is driven by three distinct and independent internal ribosome entry segments both in vitro and ex vivo. Furthermore we used the recombinant Gag and HIV-2 protease to show that, in vitro, translation is tightly regulated by these two viral proteins. This regulation is exerted both at the level of protein production and also on the selection of the AUG initiation site which changes the ratio at which the three different Gag isoforms are produced. C1 [Ricci, Emiliano P.; Herbreteau, Cecile H.; Decimo, Didier; Schaupp, Andreas; Darlix, Jean-Luc; Ohlmann, Theophile] Ecole Normale Super Lyon, Unite Virol Humaine, IFR 128, F-69364 Lyon, France. [Ricci, Emiliano P.; Herbreteau, Cecile H.; Decimo, Didier; Schaupp, Andreas; Darlix, Jean-Luc; Ohlmann, Theophile] INSERM, U758, F-69364 Lyon, France. [Datta, Siddhartha A. K.; Rein, Alan] NCI, HIV Drug Resistant Program, Frederick, MD 21702 USA. RP Ohlmann, T (reprint author), Ecole Normale Super Lyon, Unite Virol Humaine, IFR 128, F-69364 Lyon, France. EM tohlmann@ens-lyon.fr RI ohlmann, Theophile/M-4463-2014; Ohlmann, Theophile/H-6522-2016; Ricci, Emiliano/G-7619-2012; OI Ricci, Emiliano/0000-0002-9789-5837; Herbreteau, Cecile/0000-0002-1085-5753; Datta, Siddhartha/0000-0002-4098-7490 FU Intramural NIH HHS NR 38 TC 17 Z9 17 U1 1 U2 1 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1355-8382 J9 RNA JI RNA-Publ. RNA Soc. PD JUL PY 2008 VL 14 IS 7 BP 1443 EP 1455 DI 10.1261/rna.813608 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 315KV UT WOS:000256879800019 PM 18495939 ER PT J AU Shaikh, SR Mitchell, D Carroll, E Li, M Schneck, J Edidin, M AF Shaikh, S. R. Mitchell, D. Carroll, E. Li, M. Schneck, J. Edidin, M. TI Differential effects of a saturated and a monounsaturated fatty acid on MHC class I antigen presentation SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY LA English DT Article ID DIETARY-FAT; TRIGLYCERIDE ACCUMULATION; IMMUNOLOGICAL SYNAPSE; ACTIN CYTOSKELETON; IMMUNE-RESPONSE; DENDRITIC CELLS; HUMAN MONOCYTES; OBESE MICE; B-CELLS; OIL AB Lipid overload, associated with metabolic disorders, occurs when fatty acids accumulate in non-adipose tissues. Cells of these tissues use major histocompatibility complex (MHC) class I molecules to present antigen to T cells in order to eliminate pathogens. As obesity is associated with impaired immune responses, we tested the hypothesis that the early stages of lipid overload with saturated fatty acids (SFA) alters MHC class I antigen presentation. Antigen presenting cells (APC) were treated with either the saturated palmitic acid (PA), abundant in the high fat Western diet, or the monounsaturated oleic acid (OA), a component of the Mediterranean diet. PA-treatment lowered APC lysis by activated cytotoxic T lymphocytes and inhibited APC ability to stimulate naive T cells. Inhibition of immune responses with PA was due to a significant reduction in MHC class I surface expression, inhibition in the rate of APC-T-cell conjugation, and lowering of plasma membrane F-actin levels. OA-treatment had no effect on antigen presentation and upon exposure with PA, prevented the phenotypic effects of PA. OA-treatment conferred protection against changes in antigen presentation by accumulating fatty acids into triglyceride-rich lipid droplets of APC. Our findings establish for the first time a link between the early stages of lipid overload and antigen presentation and suggest that dietary SFA could impair immunity by affecting MHC I-mediated antigen presentation; this could be prevented, paradoxically, by accumulation of triglycerides rich in monounsaturated fatty acids. C1 [Shaikh, S. R.; Carroll, E.; Edidin, M.] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. [Mitchell, D.] NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD USA. [Li, M.; Schneck, J.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21218 USA. RP Shaikh, SR (reprint author), Johns Hopkins Univ, Dept Biol, 3400 N Charles St,Mudd Hall Room 45, Baltimore, MD 21218 USA. EM saameshaikh@gmail.com FU NIAID NIH HHS [R01 AI014584, AI14584, R01 AI014584-41, AI24129, R01 AI029575, AI29575] NR 47 TC 12 Z9 14 U1 0 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0300-9475 J9 SCAND J IMMUNOL JI Scand. J. Immunol. PD JUL PY 2008 VL 68 IS 1 BP 30 EP 42 DI 10.1111/j.1365-3083.2008.02113.x PG 13 WC Immunology SC Immunology GA 309FY UT WOS:000256447300004 PM 18533931 ER PT J AU Silva, AC Bock, NA AF Silva, Afonso C. Bock, Nicholas A. TI Manganese-enhanced MRI: An exceptional tool in translational neuroimaging SO SCHIZOPHRENIA BULLETIN LA English DT Review DE manganese; magnetic resonance imaging; animal models; brain; contrast agents; brain function; neuronal tracts; brain disease ID RESONANCE-IMAGING MEMRI; SPINAL-CORD-INJURY; BRAIN IN-VIVO; MAGNETIC-RESONANCE; RAT-BRAIN; MOUSE-BRAIN; 3D MRI; SUPEROXIDE-DISMUTASE; NEURONAL ACTIVATION; ALZHEIMERS-DISEASE AB The metal manganese is a potent magnetic resonance imaging (MRI) contrast agent that is essential in cell biology. Manganese-enhanced magnetic resonance imaging (MEMRI) is providing unique information in an ever-growing number of applications aimed at understanding the anatomy, the integration, and the function of neural circuits both in normal brain physiology as well as in translational models of brain disease. A major drawback to the use of manganese as a contrast agent, however, is its cellular toxicity. Therefore, paramount to the successful application of MEMRI is the ability to deliver Mn2+ to the site of interest using as low a dose as possible while preserving detectability by MRI. In the present work, the different approaches to MEMRI in translational neuroimaging are reviewed and challenges for future identified from a practical standpoint. C1 [Silva, Afonso C.; Bock, Nicholas A.] Natl Inst Neurol Disorders & Stroke, Cerebral Microcirculat Unit, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. RP Silva, AC (reprint author), Natl Inst Neurol Disorders & Stroke, Cerebral Microcirculat Unit, Lab Funct & Mol Imaging, NIH, 10 Ctr Dr MSC1065,Bldg 10,Room B1D106, Bethesda, MD 20892 USA. EM silvaa@ninds.nih.gov RI Silva, Afonso/A-7129-2009 FU Intramural NIH HHS NR 111 TC 98 Z9 100 U1 2 U2 15 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD JUL PY 2008 VL 34 IS 4 BP 595 EP 604 DI 10.1093/schbul/sbn056 PG 10 WC Psychiatry SC Psychiatry GA 323AV UT WOS:000257417300003 PM 18550591 ER PT J AU Simon, R AF Simon, Richard TI Interpretation of genomic data: Questions and answers SO SEMINARS IN HEMATOLOGY LA English DT Article ID GENE-EXPRESSION DATA; DNA MICROARRAY DATA; BREAST-CANCER; PROGNOSTIC CLASSIFICATION; ERROR ESTIMATION; CLASSIFIERS; PREDICTION; SELECTION; PROFILES; DESIGN AB Using a question and answer format we describe important aspects of using genomic technologies in cancer research. The main challenges are not managing the mass of data, but rather the design, analysis, and accurate reporting of studies that result in increased biological knowledge and medical utility. Many analysis issues address the use of expression microarrays but are also applicable to other whole genome assays. Microarray-based clinical investigations have generated both unrealistic hype and excessive skepticism. Genomic technologies are tremendously powerful and will play instrumental roles in elucidating the mechanisms of oncogenesis and in bringing on an era of predictive medicine in which treatments are tailored to individual tumors. Achieving these goals involves challenges in rethinking many paradigms for the conduct of basic and clinical cancer research and for the organization of interdisciplinary collaboration. C1 NCI, Biometr Res Branch, Bethesda, MD 20892 USA. RP Simon, R (reprint author), NCI, Biometr Res Branch, 9000 Rockville Pike,MSC 7434, Bethesda, MD 20892 USA. EM rsimon@nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 53 TC 10 Z9 10 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD JUL PY 2008 VL 45 IS 3 BP 196 EP 204 DI 10.1053/j.seminhematol.2008.04.008 PG 9 WC Hematology SC Hematology GA 324EX UT WOS:000257501600010 PM 18582627 ER PT J AU Rada, B Hably, C Meczner, A Timar, C Lakatos, G Enyedi, P Ligeti, E AF Rada, Balazs Hably, Csilla Meczner, Andras Timar, Csaba Lakatos, Gergely Enyedi, Peter Ligeti, Erzsebet TI Role of Nox2 in elimination of microorganisms SO SEMINARS IN IMMUNOPATHOLOGY LA English DT Review DE phagocytes; neutrophilic granulocytes; killing; NADPH oxidase; reactive oxygen species; ion movements ID CHRONIC GRANULOMATOUS-DISEASE; NEUTROPHIL EXTRACELLULAR TRAPS; PHAGOCYTIC NADPH OXIDASE; HUMAN POLYMORPHONUCLEAR LEUKOCYTES; BIOLOGICAL DEFENSE-MECHANISMS; POTASSIUM CHANNEL ACTIVITY; REACTIVE OXYGEN; RESPIRATORY BURST; HYDROGEN-PEROXIDE; PLASMA-MEMBRANE AB NADPH oxidase of the phagocytic cells (Nox2) transfers electrons from cytosolic NADPH to molecular oxygen in the extracellular or intraphagosomal space. The produced superoxide anion (O-2(center dot-)) provides the source for formation of all toxic oxygen derivatives, but continuous O-2(center dot-) generation depends on adequate charge compensation. The vital role of Nox2 in efficient elimination of microorganisms is clearly indicated by human pathology as insufficient activity of the enzyme results in severe, recurrent bacterial infections, the typical symptoms of chronic granulomatous disease. The goals of this contribution are to provide critical review of the Nox2-dependent cellular processes that potentially contribute to bacterial killing and degradation and to indicate possible targets of pharmacological interventions. C1 [Hably, Csilla; Meczner, Andras; Timar, Csaba; Lakatos, Gergely; Enyedi, Peter; Ligeti, Erzsebet] Semmelweis Univ, Dept Physiol, H-1088 Budapest, Hungary. [Rada, Balazs] NIAID, Natl Inst Hlth, Mol Def Sect, Host Def Lab, Rockville, MD USA. RP Ligeti, E (reprint author), Semmelweis Univ, Dept Physiol, Puskin U 9, H-1088 Budapest, Hungary. EM Ligeti@puskin.sote.hu NR 138 TC 38 Z9 41 U1 0 U2 4 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1863-2297 J9 SEMIN IMMUNOPATHOL JI Semin. Immunopathol. PD JUL PY 2008 VL 30 IS 3 BP 237 EP 253 DI 10.1007/s00281-008-0126-3 PG 17 WC Immunology; Pathology SC Immunology; Pathology GA 324BO UT WOS:000257492900004 PM 18574584 ER PT J AU Blake, DR Maldeis, N Barnes, MR Hardick, A Quinn, TC Gaydos, CA AF Blake, Diane R. Maldeis, Nancy Barnes, Mathilda R. Hardick, Andrew Quinn, Thomas C. Gaydos, Charlotte A. TI Cost-effectiveness of screening strategies for Chlamydia trachomatis using cervical swabs, urine, and self-obtained vaginal swabs in a sexually transmitted disease clinic setting SO SEXUALLY TRANSMITTED DISEASES LA English DT Article; Proceedings Paper CT 16th Biennial Meeting of the International-Society-for-Sexually-Transmitted-Diseases-Research CY JUL 10-13, 2005 CL Amsterdam, NETHERLANDS SP Int Soc Sexually Transmitted Dis Res ID PELVIC-INFLAMMATORY-DISEASE; FEMALE-ARMY-RECRUITS; ACID AMPLIFICATION TESTS; NEISSERIA-GONORRHOEAE; ENDOCERVICAL SPECIMENS; UNITED-STATES; COMBO-2 ASSAY; HEALTH PEACH; PACE 2; WOMEN AB Background: We evaluated the cost-effectiveness of Chlamydia screening strategies that use different methods of specimen collection: cervical swabs, urines, and self-obtained vaginal swabs. Methods: A decision analysis was modeled for a hypothetical cohort of 10,000 per year of women attending sexually transmitted disease (STD) clinics. Incremental cost-effectiveness of 4 screening strategies were compared: 1) Endocervical DNA probe test (PACE2, Gen-Probe), 2) Endocervical AC2 (Aptima Combo 2, Gen-Probe), 3) Self-Obtained Vaginal AC2, and 4) Urine AC2. Sensitivities of the vaginal, urine, and cervical AC2 tests were derived from 324 women attending STD clinics. The primary outcome was cases of pelvic inflammatory disease prevented. The model incorporated programmatic screening and treatment costs and medical cost savings from sequelae prevented. Results: Chlamydia prevalence in the sampled population was 11.1%. Sensitivities of vaginal, urine, and cervical AC2 were 97.2%, 91.7%, and 91.7%, respectively. The sensitivity of the DNA probe was derived from the literature and estimated at 68.8%. The self-obtained vaginal AC2 strategy was the least expensive and the most cost-effective, preventing 17 more cases of pelvic inflammatory disease than the next least expensive strategy. Conclusions: Use of a vaginal swab to detect Chlamydia in this STD clinic population was cost-saving and cost-effective. C1 [Blake, Diane R.] Univ Massachusetts, Sch Med, Dept Pediat, Div Adolescent Med, Worcester, MA 01655 USA. [Maldeis, Nancy; Barnes, Mathilda R.; Hardick, Andrew; Quinn, Thomas C.; Gaydos, Charlotte A.] Johns Hopkins Univ, Sch Med, Div Infect Dis, Dept Med, Baltimore, MD 21205 USA. [Quinn, Thomas C.] NIAID, NIH, Bethesda, MD 20892 USA. RP Blake, DR (reprint author), Univ Massachusetts, Sch Med, Dept Pediat, Div Adolescent Med, 55 Lake Ave N, Worcester, MA 01655 USA. EM diane.blake@umassmed.edu RI Gaydos, Charlotte/E-9937-2010 FU Intramural NIH HHS [Z01 AI000358-25]; NIAID NIH HHS [U01 AI068613, U01-AI-068613, U01 AI068613-03] NR 59 TC 24 Z9 24 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD JUL PY 2008 VL 35 IS 7 BP 649 EP 655 DI 10.1097/OLQ.0b013e31816ddb9a PG 7 WC Infectious Diseases SC Infectious Diseases GA 319GD UT WOS:000257151200003 PM 18461013 ER PT J AU Cai, TX Dodd, LE AF Cai, Tianxi Dodd, Lori E. TI Regression analysis for the partial area under the ROC curve SO STATISTICA SINICA LA English DT Article DE diagnostic accuracy; generalized linear model; model checking ID OPERATING CHARACTERISTIC CURVES; SEMIPARAMETRIC REGRESSION; PLACEMENT VALUES; MODEL-CHECKING; CANCER; MARKERS; DESIGN AB Performance evaluation of any classification method is fundamental to its acceptance in practice. Evaluation should consider the dependence of a classifier's accuracy on relevant covariates in addition to its overall accuracy. When developing a classifier with a continuous output that allocates units into one of two groups, receiver operating characteristic (ROC) curve analysis is appropriate. The partial area under the ROC curve (pAUC) is a summary measure of the ROC curve used to make statistical inference when only a region of the ROC space is of interest. We propose a new pAUC regression method to evaluate covariate effects on the diagnostic accuracy. We provide asymptotic distribution theory and inference procedures that allow for correlated observations. Graphical methods and goodness-of-fit statistics for model checking are also developed. Simulation studies demonstrate that the large-sample theory provides reasonable inference in small samples and the new estimator is considerably more efficient than the estimator proposed by Dodd and Pepe (2003a). Application to an analysis of prostate-specific antigen (PSA), a biomarker for early detection of prostate cancer, demonstrates the utility of the method in practice. C1 [Cai, Tianxi] Harvard Univ, Dept Biostat, Boston, MA 02115 USA. [Dodd, Lori E.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Cai, TX (reprint author), Harvard Univ, Dept Biostat, Boston, MA 02115 USA. EM tcai@hsph.harvard.edu; doddl@mail.nih.gov NR 30 TC 14 Z9 14 U1 0 U2 4 PU STATISTICA SINICA PI TAIPEI PA C/O DR H C HO, INST STATISTICAL SCIENCE, ACADEMIA SINICA, TAIPEI 115, TAIWAN SN 1017-0405 J9 STAT SINICA JI Stat. Sin. PD JUL PY 2008 VL 18 IS 3 BP 817 EP 836 PG 20 WC Statistics & Probability SC Mathematics GA 337UA UT WOS:000258459800004 ER PT J AU Burgess, RE Warach, S Schaewe, TJ Copenhaver, BR Alger, JR Vespa, P Martin, N Saver, JL Kidwell, CS AF Burgess, Richard E. Warach, Steven Schaewe, Timothy J. Copenhaver, Brittany R. Alger, Jeffry R. Vespa, Paul Martin, Neil Saver, Jeffrey L. Kidwell, Chelsea S. TI Development and validation of a simple conversion model for comparison of intracerebral hemorrhage volumes measured on CT and gradient recalled echo MRI SO STROKE LA English DT Article DE intracerebral hemorrhage; MRI; CT ID STROKE; MORTALITY AB Background and Purpose - Gradient recalled echo MRI (GRE) has been shown to be as accurate as CT for the detection of acute intracerebral hemorrhage (ICH). However, because of the differences in the signal parameter being detected, apparent hemorrhage size is expected to vary by imaging modality, with GRE providing larger volumes attributable to susceptibility effects. Methods - Image data from patients participating in 3 ICH studies were retrospectively reviewed. Patients with acute ICH were included if (1) concurrent MRI and CT were performed within 72 hours of symptom onset, and (2) each modality was performed within 240 minutes of each other. ICH volumes were calculated using a semiautomated image analysis program. The least squares method was used to develop a conversion equation based on a linear regression of GRE volume on CT volume. Results - Thirty-six patients met inclusion criteria. MRI was performed first in 18, CT first in 18. Mean hemorrhage volume was 25.2cc (range 0.1 to 83.9cc) on CT and 32.7cc (range 0.1 to 98.7cc) measured on GRE. A linear relationship defined by CT Volume = GRE Volume*0.8 (Spearman's correlation coefficient = 0.992, P < 0.001) was derived. Conclusions - Acute ICH volumes as measured on GRE pulse sequences are consistently larger than CT volumes. A simple mathematical conversion model has been developed: CT volume = 0.8* GRE volume. This formula can be used in studies using both imaging modalities, across different studies, or to track ICH growth over time independent of imaging modality in an individual patient. C1 [Burgess, Richard E.; Copenhaver, Brittany R.; Kidwell, Chelsea S.] Georgetown Univ, Dept Neurol, Washington, DC USA. [Burgess, Richard E.; Warach, Steven] NINDS, NIH, Bethesda, MD 20892 USA. [Schaewe, Timothy J.; Alger, Jeffry R.; Saver, Jeffrey L.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Vespa, Paul; Martin, Neil] Univ Calif Los Angeles, Dept Neurosurg, Los Angeles, CA USA. [Kidwell, Chelsea S.] Washington Hosp Ctr, Washington, DC 20010 USA. RP Burgess, RE (reprint author), Georgetown Univ Hosp, 3800 Reservoir Rd NW,7th Floor,PHC Bldg, Washington, DC 20007 USA. EM burgessri@ninds.nih.gov OI Martin, Neil/0000-0002-6565-4131; Saver, Jeffrey/0000-0001-9141-2251 FU Intramural NIH HHS; NINDS NIH HHS [P50-NS044378, P50 NS044378, P50 NS044378-06] NR 8 TC 19 Z9 19 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JUL PY 2008 VL 39 IS 7 BP 2017 EP 2020 DI 10.1161/STROKEAHA.107.505719 PG 4 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 317KP UT WOS:000257019400015 PM 18483414 ER PT J AU Merino, JG Latour, LL An, L Hsia, AW Kang, DW Warach, S AF Merino, Jose G. Latour, Lawrence L. An, Li Hsia, Amie W. Kang, Dong-Wha Warach, Steven TI Reperfusion half-life - A novel pharmacodynamic measure of thrombolytic activity SO STROKE LA English DT Article DE MRI; reperfusion; stroke; thrombolytic therapy ID ISCHEMIC-STROKE; MRI; DESMOTEPLASE; DIFFUSION AB Background and Purpose - We hypothesized that the probability of reperfusion can be modeled by an exponential decay ( ie, half- life) function and that this reperfusion half- life is decreased by thrombolytic treatment. Methods - Serial perfusion MRI scans were evaluated for evidence of reperfusion in intravenous tissue plasminogen activator-treated (n = 45) and untreated (n = 103) patients. The cumulative probability of reperfusion for each group was fit with exponential decay functions. The resulting reperfusion half- life ( ie, the time it takes half the sample to reperfuse) was calculated. Results - In untreated patients, a monoexponential decay function fit the data well ( R-2 = 0.95) with a half- life of 29.1 hours. In tissue plasminogen activator-treated patients, the data were best fit with a biexponential decay function (R-2 = 0.99) that had a fast and a slow component. The fast component is attributable to tissue plasminogen activator therapy and has a half- life of 0.71 hours, whereas the slow component was similar to that of the untreated group. Approximately 3.5 hours after the start of treatment, the effect of tissue plasminogen activator on the probability of reperfusion was negligible. Conclusion - The probability of reperfusion can be well described by the reperfusion half- life. Determination of the fast component reperfusion half- life may be an approach to compare the relative potency of different thrombolytic agents. C1 [Merino, Jose G.; Latour, Lawrence L.; An, Li; Warach, Steven] NINDS, Sect Stroke Diagnost & Therapeut, NIH, Bethesda, MD 20892 USA. [Kang, Dong-Wha] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Neurol, Seoul, South Korea. [Hsia, Amie W.] Washington Hosp Ctr, Stroke Ctr, Washington, DC 20010 USA. RP Merino, JG (reprint author), Suburban Hosp, Stroke Program, 8600 Old Georgetown Rd, Bethesda, MD 20814 USA. EM merinoj@ninds.nih.gov OI Merino, Jose/0000-0002-6676-0008 FU Intramural NIH HHS [Z99 NS999999] NR 9 TC 12 Z9 12 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JUL PY 2008 VL 39 IS 7 BP 2148 EP 2150 DI 10.1161/STROKEAHA.107.510818 PG 3 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 317KP UT WOS:000257019400035 PM 18451344 ER PT J AU Menetret, JF Hegde, RS Aguiar, M Gygi, SP Park, E Rapoport, TA Akey, CW AF Menetret, Jean-Francois Hegde, Ramanujan S. Aguiar, Mike Gygi, Steven P. Park, Eunyong Rapoport, Tom A. Akey, Christopher W. TI Single copies of Sec61 and TRAP associate with a nontranslating mammalian ribosome SO STRUCTURE LA English DT Article ID SIGNAL RECOGNITION PARTICLE; PROTEIN-CONDUCTING CHANNEL; ENDOPLASMIC-RETICULUM; ER MEMBRANE; TRANSLOCATION CHANNEL; POLYPEPTIDE TRANSLOCATION; ANGSTROM RESOLUTION; COMPLEX; BINDING; SECYEG AB During cotranslational protein translocation, the ribosome associates with a membrane channel, formed by the Sec61 complex, and recruits the translocon-associated protein complex (TRAP). Here we report the structure of a ribosome-channel complex from mammalian endoplasmic reticulum in which the channel has been visualized at 11 angstrom resolution. In this complex, single copies of Sec61 and TRAP associate with a nontranslating ribosome and this stoichiometry was verified by quantitative mass spectrometry. A bilayer-like density surrounds the channel and can be attributed to lipid and detergent. The crystal structure of an archaeal homolog of the Sec61 complex was then docked into the map. In this model, two cytoplasmic loops of Sec61 may interact with RNA helices H6, H7, and H50, while the central pore is located below the ribosome tunnel exit. Hence, this copy of Sec61 is positioned to capture and translocate the nascent chain. Finally, we show that mammalian and bacterial ribosome-channel complexes have similar architectures. C1 [Aguiar, Mike; Gygi, Steven P.; Park, Eunyong; Rapoport, Tom A.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Rapoport, Tom A.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. [Menetret, Jean-Francois; Akey, Christopher W.] Boston Univ, Sch Med, Dept Physiol & Biophys, Boston, MA 02118 USA. [Hegde, Ramanujan S.] NICHHD, Cell Biol & Metab Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Rapoport, TA (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, 240 Longwood Ave, Boston, MA 02115 USA. EM tom_rapoport@hms.harvard.edu; cakey@bu.edu OI Akey, Christopher/0000-0002-3059-3121; Hegde, Ramanujan/0000-0001-8338-852X FU NIGMS NIH HHS [R01 GM045377, R01 GM045377-13, R01 GM045377-14, R01 GM045377-15] NR 46 TC 60 Z9 64 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0969-2126 J9 STRUCTURE JI Structure PD JUL PY 2008 VL 16 IS 7 BP 1126 EP 1137 DI 10.1016/j.str.2008.05.003 PG 12 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 327MA UT WOS:000257732000017 PM 18611385 ER PT J AU Verma, V Shen, D Sieving, PC Chan, CC AF Verma, Varun Shen, Defen Sieving, Pamela C. Chan, Chi-Chao TI The role of infectious agents in the etiology of ocular adnexal neoplasia SO SURVEY OF OPHTHALMOLOGY LA English DT Review DE Chlamydia psittaci (C. psittaci); Helicobacter pylori (H. pylori); human herpes simplex virus-8 (HHV-8); human papilloma virus (HPV); Kaposi sarcoma; MALT lymphoma; ocular adnexa; papilloma; squamous cell carcinoma ID SQUAMOUS-CELL CARCINOMA; SARCOMA-ASSOCIATED HERPESVIRUS; HELICOBACTER-PYLORI INFECTION; LYMPHOID-TISSUE LYMPHOMA; HUMAN-PAPILLOMAVIRUS DNA; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; POLYMERASE-CHAIN-REACTION; NON-HODGKINS-LYMPHOMA; C VIRUS-INFECTION; RECURRENT CONJUNCTIVAL PAPILLOMA AB Given the fact that infectious agents contribute to around 18% of human cancers worldwide, it would seem prudent to explore their role in neoplasms of the ocular adnexa: primary malignancies of the conjunctiva, lacrimal glands, eyelids, and orbit. By elucidating the mechanisms by which infectious agents contribute to oncogenesis, the management, treatment, and prevention of these neoplasms may one day parallel what is already in place for cancers such as cervical cancer, hepatocellular carcinoma, gastric mucosa-associated lymphoid tissue lymphoma and gastric adenocarcinoma. Antibiotic treatment and vaccines against infectious agents may herald a future with a curtailed role for traditional therapies of surgery, radiation, and chemotherapy. Unlike other malignancies for which large epidemiological studies are available, analyzing ocular adnexal neoplasms is challenging as they are relatively rare. Additionally, putative infectious agents seemingly display an immense geographic variation that has led to much debate regarding the relative importance of one organism versus another. This review discusses the pathogenetic role of several microorganisms in different ocular adnexal malignancies, including human papilloma Virus in conjunctival papilloma and squamous cell carcinoma, human immunodeficiency virus in conjunctival squamous carcinoma, Kaposi sarcoma-associated herpes virus or human herpes simplex virus-8 (KSHV/HHV-8) in conjunctival Kaposi sarcoma, Helicobacter pylori (H. pylori,), Chlamydia, and hepatitis C Virus in ocular adnexal mucosa-associated lymphoid tissue lymphomas. Unlike cervical cancer where a single infectious agent, human papilloma virus, is found in greater than 99% of lesions, multiple organisms may play a role in the etiology of certain ocular adnexal neoplasms by acting through similar mechanisms of oncogenesis, including chronic antigenic stimulation and the action of infectious oncogenes. However, similar to other human malignancies, ultimately the role of infectious agents in ocular adnexal neoplasms is most likely as a cofactor to genetic and environmental risk factors. C1 [Verma, Varun; Shen, Defen; Chan, Chi-Chao] NEI, NIH, Immunol Lab, Immunopathol Sect, Bethesda, MD 20892 USA. [Sieving, Pamela C.] Natl Inst Hlth Lib, NIH, Bethesda, MD USA. RP Chan, CC (reprint author), NEI, NIH, Immunol Lab, Immunopathol Sect, Bldg 10,Rm 10N103,10 Ctr Dr, Bethesda, MD 20892 USA. EM chanc@nei.nih.gov OI Sieving, Pamela/0000-0003-3794-5000 FU Intramural NIH HHS [Z01 EY000222-22] NR 251 TC 41 Z9 44 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6257 J9 SURV OPHTHALMOL JI Surv. Ophthalmol. PD JUL-AUG PY 2008 VL 53 IS 4 BP 312 EP 331 DI 10.1016/j.survophthal.2008.04.008 PG 20 WC Ophthalmology SC Ophthalmology GA 321ZH UT WOS:000257344500002 PM 18572051 ER PT J AU Thanos, PK Michaelides, M Umegaki, H Volkow, ND AF Thanos, Panayotis K. Michaelides, Michael Umegaki, Hiroyuki Volkow, Nora D. TI D2R DNA transfer into the nucleus accumbens attenuates cocaine self-administration in rats SO SYNAPSE LA English DT Article DE drug abuse; addiction; gene therapy; psychostimulant ID CONDITIONED PLACE PREFERENCE; DOPAMINE-RECEPTOR GENE; KNOCKOUT MICE; ALCOHOL-DRINKING; SEEKING BEHAVIOR; D-2 RECEPTOR; A1 ALLELE; ANTAGONISTS; RELEASE; D1 AB Dopamine (DA) D2 receptor (D2R) agonists and antagonists can modulate self-administration behavior, conditioned place preference, and locomotor responses to cocaine. Low levels of D2R have also been observed in cocaine addicted subjects and in non human primates after chronic cocaine exposures. Prior studies had shown that D2R upregulation in the nucleus accumbens (NAc) in rodents trained to self-administer alcohol markedly attenuated alcohol preference and intake. Here we assess the effects of D2R upregulation in the NAc on cocaine intake in rats trained to self-administer cocaine. Following 2 weeks of i.v. cocaine self-administration (CSA), rats were stereotaxically treated with an adenovirus that carried the D2R gene to upregulate D2R in the NAc. D2R vector treatment resulted in a significant decrease (75%) in cocaine infusions and lever presses (70%) for cocaine. This effect lasted 6 days before cocaine consumption returned to baseline levels, which corresponds roughly to the time it takes D2R to return to baseline levels. These findings show that CSA and D2R in the NAc are negatively correlated and suggest that cocaine intake is modulated in part by D2R levels in NAc. Thus strategies aimed at increasing D2R expression in NAc may be beneficial in treating cocaine abuse and addiction. C1 [Thanos, Panayotis K.; Michaelides, Michael] Brookhaven Natl Lab, Behav Neuropharmacol & Neuroimaging Lab, Dept Med, Upton, NY 11973 USA. [Thanos, Panayotis K.; Michaelides, Michael; Volkow, Nora D.] NIAAA, Lab Neuroimaging, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Umegaki, Hiroyuki] Nagoya Univ, Sch Med, Dept Geriatr, Aichi 4668550, Japan. RP Thanos, PK (reprint author), Brookhaven Natl Lab, Behav Neuropharmacol & Neuroimaging Lab, Dept Med, Bldg 490, Upton, NY 11973 USA. EM thanos@bnl.gov RI Michaelides, Michael/K-4736-2013 OI Michaelides, Michael/0000-0003-0398-4917 FU Intramural NIH HHS [Z01 AA000551-04]; NIAAA NIH HHS [AA07611, AA 11034, P50 AA007611, R01 AA011034, T32 AA007574, AA07574] NR 42 TC 59 Z9 59 U1 0 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD JUL PY 2008 VL 62 IS 7 BP 481 EP 486 DI 10.1002/syn.20523 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 311LB UT WOS:000256600600001 PM 18418874 ER PT J AU Cai, NS Cadet, JL AF Cai, Ning Sheng Cadet, Jean Lud TI The combination of methamphetamine and of the HIV protein, Tat, induces death of the human neuroblastoma cell line, SH-SY5Y SO SYNAPSE LA English DT Article DE methamphetamine; HIV-1 Tat protein; SH-SY5Y AB Human immunodeficiency virus (HIV)-infected methamphetamine (METH) abusers show greater neuropathological abnormalities than HIV negative METH abusers or HIV positive non-METH users. Herein, we investigated the effects of METH and of the HIV protein, Tat, using the human neuroblastoma cell line, SHY5Y METH and Tat alone caused no toxic effects. In contrast, the combination of METH and Tat caused significant increases in the percentage of dead cells observed after 48 h of exposure. These results suggest the possibility of using this model to elucidate cellular and molecular mechanisms involved in the potentiation of clinical effects observed in patient populations of HIV positive METH-abusing patients. C1 [Cai, Ning Sheng; Cadet, Jean Lud] NIDA, Mol Neuropsychiat Branch, NIH, Intramural Res Program, Baltimore, MD 21224 USA. RP Cadet, JL (reprint author), NIDA, Mol Neuropsychiat Branch, NIH, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM jcadet@intra.nida.nih.gov FU Intramural NIH HHS NR 8 TC 8 Z9 9 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD JUL PY 2008 VL 62 IS 7 BP 551 EP 552 DI 10.1002/syn.20512 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 311LB UT WOS:000256600600009 PM 18435425 ER PT J AU Nurden, AT Nurden, P Bermejo, E Combrie, R McVicar, DW Washington, AV AF Nurden, Alan T. Nurden, Paquita Bermejo, Emilse Combrie, Robert McVicar, Daniel W. Washington, A. Valance TI Phenotypic heterogeneity in the gray platelet syndrome extends to the expression of TREM family member, TLT-I SO THROMBOSIS AND HAEMOSTASIS LA English DT Article DE gray platelet syndrome; inherited/acquired platelet disorders; protein trafficking; secretion/excicytosis ID ALPHA-GRANULES; P-SELECTIN; GLYCOPROTEIN-VI; AGGREGATION; THROMBIN; ACTIVATION; PATIENT; VITRO; METALLOPROTEINASES; MEGAKARYOCYTES AB The Gray platelet syndrome (GPS) is a rare inherited disorder linked to undefined molecular abnormalities that prevent the formation and maturation of a-granules. Here, we report studies on two patients from unrelated families that confirm phenotypic heterogeneity in the disease. First we used immunoelectron microscopy (I-EM) to confirm that TREM-like transcript-I (TLT-I) is mostly localized to a-granule membranes of normal platelets. Then we performed Western blotting (WB) and flow cytometry with permeabilized platelets to show that TLT-I is selectively reduced in the platelets of patient I previously noted to be deficient in glycoprotein (GP)VI (Nurden et al., Blood 2004; 104: 107-114). Yet both TLT-I and GPVIwere normally expressed in platelets of patient 2. Usual levels of JAM-C and claudin-5, also members of the immunoglobulin receptor family, were detected in platelets of both patients. In contrast, P-selectin was markedly decreased for patient I but not patient 2. Two metalloproteases, MMP-2 and MMP-9 were normally present. As predicted, platelets of patient I showed little labelling for TLT-I in I-EM, whereas residual Fg was seen in small vesicular structures and P-selectin lining vacuoles or channels of what may be elements of the surface-connected canalicular system. Our results identify TLT-I as a glycoprotein potentially targeted in platelets of GPS patients, while decreases in at least three membrane glycoproteins suggest that an unidentified proteolytic activity may contribute to the phenotype in some patients with this rare disease. C1 [Nurden, Alan T.; Nurden, Paquita; Bermejo, Emilse; Combrie, Robert] Hop Xavier Arnozan, Ctr Reference Pathol Plaquettaires, F-33600 Pessac, France. [McVicar, Daniel W.; Washington, A. Valance] NCI, Canc & Inflammat Program, Frederick, MD USA. [Washington, A. Valance] Univ Cent Caribe, Dept Anat & Cell Biol, Bayamon, PR USA. RP Nurden, AT (reprint author), Hop Xavier Arnozan, Ctr Reference Pathol Plaquettaires, F-33600 Pessac, France. EM Alan.Nurden@cnrshl.u-bordeaux2.fr RI McVicar, Daniel/G-1970-2015 FU Intramural NIH HHS [Z01 BC010300-10] NR 36 TC 12 Z9 13 U1 0 U2 1 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD JUL PY 2008 VL 100 IS 1 BP 45 EP 51 DI 10.1160/-TH08-02-0067 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 326PL UT WOS:000257671300013 PM 18612537 ER PT J AU Caggiari, L De Zorzi, M Ahlenstiel, G Rehermann, B De Re, V AF Caggiari, L. De Zorzi, M. Ahlenstiel, G. Rehermann, B. De Re, V. TI Identification of new major histocompatibility complex-A, -B, -C alleles in chimpanzees (Pan troglodytes) SO TISSUE ANTIGENS LA English DT Editorial Material DE Patr-A; Patr-B; Patr-C; Pan troglodytes; polymerase chain reaction-sequencing based typing ID MHC CLASS-I AB Two new Patr-A, five new Patr-B and three new Patr-C alleles from Pan troglodytes are described. C1 [Caggiari, L.; De Zorzi, M.; De Re, V.] IRCCS, Natl Canc Inst, Ctr Riferimento Oncol, DOMERT,Farmacol Sperimentale & Clin, Aviano, Italy. [Ahlenstiel, G.; Rehermann, B.] NIDDK, Immunol Sect, Liver Dis Branch, US Dept HHS,NIH, Bethesda, MD USA. RP De Re, V (reprint author), IRCCS, Natl Canc Inst, Ctr Riferimento Oncol, DOMERT,Farmacol Sperimentale & Clin, Via Franco Gallini 2, Aviano, Italy. OI Ahlenstiel, Golo/0000-0003-0026-1457 FU Intramural NIH HHS; Associazione Italiana per la Ricerca sul Cancro NR 6 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD JUL PY 2008 VL 72 IS 1 BP 79 EP 83 DI 10.1111/j.1399-0039.2008.01061.x PG 5 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 314YL UT WOS:000256845000014 PM 18498290 ER PT J AU Hong, HHL Ton, TVT Kim, Y Wakamatsu, N Clayton, NP Chan, PC Sills, RC Lahousse, SA AF Hong, Hue-Hua L. Ton, Thai-Vu T. Kim, Yongbaek Wakamatsu, Nobuko Clayton, Natasha P. Chan, Po-Chuen Sills, Robert C. Lahousse, Stephanie A. TI Genetic Alterations in K-ras and p53 Cancer Genes in Lung Neoplasms from B6C3F1 Mice Exposed to Cumene SO TOXICOLOGIC PATHOLOGY LA English DT Article DE K-ras; p53; cumene; lung; mouse ID TUMOR-SUPPRESSOR GENE; OXIDATIVE DNA-DAMAGE; MOUSE-LIVER TUMORS; MOLECULAR PATHOGENESIS; BENZENE METABOLISM; RISK-ASSESSMENT; O-NITROTOLUENE; HIGH-FREQUENCY; MUTATIONS; CELL AB The incidences of alveolar/bronchiolar adenomas and carcinomas in cumene-treated B6C3F1 mice were significantly greater than those of the control animals. We evaluated these lung neoplasms for point mutations in the K-ras and p53 genes that are often mutated in humans. K-ras and p53 mutations were detected by cycle sequencing of PCR-amplified DNA isolated from paraffin-embedded neoplasms. K-ras mutations were detected in 87% of cumene-induced lung neoplasms, and the predominant mutations were exon 1 codon 12 G to T transversions and exon 2 codon 61 A to G transitions. P53 protein expression was detected by immunohistochemistry in 56% of cumene-induced neoplasms, and mutations were detected in 52% of neoplasms. The predominant mutations were exon 5, codon 155 G to A transitions, and codon 133 C to T transitions. No p53 mutations and one of seven (14%) K-ras mutations were detected in spontaneous neoplasms. Cumene-induced lung carcinomas showed loss of heterozygosity (LOH) on chromosome 4 near the p16 gene (13%) and on chromosome 6 near the K-ras gene (12%). No LOH was observed in spontaneous carcinomas or normal lung tissues examined. The pattern of mutations identified in the lung tumors suggests that DNA damage and genomic instability may be contributing factors to the mutation profile and development of lung cancer in mice exposed to cumene. C1 [Hong, Hue-Hua L.; Ton, Thai-Vu T.; Clayton, Natasha P.; Sills, Robert C.; Lahousse, Stephanie A.] NIEHS, Cellular & Mol Pathol Branch, Res Triangle Pk, NC 27709 USA. [Kim, Yongbaek] N Carolina State Univ, Coll Vet Med, Raleigh, NC USA. [Wakamatsu, Nobuko] Louisiana State Univ, Sch Vet Med, Dept Pathobiol Sci, Baton Rouge, LA 70803 USA. [Chan, Po-Chuen] NIEHS, Toxicol Operat Branch, Res Triangle Pk, NC 27709 USA. RP Hong, HHL (reprint author), NIEHS, Cellular & Mol Pathol Branch, MD C1-04,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM hong5@niehs.nih.gov FU National Institutes of Health; National Institute of Environmental Health Sciences FX The authors thank Dr. Darlene Dixon and Dr. Mark Cesta for their critical review of this manuscript. This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences. NR 44 TC 5 Z9 5 U1 1 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JUL PY 2008 VL 36 IS 5 BP 720 EP 726 DI 10.1177/0192623308320280 PG 7 WC Pathology; Toxicology SC Pathology; Toxicology GA 463VC UT WOS:000267459500010 PM 18648094 ER PT J AU Wakamatsu, N Collins, JB Parker, JS Tessema, M Clayton, NP Ton, TVT Hong, HHL Belinsky, S Devereux, TR Sills, RC Lahousse, SA AF Wakamatsu, Nobuko Collins, Jennifer B. Parker, Joel S. Tessema, Mathewos Clayton, Natasha P. Ton, Thai-Vu T. Hong, Hue-Hua L. Belinsky, Steven Devereux, Theodora R. Sills, Robert C. Lahousse, Stephanie A. TI Gene Expression Studies Demonstrate that the K-ras/Erk MAP Kinase Signal Transduction Pathway and Other Novel Pathways Contribute to the Pathogenesis of Cumene-induced Lung Tumors SO TOXICOLOGIC PATHOLOGY LA English DT Article DE K-ras; lung cancer; MAPK; histone deacetylation; epigenetics; microarray; mouse ID CANCER-CELLS; HISTONE DEACETYLATION; EPITHELIAL-CELLS; PROSTATE-CANCER; CYCLIN D1; RETINOBLASTOMA PROTEIN; EPIGENETIC REGULATION; SUPPRESSOR GENE; DOWN-REGULATION; GROWTH ARREST AB National Toxicology Program (NTP) inhalation studies demonstrated that cumene significantly increased the incidence of alveolar/bronchiolar adenomas and carcinomas in B6C3F1 mice. Cumene or isopropylbenzene is a component of crude oil used primarily in the production of phenol and acetone. The authors performed global gene expression analysis to distinguish patterns of gene regulation between cumene-induced tumors and normal lung tissue and to look for patterns based on the presence or absence of K-ras and p53 mutations in the tumors. Principal component analysis segregated the carcinomas into groups with and without K-ras mutations, but failed to separate the tumors based on p53 mutation status. Expression of genes associated with the Erk MAP kinase signaling pathway was significantly altered in carcinomas with K-ras mutations compared to tumors without K-ras mutations or normal lung. Gene expression analysis also suggested that cumene-induced carcinomas with K-ras mutations have greater malignant potential than those without mutations. In addition, significance analysis of function and expression (SAFE) demonstrated expression changes of genes regulated by histone modification in carcinomas with K-ras mutations. The gene expression analysis suggested the formation of alveolar/bronchiolar carcinomas in cumene-exposed mice typically involves mutation of K-ras, which results in increased Erk MAP kinase signaling and modification of histones. C1 [Wakamatsu, Nobuko; Clayton, Natasha P.; Ton, Thai-Vu T.; Hong, Hue-Hua L.; Devereux, Theodora R.; Sills, Robert C.; Lahousse, Stephanie A.] NIEHS, Cellular & Mol Pathol Branch, Res Triangle Pk, NC 27709 USA. [Collins, Jennifer B.] NIEHS, Mol Toxicol Lab, Res Triangle Pk, NC 27709 USA. [Parker, Joel S.] Constella Grp, Durham, NC USA. [Tessema, Mathewos; Belinsky, Steven] Lovelace Resp Res Inst, Albuquerque, NM USA. RP Lahousse, SA (reprint author), NIEHS, Cellular & Mol Pathol Branch, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM Lahousses@niehs.nih.gov FU National Institutes of Health; National Institute of Environmental Health Sciences [ES008801] FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences, and by ES008801. NR 83 TC 5 Z9 5 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JUL PY 2008 VL 36 IS 5 BP 743 EP 752 DI 10.1177/0192623308320801 PG 10 WC Pathology; Toxicology SC Pathology; Toxicology GA 463VC UT WOS:000267459500013 PM 18648096 ER PT J AU Chignell, CF Han, SK Moulthys-Mickalad, A Sik, RH Stadler, K Kadiiska, MB AF Chignell, C. F. Han, S-K. Moulthys-Mickalad, A. Sik, R. H. Stadler, K. Kadiiska, M. B. TI EPR studies of in vivo radical production by 3,3 ',5,5 '-tetrabromobisphenol A (TBBPA) in the Sprague-Dawley rat SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE 3,3 ',5,5 '-tetrabromobisphenol; bile; spin trapping; Sprague-Dawley rat; free radicals ID POLYBROMINATED DIPHENYL ETHERS; BROMINATED FLAME RETARDANTS; TETRABROMOBISPHENOL-A; METABOLISM; DISPOSITION; EXPOSURE; METHYL AB Brominated flame retardants (BFRs) are present in many consumer products ranging from fabrics to plastics and electronics. Wide use of flame retardants can pose an environmental hazard and it is of interest to determine the mechanism of their toxicity. Of all the BFRs, 3,3',5,5'-tetrabromobisphenol A (TBBPA) is produced in the largest volume. Previous studies by Szymanska et al. (2000) have shown that TBBPA is hepatotoxic in rats. We report here that when TBBPA (100 or 600 mg/kg) dissolved in DMSO and alpha-(4-pyridyl-1-oxide)-N-t-butyinitrone (POBN) was administered ip to male Sprague-Dawley rats the POBN/(center dot)CH(3) spin adduct was detected by electron paramagnetic resonance (EPR) in the bile. When (13)C-DMSO was employed the POBN/(center dot)C(13)H(3) adduct was observed. Also present in the bile was the 2,6-dibromobenzosemiquinone radical deilved from 2,6-dibromohydroquinone, a known metabolite of TBBPA. Reaction of the 2,6-dibromobenzosemiquinone radical with oxygen would generate superoxide from which hydrogen peroxide can form by dismutation. The hydroxyl radical generated via the Fenton reaction from hydrogen peroxide reacts in vivo with DMSO to give the methyl radical which is trapped by POBN. These observations suggest that the hepatotoxicity of TBBPA in rats may be due to the in vivo generation of the hydroxyl radical as a result of redox reactions involving the TBBPA metabolite 2,6-dibromohydroquinone and its corresponding semiquinone radical. Published by Elsevier Inc. C1 [Chignell, C. F.; Han, S-K.; Moulthys-Mickalad, A.; Sik, R. H.; Stadler, K.; Kadiiska, M. B.] NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. [Han, S-K.] Mokpo Natl Maritime Univ, Dept Marine Environm Engn, Mokpo 530729, South Korea. [Moulthys-Mickalad, A.] Univ Liege, Lab Oxygen Biochem, B-4000 Liege, Belgium. RP Chignell, CF (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM chignell@niehs.nih.gov FU Intramural NIH HHS NR 22 TC 21 Z9 26 U1 2 U2 16 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD JUL 1 PY 2008 VL 230 IS 1 BP 17 EP 22 DI 10.1016/j.taap.2008.01.035 PG 6 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 318NI UT WOS:000257098300003 PM 18342900 ER PT J AU Sinha, SS Shiva, S Gladwin, MT AF Sinha, Shashank S. Shiva, Sruti Gladwin, Mark T. TI Myocardial Protection by Nitrite: Evidence That This Reperfusion Therapeutic Will Not Be Lost in Translation SO TRENDS IN CARDIOVASCULAR MEDICINE LA English DT Review ID VIVO ISCHEMIA-REPERFUSION; IN-VIVO; ISCHEMIA/REPERFUSION INJURY; XANTHINE OXIDOREDUCTASE; MITOCHONDRIAL RESPIRATION; HYPOXIC VASODILATION; HUMAN CIRCULATION; SODIUM-NITRITE; RAT-KIDNEY; INHALED NO AB The circulating anion nitrite (NO2-), previously thought to be an inert product of nitric oxide (NO) oxidation, has now been identified as an important storage reservoir of bioavailable NO in the blood and tissues. Reduction of NO2- to NO over the physiologic pH and oxygen gradient by deoxyhemoglobin, myoglobin, xanthine oxidoreductase, and by nonenzymatic acidic disproportionation has been demonstrated to confer cytoprotection against ischemia-reperfusion injury in the heart, liver, brain, and kidney Here, we review the mechanisms that have been established to regulate hypoxic NO2- reduction to NO, analyze the preclinical and clinical evidence supporting NO2--mediated cytoprotection after ischemia-reperfusion injury, and examine the therapeutic potential of NO2- for cardiovascular disease. Evidence is accumulating that suggests NO2- has surmounted many of the direct challenges to reperfusion therapeutics summarized by, the National Heart, Lung, and Blood Institute Working Group in "Myocardial protection at a crossroads: the need for translation Into clinical therapy." In this context, we discuss important considerations in designing human clinical trials to test the efficacy of NO2- In the setting of ischemia-reperfusion injury, with particular attention to the study of ST-segment elevation myocardial infarction. (Trends Cardiovasc Med 2008; 18: 163-172) Published by Elsevier Inc. C1 [Sinha, Shashank S.; Shiva, Sruti; Gladwin, Mark T.] NHLBI, Pulm & Vasc Med Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20814 USA. RP Gladwin, MT (reprint author), NHLBI, Pulm & Vasc Med Branch, NIH, Bldg 10-CRC,Room 5-5140 10 Ctr Dr,MSC 1454, Bethesda, MD 20892 USA. EM mgladwin@nih.gov FU Howard Hughes Medical Institute NR 60 TC 24 Z9 24 U1 0 U2 3 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1050-1738 J9 TRENDS CARDIOVAS MED JI Trends Cardiovasc. Med. PD JUL PY 2008 VL 18 IS 5 BP 163 EP 172 AR PII S1050-1738(08)00099-6 DI 10.1016/j.tcm.2008.05.001 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 360AB UT WOS:000260028300002 PM 18790386 ER PT J AU Balaji, S Iyer, LM Babu, MM Aravind, L AF Balaji, S. Iyer, Lakshminarayan M. Babu, M. Madan Aravind, L. TI Comparison of transcription regulatory interactions inferred from high-throughput methods: what do they reveal? SO TRENDS IN GENETICS LA English DT Article ID SACCHAROMYCES-CEREVISIAE; GENE-EXPRESSION; NETWORKS; BIOLOGY AB We compared the transcription regulatory interactions inferred from three high-throughput methods. Because these methods use different principles, they have few interactions in common, suggesting they capture distinct facets of the transcription regulatory program. We show that these methods uncover disparate biological phenomena: long-range interactions between telomeres and transcription factors, downstream effects of interference with ribosome biogenesis and a protein-aggregation response. Through a detailed analysis of the latter, we predict components of the system responding to protein-aggregation stress. C1 [Balaji, S.; Iyer, Lakshminarayan M.; Aravind, L.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. [Babu, M. Madan] MRC Lab Mol Biol, Cambridge CB2 2QH, England. RP Balaji, S (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM sbalaji@ncbi.nlrn.nih.gov; madanm@mrc-lmb.cam.ac.uk FU Intramural NIH HHS [, NIH0011790914]; Medical Research Council [, MC_U105185859]; PHS HHS [NIH0011790914] NR 18 TC 16 Z9 16 U1 0 U2 1 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD JUL PY 2008 VL 24 IS 7 BP 319 EP 323 DI 10.1016/j.tig.2008.04.006 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 331JL UT WOS:000258008400002 PM 18514968 ER PT J AU Lawrence, JJ AF Lawrence, J. Josh TI Cholinergic control of GABA release: emerging parallels between neocortex and hippocampus SO TRENDS IN NEUROSCIENCES LA English DT Review ID STRATUM-ORIENS INTERNEURONS; LONG-TERM POTENTIATION; NICOTINIC ACETYLCHOLINE-RECEPTORS; CONTEXT-DEPENDENT RETRIEVAL; BASAL FOREBRAIN; IN-VITRO; INHIBITORY INTERNEURONS; GABAERGIC INTERNEURONS; ALPHA-BUNGAROTOXIN; GAMMA-OSCILLATIONS AB Release of acetylcholine (ACh) into the neocortex and hippocampus profoundly alters cellular excitability, network synchronization and behavioral state. Despite its diverse cellular and synaptic targets, the actions of ACh can be highly specific, altering the excitability of distinct inhibitory and excitatory cell types. This review presents evidence for the selectivity of cholinergic neuromodulation in GABAergic interneurons and identifies emerging parallels between the neocortex and hippocampus. In light of growing evidence that neuromodulatory specializations relate to neurochemical identity, I propose that differential engagement of neurochemically distinct interneuron subtypes is a unifying principle by which ACh orchestrates the flow of sensory information in the neocortex and hippocampus. C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Natl Inst Hlth, Lab Cellular & Synapt Neurophysiol, Bethesda, MD 20892 USA. RP Lawrence, JJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Natl Inst Hlth, Lab Cellular & Synapt Neurophysiol, Bethesda, MD 20892 USA. EM lawrenjo@mai1.nih.gov FU Intramural NIH HHS NR 92 TC 58 Z9 58 U1 1 U2 17 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD JUL PY 2008 VL 31 IS 7 BP 317 EP 327 DI 10.1016/j.tins.2008.03.008 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 330YJ UT WOS:000257978400001 PM 18556072 ER PT J AU Takizawa, T Meshorer, E AF Takizawa, Takumi Meshorer, Eran TI Chromatin and nuclear architecture in the nervous system SO TRENDS IN NEUROSCIENCES LA English DT Review ID HISTONE DEACETYLASE INHIBITORS; CEREBELLAR PURKINJE NEURONS; SPINAL MUSCULAR-ATROPHY; TRANSCRIPTIONAL REGULATION; MESSENGER-RNA; REPEAT LENGTH; POLYGLUTAMINE TOXICITY; NEURAL DIFFERENTIATION; GANGLION NEURONS; CORTICAL-NEURONS AB Neurons are arguably the most varied cell type both morphologically and functionally. Their fate during differentiation and development and the activity of mature neurons are significantly determined and regulated by chromatin. The nucleus is compartmentalized and the arrangement of these compartments, termed the nuclear architecture, distinguishes one cell type from another and dictates many nuclear processes. Nuclear architecture determines the arrangement of chromosomes, the positioning of genes within chromosomes, the distribution of nuclear bodies and the interplay between these different factors. Importantly, chromatin regulation has been shown to be the basis for a variety of central nervous system processes including grooming and nursing, depression and stress, and drug abuse, among others. Here we review the regulation and function of nuclear architecture and chromatin structure in the context of the nervous system and discuss the potential use of histone deacetylase inhibitors as chromatin-directed therapy for nervous system disorders. C1 [Meshorer, Eran] Hebrew Univ Jerusalem, Inst Life Sci, Dept Genet, IL-91904 Jerusalem, Israel. [Takizawa, Takumi] Natl Canc Inst, Natl Inst Hlth, Bethesda, MD 20892 USA. [Takizawa, Takumi] Nara Inst Sci & Technol, Grad Sch Biol Sci, Lab Mol Neurosci, Nara 6300101, Japan. RP Meshorer, E (reprint author), Hebrew Univ Jerusalem, Inst Life Sci, Dept Genet, IL-91904 Jerusalem, Israel. EM meshorer@cc.huji.ac.il NR 107 TC 36 Z9 38 U1 1 U2 5 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD JUL PY 2008 VL 31 IS 7 BP 343 EP 352 DI 10.1016/j.tins.2008.03.005 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 330YJ UT WOS:000257978400004 PM 18538423 ER PT J AU Fields, RD AF Fields, R. Douglas TI White matter in learning, cognition and psychiatric disorders SO TRENDS IN NEUROSCIENCES LA English DT Review ID MYELIN-ASSOCIATED GLYCOPROTEIN; CENTRAL-NERVOUS-SYSTEM; OLIGODENDROCYTE PRECURSOR CELLS; OLIVOCEREBELLAR CONDUCTION TIME; SCHWANN-CELLS; OPTIC-NERVE; NEURITE OUTGROWTH; ACTION-POTENTIALS; SHEATH THICKNESS; CORPUS-CALLOSUM AB White matter is the brain region underlying the gray matter cortex, composed of neuronal fibers coated with electrical insulation called myelin. Previously of interest in demyelinating diseases such as multiple sclerosis, myelin is attracting new interest as an unexpected contributor to a wide range of psychiatric disorders, including depression and schizophrenia. This is stimulating research into myelin involvement in normal cognitive function, learning and IQ. Myelination continues for decades in the human brain; it is modifiable by experience, and it affects information processing by regulating the velocity and synchrony of impulse conduction between distant cortical regions. Cell-culture studies have identified molecular mechanisms regulating myelination by electrical activity, and myelin also limits the critical period for learning through inhibitory proteins that suppress axon sprouting and synaptogenesis. C1 Natl Inst Child Hlth & Human Dev, Natl Inst Hlth, Nervous Syst Dev & Plast Sect, Bethesda, MD 20892 USA. RP Fields, RD (reprint author), Natl Inst Child Hlth & Human Dev, Natl Inst Hlth, Nervous Syst Dev & Plast Sect, Bethesda, MD 20892 USA. EM fieldsd@mail.nih.gov FU Intramural NIH HHS [Z01 HD000713-13] NR 108 TC 422 Z9 427 U1 8 U2 60 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD JUL PY 2008 VL 31 IS 7 BP 361 EP 370 DI 10.1016/j.tins.2008.04.001 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 330YJ UT WOS:000257978400006 PM 18538868 ER PT J AU Miyoshi, N Tuziuti, T Yasui, K Lida, Y Shimizu, N Riesz, P Sostaric, JZ AF Miyoshi, Norio Tuziuti, Toru Yasui, Kyuichi Lida, Yasuo Shimizu, Nobuaki Riesz, Peter Sostaric, Joe Z. TI Ultrasound-induced cytolysis of cancer cells is enhanced in the presence of micron-sized alumina particles SO ULTRASONICS SONOCHEMISTRY LA English DT Article DE free radicals; cytolysis; alumina; sonodynamic therapy; nanoparticles ID AGENT GAS BODIES; SONODYNAMIC THERAPY; CONTRAST AGENTS; IN-VITRO; SONOCHEMISTRY; CAVITATION; SONOPORATION; SURFACTANTS; ACTIVATION; EFFICIENCY AB Micron-sized alumina particles have been shown to enhance sonochemical free radical formation in aqueous solutions and simultaneously increase the solution temperature and acoustic (white) noise, effects attributable to enhanced inertial cavitation [T. Tuziuti, J. Phys. Chem. A 109 (2005) 4869-4872]. In the current study, the same ultrasound exposure system was applied to in vitro cancer cells as a model system to determine the effect of alumina particles on the long-term survival of cells and on the major pathways of cell death, i.e., either apoptosis or necrosis. Following 6 It of incubation after ultrasound treatment, it was found that the cells died mainly through necrosis, irrespective of whether the exposure was conducted in the presence of alumina particles or not. Alumina particles were nontoxic to cells alone, but were found to decrease the long-term survivability of cells that survived the initial exposure. This effect depended on the size and concentration of particles. These results correlated well with the effect of alumina particles on the sonochemical oxidation of KI under the same exposure conditions. Spin-trapping with 5,5-dimethyl-pyroline N-oxide (DMPO) and electron spin resonance spectroscopy indicated that the sonochemical formation of (center dot)OH radicals increased in the presence of alumina particles. The current study is consistent with the well known observation that micron-sized particles enhance the acoustic cavitation process. (C) 2007 Elsevier B.V. All rights reserved. C1 [Miyoshi, Norio] Univ Fukui, Div Tumor Pathol, Dept Pathol Sci, Fac Med, Fukui 9101193, Japan. [Tuziuti, Toru; Yasui, Kyuichi; Lida, Yasuo] Natl Inst Adv Ind Sci & Technol, Moriyama Ku, Nagoya, Aichi 4638560, Japan. [Shimizu, Nobuaki] Kanazawa Univ, Div Biol Measurement & Applicat, Inst Nat Environm Technol, Kanazawa, Ishikawa 9201192, Japan. [Riesz, Peter] NCI, NIH, Radiat Biol Branch, Bethesda, MD 20892 USA. [Sostaric, Joe Z.] Ohio State Univ, Davis Heart & Lung Res Inst, Columbus, OH 43210 USA. RP Miyoshi, N (reprint author), Univ Fukui, Div Tumor Pathol, Dept Pathol Sci, Fac Med, Shimoaizuki,23-3, Fukui 9101193, Japan. EM nmiyoshi@fmsrsa.fukui-med.ac.jp RI Sostaric, Joe/A-6033-2008 NR 20 TC 11 Z9 11 U1 2 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1350-4177 J9 ULTRASON SONOCHEM JI Ultrason. Sonochem. PD JUL PY 2008 VL 15 IS 5 BP 881 EP 890 DI 10.1016/j.ultsonch.2007.10.010 PG 10 WC Acoustics; Chemistry, Multidisciplinary SC Acoustics; Chemistry GA 301NA UT WOS:000255901700034 PM 18180192 ER PT J AU Sumpio, BE Allie, DE Horvath, KA Marston, WA Meites, HL Mills, JLR Orgill, DP Salazar, JD Song, DH Toursarkissian, B AF Sumpio, Bauer E. Allie, David E. Horvath, Keith A. Marston, William A. Meites, Herbert L. Mills, Joseph L. R. Orgill, Dennis P. Salazar, Jorge D. Song, David H. Toursarkissian, Boulos TI Role of Negative Pressure Wound Therapy in Treating Peripheral Vascular Graft Infections SO VASCULAR LA English DT Article DE consensus of experts; treatment guidelines; vacuum-assisted therapy; vascular graft infections; vascular wounds; wound care ID VACUUM-ASSISTED CLOSURE; MUSCLE-FLAP COVERAGE; SURGICAL-MANAGEMENT; SARTORIUS MYOPLASTY; CLINICAL-EXPERIENCE; GROIN WOUNDS; SURGERY; PRESERVATION; BYPASS; DEVICE AB Wound complications involving large subcutaneous vessels can cause significant challenges for surgeons. Negative pressure wound therapy (NPWT) has been increasingly used for treating complex wounds in vascular surgery, including groin infections, either as a bridge to surgical closure or as a primary wound treatment modality. Although a growing body of evidence exists for managing various problematic wounds, such as diabetic foot ulcers and open abdominal wounds, the role of NPWT in wounds involving large blood vessels or wounds complicating infected vascular grafts has not been well defined. A multidisciplinary advisory panel reviewed the literature relevant to wounds related to vascular surgical procedures and complications, focusing on large subcutaneous or infected vascular conduits. The results supported by the literature and the clinical practice of the consensus panel suggested that NPWT can be a useful adjunct to the management of vascular groin infections and dehiscences but must be used with caution. C1 [Sumpio, Bauer E.] Yale Univ, Sch Med, Dept Surg, New Haven, CT 06520 USA. [Allie, David E.] Lafayette Clin, Cardiovasc Inst S, Dept Surg, Lafayette, LA USA. [Horvath, Keith A.] NHLBI, Dept Surg, Bethesda, MD 20892 USA. [Horvath, Keith A.] Suburban Hosp, Bethesda, MD USA. [Marston, William A.] Univ N Carolina, Dept Surg, Chapel Hill, NC USA. [Meites, Herbert L.] Baptist Med Ctr, Dept Surg, Oklahoma City, OK 73112 USA. [Mills, Joseph L. R.] Univ Arizona, Hlth Sci Ctr, Dept Surg, Tucson, AZ USA. [Orgill, Dennis P.] Harvard Univ, Sch Med, Dept Surg, Brigham & Womens Hosp, Boston, MA 02115 USA. [Salazar, Jorge D.; Toursarkissian, Boulos] Univ Texas Hlth Sci Ctr San Antonio, Dept Surg, San Antonio, TX 78229 USA. [Song, David H.] Univ Chicago Hosp, Pritzker Sch Med, Dept Surg, Chicago, IL 60637 USA. RP Sumpio, BE (reprint author), Yale Univ, Sch Med, Dept Surg, FMB137,POB 208062, New Haven, CT 06520 USA. EM bauer.sumpio@yale.edu OI Mills, Joseph/0000-0002-4955-4384 NR 65 TC 6 Z9 7 U1 0 U2 1 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 1708-5381 J9 VASCULAR JI Vascular PD JUL-AUG PY 2008 VL 16 IS 4 BP 194 EP 200 DI 10.2310/6670.2008.00041 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 365XZ UT WOS:000260444400003 PM 18845099 ER PT J AU Klein, H AF Klein, H. TI Analysis of measures for improving blood safety SO VOX SANGUINIS LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0042-9007 J9 VOX SANG JI Vox Sang. PD JUL PY 2008 VL 95 SU 1 BP 3 EP 3 PG 1 WC Hematology SC Hematology GA 298DD UT WOS:000255665700006 ER PT J AU Klein, H AF Klein, H. TI Pathogen reduction: An American view SO VOX SANGUINIS LA English DT Meeting Abstract C1 [Klein, H.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0042-9007 J9 VOX SANG JI Vox Sang. PD JUL PY 2008 VL 95 SU 1 BP 8 EP 8 PG 1 WC Hematology SC Hematology GA 298DD UT WOS:000255665700014 ER PT J AU Liu, DZ Feng, ML Shen, T Shen, W Huang, H Zhao, TM AF Liu, D. Z. Feng, M. L. Shen, T. Shen, W. Huang, H. Zhao, T. M. TI Investigation of apheresis platelets transfusion reactions and establishment of HPA and HLA typed plateletpheresis donor registry in China SO VOX SANGUINIS LA English DT Meeting Abstract C1 [Liu, D. Z.; Feng, M. L.; Shen, T.; Shen, W.; Huang, H.] Shanghai Blood Ctr, Shanghai, Peoples R China. [Zhao, T. M.] Natl Inst Hlth, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0042-9007 J9 VOX SANG JI Vox Sang. PD JUL PY 2008 VL 95 SU 1 BP 170 EP 170 PG 1 WC Hematology SC Hematology GA 298DD UT WOS:000255665700382 ER PT J AU Kobrin, KL Thompson, PJ van de Scheur, MV Kwak, TH Kim, S Falanga, V AF Kobrin, Kendra L. Thompson, Paul J. van de Scheur, Martijn Kwak, Tae-Hee Kim, Saerom Falanga, Vincent TI Evaluation of dermal pericapillary fibrin cuffs in venous ulceration using confocal microscopy SO WOUND REPAIR AND REGENERATION LA English DT Article ID DISEASE; SKIN AB Dermal pericapillary fibrin is a hallmark of venous disease and is thought to play a pathogenic role in the development of ulceration. However, the actual spatial configuration of pericapillary fibrin is unknown, and it remains unclear whether it truly represents a barrier that can impair physiological exchanges between the blood and dermis. Using confocal microscopy on tissue specimens taken from the edges of venous ulcers in six patients, we report a detailed analysis of dermal pericapillary fibrin deposits. Sections were evaluated with an antibody to human fibrinogen/fibrin and viewed, vertically and horizontally, with confocal microscopy. The distribution of fibrin deposition was highly variable and patchy, with areas of great intensity next to others of marginal intensity. Vertical cut sections showed the highest concentration of fluorescent material next to the lumen of dermal capillaries. Horizontal sections showed that maximal fluorescence was distributed at random. Our findings indicate that fibrin deposits in venous ulcers are patchy and discontinuous around dermal vessels. As such, these deposits are unlikely to act as a true and stable anatomic barrier as originally proposed. However, pericapillary fibrin may still act as a physiological barrier under conditions of poor blood flow where even marginal or patchy fibrin deposition might have a greater effect on the exchange of oxygen and other nutrients between blood and dermis. C1 [Kobrin, Kendra L.; Thompson, Paul J.; van de Scheur, Martijn; Kwak, Tae-Hee; Kim, Saerom; Falanga, Vincent] Roger Williams Med Ctr, Dept Dermatol, Providence, RI 02908 USA. [Kobrin, Kendra L.; Thompson, Paul J.; van de Scheur, Martijn; Kwak, Tae-Hee; Kim, Saerom; Falanga, Vincent] NIH, Ctr Biomed Res Excellence COBRE, Roger Williams Med Ctr, Providence, RI 02908 USA. [Falanga, Vincent] Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02118 USA. [Falanga, Vincent] Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA. RP Falanga, V (reprint author), Roger Williams Med Ctr, Dept Dermatol & Skin Surg, Elmhurst Bldg,50 Maude St, Providence, RI 02908 USA. EM vfalanga@bu.edu OI Kobrin, Kendra/0000-0002-8466-8299 FU NCRR NIH HHS [P20 RR018757, P20RR018757]; NIDDK NIH HHS [R01 DK067836-04, R01 DK067836, DK067836] NR 11 TC 7 Z9 7 U1 1 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1067-1927 J9 WOUND REPAIR REGEN JI Wound Repair Regen. PD JUL-AUG PY 2008 VL 16 IS 4 BP 503 EP 506 DI 10.1111/j.1524-475X.2008.00396.x PG 4 WC Cell Biology; Dermatology; Medicine, Research & Experimental; Surgery SC Cell Biology; Dermatology; Research & Experimental Medicine; Surgery GA 326RF UT WOS:000257675900006 PM 18638268 ER PT J AU Frenkel, V AF Frenkel, Victor TI Ultrasound mediated delivery of drugs and genes to solid tumors SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Review DE high intensity focused ultrasound (HIFU); drug and gene delivery; hyperthermia; acoustic cavitation; acoustic radiation forces ID INTENSITY FOCUSED ULTRASOUND; TEMPERATURE-SENSITIVE LIPOSOMES; LOCALIZED PROSTATE-CANCER; BRAIN-BARRIER DISRUPTION; PLASMID DNA DELIVERY; MR CONTRAST AGENT; IN-VIVO; RADIATION-FORCE; THERMOSENSITIVE LIPOSOMES; HYDRAULIC CONDUCTIVITY AB It has long been shown that therapeutic ultrasound can be used effectively to ablate solid tumors, and a variety of cancers are presently being treated in the clinic using these types of ultrasound exposures. There is, however, an ever-increasing body of preclinical literature that demonstrates how ultrasound energy can also be used non-destructively for increasing the efficacy of drugs and genes for improving cancer treatment. In this review, a summary of the most important ultrasound mechanisms will be given with a detailed description of how each one can be employed for a variety of applications. This includes the manner by which acoustic energy deposition can be used to create changes in tissue permeability for enhancing the delivery of conventional agents, as well as for deploying and activating drugs and genes via specially tailored vehicles and formulations. Published by Elsevier B.V. C1 Natl Inst Hlth, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. RP Frenkel, V (reprint author), Natl Inst Hlth, Dept Diagnost Radiol, Ctr Clin, Bldg 10,Room 1N306a,10 Ctr Dr, Bethesda, MD 20892 USA. EM vfrenkel@cc.nih.gov FU Intramural NIH HHS [Z99 CL999999] NR 164 TC 220 Z9 228 U1 6 U2 78 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-409X EI 1872-8294 J9 ADV DRUG DELIVER REV JI Adv. Drug Deliv. Rev. PD JUN 30 PY 2008 VL 60 IS 10 BP 1193 EP 1208 DI 10.1016/j.addr.2008.03.007 PG 16 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 320XO UT WOS:000257268700009 PM 18474406 ER PT J AU Wu, WC Wang, Y Chai, CY AF Wu, Wun-Chin Wang, Yu Chai, Chok-Yung TI Acute effects of the cannabinoid receptor agonist WIN55212-2 on dopamine release in rat: An in vivo electrochemical study SO CHINESE JOURNAL OF PHYSIOLOGY LA English DT Article DE dopamine; cannabinoid receptor; striatum ID NIGRA PARS-RETICULATA; IONTOPHORETICALLY-APPLIED GABA; SUBSTANTIA-NIGRA; SYNAPTIC-TRANSMISSION; CB1 RECEPTOR; HIPPOCAMPAL-NEURONS; CALCIUM-CHANNELS; BASAL GANGLIA; PHARMACOLOGY; STIMULATION AB The aim of this study was to investigate the effects of the cannabinoid receptor agonist, WIN55212-2, and the cannabinoid receptor antagonist, SR141716A, on dopamine (DA) release evoked by KCl (120 mM) microinjected into the striatum. The cannabinoid agonist WIN55212-2 (1 and 5 mg/kg, i.p.) dose-dependently attenuated DA release in the striatum, whereas the cannabinoid receptor antagonist SR141716A (3 mg/kg, i.p.) produced the opposite effect. SR141716A (3 mg/kg, i.p.) blocked the effects on DA release by WIN55212-2 (5 mg/kg, i.p.). Vehicle alone did not change DA release. These results suggest that cannabinoids modulate DA release in the striatum. C1 [Chai, Chok-Yung] Acad Sinica, Inst Biomed Sci, Taipei 11529, Taiwan. [Wu, Wun-Chin] Natl Penghu Univ, Dept Elect Engn, Penghu, Taiwan. [Wang, Yu] Natl Inst Drug Abuse, Baltimore, MD USA. RP Chai, CY (reprint author), Acad Sinica, Inst Biomed Sci, Taipei 11529, Taiwan. EM wcwu@npu.edu.tw NR 40 TC 6 Z9 6 U1 0 U2 0 PU CHINESE PHYSIOLOGICAL SOC PI TAIPEI PA NATL YANG-MING UNIV, TAIPEI, TAIWAN SN 0304-4920 J9 CHINESE J PHYSIOL JI Chin. J. Physiol. PD JUN 30 PY 2008 VL 51 IS 3 BP 152 EP 159 PG 8 WC Physiology SC Physiology GA 316JC UT WOS:000256944600005 PM 18935910 ER PT J AU Banerjee, S Smith, S Oum, JH Liaw, HJ Hwang, JY Sikdar, N Motegi, A Lee, SE Myung, K AF Banerjee, Soma Smith, Stephanie Oum, Ji-Hyun Liaw, Hung-Jiun Hwang, Ji-Young Sikdar, Nilabja Motegi, Akira Lee, Sang Eun Myung, Kyungjae TI Mph1p promotes gross chromosomal rearrangement through partial inhibition of homologous recombination SO JOURNAL OF CELL BIOLOGY LA English DT Article ID SACCHAROMYCES-CEREVISIAE HOMOLOG; FANCONI-ANEMIA; DNA-DAMAGE; TELOMERE ELONGATION; GENOMIC INSTABILITY; REPLICATION FORKS; HELICASE; YEAST; REPAIR; PROTEIN AB ross chromosomal rearrangement (GCR) is a type of genomic instability associated with many cancers. In yeast, multiple pathways cooperate to suppress GCR. In a screen for genes that promote GCR, we identified MPH1, which encodes a 3'-5' DNA helicase. Overexpression of Mph1p in yeast results in decreased efficiency of homologous recombination (HR) as well as delayed Rad51p recruitment to double-strand breaks (DSBs), which suggests that Mph1p promotes GCR by partially suppressing HR. A function for Mph1p in suppression of HR is further supported by the observation that deletion of both mph1 and srs2 synergistically sensitize cells to methyl methanesulfonate-induced DNA damage. The GCR-promoting activity of Mph1p appears to depend on its interaction with replication protein A (RPA). Consistent with this observation, excess Mph1p stabilizes RPA at DSBs. Furthermore, spontaneous RPA foci at DSBs are destabilized by the mph 1 Delta mutation. Therefore, Mph1p promotes GCR formation by partially suppressing HR, likely through its interaction with RPA. C1 [Banerjee, Soma; Smith, Stephanie; Liaw, Hung-Jiun; Hwang, Ji-Young; Sikdar, Nilabja; Motegi, Akira; Myung, Kyungjae] NHGRI, Genome Instabil Sect, Genet & Mol Biol Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. [Oum, Ji-Hyun; Lee, Sang Eun] Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, Inst Biotechnol, San Antonio, TX 78245 USA. RP Myung, K (reprint author), NHGRI, Genome Instabil Sect, Genet & Mol Biol Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. EM kmyung@nhgri.nih.gov RI Liaw, Hungjiun/G-7034-2014; OI Liaw, Hungjiun/0000-0002-3481-709X; Hwang, Ji-Young/0000-0001-8044-1989 FU Intramural NIH HHS; NHGRI NIH HHS [Z01 HG012003]; NIGMS NIH HHS [R01 GM071011, GM071011] NR 44 TC 29 Z9 29 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JUN 30 PY 2008 VL 181 IS 7 BP 1083 EP 1093 DI 10.1083/jcb.200711146 PG 11 WC Cell Biology SC Cell Biology GA 324VJ UT WOS:000257547200006 PM 18591428 ER PT J AU Long, XY Zuo, XN Kiviniemi, V Yang, Y Zou, QH Zhu, CZ Jiang, TZ Yang, H Gong, QY Wang, L Li, KC Xie, S Zang, YF AF Long, Xiang-Yu Zuo, Xi-Nian Kiviniemi, Vesa Yang, Yihong Zou, Qi-Hong Zhu, Chao-Zhe Jiang, Tian-Zi Yang, Hong Gong, Qi-Yong Wang, Liang Li, Kun-Cheng Xie, Sheng Zang, Yu-Feng TI Default mode network as revealed with multiple methods for resting-state functional MRI analysis SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE resting-state fMRI; default mode network; correlation analysis; independent component analysis; regional homogeneity ID INDEPENDENT COMPONENT ANALYSIS; ALZHEIMERS-DISEASE; CORTICAL NETWORKS; CINGULATE CORTEX; BRAIN-FUNCTION; CONNECTIVITY; FMRI; FLUCTUATIONS; HYPOTHESIS AB Recently, human brain activity during a resting-state has attracted increasing attention. Several studies have found that there are two networks: the default mode network and its anti-correlation network. Some studies have subsequently showed that the functions of brain areas within the default mode network are crucial in human mental activity. To further discern the brain default mode network as well as its anti-correlation network during resting-state, we used three methods to analyze resting-state functional magnetic resonance imaging (fMRI) data; regional homogeneity analysis, linear correlation and independent component analysis, on four groups of dataset. Our results showed the existence of these two networks prominently and consistently during a resting- and conscious-state across the three methods. This consistency was exhibited in four independent groups of normal adults. Moreover, the current results provided evidences that the brain areas within the two anti-correlated networks are highly integrated at both the intra- and inter-regional level. 2008 Elsevier B.V. All rights reserved. C1 [Long, Xiang-Yu; Zou, Qi-Hong; Zhu, Chao-Zhe; Zang, Yu-Feng] Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing 100875, Peoples R China. [Long, Xiang-Yu; Zuo, Xi-Nian; Jiang, Tian-Zi] Chinese Acad Sci, Inst Automat, Natl Lab Pattern Recognit, Beijing 100864, Peoples R China. [Kiviniemi, Vesa] Oulu Univ Hosp, Dept Diagnost Radiol, Oulu, Finland. [Yang, Yihong] Natl Inst Drug Abuse, Neuroimaging Res Branch, Natl Inst Hlth, Baltimore, MD 21042 USA. [Yang, Hong; Gong, Qi-Yong] Sichuan Univ, W China Hosp, Dept Radiol, HMRRC, Chengdu 610064, Peoples R China. [Xie, Sheng] Peking Univ, Hosp 1, Dept Radiol, Beijing, Peoples R China. [Gong, Qi-Yong] Univ Liverpool, Dept Med Imaging, MARIARC, Liverpool L69 3BX, Merseyside, England. RP Zang, YF (reprint author), Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing 100875, Peoples R China. EM zangy@263.net RI Zuo, Xi-Nian/A-7273-2009; Wang, Liang/E-8652-2011; Jiang, Tianzi/I-4256-2012; ZANG, Yu-Feng/J-1558-2012; OI ZANG, Yu-Feng/0000-0003-1833-8010; Zuo, Xi-Nian/0000-0001-9110-585X NR 34 TC 90 Z9 92 U1 1 U2 22 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD JUN 30 PY 2008 VL 171 IS 2 BP 349 EP 355 DI 10.1016/j.jneumeth.2008.03.021 PG 7 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 315EC UT WOS:000256859800021 PM 18486233 ER PT J AU Bradley, MM Silakowski, T Lang, PJ AF Bradley, Margaret M. Silakowski, Tammy Lang, Peter J. TI Fear of pain and defensive activation SO PAIN LA English DT Article DE fear; pain; dental anxiety; startle reflex; emotion; psychophysiology ID POTENTIATED STARTLE; DENTAL PAIN; BEHAVIORAL REACTIONS; REFLEX; ANXIETY; GENDER; SENSITIZATION; EMOTION; HUMANS; THREAT AB Fear of pain and its relationship to dental fear was investigated by measuring autonomic reactions (skin conductance and heart rate) in individuals reporting high and low dental fear when in the presence of a cue that threatened the presentation of electric shock ("threat") or not ("safe"). Acoustic startle probes were also presented during both threat and safe periods, and the reflexive eye blink, the skin conductance response, and cardiac changes to the startle probe measured. All participants reacted with greater defensive reactivity, including potentiated startle blinks, heightened skin conductance, and cardiac deceleration in the context of threat, compared to safe, cues. Individuals reporting high dental fear were significantly more reactive during threat periods, compared to low fear individuals, showing larger blink reflexes and heightened electrodermal activity, as well as heightened autonomic responses to the startle probe itself. Individual differences in defensive reactivity persisted even after participants received a single mild shock halfway through the experiment. The data indicate that threat of shock elicits heightened defensive reactivity in those reporting high dental fear, consistent with the hypothesis that fear of potentially painful events may be a potent mediator of the anxiety involved in anticipated medical and dental treatment. (C) 2007 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 [Bradley, Margaret M.; Silakowski, Tammy; Lang, Peter J.] Univ Florida, NIMH, Ctr Study Emot & Attent, Gainesville, FL 32611 USA. RP Bradley, MM (reprint author), Univ Florida, NIMH, Ctr Study Emot & Attent, Box 112766, Gainesville, FL 32611 USA. EM bradley@ufl.edu FU NIDCR NIH HHS [DE 13956, R01 DE013956, R01 DE013956-01]; NIMH NIH HHS [P50 MH 72850, P50 MH072850] NR 30 TC 45 Z9 47 U1 6 U2 22 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD JUN 30 PY 2008 VL 137 IS 1 BP 156 EP 163 DI 10.1016/j.pain.2007.08.027 PG 8 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 326BC UT WOS:000257631900018 PM 17904289 ER PT J AU Diaz-Asper, C Malley, J Genderson, M Apud, J Elvevag, B AF Diaz-Asper, Catherine Malley, James Genderson, Margo Apud, Jose Elvevag, Brita TI Context binding in schizophrenia: Effects of clinical symptomatology and item content SO PSYCHIATRY RESEARCH LA English DT Article DE context binding; source monitoring; affective valence; symptomatology ID AUDITORY HALLUCINATIONS; THOUGHT-DISORDER; COGNITIVE IMPAIRMENTS; RELATIVE RISK; REALITY; DEFICITS; MEMORY; BIASES; EXPERIENCES; PSYCHOSIS AB Impairments in source monitoring have been widely reported in schizophrenia, with patients typically misattributing self-generated items to external sources. Some studies have reported that patients with more severe positive symptoms (notably hallucinations) exhibit a greater impairment on these tasks, although findings are not uniformly positive. The emotional content of the items to be remembered also may affect subsequent retrieval, with some studies suggesting a greater misattribution bias for affectively-laden material. Recently, it has been proposed that schizophrenic patients have a fundamental deficit in binding different contextual elements together in memory. The effect of clinical symptomatology and item content on source monitoring and context binding has yet to be examined in a single study. Twenty-one patients with schizophrenia and 21 healthy control subjects completed a task wherein memory for affective and neutral word pairs was assessed in conjunction with memory for both source and temporal information. Schizophrenic patients performed more poorly than controls overall, and tended to exhibit a more fractionated retrieval of word pairs across all levels of affective valence. Current intellectual level and overall verbal memory performance were significantly correlated with context binding performance for positive and neutral word pairs. Clinical symptomatology was unrelated to source monitoring performance. The results of this pilot study provide tentative support for the notion that schizophrenia is associated with an impairment in combining contextual cues together to form a coherent memory of an event, irrespective of the affective valence of the material. Clinical symptomatology bore no significant relationship to source memory performance. Published by Elsevier Ireland Ltd. C1 [Diaz-Asper, Catherine; Genderson, Margo; Apud, Jose; Elvevag, Brita] NIMH, Clin Brain Disorders Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. [Malley, James] NIMH, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Diaz-Asper, C (reprint author), 1621 Wisconsin Ave NW, Washington, DC 20016 USA. EM cdiazasper@vra.net NR 56 TC 15 Z9 15 U1 5 U2 10 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD JUN 30 PY 2008 VL 159 IS 3 BP 259 EP 270 DI 10.1016/j.psychres.2007.02.018 PG 12 WC Psychiatry SC Psychiatry GA 313MD UT WOS:000256743800001 PM 18442860 ER PT J AU Konig, IR Ziegler, A Malley, JD AF Konig, Inke R. Ziegler, Andreas Malley, James D. TI Comments on 'Practical experiences on the necessity of external validation' - Author's reply SO STATISTICS IN MEDICINE LA English DT Letter ID ACUTE STROKE TRIALS C1 [Konig, Inke R.; Ziegler, Andreas] Med Univ Lubeck, Inst Med Biometrie & Stat, D-23538 Lubeck, Germany. [Malley, James D.] NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Konig, IR (reprint author), Med Univ Lubeck, Inst Med Biometrie & Stat, D-23538 Lubeck, Germany. EM inke.koenig@imbs.uni-luebeck.de; ziegler@imbs.uni-luebeck.de; jmalley@mail.nih.gov NR 11 TC 0 Z9 0 U1 0 U2 4 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD JUN 30 PY 2008 VL 27 IS 14 BP 2738 EP 2740 DI 10.1002/sim.3193 PG 3 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 313UA UT WOS:000256764300019 ER PT J AU Yu, SC Ping, YF Yi, L Zhou, ZH Chen, HH Yao, XH Gao, L Wang, JM Bian, XW AF Yu, Shi-cang Ping, Yi-fang Yi, Liang Zhou, Zhi-hua Chen, Han-hong Yao, Xiao-hong Gao, Lei Wang, Ji Ming Bian, Xiu-wu TI Isolation and characterization of cancer stem cells from a human glioblastoma cell line U87 SO CANCER LETTERS LA English DT Article DE cancer stem cells; glioblastoma; tumor spheres ID DISTINCT SIDE POPULATION; IDENTIFICATION; RESISTANCE; LEUKEMIA; TUMORS; IDENTIFY AB A variety of malignant cancers have been found to contain a subpopulation of stem cell-like tumor cells, or cancer stem cells (CSCs). However, the existence of CSCs in U87, a most commonly used glioma cell line, is still controversial. In this study, we demonstrate that U87 cell line contained a fraction of tumor cells that could form tumor spheres and were enriched by progressively increasing the concentration of serum-free neural stem cell medium with or without low dose vincristine. These cells possessed the ability of self-renewal and multipotency, the defined characteristics of CSCs. Moreover, the tumors formed by the secondary spheres displayed typical histological features of human glioblastoma, including cellular pleomorphism, pseudopalisades surrounding necrosis, hyperchromatic nuclei, high density of microvessels and invasion to the brain parenchyma. These results indicate that gradually increasing the concentration of serum-free neural stem cell culture medium with or without vincristine is a simple and effective method for isolation of CSCs to study the initiation and progression of human glioblastoma. (C) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Yu, Shi-cang; Ping, Yi-fang; Yi, Liang; Zhou, Zhi-hua; Chen, Han-hong; Yao, Xiao-hong; Bian, Xiu-wu] Third Mil Med Univ, Southwest Hosp, Inst Pathol, Chongqing 400038, Peoples R China. [Gao, Lei] Third Mil Med Univ, Xinqiao Hosp, Dept Hematol, Chongqing 400037, Peoples R China. [Wang, Ji Ming] Natl Canc Inst Frederick, Ctr Canc Res, Canc & Inflammat Program, Mol Immunoregulat Lab, Frederick, MD 21702 USA. RP Bian, XW (reprint author), Third Mil Med Univ, Southwest Hosp, Inst Pathol, Gaotanyan 30, Chongqing 400038, Peoples R China. EM bianxiuwu@263.net RI Bian, Xiuwu/F-1569-2011; yi, liang/K-6010-2012; Bian, Xiu-wu/D-4736-2017 OI Bian, Xiu-wu/0000-0003-4383-0197 NR 41 TC 131 Z9 145 U1 5 U2 32 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD JUN 28 PY 2008 VL 265 IS 1 BP 124 EP 134 DI 10.1016/j.canlet.2008.02.010 PG 11 WC Oncology SC Oncology GA 313GX UT WOS:000256730200013 PM 18343028 ER PT J AU Courter, LA Luch, A Musafia-Jeknic, T Arlt, VM Fischer, K Bildfell, R Pereira, C Phillips, DH Poirier, MC Baird, WM AF Courter, Lauren A. Luch, Andreas Musafia-Jeknic, Tamara Arlt, Volker M. Fischer, Kay Bildfell, Robert Pereira, Cliff Phillips, David H. Poirier, Miriam C. Baird, William M. TI The influence of diesel exhaust on polycyclic aromatic hydrocarbon-induced DNA damage, gene expression, and tumor initiation in Sencar mice in vivo SO CANCER LETTERS LA English DT Article DE DNA adducts; carcinogenesis; diesel exhaust; PAH; cytochrome P450 ID STANDARDIZED COMPLEX MIXTURE; PARTICULATE AIR-POLLUTION; CDNA MICROARRAY ANALYSIS; CYTOCHROMES P450 1A1; ALDO-KETO REDUCTASES; MOUSE SKIN; METABOLIC-ACTIVATION; LUNG-CANCER; COAL-TAR; EPITHELIAL-CELLS AB The carcinogenic effects of individual polycyclic aromatic hydrocarbons (PAH) are well established. However, their potency within an environmental complex mixture is uncertain. We evaluated the influence of diesel exhaust particulate matter oil PAH-induced cytochrome P450 (CYP) activity, PAH-DNA adduct formation, expression of certain candidate genes and the frequency Of tumor initiation in the two-stage Sencar mouse model. To this end, we monitored the effects of treatment of mice with diesel exhaust, benzo[a]pyrene (BP), dibenzo[a,l]pyrene (DBP), or a combination of diesel exhaust with either carcinogenic PAH. The applied diesel particulate matter (SRM1975) altered the tumor initiating potency of DBP: a statistically significant decrease in overall tumor and carcinoma burden was observed following 25 weeks of promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA), compared with DBP exposure alone. From those mice that were treated at the beginning of the observation period with 2 nmol DBP all survivors developed tumors (9 out of 9 animals, 100%). Among all tumors counted at the end, nine carcinomas were detected and all overall tumor incidence of 2.6 tumors per tumor-bearing animal (TBA) was determined. By contrast, co-treatment of DBP with 50 mg SRM1975 led to a tumor rate of only 66% (19 out of 29 animals), occurrence of only three carcinomas in 29 animals and an overall rate of 2.1 tumors per TBA (P = 0.04). In contrast to the results with DBP, the tumor incidence induced by 200 nmol BP was found slightly increased when co-treatment With SRM1975 occurred (71% vs. 85%) after 25 weeks). Despite this difference in tumor incidence, the numbers of carcinomas and tumors per TBA did not differ statistically significant between both treatment groups possibly due to the small size of the BP treatment group. Since bioactivation of DBP, but not BP, predominantly depends on CYP1B1 enzyme activity, SRM1975 affected PAH-induced carcinogenesis in an antagonistic manner when CYP1B1-mediated bioactivation was required. The explanation most likely lies in the much stronger inhibitory effects of certain PAHs present in diesel exhaust on CYP1B1 compared to CYP1A1. In the present study we also found molecular markers such as highly elevated AKR1C21 and TNFRSF21 gene expression levels in tumor tissue derived from animals co-treated with SRM1975 plus DBP. Therefore we validate microarray data as a source to uncover transcriptional signatures that may provide insights into molecular pathways affected following exposure to environmental complex mixtures such as diesel exhaust particulates. (C) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Courter, Lauren A.; Musafia-Jeknic, Tamara; Baird, William M.] Oregon State Univ, Dept Environm & Mol Toxicol, Corvallis, OR 97331 USA. [Luch, Andreas] Fed Inst Risk Assessment, Dept Prod Safety, Berlin, Germany. [Luch, Andreas] Fed Inst Risk Assessment, Dept Sci Serv ZEBET, Berlin, Germany. [Arlt, Volker M.; Phillips, David H.] Inst Canc Res, Sect Mol Carcinogenesis, Surrey SM2 5NG, England. [Fischer, Kay; Bildfell, Robert] Oregon State Univ, Coll Vet Med, Corvallis, OR 97331 USA. [Pereira, Cliff] Oregon State Univ, Dept Stat, Corvallis, OR 97331 USA. [Poirier, Miriam C.] Natl Canc Inst, Carcinogen DNA Interact Sect, NIH, Bethesda, MD 20892 USA. RP Baird, WM (reprint author), Oregon State Univ, Dept Environm & Mol Toxicol, Corvallis, OR 97331 USA. EM william.baird@oregonstate.edu OI Phillips, David/0000-0001-8509-3485; Arlt, Volker Manfred/0000-0003-4314-9318 FU Cancer Research UK; NCI NIH HHS [CA28825, R01 CA028825, R01 CA028825-19, R01 CA028825-20, R01 CA028825-21, R01 CA028825-22, R01 CA028825-23, R01 CA028825-24]; NIEHS NIH HHS [P30 ES000210, P30 ES00210, T32 ES007060] NR 72 TC 27 Z9 29 U1 1 U2 11 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD JUN 28 PY 2008 VL 265 IS 1 BP 135 EP 147 DI 10.1016/j.canlet.2008.02.017 PG 13 WC Oncology SC Oncology GA 313GX UT WOS:000256730200014 PM 18353537 ER PT J AU Oka, H Sakai, W Sonoda, E Nakamura, J Asagoshi, K Wilson, SH Kobayashi, M Yamamoto, K Heierhorst, J Takeda, S Taniguchi, Y AF Oka, Hayato Sakai, Wataru Sonoda, Eiichiro Nakamura, Jun Asagoshi, Kenjiro Wilson, Samuel H. Kobayashi, Masahiko Yamamoto, Kenichi Heierhorst, Joerg Takeda, Shunichi Taniguchi, Yoshihito TI DNA damage response protein ASCIZ links base excision repair with immunuglobulin gene conversion SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE ASCIZ; ATMIN; DT40; base excision repair; immunoglobulin gene conversion; DNA polymerase beta; genetics ID CLASS-SWITCH RECOMBINATION; SOMATIC HYPERMUTATION; DEAMINASE AID; ROLES; CELLS; DT40; BETA; ATM AB ASCIZ (ATMIN) was recently identified as a novel DNA damage response protein. Here we report that ASCIZ-deficient chicken DT40 B lymphocyte lines displayed markedly increased Ig gene conversion rates, whereas overexpression of human ASCIZ reduced Ig gene conversion below wild-type levels. However, neither the efficiency of double-strand break repair nor hypermutation was affected by ASCIZ levels, indicating that ASCIZ does not directly control homologous recombination or formation of abasic sites. Loss of ASCIZ led to mild sensitivity to the base damaging agent methylmethane sulfonate (MMS), yet remarkably, suppressed the dramatic MMS hypersensitivity of pol beta-deficient cells. These data suggest that ASCIZ may affect the choice between competing base repair pathways in a manner that reduces the amount of substrates available for Ig gene conversion. (C) 2008 Elsevier Inc. All rights reserved. C1 [Oka, Hayato; Sakai, Wataru; Sonoda, Eiichiro; Takeda, Shunichi; Taniguchi, Yoshihito] Kyoto Univ, Grad Sch Med, Dept Radiat Genet, Sakyo Ku, Kyoto 6068501, Japan. [Nakamura, Jun] Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA. [Asagoshi, Kenjiro; Wilson, Samuel H.] NIEHS, NIH, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. [Kobayashi, Masahiko; Yamamoto, Kenichi] Kanazawa Univ, Canc Res Inst, Dept Mol Pathol, Kanazawa, Ishikawa 9200934, Japan. [Heierhorst, Joerg] Univ Melbourne, St Vincents Inst Med Res, Fitzroy, Vic 3065, Australia. [Heierhorst, Joerg] Univ Melbourne, Dept Med SVH, Fitzroy, Vic 3065, Australia. RP Taniguchi, Y (reprint author), Kyoto Univ, Grad Sch Med, Dept Radiat Genet, Sakyo Ku, Kyoto 6068501, Japan. EM taniguchi@rg.med.kyoto-u.ac.jp RI Sakai, Wataru/J-6917-2012; Taniguchi, Yoshihito/L-5746-2013 FU Intramural NIH HHS NR 17 TC 10 Z9 10 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 27 PY 2008 VL 371 IS 2 BP 225 EP 229 DI 10.1016/j.bbrc.2008.04.052 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 303OL UT WOS:000256049700010 PM 18433721 ER PT J AU Jewett, TJ Dooley, CA Mead, DJ Hackstadt, T AF Jewett, Travis J. Dooley, Cheryl A. Mead, David J. Hackstadt, Ted TI Chlamydia trachomatis tarp is phosphorylated by src family tyrosine kinases SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Chlamydia trachomatis; src; Abl; tyrosine kinases; tarp ID HELICOBACTER-PYLORI CAGA; ACTIN; PROTEIN; ENTRY; CELLS; RECRUITMENT AB The translocated actin recruiting phosphoprotein (Tarp) is injected into the cytosol shortly after Chlamydia trachomatis attachment to a target cell and subsequently phosphorylated by an unidentified tyrosine kinase. A role for Tarp phosphorylation in bacterial entry is unknown. In this study, recombinant C trachomatis Tarp was employed to identify the host cell kinase(s) required for phosphorylation. Each tyrosine rich repeat of L2 Tarp harbors a sequence similar to a Src and AN kinase consensus target. Furthermore, purified p60-src, Yes, Fyn, and Abl kinases were able to phosphorylate Tarp. Mutagenesis of potential tyrosines within a single tyrosine rich repeat peptide indicated that both Src and Abl kinases phosphorylate the same residues suggesting that C. trachomatis Tarp may serve as a substrate for multiple host cell kinases. Surprisingly, chemical inhibition of Src and Abl kinases prevented Tarp phosphorylation in culture and had no measurable effect on bacterial entry into host cells. Published by Elsevier Inc. C1 [Jewett, Travis J.; Dooley, Cheryl A.; Mead, David J.; Hackstadt, Ted] NIAID, Host Parasite Interact Sect, Intracellular Parasites Lab, NIH,Rocky Mt Labs, Hamilton, MT 59840 USA. RP Hackstadt, T (reprint author), NIAID, Host Parasite Interact Sect, Intracellular Parasites Lab, NIH,Rocky Mt Labs, 903 S 4th St, Hamilton, MT 59840 USA. EM Ted_Hackstadt@NIH.gov FU Intramural NIH HHS [Z01 AI000567-17, Z99 AI999999] NR 20 TC 43 Z9 45 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 0006-291X EI 1090-2104 J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 27 PY 2008 VL 371 IS 2 BP 339 EP 344 DI 10.1016/j.bbrc.2008.04.089 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 303OL UT WOS:000256049700032 PM 18442471 ER PT J AU Patino-Lopez, G Dong, XY Ben-Aissa, K Bernot, KM Itoh, T Fukuda, M Kruhlak, MJ Samelson, LE Shaw, S AF Patino-Lopez, Genaro Dong, Xiaoyun Ben-Aissa, Khadija Bernot, Kelsie M. Itoh, Takashi Fukuda, Mitsunori Kruhlak, Michael J. Samelson, Lawrence E. Shaw, Stephen TI Rab35 and its GAP EPI64C in T cells regulate receptor recycling and immunological synapse formation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GTPASE-ACTIVATING PROTEIN; MEMBRANE MICRODOMAINS; DOMAIN; IDENTIFICATION; COSTIMULATION; POLARIZATION; BINDING; TCR; REORGANIZATION; CYTOSKELETON AB Upon antigen recognition, T-cell receptor (TCR/CD3) and other signaling molecules become enriched in a specialized contact site between the T cell and antigen-presenting cell, i.e. the immunological synapse (IS). Enrichment occurs via mechanisms that include polarized secretion from recycling endosomes, but the Rabs and RabGAPs that regulate this are unknown. EPI64C (TBC1D10C) is an uncharacterized candidate RabGAP we identified by mass spectrometry as abundant in human peripheral blood T cells that is preferentially expressed in hematopoietic cells. EPI64C is a Rab35-GAP based both on in vitro Rab35-specific GAP activity and findings in transfection assays. EPI64C and Rab35 dominant negative (DN) constructs each impaired transferrin export from a recycling pathway in Jurkat T-cells and induced large vacuoles marked by transferrin receptor, TCR, and SNAREs implicated in TCR-polarized secretion. Rab35 localized to the plasma membrane and to intracellular vesicles where it substantially colocalized with TfR and with TCR. Rab35 was strongly recruited to the IS. Conjugate formation was impaired by transfection with Rab35-DN or EPI64C and by EPI64C knock down. TCR enrichment at the IS was impaired by Rab35-DN. Thus, EPI64C and Rab35 regulate a recycling pathway in T cells and contribute to IS formation, most likely by participating in TCR transport to the IS. C1 [Patino-Lopez, Genaro; Dong, Xiaoyun; Ben-Aissa, Khadija; Kruhlak, Michael J.; Shaw, Stephen] NIH, NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. [Bernot, Kelsie M.; Samelson, Lawrence E.] NIH, NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA. [Itoh, Takashi; Fukuda, Mitsunori] RIKEN, Fukuda Initiat Res Unit, Inst Phys & Chem Res, Wako, Saitama 3510198, Japan. [Itoh, Takashi; Fukuda, Mitsunori] Tohoku Univ, Grad Sch Life Sci, Dept Dev Biol & Neurosci, Lab Membrane Trafficking Mech, Sendai, Miyagi 9808578, Japan. RP Shaw, S (reprint author), NIH, NCI, Expt Immunol Branch, Bldg 10,Rm 4B36,10 Ctr Dr,MSC 1360, Bethesda, MD 20892 USA. EM sshaw@nih.gov RI Fukuda, MItsunori/I-1511-2015; OI Patino-Lopez, Genaro/0000-0002-8716-722X FU Intramural NIH HHS NR 40 TC 73 Z9 74 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 27 PY 2008 VL 283 IS 26 BP 18323 EP 18330 DI 10.1074/jbc.M800056200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 316KU UT WOS:000256949200060 PM 18450757 ER PT J AU Nagaoka, T Fukuda, T Hlashizume, T Nishiyama, T Tada, H Yamada, H Salomon, DS Yamada, S Kojima, I Seno, M AF Nagaoka, Tadahiro Fukuda, Takayuki Hlashizume, Toshihiro Nishiyama, Tomoko Tada, Hiroko Yamada, Hidenori Salomon, David S. Yamada, Satoko Kojima, Itaru Seno, Masaharu TI A betacellulin mutant promotes differentiation of pancreatic acinar AR42J cells into insulin-producing cells with low affinity of binding to ErbB1 SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE betacellulin; ErbB1; ErbB4; receptor-ligand interaction; cell differentiation ID EPIDERMAL-GROWTH-FACTOR; STREPTOZOTOCIN-TREATED RATS; SITE-DIRECTED MUTAGENESIS; FACTOR RECEPTOR; EXTRACELLULAR REGION; BETA-CELLS; CRYSTAL-STRUCTURE; ACTIVIN-A; DOMAIN; REGENERATION AB Betacellulin (BTC) is one of the members of the epidermal growth factor (EGF) ligand family of ErbB receptor tyrosine kinases. It is a differentiation factor as well as a potent mitogen. BTC promotes the differentiation of pancreatic acinar-derived AR42J cells into insulin-producing cells. It independently and preferentially binds to two type I tyrosine kinase receptors, the EGF receptor (ErbB1) and ErbB4. However, the physiochemical characteristics of BTC that are responsible for its preferential binding to these two receptors have not been fully defined. In this study, to investigate the essential amino acid residues of BTC for binding to the two receptors, we introduced point mutations into the EGF domain of BTC employing error-prone PCR. The receptor binding abilities of 190 mutants expressed in Escherichia coli were assessed by enzyme immunoassay. Replacement of the glutamic acid residue at position 88 with a lysine residue in BTC was found to produce a significant loss of affinity for binding to ErbB1, while the affinity of binding to ErbB4 was unchanged. In addition, the mutant of BTC-E/88/K showed less growth-promoting activity on BALB/c 3T3 cells compared with that of the wild-type BTC protein. Interestingly, the BTC mutant protein promoted differentiation of pancreatic acinar AR42J cells at a high frequency into insulin-producing cells compared with AR42J cells that were treated with wild-type BTC protein. These results indicate the possibility of designing BTC mutants, which have an activity of inducing differentiation only, without facilitating growth promotion. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Nagaoka, Tadahiro; Fukuda, Takayuki; Hlashizume, Toshihiro; Nishiyama, Tomoko; Tada, Hiroko; Yamada, Hidenori; Seno, Masaharu] Okayama Univ, Dept Med Bioengn, Grad Sch Nat Sci & Technol, Okayama 7008530, Japan. [Salomon, David S.] NCI, Mammary Biol & Tumorigenesis Lab, Bethesda, MD 20892 USA. [Yamada, Satoko; Kojima, Itaru] Gunma Univ, Inst Mol & Cellular Regulat, Maebashi, Gumma 3718512, Japan. RP Seno, M (reprint author), Okayama Univ, Dept Med Bioengn, Grad Sch Nat Sci & Technol, 3-1-1 Tsushima Naka, Okayama 7008530, Japan. EM mseno@cc.okayama-u.ac.jp RI YAMADA, Hidenori/B-2639-2011; SENO, Masaharu /B-2092-2011; OI SENO, Masaharu /0000-0001-8547-6259; Nagaoka, Tadahiro/0000-0002-9391-0243 NR 39 TC 9 Z9 12 U1 0 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JUN 27 PY 2008 VL 380 IS 1 BP 83 EP 94 DI 10.1016/j.jmb.2008.03.054 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 323SV UT WOS:000257469600007 PM 18508082 ER PT J AU Bainbridge, NK Koselke, LR Jeon, J Bailey, KR Wess, J Crawley, JN Wrenn, CC AF Bainbridge, Natalie K. Koselke, Lisa R. Jeon, Jongrye Bailey, Kathleen R. Wess, Juergen Crawley, Jacqueline N. Wrenn, Craige C. TI Learning and memory impairments in a congenic C57BL/6 strain of mice that lacks the M-2 muscarinic acetylcholine receptor subtype SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE acetylcholine; muscarinic; memory; knockout; M-2; passive avoidance; habituation; holeboard ID KNOCKOUT MICE; CORTICAL ACETYLCHOLINE; BEHAVIORAL PHENOTYPES; ALZHEIMERS-DISEASE; PERIPHERAL-TISSUES; BASAL FOREBRAIN; IMPAIRED RATS; EGF RECEPTOR; ANTAGONIST; RELEASE AB The neurotransmitter acetylcholine is an important modulator of cognitive functions including attention, learning, and memory. The actions of acetylcholine are mediated by five distinct muscarinic acetylcholine receptor subtypes (M-1-M-5). The lack of drugs with a high degree of selectivity for these subtypes has impeded the determination of which subtypes mediate which components of cholinergic neurotransmission relevant to cognitive abilities. The present study examined the behavioral functions of the M-2 muscarinic receptor subtype by utilizing congenic C57BL/6 mice possessing a null-mutation in the M-2 muscarinic receptor gene (M-2(-/-) mice). Comprehensive assessment of general health and the neurological function found no major differences between M-2(-/-) and wild-type (M-2(+/+)) mice. In the tests of learning and memory, M-2(-/-) mice were impaired in the acquisition (trials to criterion), but not the retention (72 h) of a passive avoidance task. In a novel open field, M-2(-/-) mice were impaired in between-sessions, but not within-session habituation. In a holeboard test of spatial memory, M-2(-/-) mice committed more errors in working memory than M-2(+/+) mice. Reference memory did not differ between the genotypes. M-2(-/-) mice showed no impairments in either cued or contextual fear conditioning. These findings replicate and extend earlier findings in a hybrid strain and solidify the interpretation that the M-2 receptor plays a critical role in specific components of cognitive abilities. (c) 2008 Elsevier B.V. All rights reserved. C1 [Bainbridge, Natalie K.; Koselke, Lisa R.; Wrenn, Craige C.] Drake Univ, Coll Pharm & Hlth Sci, Des Moines, IA 50311 USA. [Jeon, Jongrye; Wess, Juergen] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. [Bailey, Kathleen R.; Crawley, Jacqueline N.] NIMH, Lab Behav Neurosci, NIH, Bethesda, MD 20892 USA. RP Wrenn, CC (reprint author), Drake Univ, Coll Pharm & Hlth Sci, 2507 Univ Ave, Des Moines, IA 50311 USA. EM craige.wrenn@drake.edu FU Intramural NIH HHS [Z01 DK031133-01, Z01 MH002179-22] NR 55 TC 25 Z9 25 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD JUN 26 PY 2008 VL 190 IS 1 BP 50 EP 58 DI 10.1016/j.bbr.2008.02.001 PG 9 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 299PF UT WOS:000255766800006 PM 18346798 ER PT J AU Rosales, T Xu, JH Wu, XW Hodoseek, M Callis, P Brooks, BR Knutson, JR AF Rosales, Tilman Xu, Jianhua Wu, Xiongwu Hodoseek, Milan Callis, Patrik Brooks, Bernard R. Knutson, Jay R. TI Molecular dynamics simulations of perylene and tetracene librations: Comparison with femtosecond upconversion data SO JOURNAL OF PHYSICAL CHEMISTRY A LA English DT Article ID VIBRATIONAL-RELAXATION DYNAMICS; ROTATIONAL DIFFUSION; FLUORESCENCE ANISOTROPY; N-ALCOHOLS; ALKANES; SOLVENT; DECAY; REORIENTATION; HEXADECANE; BEHAVIOR AB In a prior manuscript by Xu et al. [Xu, J.; Shen, X.; Knutson, J. R. J. Phys. Chem. A 2003, 107, 8383], time-resolved fluorescence emission anisotropy measurements were performed on perylene and tetracene in hexadecane using an upconversion technique with similar to 100 fs resolution. The anisotropy transients contained previously unseen decay terms of similar to 300 fs. In perylene, their amplitude corresponded to the "r(o) defect" that has gathered interest over decades. We ascribed this term to a predominantly in-plane libration. In this manuscript, we present molecular dynamics simulations for the motions of perylene and tetracene using the CHARMm molecular dynamics program (version c29b2). Both rotational correlation functions contain subpicosecond decay terms that resemble experimental anisotropy decays. It was suggested that the r(o) defect might arise from excited-state distortions of perylene, so we conducted quantum mechanical calculations to show that such distortion does not significantly displace the oscillators. We compare the case of perylene, with a strongly allowed singlet emission transition, to that of the weakly allowed tetracene transition. In perylene, motion alone can explain subpicosecond anisotropy decay, while tetracene decay also contains vibrational coupling terms, as previously reported by Sarkar et al. [Sarkar, N.; Takeuchi, S.; Tahara, T. J. Phys. Chem. A 1999, 103, 4808]. C1 [Rosales, Tilman; Xu, Jianhua; Knutson, Jay R.] NHLBI, Opt Spect Sect, Mol Biophys Lab, NIH, Bethesda, MD 20892 USA. [Wu, Xiongwu; Hodoseek, Milan; Brooks, Bernard R.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. [Callis, Patrik] Montana State Univ, Dept Chem & Biochem, Bozeman, MT 59717 USA. RP Knutson, JR (reprint author), NHLBI, Opt Spect Sect, Mol Biophys Lab, NIH, Bldg 10,Magnuson CC,5D14,10 Ctr Dr, Bethesda, MD 20892 USA. EM jaysan@helix.nih.gov FU Intramural NIH HHS [ZIA HL001452-28] NR 29 TC 2 Z9 2 U1 3 U2 13 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1089-5639 J9 J PHYS CHEM A JI J. Phys. Chem. A PD JUN 26 PY 2008 VL 112 IS 25 BP 5593 EP 5597 DI 10.1021/jp7117289 PG 5 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 315ZU UT WOS:000256919500005 PM 18507364 ER PT J AU Rothenberg, ME Weller, PF Klion, A AF Rothenberg, Marc E. Weller, Peter F. Klion, Amy TI Hypereosinophilic syndrome and mepolizumab - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Rothenberg, Marc E.] Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. [Weller, Peter F.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Klion, Amy] NIH, Bethesda, MD 20892 USA. RP Rothenberg, ME (reprint author), Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. EM rothenberg@cchmc.org 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 JUN 26 PY 2008 VL 358 IS 26 BP 2839 EP 2840 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 317UO UT WOS:000257045900018 ER PT J AU Vikram, B AF Vikram, Bhadrasain TI Survival for patients with pancreatic cancer after addition of gemcitabine to fluorouracil chemoradiation SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 NCI, Clin Radiat Oncol Branch, Rockville, MD 20857 USA. RP Vikram, B (reprint author), NCI, Clin Radiat Oncol Branch, Rockville, MD 20857 USA. EM vikramb@mail.nih.gov NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 25 PY 2008 VL 299 IS 24 BP 2852 EP 2852 DI 10.1001/jama.299.24.2852-b PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 317LN UT WOS:000257021800014 PM 18577724 ER PT J AU Bjornsson, HT Sigurdsson, MI Fallin, MD Irizarry, RA Aspelund, T Cui, HM Yu, WQ Rongione, MA Ekstrom, TJ Harris, TB Launer, LJ Eiriksdottir, G Leppert, MF Sapienza, C Gudnason, V Feinberg, AP AF Bjornsson, Hans T. Sigurdsson, Martin I. Fallin, M. Daniele Irizarry, Rafael A. Aspelund, Thor Cui, Hengmi Yu, Wenqiang Rongione, Michael A. Ekstrom, Tomas J. Harris, Tamara B. Launer, Lenore J. Eiriksdottir, Gudny Leppert, Mark F. Sapienza, Carmen Gudnason, Vilmundur Feinberg, Andrew P. TI Intra-individual change over time in DNA methylation with familial clustering SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HUMAN-DISEASE; EPIGENETICS; CANCER; REGIONS; RISK AB Context Changes over time in epigenetic marks, which are modifications of DNA such as by DNA methylation, may help explain the late onset of common human diseases. However, changes in methylation or other epigenetic marks over time in a given individual have not yet been investigated. Objectives To determine whether there are longitudinal changes in global DNA methylation in individuals and to evaluate whether methylation maintenance demonstrates familial clustering. Design, Setting, and Participants We measured global DNA methylation by luminometric methylation assay, a quantitative measurement of genome- wide DNA methylation, on DNA sampled at 2 visits on average 11 years apart in 111 individuals from an Icelandic cohort ( 1991 and 2002- 2005) and on average 16 years apart in 126 individuals from a Utah sample ( 1982- 1985 and 1997- 2005). Main Outcome Measure Global methylation changes over time. Results Twenty- nine percent of Icelandic individuals showed greater than 10% methylation change over time ( P <. 001). The family- based Utah sample also showed intra-individual changes over time, and further demonstrated familial clustering of methylation change ( P=. 003). The family showing the greatest global methylation loss also demonstrated the greatest loss of gene- specific methylation by a separate methylation assay. Conclusion These data indicate that methylation changes over time and suggest that methylation maintenance may be under genetic control. C1 [Aspelund, Thor; Eiriksdottir, Gudny; Gudnason, Vilmundur] Hjartavernd, IS-201 Kopavogur, Iceland. [Bjornsson, Hans T.; Sigurdsson, Martin I.; Cui, Hengmi; Yu, Wenqiang; Rongione, Michael A.; Feinberg, Andrew P.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA. [Fallin, M. Daniele] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. [Fallin, M. Daniele; Irizarry, Rafael A.] Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21205 USA. [Bjornsson, Hans T.; Sigurdsson, Martin I.; Fallin, M. Daniele; Irizarry, Rafael A.; Cui, Hengmi; Yu, Wenqiang; Rongione, Michael A.; Feinberg, Andrew P.] Johns Hopkins Univ, Ctr Epigenet, Baltimore, MD USA. [Ekstrom, Tomas J.] Karolinska Univ Hosp Solna, Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden. [Harris, Tamara B.; Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA. [Leppert, Mark F.] Univ Utah, Dept Human Genet, Salt Lake City, UT USA. [Leppert, Mark F.] Univ Utah, Eccles Inst Human Genet, Salt Lake City, UT USA. [Sapienza, Carmen] Temple Univ, Sch Med, Fels Inst Canc Res, Philadelphia, PA 19122 USA. [Sapienza, Carmen] Temple Univ, Sch Med, Dept Pathol, Philadelphia, PA 19122 USA. RP Gudnason, V (reprint author), Hjartavernd, Holtasmari 1, IS-201 Kopavogur, Iceland. EM v.gudnason@hjarta.is; afeinberg@jhu.edu RI Aspelund, Thor/C-5983-2008; Aspelund, Thor/F-4826-2011; Bjornsson, Hans/A-2964-2013; Gudnason, Vilmundur/K-6885-2015 OI Aspelund, Thor/0000-0002-7998-5433; Bjornsson, Hans/0000-0001-6635-6753; Gudnason, Vilmundur/0000-0001-5696-0084 FU Intramural NIH HHS [Z01 AG007380-02]; NCRR NIH HHS [M01 RR000064, M01-RR00064, R01 RR021967, R01 RR021967-02]; NHGRI NIH HHS [P50 HG003233, P50-HG003233]; NIA NIH HHS [N01AG12100]; NIEHS NIH HHS [R01 ES015211, R01-ES015211]; NIGMS NIH HHS [R01 GM083084, R01 GM083084-02] NR 30 TC 380 Z9 389 U1 1 U2 21 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 25 PY 2008 VL 299 IS 24 BP 2877 EP 2883 DI 10.1001/jama.299.24.2877 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 317LN UT WOS:000257021800025 PM 18577732 ER PT J AU Chen, Z Montcouquiol, M Calderon, R Jenkins, NA Copeland, NG Kelley, MW Noben-Trauth, K AF Chen, Zheng Montcouquiol, Mireille Calderon, Rene Jenkins, Nancy A. Copeland, Neal G. Kelley, Matthew W. Noben-Trauth, Konrad TI Jxc1/Sobp, encoding a nuclear zinc finger protein, is critical for cochlear growth, cell fate, and patterning of the organ of corti SO JOURNAL OF NEUROSCIENCE LA English DT Article DE cochlea dysplasia; organ of Corti; FCS zinc finger; Kolliker's organ; Jackson circler; Jxc1 ID INNER-EAR DEVELOPMENT; SENSORY EPITHELIA; HAIR-CELLS; POLYCOMB COMPLEXES; PLANAR POLARITY; MUTANT MOUSE; MORPHOGENESIS; MECHANISMS; DEFECTS; MAMMALS AB The mouse cochlea emerges from the ventral pole of the otocyst to form a one and three-quarter coil. Little is known about the factors that control the growth of the cochlea. Jackson circler (jc) is a recessive mutation causing deafness resulting from a growth arrest of the cochlea duct at day 13.5 of embryonic development. Here, we identify the vertebrate homolog of the Drosophila Sobp (sine oculis-binding protein) gene (named Jxc1) in the jc locus. Jxc1 encodes a nuclear protein that has two FCS-type zinc finger domains (PS51024) and bears nuclear localization signals and highly conserved sequence motifs. Transiently expressed wild-type protein is targeted to the nucleus, but mutant isoforms were mislocalized in the cytoplasm. In jc mutants, the cellular patterning of the organ of Corti is severely disrupted, exhibiting supernumerary hair cells at the apex, showing mirror-image duplications of tunnel of Corti and inner hair cells, and expressing ectopic vestibular-like hair cells within Kolliker's organ. Jxc1 mRNA was detected in inner ear sensory hair cells, supporting cells, and the acoustic ganglia. Expression was also found in the developing retina, olfactory epithelium, trigeminal ganglion, and hair follicles. Collectively, our data support a role for Jxc1 in controlling a critical step in cochlear growth, cell fate, and patterning of the organ of Corti. C1 [Chen, Zheng; Calderon, Rene; Noben-Trauth, Konrad] Natl Inst Deafness & Other Commun Disorders, Neurogenet Sect, Mol Biol Lab, NIH, Rockville, MD 20850 USA. [Montcouquiol, Mireille; Kelley, Matthew W.] Natl Inst Deafness & Other Commun Disorders, Sect Dev Neurosci, Mol Biol Lab, NIH, Rockville, MD 20850 USA. [Montcouquiol, Mireille] INSERM, U862, F-33077 Bordeaux, France. [Jenkins, Nancy A.; Copeland, Neal G.] Natl Canc Inst, Mouse Canc Genet Program, Frederick, MD 21702 USA. RP Noben-Trauth, K (reprint author), 5 Res Court, Rockville, MD 20850 USA. EM nobentk@nidcd.nih.gov OI montcouquiol, mireille/0000-0001-8739-6519 FU Intramural NIH HHS [Z01 DC000056-09] NR 32 TC 22 Z9 22 U1 0 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUN 25 PY 2008 VL 28 IS 26 BP 6633 EP 6641 DI 10.1523/JNEUROSCI.1280-08.2008 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 318RW UT WOS:000257110800011 PM 18579736 ER PT J AU Caetano, FA Lopes, MH Hajj, GNM Machado, CF Arantes, CP Magalhaes, AC Vieira, MDPB Americo, TA Massensini, AR Priola, SA Vorberg, I Gomez, MV Linden, R Prado, VF Martins, VR Prado, MAM AF Caetano, Fabiana A. Lopes, Marilene H. Hajj, Glaucia N. M. Machado, Cleiton F. Arantes, Camila Pinto Magalhaes, Ana C. Vieira, Monica De Paoli B. Americo, Tatiana A. Massensini, Andre R. Priola, Suzette A. Vorberg, Ina Gomez, Marcus V. Linden, Rafael Prado, Vania F. Martins, Vilma R. Prado, Marco A. M. TI Endocytosis of prion protein is required for ERK1/2 signaling induced by stress-inducible protein 1 SO JOURNAL OF NEUROSCIENCE LA English DT Article DE neurodegeneration; endocytosis; clathrin; raft; prion diseases; flotillin; ERK ID VESICULAR ACETYLCHOLINE TRANSPORTER; CLATHRIN-COATED PITS; HEAT-SHOCK PROTEINS; CELLULAR PRION; MOLECULAR CHAPERONE; SN56 CELLS; IN-VITRO; TRAFFICKING; PRP; SURFACE AB The secreted cochaperone STI1 triggers activation of protein kinase A (PKA) and ERK1/2 signaling by interacting with the cellular prion (PrPC) at the cell surface, resulting in neuroprotection and increased neuritogenesis. Here, we investigated whether STI1 triggers PrPC trafficking and tested whether this process controls PrPC-dependent signaling. We found that STI1, but not a STI1 mutant unable to bind PrPC, induced PrPC endocytosis. STI1-induced signaling did not occur in cells devoid of endogenous PrPC; however, heterologous expression of PrPC reconstituted both PKA and ERK1/2 activation. In contrast, a PrPC mutant lacking endocytic activity was unable to promote ERK1/2 activation induced by STI1, whereas it reconstituted PKA activity in the same condition, suggesting a key role of endocytosis in the former process. The activation of ERK1/2 by STI1 was transient and appeared to depend on the interaction of the two proteins at the cell surface or shortly after internalization. Moreover, inhibition of dynamin activity by expression of a dominant-negative mutant caused the accumulation and colocalization of these proteins at the plasma membrane, suggesting that both proteins use a dynamin-dependent internalization pathway. These results show that PrPC endocytosis is a necessary step to modulate STI1-dependent ERK1/2 signaling involved in neuritogenesis. C1 [Lopes, Marilene H.; Hajj, Glaucia N. M.; Machado, Cleiton F.; Arantes, Camila Pinto; Martins, Vilma R.] Hosp Alemao Oswaldo Cruz, Ludwig Inst Canc Res, BR-01323903 Sao Paulo, Brazil. [Caetano, Fabiana A.; Magalhaes, Ana C.; Vieira, Monica De Paoli B.; Gomez, Marcus V.; Prado, Marco A. M.] Univ Fed Minas Gerais, Inst Ciencias Biol, Programa Farmacol Bioquim & Mol, Dept Farmacol, BR-30270910 Belo Horizonte, MG, Brazil. [Massensini, Andre R.] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Fisiol & Biofis, BR-30270910 Belo Horizonte, MG, Brazil. [Prado, Vania F.] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Bioquim Imunol, BR-30270910 Belo Horizonte, MG, Brazil. [Arantes, Camila Pinto] Univ Sao Paulo, Dept Bioquim, Inst Quim, BR-05508900 Sao Paulo, Brazil. [Americo, Tatiana A.; Linden, Rafael] Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, BR-21949900 Rio de Janeiro, Brazil. [Priola, Suzette A.] NIAID, Persistent Viral Dis Lab, NIH, Rocky Mt Labs, Hamilton, MT 59840 USA. [Vorberg, Ina] Tech Univ Munich, Inst Virol, D-81675 Munich, Germany. RP Martins, VR (reprint author), Hosp Alemao Oswaldo Cruz, Ludwig Inst Canc Res, Rua Joao Juliao 245 1A, BR-01323903 Sao Paulo, Brazil. EM vmartins@ludwig.org.br; mprado@icb.ufmg.br RI Martins, Vilma/E-2547-2012; Gomez, Marcus Vinicius/I-4081-2012; Massensini, Andre/J-3568-2012; Prado, Vania/K-7630-2013; Oncogenomica, Inct/H-9999-2013; Neurociencia, Inct/I-1011-2013; Prado, Marco/K-7638-2013; Linden, Rafael/F-2275-2011; Machado, Cleiton Fagundes/I-5907-2014; Massensini, Andre/C-7697-2015; Hajj, Glaucia/I-8176-2015; Francisco, Suely/D-9065-2014 OI Martins, Vilma/0000-0002-2909-8502; Massensini, Andre/0000-0002-1508-3801; Prado, Vania/0000-0003-4994-6393; Prado, Marco/0000-0002-3028-5778; Linden, Rafael/0000-0003-3287-336X; Machado, Cleiton Fagundes/0000-0002-3313-3868; Massensini, Andre/0000-0002-1508-3801; FU FIC NIH HHS [R21 TW007800, R21 TW007800-01, R03 TW007025-01, R21 TW007800-02, R03 TW007025]; Howard Hughes Medical Institute NR 69 TC 54 Z9 55 U1 0 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUN 25 PY 2008 VL 28 IS 26 BP 6691 EP 6702 DI 10.1523/JNEUROSCI.1701-08.2008 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 318RW UT WOS:000257110800018 PM 18579743 ER PT J AU Ishizuya-Oka, A Shi, YB AF Ishizuya-Oka, Atsuko Shi, Yun-Bo TI Thyroid hormone regulation of stem cell development during intestinal remodeling SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE thyroid hormone (T3); intestinal remodeling; stem cell; T3 response gene; T3 receptor (TR) ID XENOPUS-LAEVIS METAMORPHOSIS; ADULT EPITHELIAL DEVELOPMENT; MATRIX-METALLOPROTEINASE STROMELYSIN-3; MOUSE SMALL-INTESTINE; ALPHA TR-ALPHA; AMPHIBIAN METAMORPHOSIS; GENE-EXPRESSION; SONIC HEDGEHOG; POSTEMBRYONIC DEVELOPMENT; PROGENITOR CELLS AB During amphibian metamorphosis the small intestine is remodeled from larval to adult form, analogous to the mammalian intestine. The larval epithelium mostly undergoes apoptosis, while a small number of stem cells appear, actively proliferate, and differentiate into the adult epithelium possessing a cell-renewal system. Because amphibian intestinal remodeling is completely controlled by thyroid hormone (T3) through T3 receptors (TRs), it serves as an excellent model for studying the molecular mechanism of the mammalian intestinal development. TRs bind T3 response elements in target genes and have dual functions by interacting with coactivators or corepressors in a T3-dependent manner. A number of T3 response genes have been isolated from the Xenopus laevis intestine. They include signaling molecules, matrix metalloproteinases, and transcription factors. Functional studies have been carried out on many such genes in vitro and in vivo by using transgenic and culture technologies. Here we will review recent findings from such studies with a special emphasis on the adult intestinal stem cells, and discuss the evolutionarily conserved roles of T3 in the epithelial cell-renewal in the vertebrate intestine. (C) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Ishizuya-Oka, Atsuko] Nippon Med Sch, Dept Biol, Kanagawa 2110063, Japan. [Shi, Yun-Bo] NICHHD, Lab Gene Regulat & Dev, Bethesda, MD 20892 USA. RP Ishizuya-Oka, A (reprint author), Nippon Med Sch, Dept Biol, Kanagawa 2110063, Japan. EM a-oka@nms.ac.jp; shi@helix.nih.gov FU Intramural NIH HHS NR 100 TC 12 Z9 12 U1 1 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD JUN 25 PY 2008 VL 288 IS 1-2 BP 71 EP 78 DI 10.1016/j.mce.2008.02.020 PG 8 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 326DT UT WOS:000257639100009 PM 18400374 ER PT J AU Elisaphenko, EA Kolesnikov, NN Shevchenko, AI Rogozin, IB Nesterova, TB Brockdorff, N Zakian, SM AF Elisaphenko, Eugeny A. Kolesnikov, Nikolay N. Shevchenko, Alexander I. Rogozin, Igor B. Nesterova, Tatyana B. Brockdorff, Neil Zakian, Suren M. TI A Dual Origin of the Xist Gene from a Protein-Coding Gene and a Set of Transposable Elements SO PLOS ONE LA English DT Article AB X-chromosome inactivation, which occurs in female eutherian mammals is controlled by a complex X-linked locus termed the X-inactivation center (XIC). Previously it was proposed that genes of the XIC evolved, at least in part, as a result of pseudogenization of protein-coding genes. In this study we show that the key XIC gene Xist, which displays fragmentary homology to a protein-coding gene Lnx3, emerged de novo in early eutherians by integration of mobile elements which gave rise to simple tandem repeats. The Xist gene promoter region and four out of ten exons found in eutherians retain homology to exons of the Lnx3 gene. The remaining six Xist exons including those with simple tandem repeats detectable in their structure have similarity to different transposable elements. Integration of mobile elements into Xist accompanies the overall evolution of the gene and presumably continues in contemporary eutherian species. Additionally we showed that the combination of remnants of protein-coding sequences and mobile elements is not unique to the Xist gene and is found in other XIC genes producing non-coding nuclear RNA. C1 [Elisaphenko, Eugeny A.; Kolesnikov, Nikolay N.; Shevchenko, Alexander I.; Rogozin, Igor B.; Zakian, Suren M.] Russian Acad Sci, Inst Cytol & Genet, Siberian Dept, Novosibirsk 630090, Russia. [Rogozin, Igor B.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD USA. [Nesterova, Tatyana B.] Imperial Coll, Fac Med, Clin Sci Ctr, Med Res Council, London, England. [Brockdorff, Neil] Univ Oxford, Dept Biochem, Oxford, England. RP Elisaphenko, EA (reprint author), Russian Acad Sci, Inst Cytol & Genet, Siberian Dept, Novosibirsk 630090, Russia. EM zakian@bionet.nsc.ru RI Kolesnikov, Nikolay/N-7569-2015; OI Kolesnikov, Nikolay/0000-0001-7005-0888; Nesterova, Tatyana/0000-0001-7740-4386 FU Russian Foundation for Fundamental Research [06-04-48337-a, 08-04-00346-a]; Russian Academy of Sciences [10.8]; Intramural Research Program of the National Library of Medicine at National Institutes of Health/DHHS FX The work was supported by the Russian Foundation for Fundamental Research (grants no. 06-04-48337-a and 08-04-00346-a), Russian Academy of Sciences foundation program for Molecular and Cellular Biology and by grant 10.8 from the Interdisciplinary Integration Project of the Siberian Division of the Russian Academy of Sciences. I.B.R. was supported in part by the Intramural Research Program of the National Library of Medicine at National Institutes of Health/DHHS. NR 28 TC 67 Z9 70 U1 3 U2 17 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 25 PY 2008 VL 3 IS 6 AR e2521 DI 10.1371/journal.pone.0002521 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 406IK UT WOS:000263288000037 PM 18575625 ER PT J AU Jiang, HY Patel, JJ Yi, M Mu, JB Ding, JH Stephens, R Cooper, RA Ferdig, MT Su, XZ AF Jiang, Hongying Patel, Jigar J. Yi, Ming Mu, Jianbing Ding, Jinhui Stephens, Robert Cooper, Roland A. Ferdig, Michael T. Su, Xin-zhuan TI Genome-Wide Compensatory Changes Accompany Drug-Selected Mutations in the Plasmodium falciparum crt Gene SO PLOS ONE LA English DT Article ID CHLOROQUINE-RESISTANCE TRANSPORTER; TRANSMEMBRANE PROTEIN PFCRT; DIGESTIVE VACUOLAR PH; MALARIA PARASITES; LINKAGE DISEQUILIBRIUM; MEFLOQUINE RESISTANCE; ANTIBIOTIC-RESISTANCE; PFMDR1 GENE; QUININE; SENSITIVITY AB Mutations in PfCRT (Plasmodium falciparum chloroquine-resistant transporter), particularly the substitution at amino acid position 76, confer chloroquine (CQ) resistance in P. falciparum. Point mutations in the homolog of the mammalian multidrug resistance gene (pfmdr1) can also modulate the levels of CQ response. Moreover, parasites with the same pfcrt and pfmdr1 alleles exhibit a wide range of drug sensitivity, suggesting that additional genes contribute to levels of CQ resistance (CQR). Reemergence of CQ sensitive parasites after cessation of CQ use indicates that changes in PfCRT are deleterious to the parasite. Some CQR parasites, however, persist in the field and grow well in culture, which may reflect adaptive changes in the parasite genome to compensate for the mutations in PfCRT. Using three isogenic clones that have different drug resistance profiles corresponding to unique mutations in the pfcrt gene (106/1(K76), 106/1(76I), and 106/(76I-352K)), we investigated changes in gene expression in these parasites grown with and without CQ. We also conducted hybridizations of genomic DNA to identify copy number (CN) changes in parasite genes. RNA transcript levels from 45 genes were significantly altered in one or both mutants relative to the parent line, 106/1(K76). Most of the up-regulated genes are involved in invasion, cell growth and development, signal transduction, and transport activities. Of particular interest are genes encoding proteins involved in transport and/or regulation of cytoplasmic or compartmental pH such as the V-type H+ pumping pyrophosphatase 2 (PfVP2), Ca2+/H+ antiporter VCX1, a putative drug transporter and CN changes in pfmdr1. These changes may represent adaptations to altered functionality of PfCRT, a predicted member of drug/metabolite transporter superfamily found on the parasite food vacuole (FV) membrane. Further investigation of these genes may shed light on how the parasite compensates for functional changes accompanying drug resistance mutations in a gene coding for a membrane/drug transporter. C1 [Jiang, Hongying; Mu, Jianbing; Su, Xin-zhuan] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. [Patel, Jigar J.; Ferdig, Michael T.] Univ Notre Dame, Ctr Glob Hlth & Infect Dis, Dept Biol Sci, Notre Dame, IN USA. [Yi, Ming; Stephens, Robert] NCI Frederick, Advanced Biomed Comput Ctr, Frederick, MD USA. [Ding, Jinhui] NIH, NIA, Lab Neurogenet, Bioinformat Unit, Bethesda, MD USA. [Cooper, Roland A.] Old Dominion Univ, Dept Biol Sci, Norfolk, VA USA. RP Jiang, HY (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM ferdig.1@nd.edu; xsu@niaid.nih.gov RI Ferdig, Michael/C-6627-2016; OI Su, Xinzhuan/0000-0003-3246-3248 FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health [AI071121] FX This work was in part supported by Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. MTF and RAC are supported by NIH grant AI071121. NR 60 TC 58 Z9 58 U1 1 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 25 PY 2008 VL 3 IS 6 AR e2484 DI 10.1371/journal.pone.0002484 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 406IK UT WOS:000263288000014 PM 18575593 ER PT J AU Munson, L Terio, KA Kock, R Mlengeya, T Roelke, ME Dubovi, E Summers, B Sinclair, ARE Packer, C AF Munson, Linda Terio, Karen A. Kock, Richard Mlengeya, Titus Roelke, Melody E. Dubovi, Edward Summers, Brian Sinclair, Anthony R. E. Packer, Craig TI Climate Extremes Promote Fatal Co-Infections during Canine Distemper Epidemics in African Lions SO PLOS ONE LA English DT Article AB Extreme climatic conditions may alter historic host-pathogen relationships and synchronize the temporal and spatial convergence of multiple infectious agents, triggering epidemics with far greater mortality than those due to single pathogens. Here we present the first data to clearly illustrate how climate extremes can promote a complex interplay between epidemic and endemic pathogens that are normally tolerated in isolation, but with co-infection, result in catastrophic mortality. A 1994 canine distemper virus (CDV) epidemic in Serengeti lions (Panthera leo) coincided with the death of a third of the population, and a second high-mortality CDV epidemic struck the nearby Ngorongoro Crater lion population in 2001. The extent of adult mortalities was unusual for CDV and prompted an investigation into contributing factors. Serological analyses indicated that at least five "silent'' CDV epidemics swept through the same two lion populations between 1976 and 2006 without clinical signs or measurable mortality, indicating that CDV was not necessarily fatal. Clinical and pathology findings suggested that hemoparsitism was a major contributing factor during fatal epidemics. Using quantitative real-time PCR, we measured the magnitude of hemoparasite infections in these populations over 22 years and demonstrated significantly higher levels of Babesia during the 1994 and 2001 epidemics. Babesia levels correlated with mortalities and extent of CDV exposure within prides. The common event preceding the two high mortality CDV outbreaks was extreme drought conditions with wide-spread herbivore die-offs, most notably of Cape buffalo (Syncerus caffer). As a consequence of high tick numbers after the resumption of rains and heavy tick infestations of starving buffalo, the lions were infected by unusually high numbers of Babesia, infections that were magnified by the immunosuppressive effects of coincident CDV, leading to unprecedented mortality. Such mass mortality events may become increasingly common if climate extremes disrupt historic stable relationships between co- existing pathogens and their susceptible hosts. C1 [Munson, Linda] Univ Calif Davis, Dept Pathol Microbiol & Immunol, Davis, CA 95616 USA. [Terio, Karen A.] Univ Illinois, Zool Pathol Program, Maywood, IL USA. [Kock, Richard] African Union Int Bureau Anim Resources, Nairobi, Kenya. [Mlengeya, Titus; Roelke, Melody E.] Tanzania Natl Parks, Arusha, Tanzania. [Roelke, Melody E.] NCI Frederick, SAIC Frederick Inc, Lab Genom Diversity, Frederick, MD USA. [Dubovi, Edward] Cornell Univ, Dept Populat Med & Diagnost Sci, Ithaca, NY USA. [Summers, Brian] Cornell Univ, Coll Vet Med, Dept Biomed Sci, Ithaca, NY USA. [Sinclair, Anthony R. E.] Univ British Columbia, Dept Zool, Vancouver, BC, Canada. [Packer, Craig] Univ Minnesota, Dept Ecol, Evolut, & Behavior, St Paul, MN USA. RP Munson, L (reprint author), Univ Calif Davis, Dept Pathol Microbiol & Immunol, Davis, CA 95616 USA. EM packer@umn.edu FU Morris Foundation; NSF [DEB-0343960, DEB-9903416, BE-0308486]; Morris Animal Foundation; University of Illinois Research Board; Messerli Foundation, Zurich, Switzerland FX Lab assays were performed with funding from the Morris Foundation, while the field work was supported by NSF. This work was supported by the Morris Animal Foundation, University of Illinois Research Board, and National Science Foundation Grants for Ecology of Infectious Diseases (DEB-0343960), Long-Term Research in Environmental Biology (DEB-9903416) and Biocomplexity (BE-0308486), and the Messerli Foundation, Zurich, Switzerland. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 27 TC 66 Z9 66 U1 5 U2 58 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 25 PY 2008 VL 3 IS 6 AR e2545 DI 10.1371/journal.pone.0002545 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 406IK UT WOS:000263288000048 PM 18575601 ER PT J AU Tarasov, KV Tarasova, YS Tam, WL Riordon, DR Elliott, ST Kania, G Li, JL Yamanaka, S Crider, DG Testa, G Li, RA Lim, B Stewart, CL Liu, Y Van Eyk, JE Wersto, RP Wobus, AM Boheler, KR AF Tarasov, Kirill V. Tarasova, Yelena S. Tam, Wai Leong Riordon, Daniel R. Elliott, Steven T. Kania, Gabriela Li, Jinliang Yamanaka, Satoshi Crider, David G. Testa, Gianluca Li, Ronald A. Lim, Bing Stewart, Colin L. Liu, Yie Van Eyk, Jennifer E. Wersto, Robert P. Wobus, Anna M. Boheler, Kenneth R. TI B-MYB Is Essential for Normal Cell Cycle Progression and Chromosomal Stability of Embryonic Stem Cells SO PLOS ONE LA English DT Article AB Background: The transcription factor B-Myb is present in all proliferating cells, and in mice engineered to remove this gene, embryos die in utero just after implantation due to inner cell mass defects. This lethal phenotype has generally been attributed to a proliferation defect in the cell cycle phase of G1. Methodology/Principal Findings: In the present study, we show that the major cell cycle defect in murine embryonic stem (mES) cells occurs in G2/M. Specifically, knockdown of B-Myb by short-hairpin RNAs results in delayed transit through G2/M, severe mitotic spindle and centrosome defects, and in polyploidy. Moreover, many euploid mES cells that are transiently deficient in B-Myb become aneuploid and can no longer be considered viable. Knockdown of B-Myb in mES cells also decreases Oct4 RNA and protein abundance, while over-expression of B-MYB modestly up-regulates pou5f1 gene expression. The coordinated changes in B-Myb and Oct4 expression are due, at least partly, to the ability of B-Myb to directly modulate pou5f1 gene promoter activity in vitro. Ultimately, the loss of B-Myb and associated loss of Oct4 lead to an increase in early markers of differentiation prior to the activation of caspase-mediated programmed cell death. Conclusions/Significance: Appropriate B-Myb expression is critical to the maintenance of chromosomally stable and pluripotent ES cells, but its absence promotes chromosomal instability that results in either aneuploidy or differentiation-associated cell death. C1 [Tarasov, Kirill V.; Tarasova, Yelena S.; Riordon, Daniel R.; Li, Jinliang; Yamanaka, Satoshi; Crider, David G.; Testa, Gianluca; Boheler, Kenneth R.] NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. [Tam, Wai Leong; Lim, Bing] Genome Inst Singapore, Singapore, Singapore. [Elliott, Steven T.; Van Eyk, Jennifer E.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA. [Kania, Gabriela; Wobus, Anna M.] Leibniz Inst Plant Genet & Crop Plant Res, In vitro Differentiat Grp, Gatersleben, Germany. [Li, Ronald A.] Univ Calif Davis, Stem Cell Inst, Lab Stem Cell Engn & Bioelectricity, Davis, CA USA. [Lim, Bing] Harvard Med Sch, Harvard Inst Med, Boston, MA USA. [Stewart, Colin L.] NCI, Canc & Dev Biol Lab, Frederick, MD USA. [Liu, Yie] NIH, NIA, Lab Mol Genet, Baltimore, MD USA. [Wersto, Robert P.] NIH, NIA, Flow Cytometry Grp, Baltimore, MD USA. RP Tarasov, KV (reprint author), NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. EM bohelerk@grc.nia.nih.gov RI Li, Ronald/E-9833-2010; OI Tarasov, Kirill/0000-0001-7799-4670; Tam, Wai Leong/0000-0003-2365-5264 FU Intramural Research Program of the NIA/NIH [R01 HL72857]; German Research Foundation [Wo 503/3-3] FX This research was supported by the Intramural Research Program of the NIA/NIH (KRB, RPW), the German Research Foundation (Wo 503/3-3: AMW), and NIH grants (R01 HL72857: RAL). NR 42 TC 44 Z9 44 U1 0 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 25 PY 2008 VL 3 IS 6 AR e2478 DI 10.1371/journal.pone.0002478 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 406IK UT WOS:000263288000009 PM 18575582 ER PT J AU Venkataraman, V Duda, T Ravichandran, S Sharma, RK AF Venkataraman, Venkateswar Duda, Teresa Ravichandran, Sarangan Sharma, Rameshwar K. TI Neurocalcin delta modulation of ROS-GC1, a new model of Ca(2+) signaling SO BIOCHEMISTRY LA English DT Article ID MEMBRANE GUANYLATE-CYCLASE; NATRIURETIC-FACTOR RECEPTOR; FUNCTIONAL-CHARACTERIZATION; ACTIVATING PROTEIN; TRANSDUCTION MACHINERY; MUTATIONAL ANALYSIS; CRYSTAL-STRUCTURE; ADENYLYL-CYCLASE; CALCIUM; EXPRESSION AB ROS-GC1 membrane guanylate cyclase is a Ca(2+) bimodal signal transduction switch. It is turned "off" by a rise in free Ca(2+) from nanomolar to the semicromolar range in the photoreceptor outer segments and the olfactory bulb neurons; by a similar rise in the bipolar and ganglion retinal neurons it is turned "on". These opposite operational modes of the switch are specified by its Ca(2+) sensing devices, respectively termed GCAPs and CD-GCAPs. Neurocalcin delta is a CD-GCAP. In the present study, the neurocalcin delta-modulated site, V(837)-L(858), in ROS-GC1 has been mapped. The location and properties of this site are unique. It resides within the core domain of the catalytic module and does not require the alpha-helical dimerization domain structural element (amino acids 767-811) for activating the catalytic module. Contrary to the current beliefs, the catalytic module is intrinsically active; it is directly regulated by the neurocalcin delta-modulated Ca(2+) signal and is dimeric in nature. A fold recognition based model of the catalytic domain of ROS-GC1 was built, and neurocalcin delta docking simulations were carried out to define the three-dimensional features of the interacting domains of the two molecules. These findings define a new transduction model for the Ca(2+) signaling of ROS-GC1. C1 [Duda, Teresa; Sharma, Rameshwar K.] Penn Coll Optometry, Div Biochem & Mol Biol, Unit Regulatory & Mol Biol, Elkins Pk, PA 19027 USA. [Venkataraman, Venkateswar] Univ Med & Dent New Jersey, Sch Osteopath Med, Dept Cell Biol, Stratford, NJ 08084 USA. [Ravichandran, Sarangan] SAIC Frederick, Natl Canc Inst, Adv Biomed Computing Ctr, Frederick, MD 21702 USA. RP Sharma, RK (reprint author), Penn Coll Optometry, Div Biochem & Mol Biol, Unit Regulatory & Mol Biol, Elkins Pk, PA 19027 USA. EM rsharma@pco.edu FU NHLBI NIH HHS [HL070015, HL 084584, R01 HL084584, R01 HL084584-01A2, R15 HL070015]; NIDCD NIH HHS [DC005349, R01 DC005349, R01 DC005349-06] NR 55 TC 24 Z9 24 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 24 PY 2008 VL 47 IS 25 BP 6590 EP 6601 DI 10.1021/bi800394s PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 315BM UT WOS:000256852900008 PM 18500817 ER PT J AU Le, DT Liang, XW Fomenko, DE Raza, AS Chong, CK Carlson, BA Hatfield, DL Gladyshev, VN AF Le, Dung Tien Liang, Xinwen Fomenko, Dmitri E. Raza, Ashraf S. Chong, Chom-Kyu Carlson, Bradley A. Hatfield, Dolph L. Gladyshev, Vadim N. TI Analysis of methionine/selenomethionine oxidation and methionine sulfoxide reductase function using methionine-rich proteins and antibodies against their oxidized forms SO BIOCHEMISTRY LA English DT Article ID SUBSTRATE-SPECIFICITY; AMINO-ACIDS; LIFE-SPAN; MAMMALS; MSRA; GENE AB Methionine (Met) residues are present in most proteins. However, this sulfur-containing amino acid is highly susceptible to oxidation. In cells, the resulting Met sulfoxides are reduced back to Met by stereospecific reductases MsrA and MsrB. Reversible Met oxidation occurs even in the absence of stress, is elevated during aging and disease, but is notoriously difficult to monitor. In this work, we computationally identified natural Met-rich proteins (MRPs) and characterized three such proteins containing 21-33% Met residues. Oxidation of multiple Met residues in MRPs with H2O2 and reduction of Met sulfoxides with MsrA/MsrB dramatically influenced the mobility of these proteins on polyacrylamide gels and could be monitored by simple SDS-PAGE. We further prepared antibodies enriched for reduced and Met sulfoxide forms of these proteins and used them to monitor Met oxidation and reduction by immunoblot assays. We describe applications of these reagents for the analysis of MsrA and MsrB functions, as well as the development of the assay for high-throughput analysis of their activities. We also show that all Met sulfoxide residues in an MRP can be reduced by MsrA and MsrB. Furthermore, we prepared a selenomethionine form of an MRP and found that selenomethionine selenoxide residues can be efficiently reduced nonenzymatically by glutathione and other thiol compounds. Selenomethionine selenoxide residues were not recognized by antibodies specific for the Met sulfoxide form of an MRP. These findings, reagents, assays, and approaches should facilitate research and applications in the area of Met sulfoxide reduction, oxidative stress, and aging. C1 [Le, Dung Tien; Liang, Xinwen; Fomenko, Dmitri E.; Raza, Ashraf S.; Gladyshev, Vadim N.] Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. [Le, Dung Tien; Liang, Xinwen; Fomenko, Dmitri E.; Raza, Ashraf S.; Gladyshev, Vadim N.] Univ Nebraska, Redox Biol Ctr, Lincoln, NE 68588 USA. [Chong, Chom-Kyu] Bioland Ltd, Human Sci Lab, Cheongwon 363883, Chungbuk, South Korea. [Carlson, Bradley A.; Hatfield, Dolph L.] NCI, NCI, Ctr Canc Res, Lab Canc Prevent,Sect Mol Biol Selenium, Bethesda, MD 20892 USA. RP Gladyshev, VN (reprint author), Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. EM vgladyshev1@unl.edu RI LE, Dung/A-7276-2008; Gladyshev, Vadim/A-9894-2013 OI LE, Dung/0000-0002-5117-3476; FU Intramural NIH HHS [Z01 BC005317-24, Z01 BC010767-01]; NCRR NIH HHS [RR017675, P20 RR017675, P20 RR017675-06, P20 RR017675-07]; NIA NIH HHS [AG021518, R01 AG021518, R01 AG021518-06] NR 25 TC 25 Z9 25 U1 1 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 24 PY 2008 VL 47 IS 25 BP 6685 EP 6694 DI 10.1021/bi800422s PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 315BM UT WOS:000256852900017 PM 18505275 ER PT J AU Stanley, C Rau, DC AF Stanley, Christopher Rau, Donald C. TI Assessing the interaction of urea and protein-stabilizing osmolytes with the nonpolar surface of hydroxypropylcellulose SO BIOCHEMISTRY LA English DT Article ID PREFERENTIAL HYDRATION; GLYCINE BETAINE; OSMOTIC-STRESS; INTERMOLECULAR FORCES; UNCHARGED SOLUTES; PRACTICAL GUIDE; DNA; EXCLUSION; WATER; DENATURATION AB The interaction of urea and several naturally occurring protein-stabilizing osmolytes, glycerol, sorbitol, glycine betaine, trimethylamine oxide (TMAO), and proline, with condensed arrays of a hydrophobically modified polysaccharide, hydroxypropylcellulose (HPC), has been inferred from the effect of these solutes on the forces acting between HPC polymers. Urea interacts only very weakly. The protein-stabilizing osmolytes are strongly excluded. The observed energies indicate that the exclusion of the protein-stabilizing osmolytes from protein hydrophobic side chains would add significantly to protein stability. The temperature dependence of exclusion indicates a significant contribution of enthalpy to the interaction energy in contrast to expectations from "molecular crowding" theories based on steric repulsion. The dependence of exclusion on the distance between HPC polymers rather indicates that perturbations of water structuring or hydration forces underlie exclusion. C1 [Stanley, Christopher; Rau, Donald C.] NICHHD, NIH, Lab Phys & Struct Biol, Bethesda, MD 20892 USA. [Stanley, Christopher] Natl Inst Stand & Technol, Ctr Neutron Res, Gaithersburg, MD 20899 USA. RP Rau, DC (reprint author), NICHHD, NIH, Lab Phys & Struct Biol, Bethesda, MD 20892 USA. EM raud@mail.nih.gov OI Stanley, Christopher/0000-0002-4226-7710 FU Intramural NIH HHS [Z01 HD008747-06] NR 48 TC 16 Z9 16 U1 2 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 24 PY 2008 VL 47 IS 25 BP 6711 EP 6718 DI 10.1021/bi800117f PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 315BM UT WOS:000256852900020 PM 18512956 ER PT J AU Hirata-Fukae, C Li, HF Hoe, HS Gray, AJ Minami, SS Hamada, K Niikura, T Hua, F Tsukagoshi-Nagai, H Horikoshi-Sakuraba, Y Mughal, M Rebeck, GW LaFerla, FM Mattson, MP Iwata, N Saido, TC Klein, WL Duff, KE Aisen, PS Matsuoka, Y AF Hirata-Fukae, Chiho Li, Hui-Fang Hoe, Hyang-Sook Gray, Audrey J. Minami, S. Sakura Hamada, Katsuyoshi Niikura, Takako Hua, Fang Tsukagoshi-Nagai, Hiroe Horikoshi-Sakuraba, Yuko Mughal, Mohamed Rebeck, G. William LaFerla, Frank M. Mattson, Mark P. Iwata, Nobuhisa Saido, Takaomi C. Klein, William L. Duff, Karen E. Aisen, Paul S. Matsuoka, Yasuji TI Females exhibit more extensive amyloid, but not tau, pathology in an Alzheimer transgenic model SO BRAIN RESEARCH LA English DT Article DE Alzheimer's disease; transgenic mice; amyloid beta; beta-secretase; neprilysin; gender difference; oligomer; tau; hyperphosphorylation ID ESTROGEN REPLACEMENT THERAPY; PAIRED HELICAL FILAMENTS; A-BETA; MOUSE MODEL; PRECURSOR-PROTEIN; NEUROFIBRILLARY TANGLES; CONTROLLED-TRIAL; MEMORY DEFICITS; DISEASE; MICE AB Epidemiological studies indicate that women have a higher risk of Alzheimer's disease (AD) even after adjustment for age. Though transgenic mouse models of AD develop AD-related amyloid beta (Abeta) and/or tau pathology, gender differences have not been well documented in these models. In this study, we found that female 3xTg-AD transgenic mice expressing mutant APP, presenilin-1 and tau have significantly more aggressive Abeta pathology. We also found an increase in beta-secretase activity and a reduction of neprilysin in female mice compared to males; this suggests that a combination of increased Abeta production and decreased Abeta degradation may contribute to higher risk of AD in females. In contrast to significantly more aggressive Abeta pathology in females, gender did not affect the levels of phosphorylated tau in 3xTg-AD mice. These results point to the involvement of Abeta pathways in the higher risk of AD in women. In addition to comparison of pathology between genders at 9, 16 and 23 months of age, we examined the progression of Abeta pathology at additional age points; i.e., brain Abeta load, intraneuronal oligomeric Abeta distribution and plaque load, in male 3xTg-AD mice at 3,6,9,12,16,20 and 23 months of age. These findings confirm progressive Abeta pathology in 3xTg-AD transgenic mice, and provide guidance for their use in therapeutic research. (C) 2008 Elsevier B.V. All rights reserved. C1 [Hirata-Fukae, Chiho; Li, Hui-Fang; Hoe, Hyang-Sook; Gray, Audrey J.; Minami, S. Sakura; Niikura, Takako; Hua, Fang; Aisen, Paul S.; Matsuoka, Yasuji] Georgetown Univ, Med Ctr, Dept Neurol, Washington, DC 20057 USA. [Minami, S. Sakura; Rebeck, G. William] Georgetown Univ, Med Ctr, Dept Neurosci, Washington, DC 20057 USA. [Hamada, Katsuyoshi; Tsukagoshi-Nagai, Hiroe; Horikoshi-Sakuraba, Yuko] Immunobiol Labs, Gunma 3700831, Japan. [Mughal, Mohamed; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. [LaFerla, Frank M.] Univ Calif Irvine, Dept Neurobiol & Behav, Irvine, CA 92697 USA. [Iwata, Nobuhisa; Saido, Takaomi C.] RIKEN, Brain Sci Inst, Lab Proteolyt Neurosci, Wako, Saitama 3510198, Japan. [Klein, William L.] Northwestern Univ, Inst Neurosci, Cognit Neurol & Alzheimers Dis Ctr, Evanston, IL 60208 USA. [Duff, Karen E.] Columbia Univ, Taub Inst Alzheimers Dis Res, New York, NY 10032 USA. [Aisen, Paul S.] Univ Calif San Diego, Dept Neurosci, Alzheimers Dis Cooperat Study, Sch Med, La Jolla, CA 92093 USA. [Matsuoka, Yasuji] GlaxoSmithKline Inc, Neurodegenerat Res, Shanghai 201203, Peoples R China. RP Matsuoka, Y (reprint author), Georgetown Univ, Med Ctr, Dept Neurol, 4000 Reservoir Rd NW, Washington, DC 20057 USA. EM ym56@georgetown.edu RI Mattson, Mark/F-6038-2012 FU Intramural NIH HHS; NIA NIH HHS [AG022455, AG026478] NR 61 TC 104 Z9 105 U1 3 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUN 24 PY 2008 VL 1216 BP 92 EP 103 DI 10.1016/j.brainres.2008.03.079 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 323CN UT WOS:000257421700010 PM 18486110 ER PT J AU Koh, KK Park, SM Quon, MJ AF Koh, Kwang Kon Park, Sang Min Quon, Michael J. TI Leptin and cardiovascular disease - Response to therapeutic interventions SO CIRCULATION LA English DT Review DE atherosclerosis; cardiovascular diseases; diabetes mellitus; drugs; hypertension; insulin; obesity ID DENSITY-LIPOPROTEIN CHOLESTEROL; POLYUNSATURATED FATTY-ACIDS; BODY-MASS INDEX; PLASMA LEPTIN; SERUM LEPTIN; ESSENTIAL-HYPERTENSION; INSULIN-RESISTANCE; ANGIOTENSIN-II; NITRIC-OXIDE; ENDOTHELIAL DYSFUNCTION C1 [Koh, Kwang Kon; Park, Sang Min] Gachon Univ Gil Med Ctr, Div Cardiol, Vasc Med & Atherosclerosis Unit, Gil Heart Ctr, Inchon 405760, South Korea. [Quon, Michael J.] Natl Ctr Complementary & Alternat Med, Diabet Unit, Clin Invest Lab, Natl Inst Hlth, Bethesda, MD USA. RP Koh, KK (reprint author), Gachon Univ Gil Med Ctr, Div Cardiol, Vasc Med & Atherosclerosis Unit, Gil Heart Ctr, 1198 Kuwol Dong, Inchon 405760, South Korea. EM kwangk@gilhospital.com RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 FU Intramural NIH HHS [Z99 AT999999] NR 119 TC 116 Z9 123 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 24 PY 2008 VL 117 IS 25 BP 3238 EP 3249 DI 10.1161/CIRCULATIONAHA.107.741645 PG 12 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 318DV UT WOS:000257072700011 PM 18574061 ER PT J AU Coppey, M Boettiger, AN Berezhkovskii, AM Shvartsman, SY AF Coppey, Mathieu Boettiger, Alistair N. Berezhkovskii, Alexander M. Shvartsman, Stanislav Y. TI Nuclear trapping shapes the terminal gradient in the Drosophila embryo SO CURRENT BIOLOGY LA English DT Article ID RECEPTOR TYROSINE KINASE; DPP MORPHOGEN GRADIENT; BODY PATTERN; TORSO; DYNAMICS; PROTEIN AB Patterning of the terminal regions of the Drosophila embryo relies on the gradient of phosphorylated ERK/MAPK (dpERK), which is controlled by the localized activation of the Torso receptor tyrosine kinase [1-4]. This model is supported by a large amount of data, but the gradient itself has never been quantified. We present the first measurements of the dpERK gradient and establish a new intracellular layer of its regulation. Based on the quantitative analysis of the spatial pattern of dpERK in mutants with different levels of Torso as well as the dynamics of the wild-type dpERK pattern, we propose that the terminal-patterning gradient is controlled by a cascade of diffusion-trapping modules. A ligand-trapping mechanism establishes a sharply localized pattern of the Torso receptor occupancy on the surface of the embryo. Inside the syncytial embryo, nuclei play the role of traps that localize diffusible dpERK. We argue that the length scale of the terminal-patterning gradient is determined mainly by the intracellular module. C1 [Coppey, Mathieu; Boettiger, Alistair N.; Shvartsman, Stanislav Y.] Princeton Univ, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08540 USA. [Berezhkovskii, Alexander M.] NIH, Div Computat Biosci, Ctr Informat Technol, Math & Stat Comp Lab, Bethesda, MD 20892 USA. RP Shvartsman, SY (reprint author), Princeton Univ, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08540 USA. EM stas@princeton.edu RI Boettiger, Alistair/G-1988-2011 FU Intramural NIH HHS [Z01 CT000227-16, Z01 CT000266-09]; NIGMS NIH HHS [P50 GM071508, R01 GM078079, R01 GM078079-01, R01 GM078079-02] NR 22 TC 47 Z9 48 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD JUN 24 PY 2008 VL 18 IS 12 BP 915 EP 919 DI 10.1016/j.cub.2008.05.034 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 319GK UT WOS:000257151900032 PM 18571412 ER PT J AU Pan, XG Guan, JJ Yoo, JW Epstein, AJ Lee, LJ Lee, RJ AF Pan, Xiaogang Guan, Jingjiao Yoo, Jung-Woo Epstein, Arthur J. Lee, L. James Lee, Robert J. TI Cationic lipid-coated magnetic nanoparticles associated with transferrin for gene delivery SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article DE gene delivery; magnetic nanoparticles; transferrin; cationic lipid; magnetofection ID IN-VITRO; DNA; CELLS; TRANSFECTION; MAGNETOFECTION; COMPLEXES; EXPRESSION; THERAPY; VIVO; POLYETHYLENIMINE AB Cationic lipid-coated magnetic nanoparticles (MPs) associated with transferrin were evaluated as gene transfer vectors in the presence of a static magnetic field. MPs were prepared by chemical precipitation and were surface-coated with cationic lipids, composed of DDAB/soy PC (60:40mole/mole). These cationic MPs were then combined with polyethylenimine (PEI) condensed plasmid DNA, followed by transferrin. The resulting magnetic electrostatic complexes retained relatively compact particle size and showed complete DNA condensation. Their transfection activity in the presence of a static magnetic field was evaluated by luciferase and green fluorescent protein (GFP) reporter genes. The magnetic complexes exhibited up to 300-fold higher transfection activity compared to commonly used cationic liposomes or cationic polymer complexes, based on luciferase assay. The enhancement in transfection activity was maximized when the cells were exposed to the vectors for a relatively short period of time (15 min), or were treated in media containing 10% serum. Incorporation of transferrin further improved transfection efficiency of the cationic MPs. However, when cells were incubated for 4 h in serum-free media, magnetic and non-magnetic vectors showed similar transfection efficiencies. in conclusion, transferrin-associated cationic MPs are excellent gene transfer vectors that can mediate very rapid and efficient gene transfer in vitro in the presence of a magnetic field. (C) 2008 Elsevier B.V. All rights reserved. C1 [Pan, Xiaogang; Lee, Robert J.] Ohio State Univ, Coll Pharm, Div Pharmaceut, Columbus, OH 43210 USA. [Pan, Xiaogang; Guan, Jingjiao; Lee, L. James; Lee, Robert J.] Ohio State Univ, CANPBD, NSF, Nanoscale Sci & Engn Ctr NSEC, Columbus, OH 43210 USA. [Guan, Jingjiao; Lee, L. James] Ohio State Univ, Dept Chem & Biomol Engn, Columbus, OH 43210 USA. [Yoo, Jung-Woo; Epstein, Arthur J.] Ohio State Univ, Dept Phys, Columbus, OH 43210 USA. [Epstein, Arthur J.] Ohio State Univ, Ctr Mat Res, Columbus, OH 43210 USA. [Lee, Robert J.] Ohio State Univ, NCI, Ctr Comprehens Canc, Columbus, OH 43210 USA. RP Lee, RJ (reprint author), Ohio State Univ, Coll Pharm, Div Pharmaceut, 500 W 12Th Ave, Columbus, OH 43210 USA. EM lee.1339@osu.edu RI Yoo, Jung-Woo/F-9288-2011 FU NCRR NIH HHS [UL1 RR025755] NR 37 TC 55 Z9 58 U1 1 U2 26 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5173 J9 INT J PHARM JI Int. J. Pharm. PD JUN 24 PY 2008 VL 358 IS 1-2 BP 263 EP 270 DI 10.1016/j.ijpharm.2008.02.020 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 325GQ UT WOS:000257577400036 PM 18384982 ER PT J AU Bonini, MG Staldler, K Silva, SO Corbett, J Dores, M Petranka, J Fernandes, DC Tanaka, LY Duma, D Laurindo, FRM Mason, RP AF Bonini, Marcelo G. Staldler, Krisztian Silva, Sueli de Oliveira Corbett, Jean Dores, Michael Petranka, John Fernandes, Denise C. Tanaka, Leonardo Y. Duma, Danielle Laurindo, Francisco R. M. Mason, Ronald P. TI Constitutive nitric oxide synthase activation is a significant route for nitroglycerin-mediated vasodilation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE endothelial NOS; neuronal NOS; blood pressure ID MITOCHONDRIAL ALDEHYDE DEHYDROGENASE; INDUCED OXIDATIVE STRESS; PROTEIN-KINASE-C; GLYCERYL TRINITRATE; IN-VIVO; ENDOTHELIAL-CELLS; CORONARY-ARTERY; BLOOD-PRESSURE; PHOSPHORYLATION; PATHWAY AB The physiological effects of nitroglycerin as a potent vasodilator have long been documented. However, the molecular mechanisms by which nitroglycerin exerts its biological functions are still a matter of intense debate. Enzymatic pathways converting nitroglycerin to vasoactive compounds have been identified, but none of them seems to fully account for the reported clinical observations. Here, we demonstrate that nitroglycerin triggers constitutive nitric oxide synthase (NOS) activation, which is a major Source of NO responsible for low-dose (1-10 nM) nitroglycerin-induced vasorelaxation. Our studies in cell cultures, isolated vessels, and whole animals identified endothelial NOS activation as a fundamental requirement for nitroglycerin action at pharmacologically relevant concentrations in WT animals. C1 [Bonini, Marcelo G.; Staldler, Krisztian; Silva, Sueli de Oliveira; Corbett, Jean; Mason, Ronald P.] NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. [Dores, Michael; Petranka, John; Duma, Danielle] NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. [Fernandes, Denise C.; Tanaka, Leonardo Y.; Laurindo, Francisco R. M.] Univ Sao Paulo, Inst Heart, Sch Med, Vasc Biol Lab, BR-05403000 Sao Paulo, Brazil. RP Bonini, MG (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. EM bonini@niehs.nih.gov RI Tanaka, Leonardo/H-9832-2013; Laurindo, Francisco/J-6575-2015 FU Intramural NIH HHS NR 38 TC 16 Z9 17 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 24 PY 2008 VL 105 IS 25 BP 8569 EP 8574 DI 10.1073/pnas.0708615105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 319TA UT WOS:000257185700017 PM 18562300 ER PT J AU Griswoldt, AJ Chang, KT Runko, AP Knightt, MA Min, KT AF Griswoldt, Anthony J. Chang, Karen T. Runko, Alexander P. Knightt, Melanie A. Min, Kyung-Tai TI Sir2 mediates apoptosis through JNK-dependent pathways in Drosophila SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE FOXO; cell death; cleacetylase; dnaJ-H ID POSITION-EFFECT VARIEGATION; PROGRAMMED CELL-DEATH; EXTENDS LIFE-SPAN; SACCHAROMYCES-CEREVISIAE; CAENORHABDITIS-ELEGANS; TRANSCRIPTION FACTORS; TNF SUPERFAMILY; RESVERATROL; GENE; MELANOGASTER AB increased expression of the histone deacetylase sir2 has been reported to extend the life span of diverse organisms including yeast, Caenorhabditis elegans, and Drosophila melanogaster. A small molecule activator of Sir2, resveratrol, has also been suggested to extend the fitness and survival of these simple model organisms as well as mice fed high calorie diets. However, other studies in yeast have shown that Sir2 itself may prevent life extension, and high expression levels of Sir2 can be toxic to yeast and mouse cells. This conflicting evidence highlights the importance of understanding the mechanisms by which Sir2 expression or activation affects survival of organisms. To investigate the downstream signaling pathways affected by Sir2 in Drosophila, we generated transgenic flies expressing sir2. Here, we show that overexpression of sir2 in Drosophila promotes caspase-dependent but p53-independent apoptosis that is mediated by the JNK and FOXO signaling pathways. Furthermore, we find that a loss-of-function sir2 mutant partially prevents apoptosis induced by UV irradiation in the eye. Together, these results suggest that Sir2 normally participates in the regulation of cell survival and death in Drosophila. C1 [Griswoldt, Anthony J.; Chang, Karen T.; Min, Kyung-Tai] Indiana Univ, Dept Biol, Bloomington, IN 47405 USA. [Griswoldt, Anthony J.; Runko, Alexander P.; Knightt, Melanie A.] NINDS, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA. RP Min, KT (reprint author), Indiana Univ, Dept Biol, Bloomington, IN 47405 USA. EM kyumin@indiana.edu RI Griswold, Anthony/B-7507-2012; OI min, kyung-tai/0000-0003-0983-4258 NR 41 TC 41 Z9 44 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 24 PY 2008 VL 105 IS 25 BP 8673 EP 8678 DI 10.1073/pnas.0803837105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 319TA UT WOS:000257185700035 PM 18562277 ER PT J AU Kubler-Kielb, J Vinogradov, E Hu, HJ Leppla, SH Robbins, JB Schneerson, R AF Kubler-Kielb, Joanna Vinogradov, Evgeny Hu, Haijing Leppla, Stephen H. Robbins, John B. Schneerson, Rachel TI Saccharides cross-reactive with Bacillus anthracis spore glycoprotein as an anthrax vaccine component SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE anthrose; capsule; pseudomonas syringae; Shewanella; flagellae ID INFLUENZAE TYPE-B; O-SPECIFIC POLYSACCHARIDE; CAPSULAR POLYSACCHARIDE; MAJOR GLYCOPROTEIN; EXOSPORIUM; OLIGOSACCHARIDE; TETRASACCHARIDE; IMMUNOGENICITY; ANTIBODIES; FLAGELLIN AB Bacillus anthracis is a spore-forming bacterium that causes anthrax in humans and in other mammals. The glycoprotein BclA (Bacillus collagen-like protein of anthracis) is a major constituent of the exosporium, the outermost surface of B. anthracis spores. The glycosyl part of BclA is an oligosaccharide composed of 2-O-methyl-4-(3-hydroxy-3-methylbutanamido)-4,6-dideoxy-D-glucose, referred to as anthrose, and three rhamnose residues. A structure similar to anthrose, 4-(3-hydroxy-3-methylbutanamido)-4,6-dideoxy-D-glucose is found in the side chain of the capsular polysaccharide (CPS) of Shewanella spp. MR-4. Under certain growth conditions the! bacteria produce a variant CPS lacking one methyl group on the hydroxylbutyrate, 4-(3-hydroxybutanamido)-4,6-dideoxy-D-glucose. Contrary to anthrose, neither of the Shewanella CPSs is 2-O methylated. Here, we report that both Shewanella CPS variants react with anti-B. anthracis spore sera. We also found thatthese antisera reacted with flagellae of Pseudomonas syringae, reported to be glycosylated with a similar terminal saccharide, 4-(3-hydroxybutanamido)-4,6-dideoxy-2-O-methyl-D-glucose. Sera produced by immunization with Shewanella or A syringae cells bound to B. anthracis spores but not to Bacillus cereus spores in a fluorestent microscopy assay. These experiments show that methylation of the anthrose at the O-2 of the sugar ring and at the C-3 of 3-hydroxybutyrate are not essential for induction of cross-reactive antibodies. We report the preparation, characterization, and antibody responses to protein conjugates of the two variants of Shewanella CPS. Both conjugates induced antibodies that bound to both Shewanella CPS variants by ELISA and to B. anthracis spores, as detected by fluorescent microscopy. We propose the use of Shewanella CPS conjugates as a component of an anthrax vaccine. C1 [Kubler-Kielb, Joanna; Robbins, John B.; Schneerson, Rachel] NICHHD, NIH, Bethesda, MD 20892 USA. [Vinogradov, Evgeny] Natl Res Council Canada, Inst Biol Sci, Ottawa, ON K1A 0R6, Canada. [Hu, Haijing] NIAID, NIH, Bethesda, MD 20892 USA. RP Kubler-Kielb, J (reprint author), NICHHD, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM kielbj@mail.nih.gov; robbinsjo@nichd.nih.gov OI Vinogradov, Evgeny/0000-0002-5364-1376 FU Intramural NIH HHS NR 30 TC 16 Z9 16 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 24 PY 2008 VL 105 IS 25 BP 8709 EP 8712 DI 10.1073/pnas.0803897105 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 319TA UT WOS:000257185700041 PM 18562275 ER PT J AU Maeng, SH Hunsberger, JG Pearson, B Yuan, PX Wang, Y Wei, YL McCammon, J Schloesser, RJ Zhou, RL Du, J Chen, G McEwen, B Reed, JC Manji, HK AF Maeng, Sungho Hunsberger, Joshua G. Pearson, Brandon Yuan, Peixiong Wang, Yun Wei, Yanling McCammon, Joseph Schloesser, Robert J. Zhou, Rulun Du, Jing Chen, Guang McEwen, Bruce Reed, John C. Manji, Husseini K. TI BAG1 plays a critical role in regulating recovery from both manic-like and depression-like behavioral impairments SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE FKBP51; lithium; valproate; mood disorders; resilience ID GLUCOCORTICOID-RECEPTOR; BIPOLAR DISORDER; LEARNED HELPLESSNESS; MOOD STABILIZERS; PROTEIN BAG-1; OVEREXPRESSION; LITHIUM; BRAIN; MICE; DIFFERENTIATION AB Recent microarray studies with stringent validating criteria identified Bcl-2-associated athanogene (BAG1) as a target for the actions of medications that are mainstays in the treatment of bipolar disorder (BPD). BAG1 is a Hsp70/Hsc70-regulating cochaperone that also interacts with glucocorticoid receptors (GRs) and attenuates their nuclear trafficking and function. Notably, glucocorticoids are one of the few agents capable of triggering both depressive and manic episodes in patients with BPD. As a nexus for the actions of glucocorticoids and bipolar medications, we hypothesized that the level of BAG1 expression would play a pivotal role in regulating affective-like behaviors. This hypothesis was investigated in neuron-selective BAG1 transgenic (TG) mice and BAG1 heterozygous knockout (+/-) mice. On mania-related tests, BAG1 TG mice recovered much faster than wild-type (WT) mice in the amphetamine-induced hyperlocomotion test and displayed a clear resistance to cocaine-induced behavioral sensitization. In contrast, BAG1+/- mice displayed an enhanced response to cocaine-induced behavioral sensitization. The BAG1 TG mice showed less anxious-like behavior on the elevated plus maze test and had higher spontaneous recovery rates from helplessness behavior compared with WT mice. In contrast, fewer BAG1+/- mice recovered from helplessness behavior compared with their WT controls. BAG1 TG mice also exhibited specific alterations of hippocampal proteins known to regulate GR function, including Hsp70 and FKBP51. These data suggest that BAG1 plays a key role in affective resilience and in regulating recovery from both manic-like and depression-like behavioral impairments. C1 [McEwen, Bruce] Rockefeller Univ, Neuroendocrinol Lab, New York, NY 10021 USA. [Reed, John C.] Burnham Inst Med Res, La Jolla, CA 92037 USA. [Maeng, Sungho; Hunsberger, Joshua G.; Pearson, Brandon; Yuan, Peixiong; Wang, Yun; Wei, Yanling; McCammon, Joseph; Schloesser, Robert J.; Zhou, Rulun; Du, Jing; Chen, Guang; Manji, Husseini K.] NIMH, Lab Mol Pathophysiol & Expt Therapeut, Mood & Anxiety Disorders Program, Natl Inst Hlth,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP McEwen, B (reprint author), Rockefeller Univ, Neuroendocrinol Lab, New York, NY 10021 USA. EM mcewen@mail.rockefeller.edu; manjih@mail.nih.gov RI Du, Jing/A-9023-2012; Chen, Guang/A-2570-2017; OI Pearson, Brandon/0000-0003-4807-137X FU Intramural NIH HHS [Z99 MH999999]; NCI NIH HHS [R01 CA067329, CA-67329] NR 34 TC 43 Z9 45 U1 3 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 24 PY 2008 VL 105 IS 25 BP 8766 EP 8771 DI 10.1073/pnas.0803736105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 319TA UT WOS:000257185700051 PM 18562287 ER PT J AU Goila-Gaur, R Strebel, K AF Goila-Gaur, Ritu Strebel, Klaus TI HIV-I Vif, APOBEC, and intrinsic immunity SO RETROVIROLOGY LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; HEPATITIS-B-VIRUS; URACIL-DNA GLYCOSYLASE; CYTIDINE DEAMINASE APOBEC3G; ANTIVIRAL PROTEIN APOBEC3G; VIRION INFECTIVITY FACTOR; RNA-EDITING PROTEIN; HUMAN LINE-1 RETROTRANSPOSITION; E3 UBIQUITIN LIGASE; SINGLE-STRANDED-DNA AB Members of the APOBEC family of cellular cytidine deaminases represent a recently identified group of proteins that provide immunity to infection by retroviruses and protect the cell from endogenous mobile retroelements. Yet, HIV-I is largely immune to the intrinsic antiviral effects of APOBEC proteins because it encodes Vif (viral infectivity factor), an accessory protein that is critical for in vivo replication of HIV-I. In the absence of Vif, APOBEC proteins are encapsidated by budding virus particles and either cause extensive cytidine to uridine editing of negative sense single-stranded DNA during reverse transcription or restrict virus replication through deaminase-independent mechanisms. Thus, the primary function of Vif is to prevent encapsidation of APOBEC proteins into viral particles. This is in part accomplished by the ability of Vif to induce the ubiquitindependent degradation of some of the APOBEC proteins. However, Vif is also able to prevent encapsidation of APOBEC3G and APOBEC3F through degradation-independent mechanism(s). The goal of this review is to recapitulate current knowledge of the functional interaction of HIV-I and its Vif protein with the APOBEC3 subfamily of proteins and to summarize our present understanding of the mechanism of APOBEC3-dependent retrovirus restriction. C1 [Goila-Gaur, Ritu; Strebel, Klaus] NIAID, Mol Microbiol Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Strebel, K (reprint author), NIAID, Mol Microbiol Lab, Natl Inst Hlth, 4-312, Bethesda, MD 20892 USA. EM rgaur@niaid.nih.gov; kstrebel@niaid.nih.gov FU Intramural NIH HHS NR 187 TC 194 Z9 200 U1 0 U2 12 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD JUN 24 PY 2008 VL 5 AR 51 DI 10.1186/1742-4690-5-51 PG 16 WC Virology SC Virology GA 326IG UT WOS:000257651200001 PM 18577210 ER PT J AU Inzitari, M Pozzi, C Ferrucci, L Chiarantini, D Rinaldi, LA Baccini, M Pini, R Masotti, G Marchionni, N Di Bari, M AF Inzitari, Marco Pozzi, Claudia Ferrucci, Luigi Chiarantini, Daniela Rinaldi, Lucio A. Baccini, Marco Pini, Riccardo Masotti, Giulio Marchionni, Niccolo Di Bari, Mauro TI Subtle neurological abnormalities as risk factors for cognitive and functional decline, cerebrovascular events, and mortality in older community-dwelling adults SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID SUBCLINICAL CARDIOVASCULAR-DISEASE; LOWER-EXTREMITY FUNCTION; WHITE-MATTER CHANGES; 6-MINUTE WALK TEST; HEART-FAILURE; DEPRESSIVE SYMPTOMS; ICARE DICOMANO; MOBILITY; PERFORMANCE; HEALTH AB Background: Subtle, but clinically detectable, neurological abnormalities (SNAs) are associated with impaired physical performance in elderly persons without overt neurological diseases. We investigated whether SNAs were prospectively associated with cognitive and functional status, death, and cerebrovascular events (CVEs) in older community-dwelling individuals. Methods: In participants without history of stroke, parkinsonism and dementia, or cognitive impairment, a score (N-SNA) was obtained by summing SNAs detected with a simple neurological examination. Cognitive status and disability were reassessed 4 years later, and deaths and CVEs were documented over 8 years. Results: Of 506 participants free of neurological diseases (mean [SEM] age, 71.9 [0.3] years; 42% were men), 59% had an N-SNA of 1 or more (mean [SEM], 1.1 [0.06]; range, 0-8). At baseline, the N-SNA increased with age and with declining cognitive and physical performance, depressive symptoms, and disability, after adjusting for several covariates, but did not increase with falls and urinary incontinence. The N-SNA prospectively predicted worsening cognitive status and disability, adjusting for demographics and for baseline comorbidity and cognitive and physical performance. The mortality rates were 22.6, 23.3, 23.9, 58.6, and 91.9 per 1000 person-years in participants with an N-SNA of 0, 1, 2, 3, and 4 or higher, respectively. Compared with an N-SNA of less than 3, having an N-SNA of 3 or higher was associated with an increased adjusted risk of death (hazard ratio, 1.77; 95% confidence interval [CI], 1.25-2.74) and of CVE (hazard ratio, 1.94; 95% CI, 1.07-3.54) over 8 years. Conclusion: In this sample of older community-dwelling persons without overt neurological diseases, multiple SNAs were associated with cognitive and functional decline and independently predicted mortality and CVEs. C1 [Inzitari, Marco; Pozzi, Claudia; Chiarantini, Daniela; Rinaldi, Lucio A.; Pini, Riccardo; Masotti, Giulio; Marchionni, Niccolo; Di Bari, Mauro] Univ Florence, Unit Gerontol & Geriatr, Dept Crit Care Med & Surg, I-50141 Florence, Italy. [Inzitari, Marco; Pozzi, Claudia; Chiarantini, Daniela; Rinaldi, Lucio A.; Pini, Riccardo; Masotti, Giulio; Marchionni, Niccolo; Di Bari, Mauro] Univ Careggi, Azienda Osped, Florence, Italy. [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA. [Baccini, Marco] Azienda Sanitaria Locale, Unit Geriatr Rehabil, Florence, Italy. RP Inzitari, M (reprint author), Univ Florence, Unit Gerontol & Geriatr, Dept Crit Care Med & Surg, Via Oblate 4, I-50141 Florence, Italy. EM marcoinzitari@gmail.com RI DI BARI, MAURO/J-1524-2012; OI Pini, Riccardo/0000-0002-7940-7908 FU Intramural NIH HHS [ZIA AG001050-07] NR 32 TC 24 Z9 24 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUN 23 PY 2008 VL 168 IS 12 BP 1270 EP 1276 DI 10.1001/archinte.168.12.1270 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 315YR UT WOS:000256916600009 PM 18574083 ER PT J AU Wendler, D Krohmal, B Emanuel, EJ Grady, C AF Wendler, David Krohmal, Benjamin Emanuel, Ezekiel J. Grady, Christine CA ESPRIT Grp TI Why patients continue to participate in clinical research SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID INFORMED-CONSENT; THERAPEUTIC MISCONCEPTION; DEVELOPING-COUNTRIES; GUINEA-PIGS; TRIALS; SCHIZOPHRENIA; MOTIVATIONS; EXPERIENCES; INFORMATION; VOLUNTEER AB Background: Clinical research exposes patient participants to unproved methods and research procedures in order to gather generalizable knowledge to benefit others. While some commentators argue that this process inappropriately exploits patient participants, there are few data available to evaluate this claim. Methods: Human immunodeficiency virus (HIV)-infected individuals from Argentina, Brazil, and Thailand who had been participating in the Evaluation of Subcutaneous Proleukin (Interleukin-2) in a Randomized International Trial (ESPRIT) study for at least 6 months were invited to complete a self-administered survey on their experience and were asked why they continued to participate. The ESPRIT study is a phase 3, multinational, randomized trial comparing antiretroviral therapy plus interleukin 2 (IL-2) with antiretroviral therapy alone in individuals with HIV disease. Results: From a list of 12 possible reasons regarding why patient participants continue to participate, 8 options were selected as "very important" by 75% or more of 582 respondents, including the possibility of benefiting personally and the potential to help others. When asked to indicate the most important reason from this list, respondents in the IL-2 arm (n=292) selected (1) increasing their CD4 lymphocyte count (26%); (2) finding better treatments for patients with HIV in their home country (22%); and (3) getting IL-2 (12%). Respondents in the no-IL-2 arm (n=290) selected (1) finding better treatments for patients with HIV in their home country (32%); (2) finding better treatments for HIV-infected patients in other countries (12%); and (3) increasing their CD4 lymphocyte count (11%). Also, 90% of the respondents indicated that participation in ESPRIT involved making a "major" or "moderate" contribution to society, and 84% felt "very" or "somewhat" proud to be making this contribution. Conclusions: Most respondents continue to participate in the ESPRIT study in hopes of benefiting personally. The majority also recognized that by participating in ESPRIT they were contributing to helping others; they experienced pride regarding this contribution and considered it an important reason to continue to participate. These results indicate that it is possible for patient participants, even those seeking treatment for a life-threatening illness, to recognize and embrace the goals of the research in which they participate. Future studies will be needed to determine to what extent these findings generalize to other studies and other countries and what steps can help patient participants recognize and embrace the goals of clinical research. C1 [Wendler, David; Krohmal, Benjamin; Emanuel, Ezekiel J.; Grady, Christine] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA. RP Wendler, D (reprint author), NIH, Dept Bioeth, Ctr Clin, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM dwendler@nih.gov FU Intramural NIH HHS NR 31 TC 33 Z9 33 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUN 23 PY 2008 VL 168 IS 12 BP 1294 EP 1299 DI 10.1001/archinte.168.12.1294 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 315YR UT WOS:000256916600013 PM 18574086 ER PT J AU Folsom, AR Kronmal, RA Detrano, RC O'Leary, DH Bild, DE Bluemke, DA Budoff, MJ Liu, K Shea, S Szklo, M Tracy, RP Watson, KE Burke, GL AF Folsom, Aaron R. Kronmal, Richard A. Detrano, Robert C. O'Leary, Daniel H. Bild, Diane E. Bluemke, David A. Budoff, Matthew J. Liu, Kiang Shea, Steven Szklo, Moyses Tracy, Russell P. Watson, Karol E. Burke, Gregory L. TI Coronary artery calcification compared with carotid intima-media thickness in the prediction of cardiovascular disease incidence - The Multi-Ethnic Study of Atherosclerosis (MESA) SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID COMPUTED-TOMOGRAPHY; ETHNIC-DIFFERENCES; CALCIUM; ADULTS; ASSOCIATION; ROTTERDAM; CT AB Background: Coronary artery calcium (CAC) and carotid intima-media thickness (IMT) are noninvasive measures of atherosclerosis that consensus panels have recommended as possible additions to risk factor assessment for predicting the probability of cardiovascular disease (CVD) occurrence. Our objective was to assess whether maximum carotid IMT or CAC (Agatston score) is the better predictor of incident CVD. Methods: A prospective cohort study of subjects aged 45 to 84 years in 4 ethnic groups, who were initially free of CVD (n=6698) was performed, with standardized carotid IMT and CAC measures at baseline, in 6 field centers of the Multi-Ethnic Study of Atherosclerosis (MESA). The main outcome measure was the risk of incident CVD events (coronary heart disease, stroke, and fatal CVD) over a maximum of 5.3 years of follow-up. Results: There were 222 CVD events during follow-up. Coronary artery calcium was associated more strongly than carotid IMT with the risk of incident CVD. After adjustment for each other (CAC score and IMT) and traditional CVD risk factors, the hazard ratio of CVD increased 2.1-fold (95% confidence interval [CI], 1.8-2.5) for each 1-standard deviation (SD) increment of log-transformed CAC score, vs 1.3-fold (95% CI, 1.1-1.4) for each 1-SD increment of the maximum IMT. For coronary heart disease, the hazard ratios per 1-SD increment increased 2.5-fold (95% CI, 2.1-3.1) for CAC score and 1.2-fold (95% CI, 1.0-1.4) for IMT. A receiver operating characteristic curve analysis also suggested that CAC score was a better predictor of incident CVD than was IMT, with areas under the curve of 0.81 vs 0.78, respectively. Conclusion: Although whether and how to clinically use bioimaging tests of subclinical atherosclerosis remains a topic of debate, this study found that CAC score is a better predictor of subsequent CVD events than carotid IMT. C1 [Folsom, Aaron R.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN 55454 USA. [Kronmal, Richard A.] Univ Washington, Collaborat Hlth Studies Coordinating Ctr, Seattle, WA 98195 USA. [Detrano, Robert C.] Univ Calif Irvine, Dept Radiol Sci, Irvine, CA 92717 USA. [O'Leary, Daniel H.] Caritas Carney Hosp, Dorchester, MA USA. [Bild, Diane E.] NHLBI, Div Prevent & Populat Sci, Bethesda, MD 20892 USA. [Bluemke, David A.] Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA. [Szklo, Moyses] Johns Hopkins Univ, Sch Med, Dept Epidemiol, Baltimore, MD USA. [Budoff, Matthew J.] Univ Calif Los Angeles, Med Ctr, Los Angeles Biomed Res Inst Harbor, Div Cardiol, Torrance, CA 90509 USA. [Liu, Kiang] Northwestern Univ, Sch Med, Dept Prevent Med, Chicago, IL USA. [Shea, Steven] Columbia Univ, Dept Med, New York, NY USA. [Shea, Steven] Columbia Univ, Dept Epidemiol, New York, NY USA. [Tracy, Russell P.] Univ Vermont, Dept Pathol, Colchester, Essex, England. [Tracy, Russell P.] Univ Vermont, Dept Biochem, Colchester, Essex, England. [Watson, Karol E.] Univ Calif Los Angeles, Sch Med, Div Cardiol, Los Angeles, CA 90024 USA. [Burke, Gregory L.] Wake Forest Univ Hlth Sci, Div Publ Hlth Sci, Winston Salem, NC USA. RP Folsom, AR (reprint author), Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, 1300 S 2nd St,Ste 300, Minneapolis, MN 55454 USA. EM folso001@umn.edu OI Bluemke, David/0000-0002-8323-8086 FU NHLBI NIH HHS [N01-HC-95159, N01 HC095163, N01-HC-95169, N01HC95159, N01HC95169] NR 23 TC 388 Z9 404 U1 3 U2 12 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUN 23 PY 2008 VL 168 IS 12 BP 1333 EP 1339 DI 10.1001/archinte.168.12.1333 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 315YR UT WOS:000256916600018 PM 18574091 ER PT J AU Svirshchevskaya, EV Mariotti, J Wright, MH Viskova, NY Telford, W Fowler, DH Varticovski, L AF Svirshchevskaya, Elena V. Mariotti, Jacopo Wright, Mollie H. Viskova, Natalia Y. Telford, William Fowler, Daniel H. Varticovski, Lyuba TI Rapamycin delays growth of Wnt-1 tumors in spite of suppression of host immunity SO BMC CANCER LA English DT Article ID BREAST-CANCER CELLS; REGULATORY T-CELLS; IN-VIVO; PHASE-II; MAMMALIAN TARGET; TEMSIROLIMUS CCI-779; INHIBITS GROWTH; MOUSE MODEL; APOPTOSIS; CARCINOMA AB Background: Rapamycin, an inhibitor of mammalian target of Rapamycin ( mTOR), is an immunosuppressive agent that has anti-proliferative effects on some tumors. However, the role of Rapamycin-induced immune suppression on tumor progression has not been examined. Methods: We developed a transplantation model for generation of mammary tumors in syngeneic recipients that can be used to address the role of the immune system on tumor progression. We examined the effect of Rapamycin on the immune system and growth of MMTV-driven Wnt-1 mammary tumors which were transplanted into irradiated and bone marrow-reconstituted, or naive mice. Results: Rapamycin induced severe immunosuppression and significantly delayed the growth of Wnt-1 tumors. T cell depletion in spleen and thymus and reduction in T cell cytokine secretion were evident within 7 days of therapy. By day 20, splenic but not thymic T cell counts, and cytokine secretion recovered. We determined whether adoptive T cell therapy enhances the anti-cancer effect using ex vivo generated Rapamycin-resistant T cells. However, T cell transfer during Rapamycin therapy did not improve the outcome relative to drug therapy alone. Thus, we could not confirm that suppression of T cell immunity contributes to tumor growth in this model. Consistent with suppression of the mTOR pathway, decreased 4E-BP1, p70 S6-kinase, and S6 protein phosphorylation correlated with a decrease in Wnt- 1 tumor cell proliferation. Conclusion: Rapamycin has a direct anti- tumor effect on Wnt- 1 breast cancer in vivo that involves inhibition of the mTOR pathway at doses that also suppress host immune responses. C1 [Svirshchevskaya, Elena V.; Viskova, Natalia Y.] RAS, Shemyakin Ovchinnikov Inst Bioorgan Chem, Moscow 117997, Russia. [Svirshchevskaya, Elena V.; Mariotti, Jacopo; Wright, Mollie H.; Telford, William; Fowler, Daniel H.; Varticovski, Lyuba] NCI, NIH, Bethesda, MD 20892 USA. RP Svirshchevskaya, EV (reprint author), RAS, Shemyakin Ovchinnikov Inst Bioorgan Chem, Miklukho Maklaya St 16-10, Moscow 117997, Russia. EM esvir@mail.ibch.ru; mariottj@mail.nih.gov; writghtmo@mail.nih.gov; visk@mail.ibch.ru; telfordw@mail.nih.gov; dhfowler@helix.nih.gov; varticol@mail.nih.gov FU Intramural NIH HHS NR 49 TC 15 Z9 15 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD JUN 21 PY 2008 VL 8 AR 176 DI 10.1186/1471-2407-8-176 PG 14 WC Oncology SC Oncology GA 326VM UT WOS:000257687200001 PM 18570671 ER PT J AU Small, AR Neagu, A Amyot, F Sackett, D Chernomordik, V Gandjbakhche, A AF Small, Alexander R. Neagu, Adrian Amyot, Franck Sackett, Dan Chernomordik, Victor Gandjbakhche, Amir TI Spatial distribution of VEGF isoforms and chemotactic signals in the vicinity of a tumor SO JOURNAL OF THEORETICAL BIOLOGY LA English DT Article DE tumor-induced angiogenesis; vascular endothelial growth factor (VEGF); matrix metalloproteases (MMPs); reaction-diffusion equations; chemotaxis ID ENDOTHELIAL GROWTH-FACTOR; MARROW-DERIVED CELLS; MATRIX METALLOPROTEINASES; ANGIOGENIC SWITCH; EXTRACELLULAR-MATRIX; CANCER; MATRIX-METALLOPROTEINASE-9; CARCINOGENESIS; TUMORIGENESIS; EXPRESSION AB We propose a mathematical model that describes the formation of gradients of different isoforms of vascular endothelial growth factor (VEGF). VEGF is crucial in the process of tumor-induced angiogenesis, and recent experiments strongly suggest that the molecule is most potent when bound to the extracellular matrix (ECM). Using a system of reaction-diffusion equations, we study diffusion of VEGF, binding of VEGF to the ECM, and cleavage of VEGF from the ECM by matrix metalloproteases (MMPs). We find that spontaneous gradients of matrix-bound VEGF are possible for an isoform that binds weakly to the ECM (i.e. VEGF(165)), but cleavage by MMPs is required to form long-range gradients of isoforms that bind rapidly to the ECM (i.e. VEGF(189)). We also find that gradient strengths and ranges are regulated by MMPs. Finally, we find that VEGF molecules cleaved from the ECM may be distributed in patterns that are not conducive to chemotactic migration toward a tumor, depending on the spatial distribution of MMP molecules. Our model elegantly explains a number of in vivo observations concerning the significance of different VEGF isoforms, points to VEGF(165) as an especially significant therapeutic target and indicator of a tumor's angiogenic potential, and enables predictions that are subject to testing with in vitro experiments. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Small, Alexander R.] Calif State Polytech Univ Pomona, Dept Phys, Pomona, CA 91768 USA. [Small, Alexander R.; Amyot, Franck; Sackett, Dan; Chernomordik, Victor; Gandjbakhche, Amir] NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. [Neagu, Adrian] Univ Missouri, Dept Phys & Astron, Columbia, MO 65211 USA. [Neagu, Adrian] Victor Babes Univ Med & Pharm, Dept Biophys & Med Informat, Timisoara 1900, Romania. RP Small, AR (reprint author), Calif State Polytech Univ Pomona, Dept Phys, Pomona, CA 91768 USA. EM alex_small2002@yahoo.com OI Neagu, Adrian/0000-0003-3871-2188 NR 46 TC 7 Z9 7 U1 0 U2 8 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-5193 J9 J THEOR BIOL JI J. Theor. Biol. PD JUN 21 PY 2008 VL 252 IS 4 BP 593 EP 607 DI 10.1016/j.jtbi.2008.02.009 PG 15 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 321VB UT WOS:000257333500002 PM 18395755 ER PT J AU Celum, C Wald, A Hughes, J Sanchez, J Reid, S Delany-Moretlwe, S Cowan, F Casapia, M Ortiz, A Fuchs, J Buchbinder, S Koblin, B Zwerski, S Rose, S Wang, J Corey, L AF Celum, Connie Wald, Anna Hughes, James Sanchez, Jorge Reid, Stewart Delany-Moretlwe, Sinead Cowan, Frances Casapia, Martin Ortiz, Abner Fuchs, Jonathan Buchbinder, Susan Koblin, Beryl Zwerski, Sheryl Rose, Scott Wang, Jing Corey, Lawrence CA HPTN 039 Protocol Team TI Effect of aciclovir on HIV-1 acquisition in herpes simplex virus 2 seropositive women and men who have sex with men: a randomised, double-blind, placebo-controlled trial SO LANCET LA English DT Article ID HERPES-SIMPLEX-VIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; LINKED-IMMUNOSORBENT-ASSAY; TYPE-2 INFECTION; CLINICAL-TRIALS; GENITAL-TRACT; SUPPRESSION; METAANALYSIS; RISK; TRANSMISSION AB Background Across many observational studies, herpes simplex virus type 2 (HSV-2) infection is associated with two-fold to three-fold increased risk for HIV-1 infection. We investigated whether HSV-2 suppression with aciclovir would reduce the risk of HIV-1 acquisition. Methods We undertook a double-blind, randomised, placebo-controlled phase III trial in HIV-negative, HSV-2 seropositive women in Africa and men who have sex with men (MSM) from sites in Peru and the USA. Participants were randomly assigned by block randomisation to twice daily aciclovir 400 mg (n=1637) or matching placebo (n=1640) for 12-18 months, and were seen monthly for dispensation of study drug, adherence counselling and measurement by pill count and self-reporting, and risk reduction counselling, and every 3 months for genital examination and HIV testing. The primary outcome was HIV-1 acquisition and secondary was incidence of genital ulcers. Analysis was by intention to treat. This study is registered with Clinicaltrials.gov, number NCT00076232. Findings 3172 participants (1358 women, 1814 MSM) were included in the primary dataset (1581 in aciclovir group, 1591 in control group). The incidence of HIV-1 was 3.9 per 100 person-years in the aciclovir group (75 events in 1935 person-years of follow-up) and 3.3 per 100 person-years in the placebo group (64 events in 1969 person-years of follow-up; hazard ratio 1 . 16 [95% CI 0 . 83-1.62]). Incidence of genital ulcers on examination was reduced by 47% (relative risk 0 . 53 [0.46-0.62]) and HSV-2 positive genital ulcers by 63% (0.37 [0.31-0.45]) in the aciclovir group. Adherence to dispensed study drug was 94% in the aciclovir group and 94% in the placebo group, and 85% of expected doses in the aciclovir group and 86% in the placebo group. Retention was 85% at 18 months in both groups (1028 of 1212 in aciclovir group, 1030 of 1208 in placebo group). We recorded no serious events related to the study drug. Interpretation Our results show that suppressive therapy with standard doses of aciclovir is not effective in reduction of HIV-1 acquisition in HSV-2 seropositive women and MSM. Novel strategies are needed to interrupt interactions between HSV-2 and HIV-1. Funding US National Institute of Allergy and Infectious Diseases, US National Institute of Child Health and Human Development, US National Institute of Drug Abuse, US National Institute of Mental Health, US Office of AIDS Research, and GlaxoSmithKline. C1 [Celum, Connie] Univ Washington, Harborview Med Ctr, Dept Global Hlth, Seattle, WA 98104 USA. [Celum, Connie; Wald, Anna; Corey, Lawrence] Univ Washington, Dept Med, Seattle, WA 98104 USA. [Celum, Connie; Wald, Anna] Univ Washington, Dept Epidemiol, Seattle, WA 98104 USA. [Wald, Anna; Corey, Lawrence] Univ Washington, Dept Lab Med, Seattle, WA 98104 USA. [Hughes, James] Univ Washington, Dept Biostat, Seattle, WA 98104 USA. [Wald, Anna; Wang, Jing; Corey, Lawrence] Fred Hutchinson Canc Res Ctr, Program Infect Dis, Seattle, WA 98104 USA. [Sanchez, Jorge; Casapia, Martin; Ortiz, Abner] Asociac Civil Salud & Educ, Lima, Peru. [Reid, Stewart] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. [Reid, Stewart] Ctr Infect Dis Res, Lusaka, Zambia. [Delany-Moretlwe, Sinead] Univ Witwatersrand, Reprod Hlth & HIV Res Unit, Johannesburg, South Africa. [Cowan, Frances] UCL, Royal Free & Univ Coll Med Sch, London, England. [Fuchs, Jonathan; Buchbinder, Susan] San Francisco Dept Publ Hlth, San Francisco, CA USA. [Koblin, Beryl] New York Blood Ctr, New York, NY 10021 USA. [Zwerski, Sheryl] NIH, Div AIDS, Bethesda, MD 20892 USA. [Rose, Scott] Family Hlth Int, Res Triangle Pk, NC 27709 USA. RP Celum, C (reprint author), Univ Washington, Harborview Med Ctr, Dept Global Hlth, Box 359927,325 9th Ave, Seattle, WA 98104 USA. EM ccelum@u.washington.edu RI Wald, Anna/B-6272-2012; OI Wald, Anna/0000-0003-3486-6438; Reid, Stewart/0000-0001-7779-4820; Cowan, Frances/0000-0003-3087-4422 FU NIAID NIH HHS [P30 AI027757, U01 AI046749, U01 AI052054, U01 AI052054-06, U01 AI069466, U01 AI069466-02, U01 AI46749, U01 AI52054] NR 31 TC 280 Z9 286 U1 6 U2 23 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD JUN 21 PY 2008 VL 371 IS 9630 BP 2109 EP 2119 DI 10.1016/S0140-6736(08)60920-4 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 316ER UT WOS:000256932200031 PM 18572080 ER PT J AU Lewers, KS Saski, CA Cuthbertson, BJ Henry, DC Staton, ME Main, DS Dhanaraj, AL Rowland, LJ Tomkins, JP AF Lewers, Kim S. Saski, Chris A. Cuthbertson, Brandon J. Henry, David C. Staton, Meg E. Main, Dorrie S. Dhanaraj, Anik L. Rowland, Lisa J. Tomkins, Jeff P. TI A blackberry (Rubus L.) expressed sequence tag library for the development of simple sequence repeat markers SO BMC PLANT BIOLOGY LA English DT Article ID GENETIC-LINKAGE MAP; SSR MARKERS; RASPBERRY; MODEL; CONSTRUCTION; PREDICTION; STRAWBERRY; RESOURCE; DATABASE; ERECT AB Background: The recent development of novel repeat-fruiting types of blackberry (Rubus L.) cultivars, combined with a long history of morphological marker-assisted selection for thornlessness by blackberry breeders, has given rise to increased interest in using molecular markers to facilitate blackberry breeding. Yet no genetic maps, molecular markers, or even sequences exist specifically for cultivated blackberry. The purpose of this study is to begin development of these tools by generating and annotating the first blackberry expressed sequence tag (EST) library, designing primers from the ESTs to amplify regions containing simple sequence repeats (SSR), and testing the usefulness of a subset of the EST-SSRs with two blackberry cultivars. Results: A cDNA library of 18,432 clones was generated from expanding leaf tissue of the cultivar Merton Thornless, a progenitor of many thornless commercial cultivars. Among the most abundantly expressed of the 3,000 genes annotated were those involved with energy, cell structure, and defense. From individual sequences containing SSRs, 673 primer pairs were designed. Of a randomly chosen set of 33 primer pairs tested with two blackberry cultivars, 10 detected an average of 1.9 polymorphic PCR products. Conclusion: This rate predicts that this library may yield as many as 940 SSR primer pairs detecting 1,786 polymorphisms. This may be sufficient to generate a genetic map that can be used to associate molecular markers with phenotypic traits, making possible molecular marker-assisted breeding to compliment existing morphological marker-assisted breeding in blackberry. C1 [Lewers, Kim S.; Dhanaraj, Anik L.; Rowland, Lisa J.] USDA ARS, Beltsville Agr Res Ctr, Genet Improvement Fruits & Vegetables Lab, Beltsville, MD 20705 USA. [Saski, Chris A.; Cuthbertson, Brandon J.; Henry, David C.; Staton, Meg E.; Main, Dorrie S.; Tomkins, Jeff P.] Clemson Univ, Genom Inst, Clemson, SC 29634 USA. [Cuthbertson, Brandon J.] Natl Inst Environm Hlth Sci, Lab Signal Transduct, Peptide Hormone Act Grp, Res Triangle Pk, NC 27709 USA. [Main, Dorrie S.] Washington State Univ, Dept Hort & Landscape Architecture, Ctr Integrated Biotechnol, Pullman, WA 99164 USA. [Dhanaraj, Anik L.] Monsanto Res Ctr, Bangalore 560092, Karnataka, India. RP Lewers, KS (reprint author), USDA ARS, Beltsville Agr Res Ctr, Genet Improvement Fruits & Vegetables Lab, Bldg 010A,BARC W,10300 Baltimore Ave, Beltsville, MD 20705 USA. EM kim.lewers@ars.usda.gov; saski@clemson.edu; brandoncuthbertson@gmail.com; henry5@clemson.edu; mestato@clemson.edu; dorrie@wsu.edu; aldhana@monsanto.com; jeannie.rowland@ars.usda.gov; jeff@genome.clemson.edu NR 33 TC 23 Z9 29 U1 3 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2229 J9 BMC PLANT BIOL JI BMC Plant Biol. PD JUN 20 PY 2008 VL 8 AR 69 DI 10.1186/1471-2229-8-69 PG 8 WC Plant Sciences SC Plant Sciences GA 336PK UT WOS:000258376900002 PM 18570660 ER PT J AU Gutti, RK Tsai-Morris, CH Dufau, ML AF Gutti, Ravi K. Tsai-Morris, Chon-Hwa Dufau, Maria L. TI Gonadotropin-regulated testicular helicase (DDX25), an essential regulator of spermatogenesis, prevents testicular germ cell apoptosis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NF-KAPPA-B; RNA HELICASE; GENE-EXPRESSION; PROTEIN-KINASE; BCL-2 FAMILY; RAT TESTIS; PHOSPHORYLATION; SURVIVAL; DEATH; BAD AB Gonadotropin-regulated testicular helicase (GRTH)/DDX25 is an essential post-transcriptional regulator of spermatogenesis. In GRTH null mice severe apoptosis was observed in spermatocytes entering the metaphase of meiosis. Pro- and antiapoptotic factors were found to be under GRTH regulation in comparative studies of spermatocytes from wild type and GRTH(-/-) knock-out (KO) mice. KO mice displayed decreased levels of Bcl-2 and Bcl-xL (anti-apoptotic factors), an increase in Bid, Bak, and Bad (pro-apoptotic), reduced phospho-Bad, and release of cytochrome c. Also, an increase on Smac, a competitor of inhibitor apoptotic proteins that release caspases, was observed. These changes caused an increase in cleavage of caspases 9 and 3, activation of caspase 3 and increases in cleavage products of PARP. The half-life of caspase 3 transcripts was markedly increased in KO, indicating that GRTH had a negative role on its mRNA stability. I kappa B alpha, which sequesters NF-kappa B from its transcriptional activation of pro-apoptotic genes, was highly elevated in KO, and its phospho-form, which promotes its dissociation, was reduced. The increase of HDAC1 and abolition of p300 expression in KO indicated a nuclear action of GRTH on the NF-kappa B-mediated transcription of anti-apoptotic genes. It also regulates the associated death domain pathway and caspase 8-mediated events. GRTH-mediated apoptotic regulation was further indicated by its selective binding to pro- and anti-apoptotic mRNAs. These studies have demonstrated that GRTH, as a component of mRNP particles, acts as a negative regulator of the tumor necrosis factor receptor 1 and caspase pathways and promotes NF-kappa B function to control apoptosis in spermatocytes of adult mice. C1 [Gutti, Ravi K.; Tsai-Morris, Chon-Hwa; Dufau, Maria L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, Endocrinol & Reprod Res Branch, NIH,Sect Mol Endocrinol, Bethesda, MD 20892 USA. RP Dufau, ML (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, Endocrinol & Reprod Res Branch, NIH,Sect Mol Endocrinol, Bldg 49,Rm 6A-36,49 Convent Dr,MSC 4510, Bethesda, MD 20892 USA. EM dufaum@mail.nih.gov OI Gutti, Ravi/0000-0002-0912-5796 FU Intramural NIH HHS NR 36 TC 20 Z9 22 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 20 PY 2008 VL 283 IS 25 BP 17055 EP 17064 DI 10.1074/jbc.M708449200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 313DF UT WOS:000256720600012 PM 18430733 ER PT J AU Dostalek, M Hardy, KD Milne, GL Morrow, JD Chen, C Gonzalez, FJ Gu, J Ding, X Johnson, DA Johnson, JA Martin, MV Guengerich, FP AF Dostalek, Miroslav Hardy, Klarissa D. Milne, Ginger L. Morrow, Jason D. Chen, Chi Gonzalez, Frank J. Gu, Jun Ding, Xinxin Johnson, Delinda A. Johnson, Jeffrey A. Martin, Martha V. Guengerich, F. Peter TI Development of oxidative stress by cytochrome P450 induction in rodents is selective for barbiturates and related to loss of pyridine nucleotide-dependent protective systems SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LIVER-SPECIFIC DELETION; NADPH-CYTOCHROME-P450 REDUCTASE GENE; NICOTINAMIDE N-METHYLTRANSFERASE; ANTIOXIDANT RESPONSE ELEMENT; HYDROGEN-PEROXIDE FORMATION; MIXED-FUNCTION OXIDATION; GLUTATHIONE-PEROXIDASE; MOUSE-LIVER; IN-VIVO; MICROSOMAL CYTOCHROME-P-450 AB Reactive oxygen species (ROS) and oxidative stress have been considered in a variety of disease models, and cytochrome P450 (P450) enzymes have been suggested to be a source of ROS. Induction of P450s by phenobarbital (PB), beta-naphthoflavone (beta NF), or clofibrate in a mouse model increased ROS parameters in the isolated liver microsomes, but isoniazid treatment did not. However, when F-2-isoprostanes (F-2-IsoPs) were measured in tissues and urine, PB showed the strongest effect and beta NF had a measurable but weaker effect. The same trend was seen when an Nfr2-based transgene reporter sensitive to ROS was analyzed in the mice. This pattern had been seen earlier with F-2-IsoPs both in vitro and in vivo with rats (Dostalek, M., Brooks, J. D., Hardy, K. D., Milne, G. L., Moore, M. M., Sharma, S., Morrow, J. D., and Guengerich, F. P. (2007) Mol. Pharmacol. 72, 1419 1424). One possibility for the general in vitro-in vivo discrepancy in oxidative stress found in both mice and rats is that PB treatment might attenuate protective systems. One potential candidate suggested by an mRNA microarray was nicotinamide N-methyltransferase. PB was found to elevate nicotinamide N-methyltransferase activity 3- to 4-fold in mice and rats and to attenuate levels of NAD(+), NADP(+), NADH, and NADPH in both species (20-40%), due to the enhanced excretion of (N-methyl)nicotinamide. PB also down-regulated glutathione peroxidase and glutathione reductase, which together constitute a key enzymatic system that uses NADPH in protecting against oxidative stress. These multiple effects on the protective systems are proposed to be more important than P450 induction in oxidative stress and emphasize the importance of studying in vivo models. C1 [Dostalek, Miroslav; Martin, Martha V.; Guengerich, F. Peter] Vanderbilt Univ, Dept Biochem, Sch Med, Nashville, TN 37232 USA. [Dostalek, Miroslav; Hardy, Klarissa D.; Milne, Ginger L.; Morrow, Jason D.; Martin, Martha V.; Guengerich, F. Peter] Vanderbilt Univ, Ctr Mol Toxicol, Sch Med, Nashville, TN 37232 USA. [Hardy, Klarissa D.; Milne, Ginger L.; Morrow, Jason D.] Vanderbilt Univ, Div Clin Pharmacol, Sch Med, Nashville, TN 37232 USA. [Chen, Chi; Gonzalez, Frank J.] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. [Gu, Jun; Ding, Xinxin] SUNY Albany, New York State Dept Hlth, Wadsworth Ctr, Albany, NY 12201 USA. [Gu, Jun; Ding, Xinxin] SUNY Albany, Sch Publ Hlth, Albany, NY 12201 USA. [Johnson, Delinda A.; Johnson, Jeffrey A.] Univ Wisconsin, Sch Pharm, Madison, WI 53705 USA. RP Guengerich, FP (reprint author), Vanderbilt Univ, Dept Biochem, Sch Med, 638 Robinson Res Bldg,2200 Pierce Ave, Nashville, TN 37232 USA. EM f.guengerich@vanderbilt.edu RI Milne, Ginger/D-7648-2014 OI Milne, Ginger/0000-0003-3890-151X FU NCI NIH HHS [R37 CA090426]; NIDDK NIH HHS [R01 DK48831]; NIEHS NIH HHS [R01 ES08089, P01 ES13125, P30 ES000267, R01 ES007462, R01 ES007462-13, R01 ES07462, R01 ES10042]; NIGMS NIH HHS [P50 GM16431] NR 76 TC 33 Z9 35 U1 0 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 20 PY 2008 VL 283 IS 25 BP 17147 EP 17157 DI 10.1074/jbc.M802447200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 313DF UT WOS:000256720600023 PM 18442974 ER PT J AU Pani, B Ong, HL Liu, XB Rauser, K Ambudkar, IS Singh, BB AF Pani, Biswaranjan Ong, Hwei Ling Liu, Xibao Rauser, Kristina Ambudkar, Indu S. Singh, Brij B. TI Lipid rafts determine clustering of STIM1 in endoplasmic reticulum-plasma membrane junctions and regulation of store-operated Ca2+ entry (SOCE) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CAPACITATIVE CALCIUM-ENTRY; TRPC CHANNELS; SIGNAL-TRANSDUCTION; CRAC CHANNELS; I-CRAC; CAVEOLAE; ACTIVATION; COMPLEX; INFLUX; ORAI1 AB Store depletion induces STIM1 to aggregate and relocate into clusters at ER-plasma membrane junctions where it functionally interacts with and activates plasma membrane channels that mediate store-operated Ca2+ entry (SOCE). Thus, the site of peripheral STIM1 clusters is critical for the regulation of SOCE. However, what determines the location of the STIM1 clusters in the ER-PM junctional regions, and whether these represent specific sites in the cell is not yet known. Here we report that clustering of STIM1 in the sub-plasma membrane region of the cell and activation of TRPC1-dependent SOCE are determined by lipid raft domains (LRD). We show that store depletion increased partitioning of TRPC1 and STIM1 into plasma membrane LRD. TRPC1 and STIM1 associated with each other within the LRD, and this association was dynamically regulated by the status of the ER Ca2+ store. Peripheral STIM1 clustering was independent of TRPC1. However, sequestration of membrane cholesterol attenuated thapsigargin-induced clustering of STIM1 as well as SOCE in HSG and HEK293 cells. Recruitment and association of STIM1 and TRPC1 in LRD was also decreased. Additionally STIM1(D76A), which is peripherally localized and constitutively activates SOCE in unstimulated cells, displayed a relatively higher partitioning into LRD and interaction with TRPC1, as compared with STIM1. Disruption of membrane rafts decreased peripheral STIM1(D76A) puncta, its association with TRPC1 and the constitutive SOCE. Together, these data demonstrate that intact LRD determine targeting of STIM1 clusters to ER-plasma membrane junctions following store depletion. This facilitates the functional interaction of STIM1 with TRPC1 and activation of SOCE. C1 [Ong, Hwei Ling; Liu, Xibao; Ambudkar, Indu S.] NIDCR, Secretory Physiol Sect, MPTB, NIH, Bethesda, MD 20892 USA. [Pani, Biswaranjan; Rauser, Kristina; Singh, Brij B.] Univ N Dakota, Sch Med & Hlth Sci, Dept Biochem & Mol Biol, Grand Forks, ND 58201 USA. RP Ambudkar, IS (reprint author), NIDCR, Secretory Physiol Sect, MPTB, NIH, Bethesda, MD 20892 USA. EM indu.ambudkar@nih.gov; bsingh@medicine.nodak.edu OI Singh, Brij/0000-0003-0535-5997 FU Intramural NIH HHS; NCRR NIH HHS [5P20RR017699, P20 RR017699, P20 RR017699-077011]; NIDCR NIH HHS [R01 DE017102-02, DE017102, R01 DE017102, R01 DE017102-01A1, R01 DE017102-03] NR 35 TC 117 Z9 117 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 20 PY 2008 VL 283 IS 25 BP 17333 EP 17340 DI 10.1074/jbc.M800107200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 313DF UT WOS:000256720600042 PM 18430726 ER PT J AU Kovanen, PE Bernard, J Al-Shami, A Liu, CY Bollenbacher-Reilley, J Young, L Pise-Masison, C Spolski, R Leonard, WJ AF Kovanen, Panu E. Bernard, Jerome Al-Shami, Amin Liu, Chengyu Bollenbacher-Reilley, Julie Young, Lynn Pise-Masison, Cynthia Spolski, Rosanne Leonard, Warren J. TI T-cell development and function are modulated by dual specificity phosphatase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FALSE DISCOVERY RATE; IMMUNE-RESPONSE; HOMEOSTATIC PROLIFERATION; SIGNAL-TRANSDUCTION; KINASE-ACTIVITY; TARGET GENES; MAP KINASES; IN-VIVO; INTERLEUKIN-2; CYTOKINES AB Interleukin-2 (IL-2) is a pleiotropic cytokine that regulates lymphocyte proliferation and peripheral tolerance. IL-2 activates mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase, and signal transducer and activator of transcription (STAT) pathways and modulates expression of target genes. Systematic analysis of IL-2 target genes has revealed regulation of potential feedback inhibitors of IL-2 signaling, including several suppressor of cytokine signaling (SOCS) family members as well as MAPK pathway-regulating dual specificity phosphatases (DUSPs). Here we have evaluated the in vivo actions of DUSP5, an extracellular signal-regulated kinase 1/2 (ERK1/2)-specific phosphatase, by generating transgenic mice overexpressing DUSP5 within the lymphoid compartment. We show that transgenic DUSP5 expression results in a block in thymocyte development at the double positive stage. We also demonstrate that DUSP5-expressing mature T cells exhibit decreased IL-2-dependent proliferation and defective IL-2-mediated induction of genes. Finally, DUSP5 transgenic mice develop autoimmune symptoms, suggesting a role for the MAPK pathway in the regulation of tolerance. Thus, proper regulation of DUSP5 activity is critical for normal immune system development, IL-2 actions, and tolerance. C1 [Kovanen, Panu E.; Bernard, Jerome; Al-Shami, Amin; Bollenbacher-Reilley, Julie; Spolski, Rosanne; Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. [Liu, Chengyu] NHLBI, Transgen Mouse Core Facil, NIH, Bethesda, MD 20892 USA. [Young, Lynn] NIH, Bioinformat & Mol Anal Sect, Computat Biosci & Engn Lab, CIT, Bethesda, MD 20892 USA. [Pise-Masison, Cynthia] NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Leonard, WJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bldg 10,Rm 7B05, Bethesda, MD 20892 USA. EM wjl@helix.nih.gov RI Al-Shami, Amin/D-3889-2009 FU Intramural NIH HHS NR 57 TC 29 Z9 30 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 20 PY 2008 VL 283 IS 25 BP 17362 EP 17369 DI 10.1074/jbc.M709887200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 313DF UT WOS:000256720600045 PM 18430737 ER PT J AU Lomonaco, SL Kahana, S Blass, M Brody, Y Okhrimenko, H Xiang, C Finniss, S Blumberg, PM Lee, HK Brodie, C AF Lomonaco, Stephanie L. Kahana, Sarit Blass, Michal Brody, Yehuda Okhrimenko, Hana Xiang, Cunli Finniss, Susan Blumberg, Peter M. Lee, Hae-Kyung Brodie, Chaya TI Phosphorylation of protein kinase C delta on distinct tyrosine residues induces sustained activation of Erk1/2 via down-regulation of MKP-1 - Role in the apoptotic effect of etoposide SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROSTATE-CANCER CELLS; PKC-DELTA; PHYSIOLOGICAL FUNCTIONS; MAPK PHOSPHATASE-1; SIGNALING PATHWAYS; GLIOMA-CELLS; P38 MAPK; SURVIVAL; INVOLVEMENT; OVEREXPRESSION AB The mechanism underlying the important role of protein kinase C delta (PKC delta) in the apoptotic effect of etoposide in glioma cells is incompletely understood. Here, we examined the role of PKC delta in the activation of Erk1/2 by etoposide. We found that etoposide induced persistent activation of Erk1/2 and nuclear translocation of phospho-Erk1/2. MEK1 inhibitors decreased the apoptotic effect of etoposide, whereas inhibitors of p38 and JNK did not. The activation of Erk1/2 by etoposide was downstream of PKC delta since the phosphorylation of Erk1/2 was inhibited by a PKC delta-KD mutant and PKC delta small interfering RNA. We recently reported that phosphorylation of PKC delta on tyrosines 64 and 187 was essential for the apoptotic effect of etoposide. Using PKC delta tyrosine mutants, we found that the phosphorylation of PKC delta on these tyrosine residues, but not on tyrosine 155, was also essential for the activation of Erk1/2 by etoposide. In contrast, nuclear translocation of PKC delta was independent of its tyrosine phosphorylation and not necessary for the phosphorylation of Erk1/2. Etoposide induced down-regulation of kinase phosphatase-1 (MKP-1), which correlated with persistent phosphorylation of Erk1/2 and was dependent on the tyrosine phosphorylation of PKC delta. Moreover, silencing of MKP-1 increased the phosphorylation of Erk1/2 and the apoptotic effect of etoposide. Etoposide induced polyubiquitylation and degradation of MKP-1 that was dependent on PKC delta and on its tyrosine phosphorylation. These results indicate that distinct phosphorylation of PKC delta on tyrosines 64 and 187 specifically activates the Erk1/2 pathway by the down-regulation of MKP-1, resulting in the persistent phosphorylation of Erk1/2 and cell apoptosis. C1 [Lomonaco, Stephanie L.; Xiang, Cunli; Finniss, Susan; Lee, Hae-Kyung; Brodie, Chaya] Henry Ford Hosp, Hermelin Brain Tumor Ctr, Dept Neurosurg, William & Karen Davidson Lab Cell Signaling & Tum, Detroit, MI 48202 USA. [Kahana, Sarit; Blass, Michal; Brody, Yehuda; Okhrimenko, Hana; Brodie, Chaya] Bar Ilan Univ, Mina & Everard Goodman Fac Life Sci, IL-52900 Ramat Gan, Israel. [Blumberg, Peter M.] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. RP Brodie, C (reprint author), Henry Ford Hosp, Hermelin Brain Tumor Ctr, Dept Neurosurg, William & Karen Davidson Lab Cell Signaling & Tum, 2799 W Grand Blvd, Detroit, MI 48202 USA. EM nscha@neuro.hfh.edu FU NCI NIH HHS [CA109196] NR 48 TC 18 Z9 19 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 20 PY 2008 VL 283 IS 25 BP 17731 EP 17739 DI 10.1074/jbc.M801727200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 313DF UT WOS:000256720600079 PM 18434324 ER PT J AU Siegel, AB Cohen, EI Ocean, A Lehrer, D Goldenberg, A Knox, JJ Chen, H Clark-Garvey, S Weinberg, A Mandeli, J Christos, P Mazumdar, M Popa, E Brown, RS Rafii, S Schwartz, JD AF Siegel, Abby B. Cohen, Emil I. Ocean, Allyson Lehrer, Deborah Goldenberg, Alec Knox, Jennifer J. Chen, Helen Clark-Garvey, Sean Weinberg, Alan Mandeli, John Christos, Paul Mazumdar, Madhu Popa, Elizabeta Brown, Robert S., Jr. Rafii, Shahin Schwartz, Jonathan D. TI Phase II trial evaluating the clinical and biologic effects of bevacizumab in unresectable hepatocellular carcinoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; COLORECTAL-CANCER; UNITED-STATES; ANGIOGENESIS; EXPRESSION AB Purpose To determine the clinical and biologic effects of bevacizumab, an anti -vascular endothelial growth factor (VEGF) monoclonal antibody, in unresectable hepatocellular carcinoma (HCC). Patients and Methods Adults with organ-confined HCC, Eastern Cooperative Oncology Group performance status of 0 to 2, and compensated liver disease were eligible. Patients received bevacizumab 5 mg/ kg (n = 12) or 10 mg/ kg (n = 34) every 2 weeks until disease progression or treatment-limiting toxicity. The primary objective was to determine whether bevacizumab improved the 6-month progression-free survival (PFS) rate from 40% to 60%. Secondary end points included determining the effects of bevacizumab on arterial enhancement and on plasma cytokine levels and the capacity of patients' plasma to support angiogenesis via an in vitro assay. Results The study included 46 patients, of whom six had objective responses (13%; 95% CI, 3% to 23%), and 65% were progression free at 6 months. Median PFS time was 6.9 months (95% CI, 6.5 to 9.1 months); overall survival rate was 53% at 1 year, 28% at 2 years, and 23% at 3 years. Grade 3 to 4 adverse events included hypertension (15%) and thrombosis (6%, including 4% with arterial thrombosis). Grade 3 or higher hemorrhage occurred in 11% of patients, including one fatal variceal bleed. Bevacizumab was associated with significant reductions in tumor enhancement by dynamic contrast-enhanced magnetic resonance imaging and reductions in circulating VEGF-A and stromal-derived factor-1 levels. Functional angiogenic activity was associated with VEGF-A levels in patient plasma. Conclusion We observed significant clinical and biologic activity for bevacizumab in nonmetastatic HCC and achieved the primary study end point. Serious bleeding complications occurred in 11% of patients. Further evaluation is warranted in carefully selected patients. C1 [Siegel, Abby B.] Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY 10032 USA. Columbia Univ, Coll Phys & Surg, Dept Surg, New York, NY 10032 USA. Columbia Univ, Coll Phys & Surg, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA. Mt Sinai Sch Med, New York, NY USA. Weill Cornell Med Coll, Dept Med, New York, NY USA. Weill Cornell Med Coll, Dept Publ Hlth, New York, NY USA. NYU, Ctr Comprehens Canc, New York, NY USA. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. Imclone Syst Inc, Branchburg, NJ USA. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. Princess Margaret Phase II Consortium, Toronto, ON, Canada. RP Siegel, AB (reprint author), Columbia Univ, Coll Phys & Surg, Dept Med, 622 W 168th St,PH-14, New York, NY 10032 USA. EM aas54@columbia.edu FU NCI NIH HHS [K24 CA100287, K23 CA-90584, K23 CA090584, K24 CA-100287-05]; NCRR NIH HHS [UL1 RR024156] NR 19 TC 239 Z9 250 U1 1 U2 9 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 JUN 20 PY 2008 VL 26 IS 18 BP 2992 EP 2998 DI 10.1200/JCO.2007.15.9947 PG 7 WC Oncology SC Oncology GA 315KU UT WOS:000256879700014 PM 18565886 ER PT J AU Bielack, SS Marina, N Ferrari, S Helman, LJ Smeland, S Whelan, JS Reaman, GH AF Bielack, Stefan S. Marina, Neyssa Ferrari, Stefano Helman, Lee J. Smeland, Sigbjorn Whelan, Jeremy S. Reaman, Gregory H. TI Osteosarcoma: The same old drugs or more? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID ADJUVANT CHEMOTHERAPY; MURAMYL TRIPEPTIDE; EXTREMITIES; SURVIVAL; SARCOMA; TRIAL C1 [Bielack, Stefan S.] Olga Hosp, Klinikum Stuttgart, Stuttgart, Germany. [Bielack, Stefan S.] Univ Klinikum Munster, Munster, Germany. [Marina, Neyssa] Stanford Univ, Med Ctr, Div Hematol Oncol, Palo Alto, CA 94304 USA. [Marina, Neyssa] Lucile Packard Childrens Hosp, Palo Alto, CA 94304 USA. [Ferrari, Stefano] Ist Ortoped Rizzoli, Sez Chemioterapia, Bologna, Italy. [Helman, Lee J.] NIH, Ctr Canc Res, Bethesda, MD 20892 USA. [Smeland, Sigbjorn] Rikshosp Univ Hosp, Norwegian Radium Hosp, Div Canc Med & Radiotherapy, Oslo, Norway. [Whelan, Jeremy S.] UCL Hosp, Dept Oncol, London, England. [Reaman, Gregory H.] George Washington Univ, Childrens Natl Med Ctr, Div Oncol, Washington, DC USA. RP Bielack, SS (reprint author), Olga Hosp, Klinikum Stuttgart, Stuttgart, Germany. NR 9 TC 40 Z9 40 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2008 VL 26 IS 18 BP 3102 EP 3103 DI 10.1200/JCO.2008.17.1108 PG 2 WC Oncology SC Oncology GA 315KU UT WOS:000256879700039 PM 18565904 ER PT J AU Hunsberger, S Freidlin, B Smith, MA AF Hunsberger, Sally Freidlin, Boris Smith, Malcolm A. TI Complexities in interpretation of osteosarcoma clinical trial results SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID MURAMYL TRIPEPTIDE C1 [Hunsberger, Sally; Freidlin, Boris] NCI, Biometr Res Branch, Bethesda, MD 20892 USA. [Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Hunsberger, S (reprint author), NCI, Biometr Res Branch, Bethesda, MD 20892 USA. NR 4 TC 21 Z9 21 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 JUN 20 PY 2008 VL 26 IS 18 BP 3103 EP 3104 DI 10.1200/JCO.2008.17.3484 PG 3 WC Oncology SC Oncology GA 315KU UT WOS:000256879700040 PM 18565905 ER PT J AU Watts, NR Cardone, G Vethanayagam, JG Cheng, NQ Hultgren, C Stahl, SJ Steven, AC Sallberg, M Wingfield, PT AF Watts, Norman R. Cardone, Giovanni Vethanayagam, Joe G. Cheng, Naiqian Hultgren, Catharina Stahl, Stephen J. Steven, Alasdair C. Sallberg, Matti Wingfield, Paul T. TI Non-canonical binding of an antibody resembling a naive B cell receptor immunoglobulin to hepatitis B virus capsids SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE virus-host interaction; antigen-antibody interaction; cryo-electron microscopy; B cell receptor; HBV ID CORE ANTIGEN; CRYOELECTRON MICROSCOPY; ESCHERICHIA-COLI; 3-DIMENSIONAL RECONSTRUCTION; MONOCLONAL-ANTIBODIES; ELECTRON-MICROSCOPY; PROTEIN; EPITOPE; MODEL; VISUALIZATION AB The hepatitis B virus capsid (core antigen) is able to bind to and activate naive B cells and these become efficient primary antigen-presenting cells for the priming of T cells. We have investigated this interaction by using cryoelectron microscopy, three-dimensional image reconstruction, and molecular modeling to visualize capsids decorated with Fab fragments of a receptor immunoglobulin, and surface plasmon resonance to measure the binding affinity. By both criteria, the mode of binding differs from those of the six monoclonal anti-core antigen. antibodies previously characterized. The Fab interacts with two sites similar to 30 angstrom apart. One interaction is canonical, whereby the CDR loops engage the tip of one of the 25 angstrom spikes that protrude from the capsid surface. The second interaction is non-canonical; in it, the Fab framework contacts the tip of an adjacent spike. The binding affinity of this Fab for capsids, K-D similar to 4 x 10(-7) M, is relatively low for an antibody-antigen interaction, but is similar to 150-fold lower still (similar to 2.5 x 10(-5) M) for unassembled capsid protein dimers. The latter observation indicates that both of the observed interactions are required to achieve stable binding of capsids by this receptor immunoglobulin. Considerations of conserved sequence motifs in other such molecules suggest that other naive B cells may interact with HBV capsids in much the same way. Published by Elsevier Ltd. C1 [Watts, Norman R.; Vethanayagam, Joe G.; Stahl, Stephen J.; Wingfield, Paul T.] NIAMSD, Natl Inst Hlth, Prot Express Lab, Bethesda, MD 20892 USA. [Cardone, Giovanni; Cheng, Naiqian; Steven, Alasdair C.] NIAMSD, Natl Inst Hlth, Struct Biol Lab, Bethesda, MD 20892 USA. [Hultgren, Catharina; Sallberg, Matti] Karolinska Inst, Div Clin Microbiol, Stockholm, Sweden. RP Watts, NR (reprint author), NIAMSD, Natl Inst Hlth, Prot Express Lab, Bethesda, MD 20892 USA. EM Norman_Watts@nih.gov FU Intramural NIH HHS [Z01 AR041117-12] NR 48 TC 12 Z9 12 U1 1 U2 5 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JUN 20 PY 2008 VL 379 IS 5 BP 1119 EP 1129 DI 10.1016/j.jmb.2008.04.009 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 314NJ UT WOS:000256815800014 PM 18486949 ER PT J AU Fang, WY Li, X Jiang, QP Liu, Z Yang, HL Wang, S Xie, SM Liu, QZ Liu, TF Huang, J Xie, WB Li, ZG Zhao, YD Wang, E Marincola, FM Yao, K AF Fang, Weiyi Li, Xin Jiang, Qingping Liu, Zhen Yang, Huiling Wang, Shuang Xie, Siming Liu, Qiuzhen Liu, Tengfei Huang, Jing Xie, Weibing Li, Zuguo Zhao, Yingdong Wang, Ena Marincola, Francesco M. Yao, Kaitai TI Transcriptional patterns, biomarkers and pathways characterizing nasopharyngeal carcinoma of Southern China SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; TUMOR-SUPPRESSOR GENE; CHROMOSOMAL IMBALANCES; SIGNALING PATHWAY; EXPRESSION; SURVIVIN; CANCER; P53; DNA; MICROARRAYS AB Background: The pathogenesis of nasopharyngeal carcinoma (NPC) is a complicated process involving genetic predisposition, Epstein-Bar Virus infection, and genetic alterations. Although some oncogenes and tumor suppressor genes have been previously reported in NPC, a complete understanding of the pathogenesis of NPC in the context of global gene expression, transcriptional pathways and biomarker assessment remains to be elucidated. Methods: Total RNA from 32 pathologically-confirmed cases of poorly-differentiated NPC was divided into pools inclusive of four consecutive specimens and each pool (T1 to T8) was cohybridized with pooled RNA from 24 normal non-cancerous nasopharyngeal tissues (NP) to a human 8K cDNA array platform. The reliability of microarray data was validated for selected genes by semi-quantitative RT-PCR and immunohistochemistry. Results: Stringent statistical filtering parameters identified 435 genes to be up-regulated and 257 genes to be down-regulated in NPC compared to NP. Seven up-regulated genes including CYCI, MIF, LAMB3, TUBB2, UBE2C and TRAPI had been previously proposed as candidate common cancer biomarkers based on a previous extensive comparison among various cancers and normal tissues which did not, however, include NPC or NP. In addition, nine known oncogenes and tumor suppressor genes, MIF, BIRC5, PTTGI, ATM, FOXOIA, TGFBR2, PRKARIA, KLF5 and PDCD4 were identified through the microarray literature-based annotation search engine MILANO, suggesting these genes may be specifically involved in the promotion of the malignant conversion of nasopharyngeal epithelium. Finally, we found that these differentially expressed genes were involved in apoptosis, MAPK, VEGF and B cell receptor signaling pathways and other functions associated with cell growth, signal transduction and immune system activation. Conclusion: This study identified potential candidate biomarkers, oncogenes/tumor suppressor genes involved in several pathways relevant to the oncogenesis of NPC. This information may facilitate the determination of diagnostic and therapeutic targets for NPC as well as provide insights about the molecular pathogenesis of NPC. C1 [Li, Xin; Wang, Ena; Marincola, Francesco M.] NIH, Warren G Magnuson Clin Ctr, Infect Dis & Immunogenet Sect, Dept Transfus Med, Bethesda, MD 20892 USA. [Zhao, Yingdong] NCI, Biometr Res Branch, Bethesda, MD 20892 USA. [Yang, Huiling] Nanhua Univ, Affiliated Hosp 1, Med Clin Res Inst, Hengyang City 421001, Hunan, Peoples R China. RP Marincola, FM (reprint author), NIH, Warren G Magnuson Clin Ctr, Infect Dis & Immunogenet Sect, Dept Transfus Med, Bethesda, MD 20892 USA. EM fangweiyi1975@yahoo.com.cn; lixin@fimmu.com; jiangqp2003@126.COM; narcissus_jane@163.com; xuhengyuy999@yahoo.com.cn; shuangwsw@hotmail.com; xsming@sina.com; liuqiuzhen@126.com; liutengfei_1968@163.com; xxhuangjing@yahoo.com.cn; xieweib@126.com; lizuguo@fimmu.com; Zhaoy@mail.nih.gov; Ewang@cc.nih.gov; Fmarincola@cc.nih.gov; ktyao@fimmu.com NR 32 TC 95 Z9 102 U1 0 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD JUN 20 PY 2008 VL 6 AR 32 DI 10.1186/1479-5876-6-32 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 325SJ UT WOS:000257608300001 PM 18570662 ER PT J AU Archin, NM Eron, JJ Palmer, S Hartmann-Duff, A Martinson, JA Wiegand, A Bandarenko, N Schmitz, JL Bosch, RJ Landay, AL Coffin, JM Margolis, DM AF Archin, Nancy M. Eron, Joseph J. Palmer, Sarah Hartmann-Duff, Anne Martinson, Jeffery A. Wiegand, Ann Bandarenko, Nicholas Schmitz, John L. Bosch, Ronald J. Landay, Alan L. Coffin, John M. Margolis, David M. TI Valproic acid without intensified antiviral therapy has limited impact on persistent HIV infection of resting CD4+ T cells SO AIDS LA English DT Article DE antiretroviral therapy; HIV; latency; resting CD4+T cells; valproic acid ID IMMUNODEFICIENCY-VIRUS TYPE-1; ACTIVE ANTIRETROVIRAL THERAPY; HUMAN-FACTORS YY1; NF-KAPPA-B; LATENT RESERVOIR; PLASMA; REPRESSION; VIREMIA; RNA; REPLICATION AB Objectives: Valproic acid and intensified antiretroviral therapy may deplete resting CD4+ T-cell HIV infection. We tested the ability of valproic acid to deplete resting CD4+ T-cell infection in patients receiving standard antiretroviral therapy. Methods: Resting CD4+ T-cell infection was measured in 11 stably aviremic volunteers twice prior to, and twice after Depakote ER 1000 mg was added to standard antiretroviral therapy. Resting CD4+ T-cell infection frequency was measured by outgrowth assay. Low-level viremia was quantitated by single copy plasma HIV RNA assay. Results: A decrease in resting CD4+ T-cell infection was observed in only four of the 11 patients. Levels of immune activation and HIV-specific T-cell response were low and stable. Valproic acid levels ranged from 26 to 96 mu g/ml when measured near trough. Single copy assay was performed in nine patients. In three patients with depletion of resting CD4+ T-cell infection following valproic acid, single copy assay ranged from less than 1-5 copies/ml. Continuous low-level viremia was observed in three patients with stable resting CD4+ T-cell infection (24-87 , 8-87, and 1-7 copies/ml respectively) in whom multiple samples were analyzed. Conclusion: The prospective addition of valproic acid to stable antiretroviral therapy reduced the frequency of resting CD4+ T-cell infection in a minority of volunteers. In patients in whom resting CD4+ T-cell infection depletion was observed, viremia was rarely detectable by single copy assay. (c) 2008 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Margolis, David M.] Univ N Carolina, Michael Hooker Res Ctr 3302, Chapel Hill, NC 27599 USA. [Palmer, Sarah; Wiegand, Ann; Coffin, John M.] NIH, NCI, HIV Drug Resistance Program, Frederick, MD USA. [Martinson, Jeffery A.; Landay, Alan L.] Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. [Bosch, Ronald J.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Margolis, DM (reprint author), Univ N Carolina, Michael Hooker Res Ctr 3302, CB 7435, Chapel Hill, NC 27599 USA. EM dmargo@med.unc.edu OI Margolis, David/0000-0001-5714-0002 FU NCRR NIH HHS [M01 RR000046]; NIAID NIH HHS [R56 AI045297, AI064074, AI45297, AI50410, P30 AI050410, R01 AI045297, R01 AI064074]; PHS HHS [R00046] NR 31 TC 101 Z9 106 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JUN 19 PY 2008 VL 22 IS 10 BP 1131 EP 1135 DI 10.1097/QAD.0b013e3282fd6df4 PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 321VP UT WOS:000257334900004 PM 18525258 ER PT J AU Zabow, G Dodd, S Moreland, J Koretsky, A AF Zabow, Gary Dodd, Stephen Moreland, John Koretsky, Alan TI Micro-engineered local field control for high-sensitivity multispectral MRI SO NATURE LA English DT Article ID IRON-OXIDE PARTICLES; CELLULAR MRI; STEM-CELLS; NANOPARTICLES; AGENTS; SPECTROSCOPY; DEVICES; SAFETY AB In recent years, biotechnology and biomedical research have benefited from the introduction of a variety of specialized nanoparticles whose well-defined, optically distinguishable signatures enable simultaneous tracking of numerous biological indicators. Unfortunately, equivalent multiplexing capabilities are largely absent in the field of magnetic resonance imaging (MRI). Comparable magnetic-resonance labels have generally been limited to relatively simple chemically synthesized superparamagnetic microparticles that are, to a large extent, indistinguishable from one another. Here we show how it is instead possible to use a top-down microfabrication approach to effectively encode distinguishable spectral signatures into the geometry of magnetic microstructures. Although based on different physical principles from those of optically probed nanoparticles, these geometrically defined magnetic microstructures permit a multiplexing functionality in the magnetic resonance radio-frequency spectrum that is in many ways analogous to that permitted by quantum dots in the optical spectrum. Additionally, in situ modification of particle geometries may facilitate radio-frequency probing of various local physiological variables. C1 [Zabow, Gary; Dodd, Stephen; Koretsky, Alan] Natl Inst Neurol Disorders & Stroke, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. [Zabow, Gary; Moreland, John] NIST, Electromagnet Div, Boulder, CO 80305 USA. RP Zabow, G (reprint author), Natl Inst Neurol Disorders & Stroke, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. EM zabow@boulder.nist.gov RI Koretsky, Alan/C-7940-2015 OI Koretsky, Alan/0000-0002-8085-4756 FU Intramural NIH HHS [Z01 NS003047-01] NR 32 TC 76 Z9 78 U1 2 U2 46 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUN 19 PY 2008 VL 453 IS 7198 BP 1058 EP U2 DI 10.1038/nature07048 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 314WM UT WOS:000256839900048 PM 18563157 ER PT J AU Rajagopal, A Rao, AU Amigo, J Tian, M Upadhyay, SK Hall, C Uhm, S Mathew, MK Fleming, MD Paw, BH Krause, M Hamza, I AF Rajagopal, Abbhirami Rao, Anita U. Amigo, Julio Tian, Meng Upadhyay, Sanjeev K. Hall, Caitlin Uhm, Suji Mathew, M. K. Fleming, Mark D. Paw, Barry H. Krause, Michael Hamza, Iqbal TI Haem homeostasis is regulated by the conserved and concerted functions of HRG-1 proteins SO NATURE LA English DT Article ID TRANSPORTER; ZEBRAFISH; BIOSYNTHESIS; DISORDERS; SENSOR AB Haems are metalloporphyrins that serve as prosthetic groups for various biological processes including respiration, gas sensing, xenobiotic detoxification, cell differentiation, circadian clock control, metabolic reprogramming and microRNA processing(1-4). With a few exceptions, haem is synthesized by a multistep biosynthetic pathway comprising defined intermediates that are highly conserved throughout evolution(5). Despite our extensive knowledge of haem biosynthesis and degradation, the cellular pathways and molecules that mediate intracellular haem trafficking are unknown. The experimental setback in identifying haem trafficking pathways has been the inability to dissociate the highly regulated cellular synthesis and degradation of haem from intracellular trafficking events(6). Caenorhabditis elegans and related helminths are natural haem auxotrophs that acquire environmental haem for incorporation into haemoproteins, which have vertebrate orthologues(7). Here we show, by exploiting this auxotrophy to identify HRG-1 proteins in C. elegans, that these proteins are essential for haem homeostasis and normal development in worms and vertebrates. Depletion of hrg-1, or its paralogue hrg-4, in worms results in the disruption of organismal haem sensing and an abnormal response to haem analogues. HRG-1 and HRG-4 are previously unknown transmembrane proteins, which reside in distinct intracellular compartments. Transient knockdown of hrg-1 in zebrafish leads to hydrocephalus, yolk tube malformations and, most strikingly, profound defects in erythropoiesis-phenotypes that are fully rescued by worm HRG-1. Human and worm proteins localize together, and bind and transport haem, thus establishing an evolutionarily conserved function for HRG-1. These findings reveal conserved pathways for cellular haem trafficking in animals that define the model for eukaryotic haem transport. Thus, uncovering the mechanisms of haem transport in C. elegans may provide insights into human disorders of haem metabolism and reveal new drug targets for developing anthelminthics to combat worm infestations. C1 [Rajagopal, Abbhirami; Rao, Anita U.; Uhm, Suji; Hamza, Iqbal] Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20742 USA. [Rajagopal, Abbhirami; Rao, Anita U.; Hall, Caitlin; Uhm, Suji; Hamza, Iqbal] Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA. [Amigo, Julio; Paw, Barry H.] Harvard Univ, Sch Med, Div Hematol, Dept Med,Brigham & Womens Hosp, Boston, MA 02115 USA. [Tian, Meng; Fleming, Mark D.] Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. [Upadhyay, Sanjeev K.; Mathew, M. K.] Univ Agr Sci Bangalore, Natl Ctr Biol Sci, Tata Inst Fundamental Res, Bangalore 560065, Karnataka, India. [Krause, Michael] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Hamza, I (reprint author), Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20742 USA. EM hamza@umd.edu OI Krause, Michael/0000-0001-6127-3940 FU Howard Hughes Medical Institute; Intramural NIH HHS; NIDDK NIH HHS [R01 DK074797, R01 DK074797-01] NR 23 TC 126 Z9 139 U1 2 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUN 19 PY 2008 VL 453 IS 7198 BP 1127 EP 1131 DI 10.1038/nature06934 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 314WM UT WOS:000256839900062 PM 18418376 ER PT J AU Hudson, KL Holohan, MK Collins, FS AF Hudson, Kathy L. Holohan, M. K. Collins, Francis S. TI Keeping pace with the times - The Genetic Information Nondiscrimination Act of 2008 SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID DISCRIMINATION C1 [Hudson, Kathy L.] Johns Hopkins Univ, Genet & Publ Policy Ctr, Baltimore, MD 21218 USA. [Holohan, M. K.; Collins, Francis S.] NHGRI, NIH, Bethesda, MD 20892 USA. RP Hudson, KL (reprint author), Johns Hopkins Univ, Genet & Publ Policy Ctr, Baltimore, MD 21218 USA. NR 5 TC 106 Z9 108 U1 3 U2 8 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 19 PY 2008 VL 358 IS 25 BP 2661 EP 2663 DI 10.1056/NEJMp0803964 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 314NC UT WOS:000256815100001 PM 18565857 ER PT J AU Nelson, EAS Bresee, JS Parashar, UD Widdowson, MA Glass, RI AF Nelson, E. A. S. Bresee, J. S. Parashar, U. D. Widdowson, M. -A. Glass, R. I. CA Asian Rotavirus Surveillance Netwo TI Rotavirus epidemiology: The Asian Rotavirus Surveillance Network SO VACCINE LA English DT Review DE rotavirus; immunization; disease burden; surveillance; policy; economic evaluation ID SENTINEL HOSPITAL SURVEILLANCE; HONG-KONG; COST-EFFECTIVENESS; JULY 2002; DIARRHEA; VACCINE; INTUSSUSCEPTION; BURDEN; CHILDREN; STRAINS AB Availability of new rotavirus vaccines has highlighted the need to collect local disease and economic burden data to aid decision makers at global, regional and country level. The World Health Organization and the GAVI Alliance recommended that generic protocols be used and that regional surveillance networks be established to collect these data, thereby helping to fast-track the introduction of these new vaccines into developing countries. Nine countries and regions participated in the first phase of the Asian Rotavirus Surveillance Network (ARSN), which collected data over a 2-year period during 2001-2003. Overall 45% of diarrhoea admissions in the region were positive for rotavirus, which was higher than had been anticipated. Significant rotavirus strain diversity was noted during the surveillance period. Data collection for a second phase of the ARSN commenced in 2004 and included a greater proportion of poorer countries that would in future be eligible for funding support for rotavirus immunization from GAVI. Limited economic evaluations in Asia have demonstrated the potential for new rotavirus vaccines to be cost-effective but more local analyses are required. Despite the ARSN's comprehensive data from a mix of developed and developing countries, Asia has lagged the Americas in terms of the introduction of rotavirus vaccines into National Immunization Programmes (NIPs). Lack on rotavirus vaccine efficacy data in Asia, particularly in poorer populations, will have contributed to this delay. Thus ensuring that all global regions are simultaneously involved in the evaluation of new vaccines from the beginning and also encouraging more regional collaborations of Ministry of Health representatives could help to accelerate the introduction of new vaccines into NIPs. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Nelson, E. A. S.] Chinese Univ Hong Kong, Dept Paediat, Hong Kong, Hong Kong, Peoples R China. [Bresee, J. S.; Parashar, U. D.; Widdowson, M. -A.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Glass, R. I.] Natl Inst Hlth, Fogarty Int Ctr, Bethesda, MD USA. RP Nelson, EAS (reprint author), Chinese Univ Hong Kong, Prince Wales Hosp, 6-F Clin Sci Bldg, Shatin, Hong Kong, Peoples R China. EM tony-nelson@cuhk.edu.hk RI Yu, LM/J-4284-2012; OI Widdowson, Marc-Alain/0000-0002-0682-6933; Nelson, Edmund Anthony Severn/0000-0002-2521-3403; Yu, Ly-Mee/0000-0003-0331-7364; Kilgore, Paul/0000-0003-3214-4482; Fischer, Thea Kolsen/0000-0003-4812-980X NR 39 TC 50 Z9 57 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD JUN 19 PY 2008 VL 26 IS 26 BP 3192 EP 3196 DI 10.1016/j.vaccine.2008.03.073 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 326BG UT WOS:000257632300003 PM 18485546 ER PT J AU Florese, RH Wiseman, RW Venzon, D Karl, JA Demberg, T Larsen, K Flanary, L Kalyanaraman, VS Pal, R Titti, F Patterson, LJ Heath, MJ O'Connor, DH Cafaro, A Ensoli, B Robert-Guroff, M AF Florese, Ruth H. Wiseman, Roger W. Venzon, David Karl, Julie A. Demberg, Thorsten Larsen, Kay Flanary, Leon Kalyanaraman, V. S. Pal, Ranajit Titti, Fausto Patterson, L. Jean Heath, Megan J. O'Connor, David H. Cafaro, Aurelio Ensoli, Barbara Robert-Guroff, Marjorie TI Comparative study of Tat vaccine regimens in Mauritian cynomolgus and Indian rhesus macaques: Influence of Mauritian MHC haplotypes on susceptibility/resistance to SHIV89.6P infection SO VACCINE LA English DT Article DE HIV Tat vaccines; Mauritian cynomolgus macaques; Indian rhesus macaques; MHC haplotypes; host susceptibility/resistance factors ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-LYMPHOCYTE RESPONSES; CLASS-I ALLELES; SIMIAN IMMUNODEFICIENCY; HIV-1 INFECTION; HLA-B; SIVMAC239 REPLICATION; TRANSACTIVATOR GENE; DISEASE PROGRESSION; CELLULAR-IMMUNITY AB Protection afforded by HIV Tat-based vaccines has differed in Indian rhesus and Mauritian cynomolgus macaques. We evaluated native Tat and Ad-HIVtat priming/Tat-boosting regimens in both species. Both vaccines were immunogenic. Only the Ad-tat regimen modestly reduced acute viremia in rhesus macaques after SHIV89.6P challenge. Confounding variables uncovered in Mauritian macaques included significant associations of susceptibility to infection with MHC class IB and class II H2 and H5 haplotypes, and resistance to infection with class IB haplotypes H3 and H6. Although protection here was limited, Tat-based vaccines incorporating other HIV components have shown greater efficacy. Combination strategies should be further explored. Published by Elsevier Ltd. C1 [Florese, Ruth H.; Demberg, Thorsten; Patterson, L. Jean; Heath, Megan J.; O'Connor, David H.; Robert-Guroff, Marjorie] NCI, NIH, Vaccine Branch, Bethesda, MD 20892 USA. [Wiseman, Roger W.; Karl, Julie A.] Univ Wisconsin, Wisconsin Natl Primate Res Ctr, Madison, WI 53706 USA. [Wiseman, Roger W.; Karl, Julie A.] Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53706 USA. [Venzon, David] NCI, NIH, Biostat & Data Management Sect, Bethesda, MD 20892 USA. [Larsen, Kay; Flanary, Leon] Washington Natl Primate Res Ctr, Seattle, WA 98109 USA. [Kalyanaraman, V. S.; Pal, Ranajit] Adv BioSci Labs Inc, Kensington, MD 20895 USA. [Titti, Fausto; Cafaro, Aurelio; Ensoli, Barbara] Ist Super Sanita, Natl AIDS Ctr, I-00161 Rome, Italy. RP Robert-Guroff, M (reprint author), NCI, NIH, Vaccine Branch, Bldg 41,Room D804, Bethesda, MD 20892 USA. EM guroffm@mail.nih.gov RI Ensoli, Barbara/J-9169-2016; Cafaro, Aurelio/K-5314-2016; OI Ensoli, Barbara/0000-0002-0545-8737; o'connor, david/0000-0003-2139-470X FU Intramural NIH HHS [Z01 BC005536-21]; NCRR NIH HHS [P51 RR000167]; NIAID NIH HHS [N01 AI 40088, 1 R21 AI 068488-01A2, N01 AI 15431, N01AI15431, N01AI40088, R21 AI068488]; NIH HHS [P51 OD011106] NR 64 TC 33 Z9 34 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD JUN 19 PY 2008 VL 26 IS 26 BP 3312 EP 3321 DI 10.1016/j.vaccine.2008.03.100 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 326BG UT WOS:000257632300018 PM 18486283 ER PT J AU Hansson, AC Fuxe, K AF Hansson, Anita C. Fuxe, Kjell TI Time-course of immediate early gene expression in hippocampal subregions of adrenalectomized rats after acute corticosterone challenge SO BRAIN RESEARCH LA English DT Article DE glucocorticoid hormone; transcription factors; fos family proteins; neuroplasticity; in situ hybridization; rat brain ID NEUROTROPHIC FACTOR EXPRESSION; MESSENGER-RNA EXPRESSION; FIBROBLAST-GROWTH-FACTOR; GLUCOCORTICOID-RECEPTOR; C-FOS; NERVOUS-SYSTEM; DEXAMETHASONE TREATMENT; TRANSCRIPTION FACTORS; GLIAL-CELLS; DNA-BINDING AB Corticosterone hormones mediate the stress response and function in the survival of hippocampal neurons via activation of gluco-(GR) and mineralocorticoid (MR) receptors. Activated GR and MR couple the corticosterone signal through immediate early genes (IEGs) to the late expression of downstream genes, such as neurotrophic factors. The potential importance of IEGs in GR/MR-dependent plasticity in the brain is largely unknown. We examined the region- and time-dependent transcriptional profiles of six IEGs (c-fos, fosB, fra-1, junB, c-jun and egr-1) by in situ hybridization after acute corticosterone challenge in the hippocampus and the primary somatosensory cortex (S1). Adrenalectomized rats and subsequent hormone injections were used as a model system to eliminate interference of endogenous corticosterone on IEG expression. In the hippocampus, a single corticosterone dose (10 mg/kg, s.c.) caused a widespread and transient reduction of fosB mRNA after 0.8 h, whereas changes in both c-fos and fra-1 mRNA levels were restricted to the dentate gyrus region. Corticosterone treatment gave rise to a delayed and significant reduction of junB mRNA signals after 2 h in all hippocampal regions, which reversed to increase at 4 h. c-jun and egr-1 mRNA levels were unaffected by corticosterone treatment. On the contrary, in the S1, IEG expression seems to be unaffected by corticosterone treatment, with the exception of a transient increase of junB transcripts at 0.8 h. The early reduction in c-fos family and junB transcripts may contribute to the GR/MR-dependent changes on hippocampal plasticity and may be dependent on rapid corticosteroid signaling. Published by Elsevier B.V. C1 [Hansson, Anita C.; Fuxe, Kjell] Karolinska Inst, Dept Neurosci, S-10401 Stockholm, Sweden. RP Hansson, AC (reprint author), NIAAA, LCTS, NIH, 10 Ctr Dr,CRC 1-5330, Bethesda, MD 20892 USA. EM anita.hansson@mail.nih.gov OI Fuxe, Kjell/0000-0001-8491-4288 FU Intramural NIH HHS [NIH0012006624]; PHS HHS [NIH0012006624] NR 50 TC 17 Z9 18 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUN 18 PY 2008 VL 1215 BP 1 EP 10 DI 10.1016/j.brainres.2008.03.080 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 323CK UT WOS:000257421400001 PM 18485334 ER PT J AU Hahn, B Wolkenberg, FA Ross, TJ Myers, CS Heishman, SJ Stein, DJ Kurup, PK Stein, EA AF Hahn, Britta Wolkenberg, Frank A. Ross, Thomas J. Myers, Carol S. Heishman, Stephen J. Stein, Dan J. Kurup, Pradeep K. Stein, Elliot A. TI Divided versus selective attention: Evidence for common processnng mechanisms SO BRAIN RESEARCH LA English DT Article DE attention; selective; divided; dual-task; fMRI ID ANTERIOR CINGULATE CORTEX; POSITRON-EMISSION-TOMOGRAPHY; TOP-DOWN CONTROL; NEURAL MECHANISMS; FUNCTIONAL-ANATOMY; VISUAL-ATTENTION; COLOR; FMRI; COGNITION; SYSTEM AB The current study revisited the question of whether there are brain mechanisms specific to divided attention that differ from those used in selective attention. Increased neuronal activity required to simultaneously process two stimulus dimensions as compared with each separate dimension has often been observed, but rarely has activity induced by a divided attention condition exceeded the sum of activity induced by the component tasks. Healthy participants performed a selective-divided attention paradigm while undergoing functional Magnetic Resonance Imaging (fMRI). The task required participants to make a same-different judgment about either one of two simultaneously presented stimulus dimensions, or about both dimensions. Performance accuracy was equated between tasks by dynamically adjusting the stimulus display time. Blood Oxygenation Level Dependent (BOLD) signal differences between tasks were identified by whole-brain voxel-wise comparisons and by region-specific analyses of all areas modulated by the divided attention task (DIV). No region displayed greater activation or deactivation by DIV than the sum of signal change by the two selective attention tasks. instead, regional activity followed the tasks' processing demands as reflected by reaction time. Only a left cerebellar region displayed a correlation between participants' BOLD signal intensity and reaction time that was selective for DIV. The correlation was positive, reflecting slower responding with greater activation. Overall, the findings do riot support the existence of functional brain activity specific to DIV. Increased activity appears to reflect additional processing demands by introducing a secondary task, but those demands do not appear to qualitatively differ from processes of selective attention. Published by Elsevier B.V. C1 [Hahn, Britta; Wolkenberg, Frank A.; Ross, Thomas J.; Kurup, Pradeep K.; Stein, Elliot A.] NIDA, NIH, IRP, Neuroimaging Res Branch, Baltimore, MD 21224 USA. [Stein, Dan J.] Univ Cape Town, Dept Psychiat, Groote Schuur Hosp J2, ZA-7925 Cape Town, South Africa. RP Hahn, B (reprint author), NIDA, NIH, IRP, Neuroimaging Res Branch, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM britta.hahn@gmail.com RI Ross, Thomas/B-7469-2008; Hahn, Britta/G-4593-2012; Stein, Dan/A-1752-2008 OI Ross, Thomas/0000-0002-7745-3572; Stein, Dan/0000-0001-7218-7810 FU Intramural NIH HHS [Z01 DA000405-11] NR 36 TC 7 Z9 7 U1 3 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 EI 1872-6240 J9 BRAIN RES JI Brain Res. PD JUN 18 PY 2008 VL 1215 BP 137 EP 146 DI 10.1016/j.brainres.2008.03.058 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 323CK UT WOS:000257421400014 PM 18479670 ER PT J AU Emanuel, EJ Fuchs, VR AF Emanuel, Ezekiel J. Fuchs, Victor R. TI The perfect storm of overutilization SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 [Emanuel, Ezekiel J.] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA. [Fuchs, Victor R.] Stanford Univ, Dept Econ, Stanford, CA 94305 USA. RP Emanuel, EJ (reprint author), NIH, Dept Bioeth, Ctr Clin, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM eemanuel@nih.gov NR 12 TC 141 Z9 141 U1 2 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 18 PY 2008 VL 299 IS 23 BP 2789 EP 2791 DI 10.1001/jama.299.23.2789 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 314JH UT WOS:000256805200027 PM 18560006 ER PT J AU Lorieau, J Yao, LS Bax, A AF Lorieau, Justin Yao, Lishan Bax, Ad TI Liquid crystalline phase of G-tetrad DNA for NMR study of detergent-solubilized proteins SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID DINUCLEOSIDE PHOSPHATE D(GPG); RESIDUAL DIPOLAR COUPLINGS; MEMBRANE-PROTEINS; INDUCED ALIGNMENT; POLYACRYLAMIDE GELS; FIELD; SPECTROSCOPY; MICELLES; PF1; FD AB The liquid crystalline phase consisting of the potassium salt of the dinucleotide d(GpG) is compatible with detergents commonly used for solubilizing membrane proteins, including dodecylphosphocholine, the lysolipid 1-palmitoyl-2-hydroxy-sn-glycero-3-phosphocholine, and small bicelles consisting of dihexanoyl phosphatidylcholine and dimyristoyl phosphatidylcholine. The chiral nematic liquid crystalline phase of d(GpG) consists of long columns of stacked G-tetrad structures and carry a net negative charge. For water-soluble systems, the protein alignment induced by d(GpG) is very similar to that observed for liquid crystalline Pf1 bacteriophage, but of opposite sign. Alignment of the detergent-solubilized fusion domain of hemagglutinin is demonstrated to be homogenous and stable, resulting in high quality NMR spectra suitable for the measurement of residual dipolar couplings. C1 [Lorieau, Justin; Yao, Lishan; Bax, Ad] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Bax, A (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM bax@nih.gov RI Yao, Lishan /C-6961-2009; yao, lishan/H-3662-2012 OI yao, lishan/0000-0003-1797-922X FU Intramural NIH HHS NR 21 TC 37 Z9 38 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD JUN 18 PY 2008 VL 130 IS 24 BP 7536 EP + DI 10.1021/ja801729f PG 3 WC Chemistry, Multidisciplinary SC Chemistry GA 312KX UT WOS:000256671400010 PM 18498162 ER PT J AU Taplin, S Abraham, L Barlow, WE Fenton, JJ Berns, EA Carney, PA Cutter, GR Sickles, EA D'Orsi, C Elmore, JG AF Taplin, Stephen Abraham, Linn Barlow, William E. Fenton, Joshua J. Berns, Eric A. Carney, Patricia A. Cutter, Gary R. Sickles, Edward A. D'Orsi, Carl Elmore, Joann G. TI Mammography facility characteristics associated with interpretive accuracy of screening mammography SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID FALSE-POSITIVE RATES; COMMUNITY RADIOLOGISTS; BREAST DENSITY; UNITED-STATES; VARIABILITY; WOMEN; AGE AB Background Although interpretive performance varies substantially among radiologists, such variation has not been examined among mammography facilities. Understanding sources of facility variation could become a foundation for improving interpretive performance. Methods In this cross-sectional study conducted between 1996 and 2002, we surveyed 53 facilities to evaluate associations between facility structure, interpretive process characteristics, and interpretive performance of screening mammography (ie, sensitivity, specificity, positive predictive value [PPV1], and the likelihood of cancer among women who were referred for biopsy [PPV2]). Measures of interpretive performance were ascertained prospectively from mammography interpretations and cancer data collected by the Breast Cancer Surveillance Consortium. Logistic regression and receiver operating characteristic (ROC) curve analyses estimated the association between facility characteristics and mammography interpretive performance or accuracy (area under the ROC curve [AUC]). All p values were two-sided. Results Of the 53 eligible facilities, data on 44 could be analyzed. These 44 facilities accounted for 484 463 screening mammograms performed on 237 669 women, of whom 2686 were diagnosed with breast cancer during follow-up. Among the 44 facilities, mean sensitivity was 79.6% (95% confidence interval [CI] = 74.3% to 84.9%), mean specificity was 90.2% (95% CI = 88.3% to 92.0%), mean PPV1 was 4.1% (95% CI = 3.5% to 4.7%), and mean PPV2 was 38.8% (95% CI = 32.6% to 45.0%). The facilities varied statistically significantly in specificity (P < .001), PPV1 (P < .001), and PPV2 (P = .002) but not in sensitivity (P = .99). AUC was higher among facilities that offered screening mammograms alone vs those that offered screening and diagnostic mammograms (0.943 vs 0.911, P= .006), had a breast imaging specialist interpreting mammograms vs not (0.932 vs 0.905, P = .004), did not perform double reading vs independent double reading vs consensus double reading (0.925 vs 0.915 vs 0.887, P = .034), or conducted audit reviews two or more times per year vs annually vs at an unknown frequency (0.929 vs 0.904 vs 0.900, P = .018). Conclusion Mammography interpretive performance varies statistically significantly by facility. C1 [Taplin, Stephen] NCI, Div Canc Control & Populat Sci, Appl Res Program, Bethesda, MD 20892 USA. [Abraham, Linn] Ctr Hlth Studies, Grp Hlth, Seattle, WA USA. [Barlow, William E.] Canc Res & Biostat, Seattle, WA USA. [Fenton, Joshua J.] Univ Calif Davis Hlth Syst, Dept Family & Community Med, Sacramento, CA USA. [Berns, Eric A.] Northwestern Univ, Feinberg Sch Med, Lynn Sage Comprehens Breast Canc Ctr, Dept Radiol, Chicago, IL 60611 USA. [Carney, Patricia A.] Oregon Hlth & Sci Univ, Portland, OR USA. [Cutter, Gary R.] Univ Alabama, Dept Biostat, Birmingham, AL 35294 USA. [Sickles, Edward A.] Univ Calif San Francisco, Sch Med, Dept Radiol, San Francisco, CA 94143 USA. [D'Orsi, Carl] Emory Univ, Dept Radiol, Atlanta, GA 30322 USA. [Elmore, Joann G.] Univ Washington, Sch Med, Dept Internal Med, Seattle, WA USA. RP Taplin, S (reprint author), 6130 Executive Blvd,MSC 7344,EPN 4005, Bethesda, MD 20892 USA. EM taplins@mail.nih.gov OI Fenton, Joshua/0000-0002-0581-835X FU AHRQ HHS [R01 HS010591]; NCI NIH HHS [5 U01 CA63736-09, 5 U01 CA86076, K05 CA104699, R01 CA107623, U01 CA086082, U01 CA63731, U01 CA86082-01] NR 23 TC 53 Z9 55 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 18 PY 2008 VL 100 IS 12 BP 876 EP 887 DI 10.1093/jnci/djn172 PG 12 WC Oncology SC Oncology GA 316VY UT WOS:000256979000011 PM 18544742 ER PT J AU Warren, JL Yabroff, KR Meekins, A Topor, M Lamont, EB Brown, ML AF Warren, Joan L. Yabroff, K. Robin Meekins, Angela Topor, Marie Lamont, Elizabeth B. Brown, Martin L. TI Evaluation of trends in the cost of initial cancer treatment SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CELL LUNG-CANCER; STAGE BREAST-CANCER; SEER-MEDICARE DATA; HEALTH-CARE COSTS; ADJUVANT CHEMOTHERAPY; CLAIMS; METAANALYSIS; POPULATION; RADIATION; ACCURACY AB Background Despite reports of increases in the cost of cancer treatment, little is known about how costs of cancer treatment have changed over time and what services have contributed to the increases. Methods We used data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database for 306 709 persons aged 65 and older and diagnosed with breast, lung, colorectal, or prostate cancer between 1991 and 2002 to assess the number of patients assigned to initial cancer care, from 2 months before diagnosis to 12 months after diagnosis, and mean annual Medicare payments for this care according to cancer type and type of treatment. Mutually exclusive treatment categories were cancer-related surgery, chemotherapy, radiation therapy, and other hospitalizations during the period of initial cancer care. Linear regression models were used to assess temporal trends in the percentage of patients receiving treatment and costs for those treated. We extrapolated our results based on the SEER data to the US Medicare population to estimate national Medicare payments by cancer site and treatment category. All statistical tests were two-sided. Results For patients diagnosed in 2002, Medicare paid an average of $39 891 for initial care for each lung cancer patient, $41 134 for each colorectal cancer patient, and $20 964 for each breast cancer patient, corresponding to inflation-adjusted increases from 1991 of $7139, $5345, and $4189, respectively. During the same interval, the mean Medicare payment for initial care for prostate cancer declined by $196 to $18261 in 2002. Costs for any hospitalization accounted for the largest portion of payments for all cancers. Chemotherapy use increased markedly for all cancers between 1991 and 2002, as did radiation therapy use (except for colorectal cancers). Total 2002 Medicare payments for initial care for these four cancers exceeded $6.7 billion, with colorectal and lung cancers being the most costly overall. Conclusions The statistically significant increase in costs of initial cancer treatment reflects more patients receiving surgery and adjuvant therapy and rising prices for these treatments. These trends are likely to continue in the near future, although more efficient targeting of costly therapies could mitigate the overall economic impact of this trend. C1 [Warren, Joan L.; Yabroff, K. Robin; Brown, Martin L.] NCI, Div Canc Control & Populat Sci, Appl Res Program, Hlth Serv & Econ Branch, Bethesda, MD 20892 USA. [Meekins, Angela; Topor, Marie] Management Informat Serv, Silver Spring, MD USA. [Lamont, Elizabeth B.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Lamont, Elizabeth B.] Harvard Univ, Sch Med, Boston, MA USA. RP Warren, JL (reprint author), NCI, Div Canc Control & Populat Sci, Appl Res Program, Hlth Serv & Econ Branch, Execut Plaza N,Rm 4005,6130 Execut Blvd,MSC 7344, Bethesda, MD 20892 USA. EM joan_warren@nih.gov OI Yabroff, K. Robin/0000-0003-0644-5572 NR 39 TC 170 Z9 173 U1 2 U2 14 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 18 PY 2008 VL 100 IS 12 BP 888 EP 897 DI 10.1093/jnci/djn175 PG 10 WC Oncology SC Oncology GA 316VY UT WOS:000256979000012 PM 18544740 ER PT J AU Dahiya, N Sherman-Baust, CA Wang, TL Davidson, B Shih, IM Zhang, YQ Wood, W Becker, KG Morin, PJ AF Dahiya, Neetu Sherman-Baust, Cheryl A. Wang, Tian-Li Davidson, Ben Shih, Ie-Ming Zhang, Yongqing Wood, William, III Becker, Kevin G. Morin, Patrice J. TI MicroRNA Expression and Identification of Putative miRNA Targets in Ovarian Cancer SO PLOS ONE LA English DT Article AB Background: MicroRNAs (miRNAs) represent a class of small non-coding RNAs that control gene expression by targeting mRNAs and triggering either translation repression or RNA degradation. Emerging evidence suggests the potential involvement of altered regulation of miRNA in the pathogenesis of cancers, and these genes are thought to function as both tumor suppressors and oncogenes. Methodology/Principal Findings: Using microRNA microarrays, we identify several miRNAs aberrantly expressed in human ovarian cancer tissues and cell lines. miR-221 stands out as a highly elevated miRNA in ovarian cancer, while miR-21 and several members of the let-7 family are found downregulated. Public databases were used to reveal potential targets for the highly differentially expressed miRNAs. In order to experimentally identify transcripts whose stability may be affected by the differentially expressed miRNAs, we transfected precursor miRNAs into human cancer cell lines and used oligonucleotide microarrays to examine changes in the mRNA levels. Interestingly, there was little overlap between the predicted and the experimental targets or pathways, or between experimental targets/pathways obtained using different cell lines, highlighting the complexity of miRNA target selection. Conclusion/Significance: Our results identify several differentially expressed miRNAs in ovarian cancer and identify potential target transcripts that may be regulated by these miRNAs. These miRNAs and their targets may have important roles in the initiation and development of ovarian cancer. C1 [Dahiya, Neetu; Sherman-Baust, Cheryl A.; Morin, Patrice J.] Hopkins Med Inst, Cellular & Mol Biol Lab, Baltimore, MD USA. [Wang, Tian-Li; Shih, Ie-Ming; Morin, Patrice J.] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD USA. [Davidson, Ben] Norwegian Radium Hosp, Oslo, Norway. [Zhang, Yongqing; Wood, William, III; Becker, Kevin G.] NIA, Res Resource Branch, Baltimore, MD USA. RP Dahiya, N (reprint author), Hopkins Med Inst, Cellular & Mol Biol Lab, Baltimore, MD USA. EM morinp@grc.nia.nih.gov RI Dahiya, Neetu/E-5208-2011; OI Becker, Kevin/0000-0002-6794-6656 FU Intramural Research Program of the NIH, National Institute on Aging. FX This research was supported by the Intramural Research Program of the NIH, National Institute on Aging. NR 51 TC 193 Z9 208 U1 0 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 18 PY 2008 VL 3 IS 6 AR e2436 DI 10.1371/journal.pone.0002436 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 406FP UT WOS:000263280700021 PM 18560586 ER PT J AU Rao, S Kong, WP Wei, CJ Yang, ZY Nason, M Styles, D DeTolla, LJ Sorrell, EM Song, HC Wan, HQ Ramirez-Nieto, GC Perez, D Nabel, GJ AF Rao, Srinivas Kong, Wing-Pui Wei, Chih-Jen Yang, Zhi-Yong Nason, Martha Styles, Darrel DeTolla, Louis J. Sorrell, Erin M. Song, Haichen Wan, Hongquan Ramirez-Nieto, Gloria C. Perez, Daniel Nabel, Gary J. TI Multivalent HA DNA Vaccination Protects against Highly Pathogenic H5N1 Avian Influenza Infection in Chickens and Mice SO PLOS ONE LA English DT Article AB Background: Sustained outbreaks of highly pathogenic avian influenza (HPAI) H5N1 in avian species increase the risk of reassortment and adaptation to humans. The ability to contain its spread in chickens would reduce this threat and help maintain the capacity for egg-based vaccine production. While vaccines offer the potential to control avian disease, a major concern of current vaccines is their potency and inability to protect against evolving avian influenza viruses. Methodology/Principal Findings: The ability of DNA vaccines encoding hemagglutinin (HA) proteins from different HPAI H5N1 serotypes was evaluated for its ability to elicit neutralizing antibodies and to protect against homologous and heterologous HPAI H5N1 strain challenge in mice and chickens after DNA immunization by needle and syringe or with a pressure injection device. These vaccines elicited antibodies that neutralized multiple strains of HPAI H5N1 when given in combinations containing up to 10 HAs. The response was dose-dependent, and breadth was determined by the choice of the influenza virus HA in the vaccine. Monovalent and trivalent HA vaccines were tested first in mice and conferred protection against lethal H5N1 A/Vietnam/1203/2004 challenge 68 weeks after vaccination. In chickens, protection was observed against heterologous strains of HPAI H5N1 after vaccination with a trivalent H5 serotype DNA vaccine with doses as low as 5 mg DNA given twice either by intramuscular needle injection or with a needle-free device. Conclusions/Significance: DNA vaccines offer a generic approach to influenza virus immunization applicable to multiple animal species. In addition, the ability to substitute plasmids encoding different strains enables rapid adaptation of the vaccine to newly evolving field isolates. C1 [Rao, Srinivas; Kong, Wing-Pui; Wei, Chih-Jen; Yang, Zhi-Yong; Nason, Martha; Nabel, Gary J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD USA. [Styles, Darrel] United States Dept Agr, Anim & Plant Hlth Inspect Serv, Riverdale, MD USA. [Sorrell, Erin M.; Song, Haichen; Wan, Hongquan; Ramirez-Nieto, Gloria C.; Perez, Daniel] Univ Maryland, Coll Vet Med, College Pk, MD USA. [DeTolla, Louis J.] Univ Maryland Baltimore, Baltimore, MD USA. RP Rao, S (reprint author), NIAID, Vaccine Res Ctr, NIH, Bethesda, MD USA. EM gnabel@nih.gov OI Perez, Daniel/0000-0002-6569-5689 FU Intramural Research Program of the Vaccine Research Center, NIAID, National Institutes of Health FX This research was supported by the Intramural Research Program of the Vaccine Research Center, NIAID, National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 55 TC 34 Z9 37 U1 1 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 18 PY 2008 VL 3 IS 6 AR e2432 DI 10.1371/journal.pone.0002432 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 406FP UT WOS:000263280700017 PM 19293944 ER PT J AU Tie, JK Zheng, MY Hsiao, KLN Perera, L Stafford, DW Straight, DL AF Tie, Jian-Ke Zheng, Mei-Yan Hsiao, Kuang-Ling N. Perera, Lalith Stafford, Darrel W. Straight, David L. TI Transmembrane domain interactions and residue proline 378 are essential for proper structure, especially disulfide bond formation, in the human vitamin K-dependent gamma-glutamyl carboxylase SO BIOCHEMISTRY LA English DT Article ID PROPEPTIDE BINDING-SITE; HELICAL MEMBRANE-PROTEINS; PEPTIDE-SUBSTRATE; ESCHERICHIA-COLI; ACTIVE-SITE; MOTIFS; SPLIT; IDENTIFICATION; LOCALIZATION; HYDROQUINONE AB We used recombinant techniques to create a two-chain form (residues 1-345 and residues 346-758) of the vitamin K-dependent gamma-glutamyl carboxylase, a glycoprotein located in the endoplasmic reticulum containing five transmembrane domains. The two-chain carboxylase had carboxylase and epoxidase activities similar to those of one-chain carboxylase. In addition, it had normal affinity for the propeptide of factor IX. We employed this molecule to investigate formation of the one disulfide bond in carboxylase, the transmembrane structure of carboxylase, and the potential interactions among the carboxylase's transmembrane domains. Our results indicate that the two peptides of the two-chain carboxylase are joined by a disulfide bond. Proline 378 is important for the structure necessary for disulfide formation. Results with the P378L carboxylase indicate that noncovalent bonds maintain the two-chain structure even when the disulfide bond is disrupted. As we had previously proposed, the fifth transmembrane domain of carboxylase is the last and only transmembrane domain in the C-terminal peptide of the two-chain carboxylase. We show that the noncovalent association between the two chains of carboxylase involves an interaction between the fifth transmembrane domain and the second transmembrane domain. Results of a homology model of transmembrane domains 2 and 5 suggest that not only do these two domains associate but that transmembrane domain 2 may interact with another transmembrane domain. This latter interaction may be mediated at least in part by a motif of glycine residues in the second transmembrane domain. C1 [Tie, Jian-Ke; Zheng, Mei-Yan; Hsiao, Kuang-Ling N.; Stafford, Darrel W.; Straight, David L.] Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA. [Perera, Lalith] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Tie, JK (reprint author), Univ N Carolina, Dept Biol, CB 3280, Chapel Hill, NC 27599 USA. EM jktie@email.unc.edu RI perera, Lalith/B-6879-2012 OI perera, Lalith/0000-0003-0823-1631 FU Intramural NIH HHS [Z99 ES999999]; NHLBI NIH HHS [HL48318, R01 HL048318] NR 43 TC 9 Z9 9 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 JUN 17 PY 2008 VL 47 IS 24 BP 6301 EP 6310 DI 10.1021/bi800235r PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 312GA UT WOS:000256655900003 PM 18498174 ER PT J AU Smith, TK Hager, HA Francis, R Kilkenny, DM Lo, CW Bader, DM AF Smith, T. K. Hager, H. A. Francis, R. Kilkenny, D. M. Lo, C. W. Bader, D. M. TI Bves directly interacts with GEFT, and controls cell shape and movement through regulation of Rac1/Cdc42 activity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Popdc; cell motility; GEF ID GUANINE-NUCLEOTIDE-EXCHANGE; CONTAINING GENE FAMILY; SKELETAL-MUSCLE; RHO-GTPASES; CONVERGENT EXTENSION; XENOPUS GASTRULATION; DEPENDENT ACTIVATION; NEURITE OUTGROWTH; LIVING CELLS; RAC AB Bves is an integral membrane protein with no determined function and no homology to proteins outside of the Popdc family. It is widely expressed throughout development in myriad organisms. Here, we demonstrate an interaction between Bves and guanine nucleotide exchange factor T (GEFT), a GEF for Rho-family GTPases. This interaction represents the first identification of any protein that has a direct physical interaction with any member of the Popdc family. Bves and GEFT are shown to colocalize in adult skeletal muscle. We also demonstrate that exogenous expression of Bves reduces Rac1 and Cdc42 activity levels while not affecting levels of active RhoA. Consistent With a. repression of Rac1 and Cdc42 activity, we show changes in speed of cell locomotion and cell roundness also result from exogenous expression of Bves. Modulation of Rho-family GTPase signaling by Bves would be highly consistent with previously described phenotypes occurring upon disruption of Bves function in a wide variety of model systems. Therefore, we propose Bves as a novel regulator of the Rac1 and Cdc42 signaling cascades. C1 [Smith, T. K.; Hager, H. A.; Kilkenny, D. M.; Bader, D. M.] Vanderbilt Univ, Med Ctr, Stahlman Cardiovasc Res Labs, Program Dev Biol, Nashville, TN 37232 USA. [Smith, T. K.; Hager, H. A.; Kilkenny, D. M.; Bader, D. M.] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN 37232 USA. [Francis, R.; Lo, C. W.] NHLBI, Dev Biol Lab, NIH, Rockville, MD 20850 USA. RP Bader, DM (reprint author), Vanderbilt Univ, Med Ctr, Stahlman Cardiovasc Res Labs, Program Dev Biol, Nashville, TN 37232 USA. EM david.bader@vanderbilt.edu RI Francis, Richard/P-2524-2015 FU NHLBI NIH HHS [HL07411, HL079050, HL37675, HL79050, R01 HL037675, R01 HL079050, T32 HL007411] NR 55 TC 28 Z9 31 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 17 PY 2008 VL 105 IS 24 BP 8298 EP 8303 DI 10.1073/pnas.0802345105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 317HR UT WOS:000257011200025 PM 18541910 ER PT J AU Ghuman, AS Bar, M Dobbins, IG Schnyeri, DM AF Ghuman, Avniel S. Bar, Moshe Dobbins, Ian G. Schnyeri, David M. TI The effects of priming on frontal-temporal communication SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE functional communication; learning; magnetoencepholography; synchrony memory ID PREFRONTAL CORTEX; NEURAL MECHANISMS; CORTICAL ACTIVITY; FUSIFORM CORTEX; HUMAN BRAIN; REPETITION; SYNCHRONIZATION; OSCILLATIONS; SPECIFICITY; PREDICTIONS AB Repeated exposure to a stimulus facilitates its processing. This is reflected in faster and more accurate identification, reduced perceptual identification thresholds, and more efficient classifications for repeated compared with novel items. Here, we test a hypothesis that this experience-based behavioral facilitation is a result of enhanced communication between distinct cortical regions, which reduces local processing demands. A magnetoencephalographic investigation revealed that repeated object classification led to decreased neural responses in the prefrontal cortex and temporal cortex. Critically, this decrease in absolute activity was accompanied by greater neural synchrony (a measure of functional connectivity) between these regions with repetition. Additionally, the onset of the enhanced interregional synchrony predicted the degree of behavioral facilitation. These findings suggest that object repetition results in enhanced interactions between brain regions, which facilitates performance and reduces processing demands on the regions involved. C1 [Ghuman, Avniel S.; Bar, Moshe; Schnyeri, David M.] Harvard Univ, Sch Med, MIT,Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02115 USA. [Dobbins, Ian G.] Duke Univ, Dept Psychol & Neurosci, Durham, NC 27708 USA. [Ghuman, Avniel S.] Harvard Univ, Program Biophys, Cambridge, MA 02138 USA. [Schnyeri, David M.] Boston Vet Adm Healthcare Syst, Memory Disorders Res Ctr, Boston, MA 02215 USA. [Schnyeri, David M.] Boston Univ, Sch Med, Boston, MA 02215 USA. RP Ghuman, AS (reprint author), NIMH, Lab Brain & Cognit, 10 Ctr Dr,Room 4C116,MSC 1366, Bethesda, MD 20892 USA. EM ghumana@mail.nih.gov OI Ghuman, Avniel/0000-0003-1746-4656 FU NCRR NIH HHS [P41 RR014075, P41RR14075]; NIMH NIH HHS [K23 MH064004, K23MH64004, R01 MH073982, R01 MH073982-01A1]; NINDS NIH HHS [R01 NS044319, R01 NS050615, R01 NS44319-01] NR 44 TC 63 Z9 67 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 17 PY 2008 VL 105 IS 24 BP 8405 EP 8409 DI 10.1073/pnas.0710674105 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 317HR UT WOS:000257011200043 PM 18541919 ER PT J AU Huang, L Heinloth, AN Zeng, ZB Paules, RS Bushel, PR AF Huang, Lingkang Heinloth, Alexandra N. Zeng, Zhao-Bang Paules, Richard S. Bushel, Pierre R. TI Genes related to apoptosis predict necrosis of the liver as a phenotype observed in rats exposed to a compendium of hepatotoxicants SO BMC GENOMICS LA English DT Article ID FACTOR-ALPHA; MICROARRAY DATA; EXPRESSION DATA; IN-VIVO; INJURY; DEATH; CELLS; HISTOPATHOLOGY; VISUALIZATION; MODEL AB Background: Some of the biochemical events that lead to necrosis of the liver are well-known. However, the pathogenesis of necrosis of the liver from exposure to hepatotoxicants is a complex biological response to the injury. We hypothesize that gene expression profiles can serve as a signature to predict the level of necrosis elicited by acute exposure of rats to a variety of hepatotoxicants and postulate that the expression profiles of the predictor genes in the signature can provide insight to some of the biological processes and molecular pathways that may be involved in the manifestation of necrosis of the rat liver. Results: Rats were treated individually with one of seven known hepatotoxicants and were analyzed for gene expression by microarray. Liver samples were grouped by the level of necrosis exhibited in the tissue. Analysis of significantly differentially expressed genes between adjacent necrosis levels revealed that inflammation follows programmed cell death in response to the agents. Using a Random Forest classifier with feature selection, 21 informative genes were identified which achieved 90%, 80% and 60% prediction accuracies of necrosis against independent test data derived from the livers of rats exposed to acetaminophen, carbon tetrachloride, and allyl alcohol, respectively. Pathway and gene network analyses of the genes in the signature revealed several gene interactions suggestive of apoptosis as a process possibly involved in the manifestation of necrosis of the liver from exposure to the hepatotoxicants. Cytotoxic effects of TNF-alpha, as well as transcriptional regulation by JUN and TP53, and apoptosis-related genes possibly lead to necrosis. Conclusion: The data analysis, gene selection and prediction approaches permitted grouping of the classes of rat liver samples exhibiting necrosis to improve the accuracy of predicting the level of necrosis as a phenotypic end-point observed from the exposure. The strategy, along with pathway analysis and gene network reconstruction, led to the identification of 1) expression profiles of genes as a signature of necrosis and 2) perturbed regulatory processes that exhibited biological relevance to the manifestation of necrosis from exposure of rat livers to the compendium of hepatotoxicants. C1 [Huang, Lingkang; Bushel, Pierre R.] Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC USA. [Heinloth, Alexandra N.; Paules, Richard S.] Natl Inst Environm Hlth Sci, Environm Stress & Canc Grp, Res Triangle Pk, NC USA. [Paules, Richard S.] Natl Inst Environm Hlth Sci, Microarray Grp, Res Triangle Pk, NC USA. [Huang, Lingkang; Zeng, Zhao-Bang] N Carolina State Univ, Bioinformat Program, Raleigh, NC USA. [Huang, Lingkang] GlaxoSmithKline Inc, Res Triangle Pk, NC 27709 USA. RP Bushel, PR (reprint author), Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC USA. EM lingkang.huang@gmail.com; heinloth@gmail.com; zeng@stat.ncsu.edu; paules@niehs.nih.gov; bushel@niehs.nih.gov FU Intramural NIH HHS NR 35 TC 24 Z9 26 U1 0 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD JUN 16 PY 2008 VL 9 AR 288 DI 10.1186/1471-2164-9-288 PG 16 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 329MR UT WOS:000257872200001 PM 18558008 ER PT J AU Devi, RR Yao, W Vijayalakshmi, P Sergeev, YV Sundaresan, P Hejtmancik, JF AF Devi, Ramachandran Ramya Yao, Wenliang Vijayalakshmi, Perumalsamy Sergeev, Yuri V. Sundaresan, Periasamy Hejtmancik, J. Fielding TI Crystallin gene mutations in Indian families with inherited pediatric cataract SO MOLECULAR VISION LA English DT Article ID AUTOSOMAL-DOMINANT CATARACT; ZONULAR PULVERULENT CATARACT; CONGENITAL NUCLEAR CATARACT; POSTERIOR POLAR CATARACT; HUMAN ALPHA-CRYSTALLIN; AMINO-ACID SEQUENCE; DNA-BINDING DOMAIN; GAMMA-D-CRYSTALLIN; MISSENSE MUTATION; NONSENSE MUTATION AB Purpose: Pediatric cataract is the most common form of treatable childhood blindness and is both clinically and genetically heterogeneous. Autosomal dominant and recessive forms of cataract have been reported to be caused by mutations in 22 different genes so far. Of the cataract mutations reported to date, about half the mutations occur in crystallins, a quarter of the mutations in connexins, and the remainder is evenly divided between intrinsic membrane proteins, intermediate filament proteins, and transcription factors. This study is aimed at identification of the spectrum and frequency of crystallin gene mutations in cataractous patients in an Indian population. Methods: Genetic analysis was extended to screen the entire coding region of the CRYAA, CRYAB, CRYBA1, CRYBA4, CRYBB1, CRYBB2, CRYBB3, CRYGC, CRYGD, and CRYGS genes using single stranded conformational polymorphism ( SSCP) analysis as a screening technique followed by direct sequencing of all subjects that displayed an electrophoretic shift. Results: This report describes the first simultaneous mutation analysis of 10 crystallin genes in the same population, represented by 60 south Indian families. The analysis allowed the identification of causative mutations in 10 of the families ( three novel and six reported). This includes six missense mutations (CRYAA-R12C, R21W, R54C, CRYAB-A171T, CRYGC-R168W, CRYGS-S39C), two nonsense mutations (CRYBB2-Q155X, CRYGD-R140X), and one splice mutation, which was identified in two families (CRYBA1-IVS3+1G > A). Conclusions: Crystallin mutations are responsible for 16.6% of the inherited pediatric cataract in this population. As causative mutations have not been found in many of the families analyzed, this study suggests the presence of further novel genes or sequence elements involved in the pathogenesis of cataract in these families. C1 [Devi, Ramachandran Ramya; Yao, Wenliang; Sergeev, Yuri V.; Hejtmancik, J. Fielding] NEI, MOGS, OGVEB, NIH, Bethesda, MD 20892 USA. [Devi, Ramachandran Ramya; Sundaresan, Periasamy] Aravind Eye Hosp, Aravind Med Res Fdn, Dr G Venketaswamy Eye Res Inst, Dept Genet, Madurai, Tamil Nadu, India. [Vijayalakshmi, Perumalsamy] Aravind Eye Hosp, Pediat Clin Ophthalmol, Madurai, Tamil Nadu, India. RP Hejtmancik, JF (reprint author), NEI, MOGS, OGVEB, NIH, Bldg 10,Room 10B10,10 Ctr Dr, Bethesda, MD 20892 USA. EM f3h@helix.nih.gov NR 72 TC 89 Z9 92 U1 0 U2 2 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD JUN 16 PY 2008 VL 14 IS 136-37 BP 1157 EP 1170 PG 14 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 329SL UT WOS:000257890800002 PM 18587492 ER PT J AU Prentice, RL Chlebowski, RT Stefanick, ML Manson, JE Langer, RD Pettinger, M Hendrix, SL Hubbell, FA Kooperberg, C Kuller, LH Lane, DS McTiernan, A O'Sullivan, MJ Rossouw, JE Anderson, GL AF Prentice, Ross L. Chlebowski, Rowan T. Stefanick, Marcia L. Manson, JoAnn E. Langer, Robert D. Pettinger, Mary Hendrix, Susan L. Hubbell, F. Allan Kooperberg, Charles Kuller, Lewis H. Lane, Dorothy S. McTiernan, Anne O'Sullivan, Mary Jo Rossouw, Jacques E. Anderson, Garnet L. TI Conjugated equine estrogens and breast cancer risk in the women's health initiative clinical trial and observational study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE breast neoplasms; clinical trial; cohort studies; estrogens; hormone replacement therapy; postmenopause ID HORMONE-REPLACEMENT THERAPY; RANDOMIZED CONTROLLED-TRIAL; POSTMENOPAUSAL WOMEN; PLUS PROGESTIN; HYSTERECTOMY; MAMMOGRAPHY; BENEFITS; CELLS AB The Women's Health Initiative randomized controlled trial found a trend (p = 0.09) toward a lower breast cancer risk among women assigned to daily 0.625-mg conjugated equine estrogens (CEEs) compared with placebo, in contrast to an observational literature that mostly reports a moderate increase in risk with estrogen-alone preparations. In 1993-2004 at 40 US clinical centers, breast cancer hazard ratio estimates for this CEE regimen were compared between the Women's Health Initiative clinical trial and observational study toward understanding this apparent discrepancy and refining hazard ratio estimates. After control for prior use of postmenopausal hormone therapy and for confounding factors, CEE hazard ratio estimates were higher from the observational study compared with the clinical trial by 43% (p = 0.12). However, after additional control for time from menopause to first use of postmenopausal hormone therapy, the hazard ratios agreed closely between the two cohorts (p = 0.82). For women who begin use soon after menopause, combined analyses of clinical trial and observational study data do not provide clear evidence of either an overall reduction or an increase in breast cancer risk with CEEs, although hazard ratios appeared to be relatively higher among women having certain breast cancer risk factors or a low body mass index. C1 [Prentice, Ross L.; Pettinger, Mary; Kooperberg, Charles; McTiernan, Anne; Anderson, Garnet L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Chlebowski, Rowan T.] Univ Calif Los Angeles, Med Ctr, Los Angeles Biomed Res Inst Harbor, Los Angeles, CA 90024 USA. [Stefanick, Marcia L.] Stanford Univ, Stanford Prevent Res Ctr, Sch Med, Stanford, CA 94305 USA. [Manson, JoAnn E.] Harvard Univ, Brigham & Womens Hosp, Div Prevent Med, Sch Med, Boston, MA 02115 USA. [Langer, Robert D.] Geisinger Hlth System, Outcomes Res Inst, Danville, PA USA. [Hendrix, Susan L.] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. [Hubbell, F. Allan] Univ Calif Irvine, Dept Med, Irvine, CA 92717 USA. [Kuller, Lewis H.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Lane, Dorothy S.] SUNY Stony Brook, Dept Prevent Med, Stony Brook, NY 11794 USA. [O'Sullivan, Mary Jo] Univ Miami, Dept Obstet & Gynecol, Miami, FL USA. [Rossouw, Jacques E.] NHLBI, Bethesda, MD 20892 USA. RP Prentice, RL (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1100 Fairview Ave N,POB 19024, Seattle, WA 98109 USA. EM rprentic@fhcrc.org FU NCI NIH HHS [CA53996, P01 CA053996]; WHI NIH HHS [N01 WH022110, N01 WH022110-024] NR 18 TC 88 Z9 89 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 15 PY 2008 VL 167 IS 12 BP 1407 EP 1415 DI 10.1093/aje/kwn090 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 313QU UT WOS:000256755900002 PM 18448442 ER PT J AU Linet, MS AF Linet, Martha S. TI Invited commentary: Postmenopausal unopposed estrogen and breast cancer risk in the women's health initiative - Before and beyond SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Editorial Material DE breast neoplasms; clinical trial; epidemiologic studies; estrogens; hormone replacement therapy; menopause; risk-benefit assessment ID HORMONE REPLACEMENT THERAPY; CORONARY-HEART-DISEASE; RANDOMIZED CONTROLLED-TRIAL; UP HERS-II; PLUS PROGESTIN; ESTROGEN/PROGESTIN REPLACEMENT; CARDIOVASCULAR-DISEASE; ENDOMETRIAL CARCINOMA; MENOPAUSAL ESTROGENS; UNITED-STATES AB Three large clinical trials provoked major debate when hormone replacement therapy (HRT) did not reduce coronary heart disease in postmenopausal women as expected from observational epidemiologic studies. Less discussion has ensued about breast cancer or other adverse events. In this issue of the Journal, investigators from the Women's Health Initiative (WHI) compare breast cancer findings from the randomized trial of unopposed estrogen with those from the large WHI observational study. This commentary briefly summarizes historical highlights of menopausal hormone use; risk-versus-benefit evaluations; scientific, clinical, and policy influences immediately before and during the WHI trial; breast cancer incidence trends; and the posttrial response in US clinical practice. Factors complicating interpretation of the results include differences in breast cancer risk profiles between women in the trial and those in the observational study cohort as well as heterogeneity in the definitions of menopause and prior use of HRT as applied by the WHI investigators to the two populations. Because millions of women use HRT, it is important to consider how the WHI and other research investigations might contribute to reducing gaps in understanding the relation between HRT and breast cancer risk. C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Linet, MS (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS Room 7048, Bethesda, MD 20892 USA. EM linetm@mail.nih.gov FU Intramural NIH HHS NR 64 TC 7 Z9 7 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 15 PY 2008 VL 167 IS 12 BP 1416 EP 1420 DI 10.1093/aje/kwn089 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 313QU UT WOS:000256755900003 PM 18448443 ER PT J AU Chia, VM Quraishi, SM Graubard, BI Rubertone, MV Erickson, RL Stanczyk, FZ McGlynn, KA AF Chia, Victoria M. Quraishi, Sabah M. Graubard, Barry I. Rubertone, Mark V. Erickson, Ralph L. Stanczyk, Frank Z. McGlynn, Katherine A. TI Insulin-like growth factor 1, insulin-like growth factor-binding protein 3, and testicular germ-cell tumor risk SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE hormones; insulin-like growth factor binding protein 3; insulin-like growth factor I; testicular neoplasms ID GROWTH-FACTOR-I; IGF-BINDING PROTEIN-3; BODY-SIZE; FACTOR BINDING-PROTEIN-3; GESTATIONAL-AGE; FACTOR (IGF)-I; BREAST-CANCER; BIRTH-WEIGHT; BORN SMALL; MEN AB Studies have consistently shown that taller men are at increased risk of testicular germ-cell tumors. Thus, it is plausible that factors associated with height may also influence risk of these tumors. The authors examined associations between testicular germ-cell tumor risk and circulating concentrations of insulin-like growth factor 1 (IGF-1) and insulin-like growth factor-binding protein 3 (IGFBP-3) among 517 cases and 790 controls from the US Servicemen's Testicular Tumor Environmental and Endocrine Determinants (STEED) Study (2002-2005). Odds ratios and 95% confidence intervals were estimated using logistic regression models, adjusting for age, race/ethnicity, height, and body mass index. All tests of significance were two-sided. Overall, there were no associations between IGF-1 or IGFBP-3 concentrations and risk of testicular germ-cell tumors (p > 0.05). However, when cases were separated by histologic type, there was a suggestion of a reduction in seminoma risk associated with the highest concentrations of IGF-1 as compared with the lowest concentrations (odds ratio = 0.66, 95% confidence interval: 0.40, 1.09). Although there were no overall associations with insulin-like growth factor, contrary to expectation, there was a suggestion that IGF-1 concentrations may be inversely associated with risk of seminoma. C1 [Chia, Victoria M.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA. [Rubertone, Mark V.] USA, Ctr Hlth Promot & Prevent Med, Washington, DC 20310 USA. [Erickson, Ralph L.] Walter Reed Army Inst Res, Forest Glen, MD USA. [Stanczyk, Frank Z.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. RP Chia, VM (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Execut Plaza S,Suite 550,6120 Execut Blvd, Rockville, MD 20892 USA. EM chiav@mail.nih.gov FU Intramural NIH HHS NR 35 TC 6 Z9 6 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 15 PY 2008 VL 167 IS 12 BP 1438 EP 1445 DI 10.1093/aje/kwn080 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 313QU UT WOS:000256755900006 PM 18408226 ER PT J AU Koster, A Leitzmann, MF Schatzkin, A Mouw, T Adams, KF van Eijk, JTM Hollenbeck, AR Harris, TB AF Koster, Annemarie Leitzmann, Michael F. Schatzkin, Arthur Mouw, Traci Adams, Kenneth F. van Eijk, Jacques Th. M. Hollenbeck, Albert R. Harris, Tamara B. TI Waist circumference and mortality SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE abdominal fat; adiposity; body composition; body fat distribution; body mass index; mortality ID BODY-MASS INDEX; ALL-CAUSE MORTALITY; SOCIETY-FOR-NUTRITION; VISCERAL FAT; ABDOMINAL ADIPOSITY; PROSPECTIVE COHORT; OBESITY-SOCIETY; RISK-FACTORS; HEALTH-RISK; HIP RATIO AB The authors examined the association between waist circumference and mortality among 154,776 men and 90,757 women aged 51-72 years at baseline (1996-1997) in the NIH-AARP Diet and Health Study. Additionally, the combined effects of waist circumference and body mass index (BMI; weight (kg)/height (m)(2)) were examined. All-cause mortality was assessed over 9 years of follow-up (1996-2005). After adjustment for BMI and other covariates, a large waist circumference (fifth quintile vs. second) was associated with an approximately 25% increased mortality risk (men: hazard ratio (HR) = 1.22, 95% confidence interval (CI): 1.15, 1.29; women: HR = 1.28, 95% CI: 1.16, 1.41). The waist circumference-mortality association was found in persons with and without prevalent disease, in smokers and nonsmokers, and across different racial/ethnic groups (non-Hispanic Whites, non-Hispanic Blacks, Hispanics, and Asians). Compared with subjects with a combination of normal BMI (18.5-< 25) and normal waist circumference, those in the normal-BMI group with a large waist circumference (men: >= 102 cm; women: >= 88 cm) had an approximately 20% higher mortality risk (men: HR = 1.23, 95% CI: 1.08, 1.39; women: HR = 1.22, 95% CI: 1.09, 1.36). The finding that persons with a normal BMI but a large waist circumference had a higher mortality risk in this study suggests that increased waist circumference should be considered a risk factor for mortality, in addition to BMI. C1 [Koster, Annemarie; Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Koster, Annemarie; van Eijk, Jacques Th. M.] Univ Maastricht, Fac Hlth Med & Life Sci, Maastricht, Netherlands. [Leitzmann, Michael F.; Schatzkin, Arthur; Mouw, Traci; Adams, Kenneth F.] NCI, Nutr Epidemiol Branch, Bethesda, MD 20892 USA. [Hollenbeck, Albert R.] Amer Assoc Retired Persons, Washington, DC USA. RP Koster, A (reprint author), NIA, Lab Epidemiol Demog & Biometry, 7201 Wisconsin Ave,Gateway Bldg,Suite 3C309, Bethesda, MD 20892 USA. EM kostera@mail.nih.gov RI Koster, Annemarie/E-7438-2010 FU Intramural NIH HHS NR 30 TC 93 Z9 96 U1 0 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 15 PY 2008 VL 167 IS 12 BP 1465 EP 1475 DI 10.1093/aje/kwn079 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 313QU UT WOS:000256755900010 PM 18417494 ER PT J AU Loewenstein, J Sutton, E Guidotti, R Shapiro, K Ball, K McLean, D Biesecker, B AF Loewenstein, Johanna Sutton, Erica Guidotti, Rick Shapiro, Kristin Ball, Karen McLean, Diane Biesecker, Barbara TI The art of coping with a craniofacial difference: Helping others through "Positive Exposure" SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE self-esteem; stigma; coping; Positive Exposure; craniofacial adaptation ID QUALITY-OF-LIFE; PSYCHOSOCIAL ADJUSTMENT; SELF-ESTEEM; STIGMA; ANOMALIES; ADOLESCENTS; HEALTH; PREADOLESCENTS; VALIDATION; CHILDREN AB Finding ways to cope with social stigmatization is an important aspect of achieving adaptation for people living with visible genetic differences. This study describes the way individuals With craniofacial differences use an innovative photography and video experience with Positive Exposure (PE), a non-profit organization based in New York City, as a way to cope with their conditions. Thirty-five individuals between 12 and 61 years of age participated in this study. We administered surveys comprised of open-ended qualitative questions and quantitative measures designed to assess self-esteem, perceived stigma, and hopefulness. Data for this analysis was generated front the written questionnaires and interview transcripts. Most participants reported high levels of self-esteem and hopefulness, suggesting that they were relatively well adapted to their condition. Almost all participants described experiences of stigmatization throughout their lives. However, participants demonstrated their ability to implement a variety of coping strategies to manage stigma. "Helping others" emerged as a prominent strategy among participants, aiding in the often lifelong process of adapting to their genetic difference. PE was described as in avenue through which participants could reach out to individuals and society at large, helping them adapt further to their condition. "Helping others" may also benefit individuals with craniofacial differences who do not consider themselves to be well adapted to their condition. Health care providers can collaborate with PE, advocacy groups and other community or support groups to identify additional Ways individuals with craniofacial differences can help themselves by reaching out to others. Published 2008 Wiley-Liss, Inc.(dagger) C1 [Loewenstein, Johanna; Shapiro, Kristin; Biesecker, Barbara] NHGRI, NIH, Social & Behav Res Branch, Bethesda, MD 20892 USA. [Sutton, Erica] Univ Toronto, Dept Publ Hlth Sci, Toronto, ON M5S 1A1, Canada. [Sutton, Erica] Univ Toronto, Joint Ctr Bioeth, Toronto, ON M5S 1A1, Canada. [Guidotti, Rick; McLean, Diane] Posit Exposure, New York, NY USA. [Ball, Karen] Sturge Weber Fdn, Mt Freedom, NJ USA. RP Loewenstein, J (reprint author), NHGRI, NIH, Social & Behav Res Branch, 31 Ctr Dr,B1B37,MSC2073, Bethesda, MD 20892 USA. EM loewensteinj@mail.nih.gov FU Intramural NIH HHS [Z99 HG999999] NR 30 TC 4 Z9 4 U1 1 U2 10 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD JUN 15 PY 2008 VL 146A IS 12 BP 1547 EP 1557 DI 10.1002/ajmg.a.32344 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 307PB UT WOS:000256329700006 PM 18478594 ER PT J AU Fichorova, RN Richardson-Harman, N Alfano, M Belec, L Carbonneil, C Chen, S Cosentino, L Curtis, K Dezzutti, CS Donoval, B Doncel, GF Donaghay, M Grivel, JC Guzman, E Hayes, M Herold, B Hillier, S Lackman-Smith, C Landay, A Margolis, L Mayer, KH Pasicznyk, JM Pallansch-Cokonis, M Poli, G Reicholderfer, P Roberts, P Rodriguez, I Saidi, H Sassi, RR Shattock, R Cummins, JE AF Fichorova, Raina N. Richardson-Harman, Nicola Alfano, Massimo Belec, Laurent Carbonneil, Cedric Chen, Silvia Cosentino, Lisa Curtis, Kelly Dezzutti, Charlene S. Donoval, Betty Doncel, Gustave F. Donaghay, Melissa Grivel, Jean-Charles Guzman, Esmeralda Hayes, Madeleine Herold, Betsy Hillier, Sharon Lackman-Smith, Carol Landay, Alan Margolis, Leonid Mayer, Kenneth H. Pasicznyk, Jenna-Malia Pallansch-Cokonis, Melanie Poli, Guido Reicholderfer, Patricia Roberts, Paula Rodriguez, Irma Saidi, Hela Sassi, Rosaria Rita Shattock, Robin Cummins, James E., Jr. TI Biological and technical variables affecting immunoassay recovery of cytokines from human serum and simulated vaginal fluid: A multicenter study SO ANALYTICAL CHEMISTRY LA English DT Article ID VIRUS TYPE-1 RNA; GENITAL-TRACT; TOPICAL MICROBICIDES; IN-VITRO; HIV; PLASMA; INFECTION; ASSAYS; WOMEN; SECRETIONS AB The increase of proinflammatory cytokines in vaginal secretions may serve as a surrogate marker of unwanted inflammatory reaction to microbicide products topically applied for the prevention of sexually transmitted diseases, including HIV-1. Interleukin (IL)-1 beta and 11,6 have been proposed as indicators of inflammation and increased risk of HIV-1 transmission; however, the lack of information regarding detection platforms optimal for vaginal fluids and interlaboratory variation limit their use for microbicide evaluation and other clinical applications. This study examines fluid matrix variants relevant to vaginal sampling techniques and proposes a model for interlaboratory comparisons across current cytokine detection technologies. IL-1 beta and IL-6 standards were measured by 12 laboratories in four countries, using 14 immunoassays and four detection platforms based on absorbance, chemiluminescence, electrochemiluminescence, and fluorescence. International reference preparations of cytokines with defined biological activity were spiked into (1) a defined medium simulating the composition of human vaginal fluid at pH 4.5 and 7.2, (2) physiologic salt solutions (phosphate-buffered saline and saline) commonly used for vaginal lavage sampling in clinical studies of cytokines, and (3) human blood serum. Assays were assessed for reproducibility, linearity, accuracy, and significantly detectable fold difference in cytokine level. Factors with significant impact on cytokine recovery were determined by Kruskal-Wallis analysis of variance with Dunn's multiple comparison test and multiple regression models. All assays showed acceptable intra-assay reproducibility; however, most were associated with significant interlaboratory variation. The smallest reliably detectable cytokine differences (P < 0.05) derived from pooled interlaboratory data varied from 1.5- to 26-fold depending on assay, cytokine, and matrix type. IL-6 but not IL-1 beta determinations were lower in both saline and phosphate-buffered saline as compared to vaginal fluid matrix, with no significant effect of pH. The (electro)chemiluminescence-based assays were most discriminative and consistently detected < 2-fold differences within each matrix type. The Luminex-based assays were less discriminative with lower reproducibility between laboratories. These results suggest the need for uniform vaginal sampling techniques and a better understanding of immunoassay platform differences and cross-validation before the biological significance of cytokine variations can be validated in clinical trials. This investigation provides the first standardized analytic approach for assessing differences in mucosal cytokine levels and may improve strategies for monitoring immune responses at the vaginal mucosal interface. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. So Res Inst, Microbicides Qual Assurance Program, Frederick, MD 21701 USA. Univ Vita Salute San Raffaele, Milan, Italy. Inst Sci, Milan, Italy. Ctr Rech Cordeliers, Paris, France. NICHHD, NIH, Bethesda, MD 20892 USA. Magee Womens Res Inst, Pittsburgh, PA 15213 USA. Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. Rush Univ, Med Ctr, Chicago, IL 60612 USA. Eastern Virginia Med Sch, CONRAD, Norfolk, VA 23507 USA. Mt Sinai Sch Med, New York, NY 10029 USA. St Georges Univ London, London, England. Brown Univ, Providence, RI 02912 USA. RP Fichorova, RN (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. EM rfichorova@rics.bwh RI Fichorova, Raina/G-9969-2014; Saidi, Hela/P-2519-2014 FU Intramural NIH HHS [Z99 HD999999]; NIAID NIH HHS [5U01AI068633, N01-AI-33350, P30 AI-42853, P30 AI042853, U01 AI068633]; NICHD NIH HHS [N01-HD-3-3350, P01HD041760] NR 26 TC 92 Z9 92 U1 0 U2 16 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD JUN 15 PY 2008 VL 80 IS 12 BP 4741 EP 4751 DI 10.1021/ac702628q PG 11 WC Chemistry, Analytical SC Chemistry GA 313TR UT WOS:000256763400037 PM 18484740 ER PT J AU Giles, JT Ling, SM Ferrucci, L Bartlett, SJ Andersen, RE Towns, M Muller, D Fontaine, KR Bathon, JM AF Giles, Jon T. Ling, Shari M. Ferrucci, Luigi Bartlett, Susan J. Andersen, Ross E. Towns, Marilyn Muller, Denis Fontaine, Kevin R. Bathon, Joan M. TI Abnormal body composition phenotypes in older rheumatoid arthritis patients: Association with disease characteristics and pharmacotherapies SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Article ID NECROSIS-FACTOR-ALPHA; X-RAY ABSORPTIOMETRY; PHYSICAL-DISABILITY; SARCOPENIC OBESITY; INSULIN-RESISTANCE; MASS INDEX; CELL MASS; INFLAMMATION; COMORBIDITY; WOMEN AB Objective. To compare measures of body fat and lean mass and the prevalence of abnormal body composition phenotypes (sarcopenia, overfat, and sarcopenic obesity) in men and women with rheumatoid arthritis (RA) versus matched controls, and to explore the disease-related predictors of abnormal body composition in patients with RA. Methods. A total of 189 men and women with RA and 189 age-, sex-, and race-matched non-RA controls underwent dual-energy x-ray absorptiometry for measurement of total and regional body fat and lean mass. Continuous and categorical measures of body composition were compared between RA and control subjects by sex anti according to categories of body mass index (BMI). Within the group of RA patients, demographic, lifestyle, and RA disease and treatment characteristics were compared for RA patients with healthy body composition versus those with abnormal body composition phenotypes. Results. Compared with non-RA controls, RA status was significantly associated with greater odds of sarcopenia, overfat, and sarcopenic obesity in women, but not in men. Relative differences in body composition phenotypes between RA and control subjects were greatest for patients in the normal weight BMI category (<25 kg/m(2)). Among RA characteristics, increasing joint deformity, self-reported disability scores, C-reactive protein levels, rheumatoid factor seropositivity, and a lack of current treatment with disease-modifying antirheumatic drugs were significantly associated with abnormal body composition. Conclusion. Abnormal body composition phenotypes are overrepresented in patients with RA, particularly in those in the normal weight BMI range. RA-associated disease and treatment characteristics contribute to this increase in abnormal body composition. C1 [Giles, Jon T.] Johns Hopkins Univ, Johns Hopkins Arthritis Ctr, Sch Med, Baltimore, MD 21224 USA. [Ling, Shari M.; Ferrucci, Luigi; Muller, Denis] NIA, Intramural Res Program, Baltimore, MD 21224 USA. RP Giles, JT (reprint author), Johns Hopkins Univ, Johns Hopkins Arthritis Ctr, Sch Med, 5501 Hopkins Bayview Circle,Suite 1B 1, Baltimore, MD 21224 USA. EM gilesjont@jhmi.edu OI Bartlett, Susan/0000-0001-9755-2490 FU Intramural NIH HHS; NIAMS NIH HHS [R01 AR050026-04, 1-K23-AR-054112-01, AR-050026-01, K23 AR054112, R01 AR050026, R55 AR050026] NR 33 TC 63 Z9 63 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRIT RHEUM-ARTHR JI Arthritis Rheum-Arthritis Care Res. PD JUN 15 PY 2008 VL 59 IS 6 BP 807 EP 815 DI 10.1002/art.23719 PG 9 WC Rheumatology SC Rheumatology GA 312TA UT WOS:000256692500007 PM 18512711 ER PT J AU Ward, MM Reveille, JD Learch, TJ Davis, JC Weisman, MH AF Ward, Michael M. Reveille, John D. Learch, Thomas J. Davis, John C., Jr. Weisman, Michael H. TI Occupational physical activities and long-term functional and radiographic outcomes in patients with ankylosing spondylitis SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Article ID RISK-FACTORS; LOW-MAGNITUDE; HEALTH-STATUS; MUSCULOSKELETAL; INDEX; FREQUENCY; SYMPTOMS; LIMITATIONS; POPULATION; PREVENTION AB Objective. We sought to identify specific occupational activities associated with functional limitations and radiographic damage in patients with longstanding ankylosing spondylitis (AS). Methods. We asked patients diagnosed with AS for >= 20 years to report all past occupations, which we mapped to specific physical activities using the Occupational Information Network, which is the US Department of Labor job classification database. For each occupation reported, we obtained ratings for 13 physical abilities of the worker and 13 aspects of the work environment or work tasks (work context) thought to be most relevant to patients with AS. Averages for each measure, weighted by the number of years in each job, were related to the degree of functional limitation as assessed by the Bath AS Functional Index (BASFI) and to the extent of spinal radiographic damage as assessed by the Bath AS Radiology Index for the spine (BASRI-s). Results. Among 397 patients, those with a history of jobs requiring dynamic flexibility (the ability to repeatedly bend, stretch, twist, or reach) had more functional limitations than those whose past jobs required little or no dynamic flexibility (adjusted mean BASFI score 48.3 in the top quartile versus 38.1 in all others). Those whose past jobs required more dynamic flexibility, extent flexibility, and exposure to whole body vibration also had significantly higher BASRI-s scores. Conclusion. Bending, twisting, and stretching are the occupational activities associated with greater functional limitations and radiographic damage in patients with longstanding AS. Exposure to whole body vibration was also associated with more radiographic damage. C1 [Ward, Michael M.] NIAMSD, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Reveille, John D.] Univ Texas Hlth Sci Ctr, Houston, TX USA. [Learch, Thomas J.] Univ So Calif, Los Angeles, CA USA. [Davis, John C., Jr.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Weisman, Michael H.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. RP Ward, MM (reprint author), NIAMSD, NIH, US Dept Hlth & Human Serv, Bldg 10 CRC,Room 4-1339,10 Ctr Dr,MSC 1468, Bethesda, MD 20892 USA. EM wardm1@mail.nih.gov FU Intramural NIH HHS [Z01 AR041153-03]; NCRR NIH HHS [M01 RR000425-360875, M01 RR002558, M01 RR000425, M01 RR000425-397345, M01 RR000425-350875, M01 RR000425-376032, M01 RR000425-388038, M01-RR-00425, M01-RR-02558]; NIAMS NIH HHS [R01 AR048465-03, R01 AR048465, R01-AR-048465] NR 37 TC 27 Z9 28 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRIT RHEUM-ARTHR JI Arthritis Rheum-Arthritis Care Res. PD JUN 15 PY 2008 VL 59 IS 6 BP 822 EP 832 DI 10.1002/art.23704 PG 11 WC Rheumatology SC Rheumatology GA 312TA UT WOS:000256692500009 PM 18512723 ER PT J AU Tolstorukov, MY Choudhary, V Olson, WK Zhurkin, VB Park, PJ AF Tolstorukov, Michael Y. Choudhary, Vidhu Olson, Wilma K. Zhurkin, Victor B. Park, Peter J. TI nuScore: a web-interface for nucleosome positioning predictions SO BIOINFORMATICS LA English DT Article ID DNA-SEQUENCE; CHROMATIN; STABILITY; DYNAMICS; CODE AB Sequence-directed mapping of nucleosome positions is of major biological interest. Here, we present a web-interface for estimation of the affinity of the histone core to DNA and prediction of nucleosome arrangement on a given sequence. Our approach is based on assessment of the energy cost of imposing the deformations required to wrap DNA around the histone surface. The interface allows the user to specify a number of options such as selecting from several structural templates for threading calculations and adding random sequences to the analysis. C1 [Tolstorukov, Michael Y.; Park, Peter J.] Brigham & Womens Hosp, Harvard Partners Ctr Genet & Genom, Boston, MA 02115 USA. [Choudhary, Vidhu; Park, Peter J.] Children Hosp, Informat Program, Boston, MA 02115 USA. [Zhurkin, Victor B.] Rutgers State Univ, Wright Rieman Labs, Piscataway, NJ 08854 USA. [Zhurkin, Victor B.] NCI, Cell Biol Lab, Bethesda, MD 20892 USA. RP Tolstorukov, MY (reprint author), Brigham & Womens Hosp, Harvard Partners Ctr Genet & Genom, 75 Francis St, Boston, MA 02115 USA. FU Intramural NIH HHS; NIGMS NIH HHS [GM20861, R01 GM020861] NR 17 TC 33 Z9 35 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD JUN 15 PY 2008 VL 24 IS 12 BP 1456 EP 1458 DI 10.1093/bioinformatics/btn212 PG 3 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 313RD UT WOS:000256756800006 PM 18445607 ER PT J AU Lekman, M Laje, G Charney, D Rush, AJ Wilson, AF Sorant, AJM Lipsky, R Wisniewski, SR Manji, H McMahon, FJ Paddock, S AF Lekman, Magnus Laje, Gonzalo Charney, Dennis Rush, A. John Wilson, Alexander F. Sorant, Alexa J. M. Lipsky, Robert Wisniewski, Stephen R. Manji, Husseini McMahon, Francis J. Paddock, Silvia TI The FKBP5-gene in depression and treatment response - An association study in the sequenced treatment alternatives to relieve depression (STAR*D) cohort SO BIOLOGICAL PSYCHIATRY LA English DT Article DE chaperone; depression; genome; HPA-axis; stress ID SEROTONIN REUPTAKE INHIBITORS; REPORT QIDS-SR; MAJOR DEPRESSION; ANTIDEPRESSANT TREATMENT; QUICK INVENTORY; PSYCHOMETRIC EVALUATION; CLINICAL-SIGNIFICANCE; MOOD DISORDERS; GLOBAL BURDEN; SYMPTOMATOLOGY AB Background: In a recent study of several antidepressant drugs in hospitalized, non-Hispanic White patients, Binder et al. reported association of markers located within the FKBP5 gene with treatment response after 2 and 5 weeks. Individuals homozygous for the TT-genotype at one of the markers (rs1360780) reported more depressive episodes and responded better to antidepressant treatment. There was no association between markers in FKBP5 and disease. The present study aimed at studying the associated FKBP5 markers in the ethnically diverse Sequenced Treatment Alternatives to Relieve Depression (STAR*D) sample of non-hospitalized patients treated with citalopram. Methods: We used clinical data and DNA samples from 1809 outpatients with non-psychotic major depressive disorder (DSM-IV criteria), who received up to 14 weeks of citalopram. A subset of 1523 patients of White non-Hispanic or Black race was matched with 739 control subjects for a case-control analysis. The markers rs1360780 and rs4713916 were genotyped on the Illumina platform. TaqMan-assay was used for marker rs3800373. Results: In the case-control analysis, marker rs1360780 was significantly associated with disease status in the White non-Hispanic sample after correction for multiple testing. A significant association was also found between rs4713916 and remission. Markers rs1360780 and rs4713916 were in strong linkage disequilibrium in the White non-Hispanic but not in the Black population. There was no significant difference in the number of previous episodes of depression between genotypes at any of the three markers. Conclusions: These results indicate that FKBP5 is an important target for further studies of depression and treatment response. C1 [Lekman, Magnus; Paddock, Silvia] Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden. [Manji, Husseini] NIMH, Mol Pathophysiol Lab, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Wilson, Alexander F.; Sorant, Alexa J. M.] NHGRI, Genometr Sect, Inherited Dis Res Branch, NIH,DHHS, Baltimore, MD USA. [Lipsky, Robert] NIAAA, Mol Genet Sect, Neurogenet Lab, NIH,DHHS, Rockville, MD 20852 USA. [Charney, Dennis] Mt Sinai Sch Med, Dept Psychiat Neurosci & Pharmacol & Biol Chem, New York, NY USA. [Rush, A. John] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA. [Rush, A. John] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Wisniewski, Stephen R.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. RP Paddock, S (reprint author), Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden. EM silvia.paddock@ki.se RI McMahon, Francis/A-7290-2009; Wilson, Alexander/C-2320-2009; Laje, Gonzalo/L-2654-2014; OI Laje, Gonzalo/0000-0003-2763-3329; Wisniewski, Stephen/0000-0002-3877-9860; Rush, Augustus/0000-0003-2004-2382; Lipsky, Robert/0000-0001-7753-1473; McMahon, Francis/0000-0002-9469-305X FU Intramural NIH HHS [Z01 MH002844-04, Z01 MH002856-03, Z01 AA000326-04, Z01 HG000200-06]; NIMH NIH HHS [N01 MH090003, N01MH90003, R01 MH059565, R01 MH059566, R01 MH059571, R01 MH059586, R01 MH059587, R01 MH059588, R01 MH060870, R01 MH060879, R01 MH061675, R01 MH067257] NR 32 TC 152 Z9 164 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUN 15 PY 2008 VL 63 IS 12 BP 1103 EP 1110 DI 10.1016/j.biopsych.2007.10.026 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 309WU UT WOS:000256491700002 PM 18191112 ER PT J AU Ko, HJ Carter, RL Cosyn, L Petrelli, R de Castro, S Besada, P Zhou, YX Cappellacci, L Franchetti, P Grifantini, M Van Calenbergh, S Harden, TK Jacobson, KA AF Ko, Hyojin Carter, Rhonda L. Cosyn, Liesbet Petrelli, Riccardo de Castro, Sonia Besada, Pedro Zhou, Yixing Cappellacci, Loredana Franchetti, Palmarisa Grifantini, Mario Van Calenbergh, Serge Harden, T. Kendall Jacobson, Kenneth A. TI Synthesis and potency of novel uracil nucleotides and derivatives as P2Y(2) and P2Y(6) receptor agonists SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE uracil nucleotide; G protein-coupled receptor; phospholipase C; UDP; UTP; dinucleotide; structure-activity relationships ID RIBONUCLEOSIDE DIPHOSPHATE REDUCTASE; CORYNEBACTERIUM-NEPHRIDII; ENHANCED STABILITY; P2 RECEPTORS; ANALOGS; URIDINE; RAT; 5'-TRIPHOSPHATE; CONFORMATION; PHARMACOLOGY AB The phosphate, uracil, and ribose moieties of uracil nucleotides were varied structurally for evaluation of agonist activity at the human P2Y(2), P2Y(4), and P2Y(6) receptors. The 2-thio modi. cation, found previously to enhance P2Y2 receptor potency, could be combined with other favorable modi. cations to produce novel molecules that exhibit high potencies and receptor selectivities. Phosphonomethylene bridges introduced for stability in analogues of UDP, UTP, and uracil dinucleotides markedly reduced potency. Truncation of dinucleotide agonists of the P2Y(2) receptor, in the form of Up(4)-sugars, indicated that a terminal uracil ring is not essential for moderate potency at this receptor and that specific SAR patterns are observed at this distal end of the molecule. Key compounds reported in this study include 9, alpha, beta-methylene-UDP, a P2Y(6) receptor agonist; 30, Up(4)-phenyl ester and 34, Up(4)-[1] glucose, selective P2Y(2) receptor agonists; dihalomethylene phosphonate analogues 16 and 41, selective P2Y(2) receptor agonists; 43, the 2-thio analogue of INS37217 (P(1)-(uridine-5')-P(4)-(2'-deoxycytidine-5') tetraphosphate), a potent and selective P2Y(2) receptor agonist. Published by Elsevier Ltd. C1 [Ko, Hyojin; de Castro, Sonia; Besada, Pedro; Jacobson, Kenneth A.] NIDDK, NIH, Dept Hlth & Human Serv, Mol Recognit Sect,Lab Bioorgan Chem, Bethesda, MD 20892 USA. [Carter, Rhonda L.; Zhou, Yixing; Harden, T. Kendall] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA. [Cosyn, Liesbet; Van Calenbergh, Serge] Univ Ghent, Fac Pharmaceut Sci FFW, Med Chem Lab, B-9000 Ghent, Belgium. [Petrelli, Riccardo; Cappellacci, Loredana; Franchetti, Palmarisa; Grifantini, Mario] Univ Camerino, Dept Chem Sci, I-62032 Camerino, Italy. RP Jacobson, KA (reprint author), NIDDK, NIH, Dept Hlth & Human Serv, Mol Recognit Sect,Lab Bioorgan Chem, Bethesda, MD 20892 USA. EM kajacobs@helix.nih.gov RI Besada Pereira, Pedro/E-6051-2012; de castro, sonia/E-7303-2012; Jacobson, Kenneth/A-1530-2009; Van Calenbergh, Serge/A-3167-2008 OI Besada Pereira, Pedro/0000-0002-9985-9063; de castro, sonia/0000-0002-3838-6856; Jacobson, Kenneth/0000-0001-8104-1493; Van Calenbergh, Serge/0000-0002-4201-1264 FU Intramural NIH HHS [Z01 DK031116-20]; NIGMS NIH HHS [GM38213, R01 GM038213] NR 33 TC 48 Z9 49 U1 0 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD JUN 15 PY 2008 VL 16 IS 12 BP 6319 EP 6332 DI 10.1016/j.bmc.2008.05.013 PG 14 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 311AY UT WOS:000256573600002 PM 18514530 ER PT J AU Todd, BA Parsegian, VA Shirahata, A Thomas, TJ Rau, DC AF Todd, Brian A. Parsegian, V. Adrian Shirahata, Akira Thomas, T. J. Rau, Donald C. TI Attractive forces between cation condensed DNA double helices SO BIOPHYSICAL JOURNAL LA English DT Article ID HYDRATION FORCES; PREFERENTIAL HYDRATION; INTERMOLECULAR FORCES; MOLECULES; SPERMIDINE; POLYELECTROLYTES; COUNTERIONS; EXCLUSION; WATER; IONS AB By combining single-molecule magnetic tweezers and osmotic stress on DNA assemblies, we separate attractive and repulsive components of the total intermolecular interaction between multivalent cation condensed DNA. Based on measurements of several different cations, we identify two invariant properties of multivalent cation-mediated DNA interactions: repulsive forces decay exponentially with a 2.3 +/- 0.1 angstrom characteristic decay length and the attractive component of the free energy is always 2.3 +/- 0.2 times larger than the repulsive component of the free energy at force-balance equilibrium. These empirical constraints are not consistent with current theories that attribute DNA-DNA attractions to a correlated lattice of counterions. The empirical constraints are consistent with theories for Debye-Huckel interactions between helical line charges and with the order-parameter formalism for hydration forces. Each of these theories posits exponentially decaying attractions and, if we assume this form, our measurements indicate a cation-independent, 4.8 +/- 0.5 angstrom characteristic decay length for intermolecular attractions between condensed DNA molecules. C1 [Todd, Brian A.; Parsegian, V. Adrian; Rau, Donald C.] NICHHD, Natl Inst Hlth, Lab Phys & Struct Biol, Bethesda, MD 20892 USA. [Shirahata, Akira] Josai Univ, Dept Biochem & Cellular Physiol, Saitama, Japan. [Thomas, T. J.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Med, New Brunswick, NJ 08903 USA. RP Todd, BA (reprint author), NICHHD, Natl Inst Hlth, Lab Phys & Struct Biol, Bethesda, MD 20892 USA. EM toddba@mail.nih.gov FU Intramural NIH HHS; NCI NIH HHS [R01 CA042439, CA42439, CA73058, CA80163, R01 CA073058, R01 CA080163] NR 44 TC 88 Z9 89 U1 4 U2 32 PU BIOPHYSICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUN 15 PY 2008 VL 94 IS 12 BP 4775 EP 4782 DI 10.1529/biophysj.107.127332 PG 8 WC Biophysics SC Biophysics GA 306ES UT WOS:000256231700022 PM 18326632 ER PT J AU Bertram, R Satin, LS Sherman, A AF Bertram, Richard Satin, Leslie S. Sherman, Arthur TI Metabolic fluxes and stoichiometry of glucose metabolism - Response to the comment by F. Diederichs SO BIOPHYSICAL JOURNAL LA English DT Editorial Material ID OSCILLATIONS; ISLETS C1 [Bertram, Richard] Florida State Univ, Dept Math, Tallahassee, FL 32306 USA. [Bertram, Richard] Florida State Univ, Program Neurosci, Tallahassee, FL 32306 USA. [Satin, Leslie S.] Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA USA. [Sherman, Arthur] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD USA. [Bertram, Richard] Florida State Univ, Program Mol Biophys, Tallahassee, FL 32306 USA. RP Bertram, R (reprint author), Florida State Univ, Dept Math, Tallahassee, FL 32306 USA. EM bertram@math.fsu.edu NR 4 TC 0 Z9 0 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUN 15 PY 2008 VL 94 IS 12 BP 5080 EP 5080 DI 10.1529/biophysj.108.128744 PG 1 WC Biophysics SC Biophysics GA 306ES UT WOS:000256231700049 ER PT J AU Rosenberg, HF AF Rosenberg, Helene F. TI Eosinophils unleashed SO BLOOD LA English DT Editorial Material ID INHIBITORY RECEPTORS C1 NIAID, Lab Allerg Dis, Bethesda, MD 20892 USA. RP Rosenberg, HF (reprint author), NIAID, Lab Allerg Dis, Bethesda, MD 20892 USA. EM hrosenberg@niaid.nih.gov NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 15 PY 2008 VL 111 IS 12 BP 5423 EP 5423 DI 10.1182/blood-2008-03-146837 PG 1 WC Hematology SC Hematology GA 314CN UT WOS:000256786500008 PM 18544694 ER PT J AU Feldman, AL Arber, DA Pittaluga, S Martinez, A Burke, JS Raffeld, M Camos, M Warnke, R Jaffe, ES AF Feldman, Andrew L. Arber, Daniel A. Pittaluga, Stefania Martinez, Antonio Burke, Jerome S. Raffeld, Mark Camos, Mireia Warnke, Roger Jaffe, Elaine S. TI Clonally related follicular lymphomas and histiocytic/dendritic cell sarcomas: evidence for transdifferentiation of the follicular lymphoma clone SO BLOOD LA English DT Article ID GRANULOMATOSIS HISTIOCYTOSIS-X; B-CELLS; LANGERHANS CELLS; MYELOID LINEAGES; T-CELLS; TUMORS; PRECURSOR; LEUKEMIA; IDENTIFICATION; MACROPHAGES AB Rare cases of histiocytic and dendritic cell (H/DC) neoplasms have been reported in patients with follicular lymphoma (FL), but the biologic relationship between the 2 neoplasms is unknown. We studied 8 patients with both FL and H/DC neoplasms using immunohistochemistry, fluorescence in situ hybridization (FISH) for t(14;18), and polymerase chain reaction (PCR)/sequencing of BCL2 and IGH rearrangements. There were 5 men and 3 women (median age, 59 years). All cases of FL were positive for t(14;18). The H/DC tumors included 7 histiocytic sarcomas, 5 of which showed evidence of dendritic differentiation, and 1 interdigitating cell sarcoma. Five H/DC tumors were metachronous, following FL by 2 months to 12 years; tumors were synchronous in 3. All 8 H/DC tumors showed presence of the t(14;18) either by FISH, or in 2 cases by PCR with the major breakpoint region (MBR) probe. PCR and sequencing identified identical IGH gene rearrangements or BCL2 gene breakpoints in all patients tested. All H/DC tumors lacked PAX5, and up-regulation of CEBP beta and PU.1 was seen in all cases tested. These results provide evidence for a common clonal origin of FL and H/DC neoplasms when occurring in the same patient, and suggest that lineage plasticity may occur in mature lymphoid neoplasms. C1 [Feldman, Andrew L.; Pittaluga, Stefania; Raffeld, Mark; Jaffe, Elaine S.] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Feldman, Andrew L.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Arber, Daniel A.; Warnke, Roger] Stanford Univ, Dept Pathol, Stanford, CA 94305 USA. [Martinez, Antonio; Camos, Mireia] Univ Barcelona, Barcelona, Spain. [Burke, Jerome S.] Alta Bates Summit Med Ctr, Dept Pathol, Berkeley, CA USA. RP Jaffe, ES (reprint author), NCI, Pathol Lab, Bldg 10,Rm 2B42,10 Ctr Dr MSC 1500, Bethesda, MD 20892 USA. EM elainejaffe@nih.gov RI Martinez, Antonio/D-8188-2012; Feldman, Andrew/D-5028-2012 OI Martinez, Antonio/0000-0003-0790-9017; NR 34 TC 111 Z9 120 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 15 PY 2008 VL 111 IS 12 BP 5433 EP 5439 DI 10.1182/blood-2007-11-124792 PG 7 WC Hematology SC Hematology GA 314CN UT WOS:000256786500012 PM 18272816 ER PT J AU Savage, KJ Harris, NL Vose, JM Ullrich, F Jaffe, ES Connors, JM Rimsza, L Pileri, SA Chhanabhai, M Gascoyne, RD Armitage, JO Weisenburger, DD AF Savage, Kerry J. Harris, Nancy Lee Vose, Julie M. Ullrich, Fred Jaffe, Elaine S. Connors, Joseph M. Rimsza, Lisa Pileri, Stefano A. Chhanabhai, Mukesh Gascoyne, Randy D. Armitage, James O. Weisenburger, Dennis D. CA Int Peripheral T Cell Lymphoma Pro TI ALK-anaplastic large-cell lymphoma is clinically and immunophenotypically different from both ALK(+) ALCL and peripheral T-cell lymphoma, not otherwise specified: report from the International Peripheral T-Cell Lymphoma Project SO BLOOD LA English DT Article ID NON-HODGKINS-LYMPHOMA; EXPRESSION; DISEASE; PROGNOSIS; MODEL AB The International Peripheral T-Cell Lymphoma Project is a collaborative effort designed to gain better understanding of peripheral T-cell and natural killer (NK)/T-cell lymphomas (PTCLs). A total of 22 institutions in North America, Europe, and Asia submitted clinical and pathologic information on PTCLs diagnosed and treated at their respective centers. Of the 1314 eligible patients, 181 had anaplastic large-cell lymphoma (ALCL; 13.8%) on consensus review: One hundred fifty-nine had systemic ALCL (12.1%) and 22 had primary cutaneous ALCL (1.7%). Patients with anaplastic lymphoma kinase-positive (ALK(+)) ALCL had a superior outcome compared with those with ALK(-)ALCL (5-year failure-free survival [FFS], 60% vs 36%; P =.015; 5-year overall survival [OS], 70% vs 49%; P =.016). However, contrary to prior reports, the 5-year FFS (36% vs 20%; P =.012) and OS (49% vs 32%; P =.032) were superior for ALK(-)ALCL compared with PTCL, not otherwise specified (PTCL-NOS). Patients with primary cutaneous ALCL had a very favorable 5-year OS (90%), but with a propensity to relapse (5-year FFS, 55%). In summary, ALK(-)ALCL should continue to be separated from both ALK(+) ALCL and PTCL-NOS. Although the prognosis of ALK(-) ALCL appears to be better than that for PTCL-NOS, it is still unsatisfactory and better therapies are needed. Primary cutaneous ALCL is associated with an indolent course. C1 [Savage, Kerry J.; Connors, Joseph M.] British Columbia Canc Agcy, Dept Med Oncol, Vancouver, BC V5Z 4E6, Canada. [Harris, Nancy Lee] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Vose, Julie M.] Univ Nebraska Med Ctr, Dept Internal Med, Omaha, NE USA. [Ullrich, Fred] Univ Nebraska Med Ctr, Dept Prevent & Societal Med, Omaha, NE USA. [Jaffe, Elaine S.] NCI, Dept Hematopathol, Bethesda, MD 20892 USA. [Rimsza, Lisa] Univ Arizona, Dept Pathol, Tucson, AZ USA. [Pileri, Stefano A.] Univ Bologna, Sch Med, Dept Pathol, Bologna, Italy. [Chhanabhai, Mukesh; Gascoyne, Randy D.] British Columbia Canc Agcy, Dept Pathol, Vancouver, BC V5Z 4E6, Canada. [Weisenburger, Dennis D.] Univ Nebraska Med Ctr, Dept Pathol, Omaha, NE USA. RP Savage, KJ (reprint author), British Columbia Canc Agcy, Dept Med Oncol, 600 W 10th Ave, Vancouver, BC V5Z 4E6, Canada. EM ksavage@bccancer.bc.ca RI Cuadros, Marta/K-1576-2014; Zinzani, Pier Luigi/J-9182-2016; OI Cuadros, Marta/0000-0002-8329-4854; Zinzani, Pier Luigi/0000-0002-2112-2651; Campo, elias/0000-0001-9850-9793 NR 25 TC 332 Z9 360 U1 2 U2 9 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 15 PY 2008 VL 111 IS 12 BP 5496 EP 5504 DI 10.1182/blood-2008-01-134270 PG 9 WC Hematology SC Hematology GA 314CN UT WOS:000256786500019 PM 18385450 ER PT J AU Toth, ZE Leker, RR Shahar, T Pastorino, S Szalayova, I Asemenew, B Key, S Parmelee, A Mayer, B Nemeth, K Bratincsak, A Mezey, E AF Toth, Zsuzsanna E. Leker, Ronen R. Shahar, Tal Pastorino, Sandra Szalayova, Ildiko Asemenew, Brook Key, Sharon Parmelee, Alissa Mayer, Balazs Nemeth, Krisztian Bratincsak, Andras Mezey, Eva TI The combination of granulocyte colony-stimulating factor and stem cell factor significantly increases the number of bone marrow-derived endothelial cells in brains of mice following cerebral ischemia SO BLOOD LA English DT Article ID TYRAMIDE SIGNAL AMPLIFICATION; FUNCTIONAL RECOVERY; PROGENITOR CELLS; C-KIT; G-CSF; STROKE; PROLIFERATION; EXPRESSION; TRANSPLANTATION; CHEMOTHERAPY AB Granulocyte colony-stimulating factor (G-CSF) induces proliferation of bone marrow-derived cells. G-CSF is neuroprotective after experimental brain injury, but the mechanisms involved remain unclear. Stem cell factor (SCF) is a cytokine important for the survival and differentiation of hematopoietic stem cells. Its receptor (c-kit or CD117) is present in some endothelial cells. We aimed to determine whether the combination of G-CSF/SCF induces angiogenesis in the central nervous system by promoting entry of endothelial precursors into the injured brain and causing them to proliferate there. We induced permanent middle cerebral artery occlusion in female mice that previously underwent sex-mismatched bone marrow transplantation from enhanced green fluorescent protein (EGFP)-expressing mice. G-CSF/SCF treatment reduced infarct volumes by more than 50% and resulted in a 1.5-fold increase in vessel formation in mice with stroke, a large percentage of which contain endothelial cells of bone marrow origin. Most cells entering the brain maintained their bone marrow identity and did not transdifferentiate into neural cells. G-CSF/SCF treatment also led to a 2-fold increase in the number of newborn cells in the ischemic hemisphere. These findings suggest that G-CSF/SCF treatment might help recovery through induction of bone marrow-derived angiogenesis, thus improving neuronal survival and functional outcome. C1 [Toth, Zsuzsanna E.; Szalayova, Ildiko; Asemenew, Brook; Key, Sharon; Parmelee, Alissa; Mayer, Balazs; Nemeth, Krisztian; Mezey, Eva] NIDCR, NIH, CSDB, Bethesda, MD 20892 USA. [Leker, Ronen R.; Shahar, Tal] NINDS, Bethesda, MD 20892 USA. [Pastorino, Sandra] NCI, Bethesda, MD 20892 USA. [Bratincsak, Andras] NIMH, NIH, Bethesda, MD 20892 USA. RP Mezey, E (reprint author), NIDCR, NIH, CSDB, Bldg 49,Rm 5A-76,49 Convent Dr, Bethesda, MD 20892 USA. EM mezeye@mail.nih.gov RI Mayer, Balazs/B-7864-2013 OI Mayer, Balazs/0000-0003-3577-3823 FU Intramural NIH HHS NR 32 TC 64 Z9 75 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 15 PY 2008 VL 111 IS 12 BP 5544 EP 5552 DI 10.1182/blood-2007-10-119073 PG 9 WC Hematology SC Hematology GA 314CN UT WOS:000256786500026 PM 18268092 ER PT J AU Grant, C Oh, U Yao, K Yamano, Y Jacobson, S AF Grant, Christian Oh, Unsong Yao, Karen Yamano, Yoshihisa Jacobson, Steven TI Dysregulation of TGF-beta signaling and regulatory and effector T-cell function in virus-induced neuroinflammatory disease SO BLOOD LA English DT Article ID I-ASSOCIATED MYELOPATHY; GROWTH-FACTOR-BETA; TROPICAL SPASTIC PARAPARESIS; CENTRAL-NERVOUS-SYSTEM; HTLV-I; PROVIRAL DNA; NEUROLOGIC DISEASE; CUTTING EDGE; SPINAL-CORD; SUPPRESSOR FUNCTION AB We previously demonstrated that CD4(+)CD25(+) T regulatory cells (Tregs), important for the maintenance of immune tolerance and prevention of autoimmune disease, from patients with human T lymphotropic virus type I (HTLV-I)associated myelopathy/tropical spastic paraparesis (HAM/TSP) exhibit reduced Foxp3 expression and Treg suppressor function compared with healthy donors. Since TGF-beta signaling has been previously reported to be critical for both Foxp3 expression and Treg function, we examined whether this signaling pathway was dysregulated in patients with HAM/TSP. Levels of TGF-beta receptor 11 (TGF-beta RII) as well as Smad7 (a TGF-beta-inducible gene) were significantly reduced in CD4(+) T cells in patients with HAM/TSP compared with healthy donors, and the expression of TGF-beta RII inversely correlated with the HTLV-I tax proviral load. Importantly, both CD4(+)CD25(+) and CD4(+)CD25(-) T cells from HAM/TSP patients exhibited reduced TGF-beta RII expression compared with healthy donors, which was associated with functional deficits in vitro, including a block in TGF-beta-inducible Foxp3 expression that inversely correlated with the HTLV-1 tax proviral load, loss of Treg suppressor function, and escape of effector T cells from Treg-mediated control. This evidence suggests that a virus-induced breakdown of immune tolerance affecting both regulatory and effector T cells contributes to the pathogenesis of HAM/TSP. C1 [Grant, Christian; Oh, Unsong; Yao, Karen; Jacobson, Steven] NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. [Yamano, Yoshihisa] Kagoshima City Hosp, Kagoshima, Japan. RP Jacobson, S (reprint author), NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, 10 Ctr Dr,Bldg 10,Rm 5B-16, Bethesda, MD 20892 USA. EM jacobsons@ninds.nih.gov FU Intramural NIH HHS NR 58 TC 22 Z9 22 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD JUN 15 PY 2008 VL 111 IS 12 BP 5601 EP 5609 DI 10.1182/blood-2007-11-123430 PG 9 WC Hematology SC Hematology GA 314CN UT WOS:000256786500032 PM 18326816 ER PT J AU Kim, SY Jun, HS Mead, PA Mansfield, BC Chou, JY AF Kim, So Youn Jun, Hyun Sik Mead, Paul A. Mansfield, Brian C. Chou, Janice Y. TI Neutrophil stress and apoptosis underlie myeloid dysfunction in glycogen storage disease type Ib SO BLOOD LA English DT Article ID UNFOLDED PROTEIN RESPONSE; 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-1; PHOSPHOHISTIDINE-ENZYME INTERMEDIATE; ENDOPLASMIC-RETICULUM STRESS; GLUCOSE-6-PHOSPHATE TRANSPORTER; CELL-DEATH; BONE-MARROW; HEXOSE-6-PHOSPHATE DEHYDROGENASE; TRANSMEMBRANE TOPOLOGY; SUPEROXIDE-DISMUTASE AB Glycogen storage disease type Ib (GSD-Ib) is caused by a deficiency in the glucose-6-phosphate (G6P) transporter (G6PT) that works with a liver/kidney/ intestine-restricted glucose-6-phosphatase-alpha (GVase-alpha) to maintain glucose homeostasis between meals. Clinically, GSD-Ib patients manifest disturbed glucose homeostasis and neutrophil dysfunctions but the cause of the latter is unclear. Neutrophils express the ubiquitously expressed G6PT and G6Pase-beta that together transport G6P into the endoplasmic reticulum (ER) lumen and hydrolyze it to glucose. Because we expected G6PT-deficient neutrophils to be unable to produce endogenous glucose, we hypothesized this would lead to ER stress and increased apoptosis. Using GSD-Ib mice, we showed that GSD-Ib neutrophils exhibited increased production of ER chaperones and oxidative stress, consistent with ER stress, and increased annexin V binding and caspase-3 activation, consistent with an increased rate of apoptosis. Bax activation, mitochondrial release of proapoptotic effectors, and caspase-9 activation demonstrated the involvement of the intrinsic mitochondrial pathway in these processes. The results demonstrate that G6P translocation and hydrolysis are required for normal neutrophil functions and support the hypothesis that neutrophil dysfunction in GSD-Ib is due, at least in part, to ER stress and increased apoptosis. C1 [Kim, So Youn; Jun, Hyun Sik; Mead, Paul A.; Mansfield, Brian C.; Chou, Janice Y.] NICHD, Sect Cellular Differentiat, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Chou, JY (reprint author), NICHD, Sect Cellular Differentiat, Heritable Disorders Branch, NIH, Bldg 10,Room 9D42,10 Ctr Dr, Bethesda, MD 20892 USA. EM chouja@mail.nih.gov RI Jun, Hyun Sik/C-6799-2013; OI Mansfield, Brian/0000-0002-8533-2789 FU Intramural NIH HHS NR 53 TC 37 Z9 40 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 15 PY 2008 VL 111 IS 12 BP 5704 EP 5711 DI 10.1182/blood-2007-12-129114 PG 8 WC Hematology SC Hematology GA 314CN UT WOS:000256786500044 PM 18420828 ER PT J AU Little, RF Denicoff, AM Trimble, EL AF Little, Richard F. Denicoff, Andrea M. Trimble, Edward L. TI Reversible features of cervical cancer in human immunodeficiency virus infection - Impaired access, impaired surveillance, impaired immunity, impaired outcomes SO CANCER LA English DT Editorial Material ID ACTIVE ANTIRETROVIRAL THERAPY; INTRAEPITHELIAL NEOPLASIA; KAPOSI-SARCOMA; AIDS; WOMEN; INTERLEUKIN-12; PATHOGENESIS; MANAGEMENT; LESIONS; IMPACT C1 [Little, Richard F.; Denicoff, Andrea M.; Trimble, Edward L.] NCI, Clin Invest Branch, Canc Therapy Evaluat Program, Div Canc Therapy & Diag, Bethesda, MD 20892 USA. RP Little, RF (reprint author), NCI, Clin Invest Branch, Canc Therapy Evaluat Program, Div Canc Therapy & Diag, EPN 7025,MSC 7436, Bethesda, MD 20892 USA. EM rl48e@nih.gov NR 23 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD JUN 15 PY 2008 VL 112 IS 12 BP 2627 EP 2630 DI 10.1002/cncr23499 PG 4 WC Oncology SC Oncology GA 311DJ UT WOS:000256580200001 PM 18429005 ER PT J AU Gergich, NLS Pfalzer, LA McGarvey, C Springer, B Gerber, LH Soballe, P AF Gergich, Nicole L. Stout Pfalzer, Lucinda A. McGarvey, Charles Springer, Barbara Gerber, Lynn H. Soballe, Peter TI Preoperative assessment enables the early diagnosis and successful treatment of lymphedema SO CANCER LA English DT Article DE breast cancer; lymphedema; early detection; physical therapy; early intervention; compression; optoelectronic volumetry; subclinical lymphedema ID BREAST-CANCER-TREATMENT; QUALITY-OF-LIFE; UPPER EXTREMITY LYMPHEDEMA; SENTINEL NODE BIOPSY; ARM LYMPHEDEMA; POSTMASTECTOMY LYMPHEDEMA; VOLUME MEASUREMENTS; SURGICAL OUTCOMES; PERIPHERAL EDEMA; FOLLOW-UP AB BACKGROUND. The incidence of breast cancer (BC)-related lymphedema (LE) ranges from 7% to 47%. Successful management of LE relies on early diagnosis using sensitive measurement techniques. In the current study, the authors demonstrated the effectiveness of a surveillance program that included preoperative limb volume measurement and interval postoperative follow-up to detect and treat subclinical LE. METHODS. LE was identified in 43 of 196 women who participated in a prospective BC morbidity trial. Limb volume was measured preoperatively and at 3-month intervals after surgery. If an increase >3% in upper limb (UL) volume developed compared with the preoperative volume, then a diagnosis of LE was made, and a compression garment intervention was prescribed for 4 weeks. Upon reduction of LE, garment wear was continued only during strenuous activity, with symptoms of heaviness, or with visible swelling. Women returned to the 3-month interval surveillance pathway. Statistical analysis was a repeated-measores analysis of variance by time and limb (P <= .001) comparing the LE cohort with an age-matched control group. RESULTS. The time to onset of LE averaged 6.9 months postoperatively. The mean (+/- standard deviation) affected limb volume increase was 83 mL (+/- 119 mL; 6.5% +/- 9.9%) at LE onset (P = .005) compared with baseline. After the intervention, a statistically significant mean 48 mL (+/- 103 mL; 4.1% +/- 8.8%) volume decrease was realized (P < .0001). The mean duration of the intervention was 4.4 weeks (+/- 2.9 weeks). Volume reduction was maintained at an average follow-up of 4.8 months (+/- 4.1 months) after the intervention. CONCLUSIONS. A short trial of compression garments effectively treated subclinical LE. C1 [Gergich, Nicole L. Stout] Natl Naval Med Ctr, Breast Canc Dept, Breast Care Ctr, Bethesda, MD 20889 USA. [Pfalzer, Lucinda A.] Univ Michigan, Phys Therapy Dept, Flint, MI 48503 USA. [McGarvey, Charles] NIH, Dept Rehabil Med, Bethesda, MD 20892 USA. [Springer, Barbara] Walter Reed Army Med Ctr, Phys Therapy Dept, Bethesda, MD USA. [Gerber, Lynn H.] George Mason Univ, Coll Hlth & Human Serv, Fairfax, VA 22030 USA. RP Gergich, NLS (reprint author), Natl Naval Med Ctr, Breast Canc Dept, Breast Care Ctr, 8901 Wisconsin Ave,Bldg 10,4th Floor W, Bethesda, MD 20889 USA. EM nicole.stout@med.navy.mil NR 68 TC 119 Z9 120 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD JUN 15 PY 2008 VL 112 IS 12 BP 2809 EP 2819 DI 10.1002/cncr.23494 PG 11 WC Oncology SC Oncology GA 311DJ UT WOS:000256580200025 ER PT J AU Lyons, JG Patel, V Roue, NC Fok, SY Soon, LL Halliday, GM Gutkind, JS AF Lyons, J. Guy Patel, Vyomesh Roue, Naomi C. Fok, Sandra Y. Soon, Lilian L. Halliday, Gary M. Gutkind, J. Silvio TI Snail up-regulates proinflammatory mediators and inhibits differentiation in oral keratinocytes SO CANCER RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMA; GENE-EXPRESSION PROFILE; TRANSCRIPTION FACTOR; NECK-CANCER; HEAD; MARKER; MICE; SLUG; DNA AB The transcriptional repressor Snail2 is overexpressed in head and neck squamous cell carcinomas (HNSCC) relative to nonmalignant head and neck mucosal epithelium, and in locally recurrent relative to nonrecurrent HNSCCs. We investigated the mechanisms by which Snails might contribute to the pathogenesis of HNSCCs using cell biological and molecular analyses. Oral keratinocytes that expressed Snails acquired an enhanced ability to attract monocytes and to invade a dense interstitial collagen matrix. They were also found to up-regulate production of proinflammatory cytokines and cyclooxygenase-2 (COX2), which have previously been shown to correlate with malignancy. Induction of nuclear factor-kappa B transcriptional activity by Snails was weak and not sufficient to account for the elevated levels of COX2, interleukin (IL)-6, IL8, or CXCL1. In addition, expression of Snails in oral keratinocytes impaired desquamation in vitro and strongly repressed expression of both ELF3 and matriptase-1, which play important roles in the terminal differentiation of keratinocytes. Reexpression of matriptase-1 in Snail-expressing cells partially rescued desquamation. This implicates Snails as contributing to malignancy both at the early stages, by impeding terminal differentiation, and at later stages, when invasion and inflammation are important. C1 [Lyons, J. Guy; Roue, Naomi C.; Halliday, Gary M.] Univ Sydney, Cent Clin Sch, Dermatol Res Labs, Sydney, NSW 2006, Australia. [Fok, Sandra Y.; Soon, Lilian L.] Univ Sydney, Key Ctr Microscopy, Sydney, NSW 2006, Australia. [Lyons, J. Guy; Roue, Naomi C.] Royal Prince Alfred Hosp, Sydney Canc Ctr, Sydney Head & Neck Canc Inst, Camperdown, NSW 2050, Australia. [Lyons, J. Guy; Patel, Vyomesh; Gutkind, J. Silvio] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA. RP Lyons, JG (reprint author), Univ Sydney, Cent Clin Sch, Dermatol Res Labs, Room W350,Blackburn Bldg, Sydney, NSW 2006, Australia. EM glyons@med.usyd.edu.au RI Gutkind, J. Silvio/A-1053-2009; Lyons, Guy/B-1319-2012 OI Lyons, Guy/0000-0002-4835-4663 FU Intramural NIH HHS [Z01 DE000558-16] NR 20 TC 41 Z9 43 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 15 PY 2008 VL 68 IS 12 BP 4525 EP 4530 DI 10.1158/1078-0432.CCR-07-6735 PG 6 WC Oncology SC Oncology GA 315CO UT WOS:000256855700008 PM 18559496 ER PT J AU Zhang, M Behbod, F Atkinson, RL Landis, MD Kittrell, F Edwards, D Medina, D Tsimelzon, A Hilsenbeck, S Green, JE Michalowska, AM Rosen, JM AF Zhang, Mei Behbod, Fariba Atkinson, Rachel L. Landis, Melissa D. Kittrell, Frances Edwards, David Medina, Daniel Tsimelzon, Anna Hilsenbeck, Susan Green, Jeffrey E. Michalowska, Aleksandra M. Rosen, Jeffrey M. TI Identification of tumor-initiating cells in a p53-null mouse model of breast cancer SO CANCER RESEARCH LA English DT Article ID ACUTE MYELOID-LEUKEMIA; MAMMARY STEM-CELLS; GENE-EXPRESSION; SELF-RENEWAL; PROGNOSTIC MARKERS; PROGENITOR CELLS; GLAND; BIOLOGY; TUMORIGENESIS; EPITHELIUM AB Using a syngeneic p53-null mouse mammary gland tumor model that closely mimics human breast cancer, we have identified, by limiting dilution transplantation and in vitro mammosphere assay, a Lin(-)CD29(H)CD24(H) subpopulation of tumor-initiating cells. Upon subsequent transplantation, this subpopulation generated heterogeneous tumors that displayed properties similar to the primary tumor. Analysis of biomarkers suggests the Lin-CD29(H)CD24(H) subpopulation may have arisen from a bipotent mammary progenitor. Differentially expressed genes in the Lin(-)CD29(H)CD24(H) mouse mammary gland tumor-initiating cell population include those involved in DNA damage response and repair, as well as genes involved in epigenetic regulation previously shown to be critical for stem cell self-renewal. These studies provide in vitro and in vivo data that support the cancer stem cell (CSC) hypothesis. Furthermore, this p53-null mouse mammary tumor model may allow us to identify new CSC markers and to test the functional importance of these markers. C1 Baylor Coll Med, Dept Mol & Cellular Biol, Grad program Translat Biol & Mol Med, Lester & Sue Smith Breast Ctr, Houston, TX 77030 USA. [Green, Jeffrey E.; Michalowska, Aleksandra M.] NCI, Canc Biol Lab, Bethesda, MD 20892 USA. RP Rosen, JM (reprint author), Baylor Coll Med, Dept Mol & Cellular Biol, Grad program Translat Biol & Mol Med, Lester & Sue Smith Breast Ctr, 1 Baylor Plaza, Houston, TX 77030 USA. EM jrosen@bcm.edu RI Zhang, Mei/G-8690-2014 FU Intramural NIH HHS [Z01 BC005740-15]; NCI NIH HHS [R01 CA016303, CA16303, K99 CA127462, K99 CA127462-02, R37 CA016303, R37 CA016303-33, U01 CA084243, U01 CA084243-10, U01-CA84243] NR 45 TC 195 Z9 201 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 15 PY 2008 VL 68 IS 12 BP 4674 EP 4682 DI 10.1158/0008-5472.CAN-07-6353 PG 9 WC Oncology SC Oncology GA 315CO UT WOS:000256855700025 PM 18559513 ER PT J AU Takahashi, Y Iwase, M Strunnikov, AV Kikuchi, Y AF Takahashi, Yoshimitsu Iwase, Masayuki Strunnikov, Alexander V. Kikuchi, Yoshiko TI Cytoplasmic sumoylation by PIAS-type Siz1-SUMO ligase SO CELL CYCLE LA English DT Review DE SUMO; septins; SUMO ligase; nuclear transport; sumoylation; SP-RING; PIAS ID NUCLEAR-PORE COMPLEX; SEPTIN-INTERACTING PROTEINS; SACCHAROMYCES-CEREVISIAE; SUMO LIGASE; CELL-CYCLE; BUDDING YEAST; CHROMOSOMAL ORGANIZATION; STRUCTURAL INSIGHTS; CONJUGATING ENZYME; TOPOISOMERASE-II AB SUMO (small ubiquitin-related modifier), a 12 kDa protein with distant similarity to ubiquitin, covalently binds to many proteins in eukaryotic cells. In contrast to ubiquitination, which mainly regulates proteasome-dependent degradation and protein sorting, sumoylation is known to regulate assembly and disassembly of protein complexes, protein localization and stability, and so on. SUMO is primarily localized to the nucleus, and many SUMO substrates are nuclear proteins involved in DNA transaction. However, certain roles of SUMO conjugates have been shown outside the nucleus. Particularly in budding yeast, SUMO is also localized to the bud-neck in a cell cycle-dependent manner. The first and prominent SUMO substrates are septins, evolutionally conserved proteins required for cytokinesis in yeast. Recent analysis of human septin structure would greatly facilitate the study of the functions of these SUMO conjugates. SUMO modification of septins is regulated by cell cycle-dependent nuclear transport of PIAS-type Siz1 SUMO E3) and Ulp1 desumoylation enzyme in yeast. Domains outside the (SUMO-ligase core (SP-RING) of Siz1 ensure its regulations. Furthermore, newly discovered ubiquitin ligases that specifically recognize poly-SUMO conjugates could lead to degradation of SUMO conjugates. Thus, protein modifications seem to be regulated in an unexpectedly complex manner. In this review, we focus on various regulations in yeast septin sumoylation and discuss its possible functions. C1 [Kikuchi, Yoshiko] Univ Tokyo, Dept Biol Sci, Grad Sch Sci, Bunkyo Ku, Tokyo 1130033, Japan. [Takahashi, Yoshimitsu; Strunnikov, Alexander V.] NICHHD, NIH, Lab Gene Regulat & Dev, Bethesda, MD 20892 USA. RP Kikuchi, Y (reprint author), Univ Tokyo, Dept Biol Sci, Grad Sch Sci, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan. EM kikuchi@biol.s.u-tokyo.ac.jp OI Strunnikov, Alexander/0000-0002-9058-2256 FU Intramural NIH HHS NR 75 TC 14 Z9 16 U1 0 U2 3 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD JUN 15 PY 2008 VL 7 IS 12 BP 1738 EP 1744 DI 10.4161/cc.7.12.6156 PG 7 WC Cell Biology SC Cell Biology GA 320QE UT WOS:000257249300009 PM 18583943 ER PT J AU Schieke, SM Mccoy, JP Finkel, T AF Schieke, Stefan M. McCoy, J. Philip, Jr. Finkel, Toren TI Coordination of mitochondrial bioenergetics with G(1) phase cell cycle progression SO CELL CYCLE LA English DT Article DE cell cycle; mitochondria; mTOR ID RAPAMYCIN; MTOR; PROTEIN; ACTIVATION; CHECKPOINT; INITIATION; EFFECTORS; PATHWAY; COMPLEX; RAPTOR AB Relatively little is known regarding how energetic demand during cell proliferation is sensed or coordinated with mitochondrial metabolism. Here we demonstrate that cell cycle progression through G(1) is associated with a significant increase in mitochondrial membrane potential (Delta Psi(m)) and respiration. We used this change in metabolic rate to isolate cells in G(1) with low and high levels of mitochondrial membrane potential (Delta Psi(m)L and Delta Psi(m)H). Biochemical and functional studies demonstrate that Delta Psi(m)L and Delta Psi(m)H cells display the distinct characteristics of early and late G(1) phase, respectively. We further demonstrate that the metabolic rate in G(1) reflects levels of the mTOR-raptor complex as well as susceptibility to rapamycin-induced cell cycle delay. In conclusion, our data suggests a coupling of mitochondrial bioenergetics and G(1) progression and points to the mTOR signaling pathway as a potential molecular coordinator of these two processes. C1 [Schieke, Stefan M.; Finkel, Toren] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA. [McCoy, J. Philip, Jr.] NHLBI, Flow Cytometry Core Facil, NIH, Bethesda, MD 20892 USA. RP Finkel, T (reprint author), Bldg 10CRC-5-3330,10 Ctr Dr, Bethesda, MD 20892 USA. EM finkelt@nih.gov FU Intramural NIH HHS [Z99 HL999999, ZIC HL005905-02, ZIC HL005905-03, ZIC HL005905-04] NR 16 TC 45 Z9 45 U1 0 U2 3 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD JUN 15 PY 2008 VL 7 IS 12 BP 1782 EP 1787 DI 10.4161/cc.7.12.6067 PG 6 WC Cell Biology SC Cell Biology GA 320QE UT WOS:000257249300014 PM 18583942 ER PT J AU Steeg, PS AF Steeg, Patricia S. TI Heterogeneity of drug target expression among metastatic lesions: Lessons from a breast cancer autopsy program SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID LYMPH-NODE METASTASES; PRIMARY TUMORS; THERAPEUTIC TARGET; ESTROGEN-RECEPTOR; PROGESTERONE; GENE; SIGNATURE; CARCINOMA; CELLS; TRIAL C1 NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Steeg, PS (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bldg 37,Room 1122, Bethesda, MD 20892 USA. EM steegp@mail.nih.gov FU Intramural NIH HHS [Z01 SC000892-24] NR 20 TC 16 Z9 17 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 JUN 15 PY 2008 VL 14 IS 12 BP 3643 EP 3645 DI 10.1158/1078-0432.CCR-08-1135 PG 3 WC Oncology SC Oncology GA 313ZS UT WOS:000256779100001 PM 18559575 ER PT J AU Doroshow, JH Parchment, RE AF Doroshow, James H. Parchment, Ralph E. TI Oncologic phase 0 trials incorporating clinical pharmacodynamics: from concept to patient SO CLINICAL CANCER RESEARCH LA English DT Article ID DRUG DEVELOPMENT; BIOMARKERS; DESIGN; AGENTS; TUMOR AB The U.S. Food and Drug Administration recently issued an Exploratory Investigational New Drug (IND) guidance that provides a platform for the evaluation of targeted anticancer agents in small, early-phase human clinical trials that can be used to establish the feasibility of proof-of-principle target modulation assays, as well as the preliminary pharmacokinetics and molecular imaging potential of new anticancer molecules. The exploratory IND allows for reduced requirements for manufacturing and toxicologic assessment. Early clinical trials done in this fashion have no therapeutic intent. In this series of articles in CCR Focus, the development of this new IND mechanism, its effect on clinical trial design and clinical pharmacodynamics, the ethical implications of nontherapeutic clinical investigations, and the perspective of the pharmaceutical industry on this approach are examined. C1 [Doroshow, James H.] NCI, Div Canc Treatment & Diag, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Doroshow, James H.] NCI, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Parchment, Ralph E.] NCI, Lab Human Toxicol & Pharmacol, Appl Dev Res Support Directorate, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21701 USA. RP Doroshow, JH (reprint author), NCI, Div Canc Treatment & Diag, Ctr Canc Res, NIH, Bldg 31,Room 3A-44,31 Ctr Dr, Bethesda, MD 20892 USA. EM doroshoj@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999]; NCI NIH HHS [N01-CO-12400, N01CO12400] NR 27 TC 38 Z9 39 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 15 PY 2008 VL 14 IS 12 BP 3658 EP 3663 DI 10.1158/1078-0432.CCR-07-4562 PG 6 WC Oncology SC Oncology GA 313ZS UT WOS:000256779100005 PM 18559579 ER PT J AU Murgo, AJ Kummar, S Rubinstein, L Gutierrez, M Collins, J Kinders, R Parchment, RE Ji, J Steinberg, SM Yang, SX Hollingshead, M Chen, A Helman, L Wiltrout, R Tomaszewski, JE Doroshow, JH AF Murgo, Anthony J. Kummar, Shivaani Rubinstein, Larry Gutierrez, Martin Collins, Jerry Kinders, Robert Parchment, Ralph E. Ji, Jiuping Steinberg, Seth M. Yang, Sherry X. Hollingshead, Melinda Chen, Alice Helman, Lee Wiltrout, Robert Tomaszewski, Joseph E. Doroshow, James H. TI Designing phase 0 cancer clinical trials SO CLINICAL CANCER RESEARCH LA English DT Article ID DRUG DEVELOPMENT; ONCOLOGY AB Phase 0 trials are designed primarily to evaluate the pharmacodynamic and/or pharmacokinetic properties of selected investigational agents before initiating more traditional phase I testing. One of the major objectives of phase 0 trials is to interrogate and refine a target or biomarker assay for drug effect in human samples implementing procedures developed and validated in preclinical models. Thus, close collaboration between laboratory scientists and clinical investigators is essential to the design and conduct of phase 0 trials. Given the relatively small number of patients and tissue samples, showing a significant drug effect in phase 0 trials requires precise and reproducible assay procedures and innovative statistical methodology. Furthermore, phase 0 trials involving limited exposure of a study agent administered at low doses and/or for a short period allow them to be initiated under the Food and Drug Administration exploratory investigational new drug guidance with less preclinical toxicity data than usually required for traditional first-in-human studies. Because of the very limited drug exposure, phase 0 trials offer no chance of therapeutic benefit, which can impede patient enrollment, particularly if invasive tumor biopsies are required. The challenges to accrual are not insurmountable, however, and well-designed and executed phase 0 trials are feasible and have great potential for improving the efficiency and success of subsequent trials, particularly those evaluating molecularly targeted agents. C1 [Murgo, Anthony J.; Rubinstein, Larry; Collins, Jerry; Yang, Sherry X.; Hollingshead, Melinda; Chen, Alice; Tomaszewski, Joseph E.; Doroshow, James H.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Murgo, Anthony J.; Kummar, Shivaani; Gutierrez, Martin; Steinberg, Seth M.; Helman, Lee; Wiltrout, Robert; Doroshow, James H.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. [Kinders, Robert; Parchment, Ralph E.; Ji, Jiuping] NCI, Lab Human Toxicol & Pharmacol, Appl Dev Res Support Directorate, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21701 USA. RP Murgo, AJ (reprint author), NCI, Div Canc Treatment & Diag, Bldg 31,Room 3A44,31 Ctr Dr, Bethesda, MD 20892 USA. EM murgoa@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999]; NCI NIH HHS [N01-CO-12400, N01CO12400] NR 16 TC 50 Z9 54 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 15 PY 2008 VL 14 IS 12 BP 3675 EP 3682 DI 10.1158/1078-0432.CCR-07-4560 PG 8 WC Oncology SC Oncology GA 313ZS UT WOS:000256779100008 PM 18559582 ER PT J AU Gutierrez, M Collyar, D AF Gutierrez, Martin Collyar, Deborah TI Patient perspectives on phase 0 clinical trials SO CLINICAL CANCER RESEARCH LA English DT Article C1 [Gutierrez, Martin] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. [Collyar, Deborah] PAIR Patient Advocates Res, Danville, PA USA. RP Gutierrez, M (reprint author), NCI, Ctr Canc Res, Bethesda, MD 20892 USA. EM mgutierr@mail.nih.gov FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 6 TC 16 Z9 16 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 15 PY 2008 VL 14 IS 12 BP 3689 EP 3691 DI 10.1158/1078-0432.CCR-07-4561 PG 3 WC Oncology SC Oncology GA 313ZS UT WOS:000256779100010 PM 18559584 ER PT J AU Abdoler, E Taylor, H Wendler, D AF Abdoler, Emily Taylor, Holly Wendler, David TI The ethics of phase 0 oncology trials SO CLINICAL CANCER RESEARCH LA English DT Article ID QUALITY-OF-LIFE; CANCER CLINICAL-TRIALS; I TRIALS; INFORMED-CONSENT; DRUG DEVELOPMENT; DECISION-MAKING; PARTICIPATION; IMPACT; ISSUES; AGENTS AB Recent guidance from the Food and Drug Administration supports the conduct of a new type of exploratory clinical trial, commonly called phase 0 clinical trials. Proponents argue that phase 0 clinical trials have the potential to expedite the development of new oncology drugs while exposing fewer research subjects to the risks of experimental treatments. At the same time, phase 0 oncology trials raise important ethical concerns that have received little attention. In particular, there is a question of whether it is ethical to enroll individuals in research that offers them no potential for clinical benefit. Further concern focuses on the inclusion of terminally ill and consequently vulnerable cancer patients in these trials. To evaluate these concerns, this article considers relevant empirical data from phase 1 oncology trials and develops several recommendations regarding the conduct of phase 0 clinical trials in oncology. C1 [Abdoler, Emily; Wendler, David] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA. [Taylor, Holly] Johns Hopkins Univ, Berman Inst Bioeth, Bethesda, MD USA. RP Wendler, D (reprint author), NIH, Dept Bioeth, Ctr Clin, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM dwendler@nih.gov NR 58 TC 24 Z9 25 U1 1 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 JUN 15 PY 2008 VL 14 IS 12 BP 3692 EP 3697 DI 10.1158/1078-0432.CCR-08-0876 PG 6 WC Oncology SC Oncology GA 313ZS UT WOS:000256779100011 PM 18559585 ER PT J AU Signoretti, S Bratslavsky, G Waldman, FM Reuter, VE Haaga, J Merino, M Thomas, GV Pins, MR Libermann, T Gillespie, J Tomaszewski, JE Compton, CC Hruszkewycz, A Linehan, WM Atkins, MB AF Signoretti, Sabina Bratslavsky, Gennady Waldman, Frederick M. Reuter, Victor E. Haaga, John Merino, Maria Thomas, George V. Pins, Michael R. Libermann, Towia Gillespie, John Tomaszewski, Joseph E. Compton, Carolyn C. Hruszkewycz, Andrew Linehan, W. Marston Atkins, Michael B. TI Tissue-based research in kidney cancer: Current challenges and future directions SO CLINICAL CANCER RESEARCH LA English DT Review ID RENAL-CELL CARCINOMA; MICROARRAY TECHNOLOGY; PERCUTANEOUS BIOPSY; MASSES; TEMSIROLIMUS; SENSITIVITY; THERAPIES; TUMORS AB The past several years have seen unprecedented advances in the application of various therapeutic strategies for the treatment of patients with renal cancer. The availability of active immunotherapy, antiangiogenic therapy, and targeted therapy for this disease has brought front and center issues related to choosing the appropriate treatment for particular patient populations. It is increasingly evident that the most promising treatment selection strategies will incorporate identifying specific features of the tumor itself. To facilitate this move toward personalized medicine, it is critically important to establish some standard principles for renal cancer tissue collection, preparation, and analysis for translational research studies. In this article, we identify and discuss some critical issues related to tissue-based kidney cancer research. We focus on five major areas as follows: (a) surgical and image-guided techniques for tissue collection; (b) quality control of specimen collection, processing, storage, and review; (c) issues related to analysis of paraffin embedded tissues; (d) genomic studies; and (e) assessment of reproducibility of assays across institutions. In addition, some practical implementation strategies are proposed. Although many of the topics discussed are specific for renal cancer, several are also relevant to tissue based biomarker investigations in a broad array of malignancies. C1 [Signoretti, Sabina] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Signoretti, Sabina] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Libermann, Towia] BIDMC Genom Ctr, Boston, MA USA. [Atkins, Michael B.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Hematol Oncol, Boston, MA 02215 USA. [Bratslavsky, Gennady; Linehan, W. Marston] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Merino, Maria] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Compton, Carolyn C.] NCI, Off Biorepositories & Biospecimen Res, Bethesda, MD 20892 USA. [Waldman, Frederick M.] Univ Calif San Francisco, Dept Lab Med, Ctr Comprehens Canc, San Francisco, CA 94143 USA. [Waldman, Frederick M.] Univ Calif San Francisco, Dept Urol, Ctr Comprehens Canc, San Francisco, CA 94143 USA. [Reuter, Victor E.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. [Haaga, John] Univ Hosp Cleveland, Dept Radiol, Cleveland, OH 44106 USA. [Haaga, John] Case Western Reserve Univ, Sch Med, Cleveland, OH USA. [Thomas, George V.] Univ Calif Los Angeles, Dept Pathol, Los Angeles, CA 90024 USA. [Pins, Michael R.] Advocate Lutheran Gen Hosp, Dept Pathol, Park Ridge, IL USA. [Gillespie, John] NCI, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21701 USA. [Tomaszewski, Joseph E.] NCI, Div Canc Treatment & Diag, Rockville, MD USA. [Hruszkewycz, Andrew] NCI, Organ Syst Branch, Rockville, MD USA. RP Signoretti, S (reprint author), Harvard Univ, Brigham & Womens Hosp, Dept Pathol, Sch Med, 75 Francis St, Boston, MA 02115 USA. EM ssignoretti@partners.org RI Libermann, Towia/F-9866-2010; OI Libermann, Towia/0000-0002-4006-8179 FU Intramural NIH HHS [Z01 SC006659-25]; NCI NIH HHS [N01 CO012400] NR 28 TC 18 Z9 19 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 15 PY 2008 VL 14 IS 12 BP 3699 EP 3705 DI 10.1158/1078-0432.CCR-07-4733 PG 7 WC Oncology SC Oncology GA 313ZS UT WOS:000256779100012 PM 18559586 ER PT J AU Holt, SK Karyadi, DM Kwon, EM Stanford, JL Nelson, PS Ostrander, EA AF Holt, Sarah K. Karyadi, Danielle M. Kwon, Erika M. Stanford, Janet L. Nelson, Peter S. Ostrander, Elaine A. TI Association of Megalin genetic polymorphisms with prostate cancer risk and prognosis SO CLINICAL CANCER RESEARCH LA English DT Article ID CELLULAR UPTAKE; LINKAGE AB Purpose: Megalin, an endocytic receptor expressed by prostate epithelial cells, can internalize biologically active androgens bound to sex hormone binding globulin. Genetic variation within megalin could potentially influence levels of steroid hormone uptake. Experimental Design: Forty haplotype-tagging single-nucleotide polymorphisms (htSNP) were analyzed in a population-based, case-control study of 553 Caucasian men who were diagnosed with prostate cancer between the ages of 40 and 64 years from the Seattle-Puget Sound region and 534 control men. Prostate cancer risk was estimated using adjusted unconditional logistic regression for both individual SNPs and haplotypes. Risks of disease recurrence/progression and prostate-specific cancer mortality were estimated using Cox proportional hazards regression. Results: We found no strong evidence of altered risk of developing prostate cancer for any of the htSNPs when they were assessed individually or in haplotypes. However, three htSNPs were significantly associated with both disease recurrence/progression and mortality. Risk of recurrence/progression alone was also associated with five additional htSNPS, and six other htSNPS showed evidence of modification by primary androgen deprivation therapy. Two additional htSNPs were significantly associated with altered risk of death from prostate cancer. Conclusions: Preliminary results suggest that common genetic variation within the megalin gene could alter both risk of recurrence/progression and prostate-specific cancer mortality. In addition, androgen deprivation therapy effectiveness may be modified by the activity of this gene. To our knowledge, this is the first study that has examined polymorphisms within the megalin gene for associations with prostate cancer risk and outcomes. C1 [Holt, Sarah K.; Stanford, Janet L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Nelson, Peter S.] Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98109 USA. [Stanford, Janet L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Karyadi, Danielle M.; Kwon, Erika M.; Ostrander, Elaine A.] Natl Human Genome Inst, Canc Genet Branch, NIH, Bethesda, MD USA. RP Ostrander, EA (reprint author), Bldg 50,Room 5351,50 S Dr, Bethesda, MD 20892 USA. EM eostrand@mail.nih.gov OI Ostrander, Elaine/0000-0001-6075-9738 FU Intramural NIH HHS; NCI NIH HHS [P50 CA097186, P50 CA097186-010001, P50-CA97186, R01 CA056678, R01 CA056678-05, R01 CA082664, R01 CA082664-01A1, R01-CA56678, R01-CA82664] NR 16 TC 22 Z9 22 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 15 PY 2008 VL 14 IS 12 BP 3823 EP 3831 DI 10.1158/1078-0432.CCR-07-4566 PG 9 WC Oncology SC Oncology GA 313ZS UT WOS:000256779100028 PM 18559602 ER PT J AU Lee, SB Hassan, M Fisher, R Chertov, O Chernomordik, V Kramer-Marek, G Gandjbakhche, A Capala, J AF Lee, Sang Bong Hassan, Moinuddin Fisher, Robert Chertov, Oleg Chernomordik, Victor Kramer-Marek, Gabriela Gandjbakhche, Amir Capala, Jacek TI Affibody molecules for in vivo characterization of HER2-positive tumors by near-infrared imaging SO CLINICAL CANCER RESEARCH LA English DT Article ID DIFFUSE OPTICAL TOMOGRAPHY; HUMAN-BREAST-CANCER; FLUORESCENT PROTEINS; INDOCYANINE GREEN; THERAPY; MAMMOGRAPHY; EXPRESSION; ANTIBODY; INHIBITORS; LIGANDS AB Purpose: HER2 overexpression has been associated with a poor prognosis and resistance to therapy in breast cancer patients. We are developing molecular probes for in vivo quantitative imaging of HER2 receptors using near-infrared (NIR) optical imaging. The goal is to provide probes that will minimally interfere with the studied system, that is, whose binding does not interfere with the binding of the therapeutic agents and whose effect on the target cells is minimal. Experimental Design: We used three different types of HER2-specific Affibody molecules [monomer ZHER(2:342), dimer (Z(HER2,477))(2), and albumin-binding domain-fused-(Z(HER2,342))(2)] as targeting agents and labeled them with Alexa Fluor dyes. Trastuzumab was also conjugated, using commercially available kits, as a standard control. The resulting conjugates were characterized in vitro by toxicity assays, Biacore affinity measurements, flow cytometry, and confocal microscopy. Semiquantitative in vivo NIR optical imaging studies were carried out using mice with s.c. xenografts of HER2-positive tumors. Results: The HER2-specific Affibody molecules were not toxic to HER2-overexpressing cells and their binding to HER2 did interfere with neither binding nor effectives of trastuzumab. The binding affinities and specificities of the Affibody-Alexa Fluor fluorescent conjugates to HER2 were unchanged or minimally affected by the modifications. Pharmacokinetics and biodistribution studies showed the albumin-binding domain-fused-(Z(HER2:342))(2)-Alexa Fluor 750 conjugate to be an optimal probe for optical imaging of HER2 in vivo. Conclusion: Our results suggest that Affibody-Alexa Fluor conjugates may be used as a specific NIR probe for the noninvasive semiquantitative imaging of HER2 expression in vivo. C1 [Lee, Sang Bong; Kramer-Marek, Gabriela; Capala, Jacek] NCI, Radiat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Hassan, Moinuddin; Chernomordik, Victor; Gandjbakhche, Amir] NICHHD, Sect Biomed Stochast Phys, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. [Fisher, Robert; Chertov, Oleg] SAIC Frederick Inc, Prot Chem Lab, NCI, Frederick, MD USA. RP Capala, J (reprint author), 10 Ctr Dr,Bldg 10,Room 1B-37A, Bethesda, MD 20892 USA. EM capalaj@mail.nih.gov FU Intramural NIH HHS [Z01 BC010727-02, Z01 BC010727-03]; NCI NIH HHS [N01-CO-12400, N01-CO-12401, N01CO12400, N02CO12401] NR 46 TC 103 Z9 104 U1 2 U2 17 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 15 PY 2008 VL 14 IS 12 BP 3840 EP 3849 DI 10.1158/1078-0432.CCR-07-4076 PG 10 WC Oncology SC Oncology GA 313ZS UT WOS:000256779100030 PM 18559604 ER PT J AU Klisovic, RB Bium, W Wei, XH Liu, SJ Liu, ZF Xie, ZL Vukosavljevic, T Kefauver, C Huynh, L Pang, JX Zwiebel, JA Devine, S Byrd, JC Grever, MR Chan, K Marcucci, G AF Klisovic, Rebecca B. Bium, William Wei, Xiaohui Liu, Shujun Liu, Zhongfa Xie, Zhiliang Vukosavljevic, Tamara Kefauver, Cheryl Huynh, LeNguyen Pang, Jiuxia Zwiebel, James A. Devine, Steven Byrd, John C. Grever, Michael R. Chan, Kenneth Marcucci, Guido TI Phase I study of GTI-2040, an antisense to ribonucleotide reductase, in combination with high-dose cytarabine in patients with acute myeloid leukemia SO CLINICAL CANCER RESEARCH LA English DT Article ID ACUTE MYELOGENOUS LEUKEMIA; COLONY-STIMULATING FACTOR; DRUG-RESISTANCE; R2 COMPONENT; CELLS; FLUDARABINE; HYDROXYUREA; CANCER; METABOLISM; BCL-2 AB Purpose: Inhibition of ribonucleotide reductase reduces the availability of the endogenous pool of deoxycytidine and may increase cytarabine (AraC) cytotoxicity. We performed a phase I dose escalation trial of AraC combined with GTI-2040, a 20-mer antisense oligonucleotide shown in preclinical studies to decrease levels of the R2 subunit of ribonucleotide reductase, to determine the maximum tolerated dose in adults with relapsed/refractory acute myeloid leukemia. Experimental Design: Twenty-three adults (ages 18-59 years) were enrolled in this dose escalation phase I trial, receiving high-dose AraC twice daily combined with infusional GTI-2040. An ELISA-based assay measured plasma and intracellular concentrations of GTI-2040. R2 protein changes were evaluated by immunoblotting in pretreatment and post-treatment bone marrow samples. Results: The maximum tolerated dose was 5 mg/kg/d GTI-2040 (days 1-6) and 3 g/m(2)/dose AraC every 12 hours for 8 doses. Neurotoxicity was dose limiting. Eight patients (35%) achieved complete remission. Mean bone marrow intracellular concentration of GTI-2040 were higher at 120 hours than at 24 hours from the start of GTI-2040 (P = 0.002), suggesting intracellular drug accumulation over time. Reductions in bone marrow levels of R2 protein (>50%) were observed at 24 and 120 hours. Higher baseline R2 protein expression (P = 0.03) and reductions after 24 hours of GTI-2040 (P = 0.04) were associated with complete remission. Conclusions: GTI-2040 and high-dose AraC were coadministered safely with successful reduction of the intended R2 target and encouraging clinical results. The clinical efficacy of this combination will be tested in an upcoming phase II study. C1 [Klisovic, Rebecca B.; Bium, William; Liu, Shujun; Vukosavljevic, Tamara; Huynh, LeNguyen; Pang, Jiuxia; Devine, Steven; Byrd, John C.; Grever, Michael R.; Chan, Kenneth; Marcucci, Guido] Ohio State Univ, Dept Med, Div Hematol & Oncol, Columbus, OH 43210 USA. [Wei, Xiaohui; Liu, Zhongfa; Xie, Zhiliang; Chan, Kenneth] Ohio State Univ, Div Pharmaceut, Coll Pharm, Columbus, OH 43210 USA. [Bium, William; Kefauver, Cheryl; Devine, Steven; Byrd, John C.; Grever, Michael R.; Marcucci, Guido] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Zwiebel, James A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Marcucci, G (reprint author), Ohio State Univ, Dept Med, Div Hematol & Oncol, A437A Starling Loving Hall,320 W 10th Ave, Columbus, OH 43210 USA. EM guido.marcucci@osumc.edu RI Klisovic, Rebecca/E-3401-2011; Liu, Zhongfa/G-8549-2013; Blum, William/E-2769-2011 FU NCI NIH HHS [R21 CA105879-02, R21 CA 105879, R21 CA105879, U01 CA 076576-10, U01 CA076576]; NCRR NIH HHS [UL1 RR025755] NR 37 TC 30 Z9 30 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 15 PY 2008 VL 14 IS 12 BP 3889 EP 3895 DI 10.1158/1078-0432.CCR-08-0109 PG 7 WC Oncology SC Oncology GA 313ZS UT WOS:000256779100036 PM 18559610 ER PT J AU Sausville, J Molinolo, AA Cheng, XF Frampton, J Takebe, N Gutkind, JS Feldman, R AF Sausville, Justin Molinolo, Alfredo A. Cheng, Xiangfei Frampton, Jon Takebe, Naoko Gutkind, J. Silvio Feldman, RicardoA. TI RCAS/SCL-TVA animal model allows targeted delivery of polyoma middle T oncogene to vascular endothelial progenitors in vivo and results in hemangioma development SO CLINICAL CANCER RESEARCH LA English DT Article ID STEM-CELL ENHANCER; HEMATOPOIETIC PROGENITORS; GENE DELIVERY; MICE; CANCER; TUMORS; GROWTH; IDENTIFICATION; TRANSFORMATION; ACTIVATION AB Purpose: To recapitulate the generation of cancer stem cells in the context of an intact animal using a retroviral vector capable of in vivo delivery of oncogenes to primitive endothelial and hematopoietic stem cells. Experimental Design: Targeting of these progenitors was achieved using transgenic mice in which the avian TVA retroviral receptor was placed under the control of the stem cell leukemia (scl/tal-1) gene promoter and SCL +19 enhancer. Results: Injection of an avian retrovirus encoding polyoma middle T (PyMT), an oncogene that transforms endothelial cells, caused rapid lethality in all SCL-TVA mice but not in control TVA(-) littermates. The infected animals exhibited hemorrhagic foci in several organs. Histopathologic analysis confirmed the presence of hemangiomas and the endothelial origin of the PyMT transformed cells. Surprisingly, the transformed endothelial cells contained readily detectable numbers of TVA(+) cells. By contrast, normal blood vessels had very few of these cells. The presence of TVA(+) cells in the lesions suggests that the cells originally infected by PyMT retained stem cell characteristics. Further analysis showed that the tumor cells exhibited activation of the phosphatidylinositol 3-kinase/Akt and S6/mammalian target of rapamycin pathways, suggesting a mechanism used by PyMT to transform endothelial progenitors in vivo. Conclusions: We conclude that this experimental system can specifically deliver oncogenes to vascular endothelial progenitors in vivo and cause a fatal neoplastic disease. This animal model should allow the generation of endothelial cancer stem cells in the natural environment of an immunocompetent animal, thereby enabling the recapitulation of genetic alterations that are responsible for the initiation and progression of human malignancies of endothelial origin. C1 [Feldman, RicardoA.] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. [Feldman, RicardoA.] Univ Maryland, Sch Med, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. [Frampton, Jon] Univ Birmingham, Inst Biomed Res, Birmingham, W Midlands, England. [Molinolo, Alfredo A.; Gutkind, J. Silvio] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA. RP Feldman, R (reprint author), Univ Maryland, Sch Med, Dept Microbiol & Immunol, 660 W Redwood St,Howard Hall 324, Baltimore, MD 21201 USA. EM rfeldman@umaryland.edu RI Gutkind, J. Silvio/A-1053-2009 NR 43 TC 6 Z9 6 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 15 PY 2008 VL 14 IS 12 BP 3948 EP 3955 DI 10.1158/1078-0432.CCR-07-5152 PG 8 WC Oncology SC Oncology GA 313ZS UT WOS:000256779100043 PM 18559617 ER PT J AU Libe, R Fratticci, A Coste, J Tissier, F Horvath, A Ragazzon, B Rene-Corail, F Groussin, L Bertagna, X Raffin-Sanson, ML Stratakis, CA Bertherat, J AF Libe, Rossella Fratticci, Amato Coste, Joel Tissier, Frederique Horvath, Anelia Ragazzon, Bruno Rene-Corail, Fernande Groussin, Lionel Bertagna, Xavier Raffin-Sanson, Marie Laure Stratakis, Constantine A. Bertherat, Jerome TI Phosphodiesterase 11A (PDE11A) and genetic predisposition to adrenocortical tumors SO CLINICAL CANCER RESEARCH LA English DT Article ID BREAST-CANCER; CODON-72 POLYMORPHISM; REGULATORY SUBUNIT; CUSHINGS-SYNDROME; CARNEY COMPLEX; PRKAR1A GENE; LARGE COHORT; MUTATIONS; PROTEIN; SUSCEPTIBILITY AB Purpose: We have reported previously nonsense inactivating mutations of the phosphodiesterase 11A (PDE11A) gene in patients with micronodular adrenocortical hyperplasia and Cushing syndrome. The aim of this study is to investigate the presence of somatic or germ-line PDE11A mutations in various types of adrenocortical tumors: ACTH-independent macronodular adrenocortical hyperplasia (AIMAH), adrenocortical adenoma (ACA), and adrenocortical cancer (ACC). Experimental Design: PDE11A was sequenced in 117 adrenocortical tumors and 192 controls subjects; immunohistochemistry for PDE11A and tumor cyclic AMP levels were studied in a subgroup of adrenocortical tumors. Results: One PDE11A inactivating mutation (R307X) was found in one ACA, 22 germ-line missense variants (18.8%) were found in adrenocortical tumors, and only 11 missense variants (5.7%) were found in controls. By comparing the common mutations, a higher frequency of mutations in adrenocortical tumors than in age/sex-matched controls were observed [16%versus 10% in ACC, 19% versus 10% in ACA, and 24% versus 9% in AIMAH; odds ratio (OR), 3.53; P = 0.05]. Somatic DNA from adrenocortical tumors with missense variants showed a wild-type allelic loss. A significant difference between ACC and controls was observed for a polymorphism in exon 6 (E421E; OR, 2.1; P = 0.03) and three associated polymorphisms located in intron 10-exon 11-intron 11 (OR, 0.5; P = 0.01). In AIMAH/ACA, cyclic AMP levels were higher than in normal adrenals and decreased PDE11A immunostaining was present in adrenocortical tumors with PDE11A variants. Conclusions: The present investigation of a large cohort of adrenocortical tumors suggests that PDE11A sequence defects predispose to a variety of lesions (beyond micronodular adrenocortical hyperplasia) and may contribute to the development of these tumors in the general population. C1 [Libe, Rossella; Fratticci, Amato; Tissier, Frederique; Ragazzon, Bruno; Rene-Corail, Fernande; Groussin, Lionel; Raffin-Sanson, Marie Laure; Bertherat, Jerome] INSERM, U567, F-75654 Paris 13, France. [Libe, Rossella; Fratticci, Amato; Tissier, Frederique; Ragazzon, Bruno; Rene-Corail, Fernande; Groussin, Lionel; Raffin-Sanson, Marie Laure; Bertherat, Jerome] CNRS, UMR8104, F-75700 Paris, France. [Libe, Rossella; Fratticci, Amato; Tissier, Frederique; Ragazzon, Bruno; Rene-Corail, Fernande; Groussin, Lionel; Raffin-Sanson, Marie Laure; Bertherat, Jerome] Univ Paris 05, F-75270 Paris 06, France. [Libe, Rossella; Groussin, Lionel; Bertagna, Xavier; Bertherat, Jerome] Hop Cochin, Assistance Publ Hop Paris, Dept Endocrinol, Reference Ctr Rare Adrenal Dis, F-75674 Paris, France. [Coste, Joel] Hop Cochin, Assistance Publ Hop Paris, Dept Biostat, F-75674 Paris, France. [Tissier, Frederique] Hop Cochin, Assistance Publ Hop Paris, Dept Pathol, F-75674 Paris, France. [Horvath, Anelia; Stratakis, Constantine A.] NICHHD, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. [Raffin-Sanson, Marie Laure] Boulogne Seine & Univ Versaille, Dept Endocrinol, Assistance Publ Hop Paris, Hop Ambroise Paris, Boulogne, France. RP Bertherat, J (reprint author), Hop Cochin, Serv Malad Endocriniennes & Metab, Pavillon Cornil,27 Rue Faubourg St Jacques, F-75014 Paris, France. EM jerome.bertherat@cch.ap-hop-paris.fr RI Ragazzon, Bruno/E-6541-2017 OI Ragazzon, Bruno/0000-0001-9476-4973 FU Intramural NIH HHS [ZIA HD000642-13]; NICHD NIH HHS [Z01 HD000642] NR 34 TC 50 Z9 51 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 15 PY 2008 VL 14 IS 12 BP 4016 EP 4024 DI 10.1158/1078-0432.CCR-08-0106 PG 9 WC Oncology SC Oncology GA 313ZS UT WOS:000256779100051 PM 18559625 ER PT J AU De Pauw, B Walsh, TJ Donnelly, JP Stevens, DA Edwards, JE Calandra, T Pappas, PG Maertens, J Lortholary, O Kauffman, CA Denning, DW Patterson, TF Maschmeyer, G Bille, J Dismukes, WE Herbrecht, R Hope, WW Kibbler, CC Kullberg, BJ Marr, KA Munoz, P Odds, FC Perfect, JR Restrepo, A Ruhnke, M Segal, BH Sobel, JD Sorrell, TC Viscoli, C Wingard, JR Zaoutis, T Bennett, JE AF De Pauw, Ben Walsh, Thomas J. Donnelly, J. Peter Stevens, David A. Edwards, John E. Calandra, Thierry Pappas, Peter G. Maertens, Johan Lortholary, Olivier Kauffman, Carol A. Denning, David W. Patterson, Thomas F. Maschmeyer, Georg Bille, Jacques Dismukes, William E. Herbrecht, Raoul Hope, William W. Kibbler, Christopher C. Kullberg, Bart Jan Marr, Kieren A. Munoz, Patricia Odds, Frank C. Perfect, John R. Restrepo, Angela Ruhnke, Markus Segal, Brahm H. Sobel, Jack D. Sorrell, Tania C. Viscoli, Claudio Wingard, John R. Zaoutis, Theoklis Bennett, John E. TI Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID LIPOSOMAL AMPHOTERICIN-B; EMPIRICAL ANTIFUNGAL THERAPY; LINKED-IMMUNOSORBENT-ASSAY; BETA-D-GLUCAN; CIRCULATING GALACTOMANNAN; PULMONARY ASPERGILLOSIS; ENZYME-IMMUNOASSAY; PERSISTENT FEVER; DIAGNOSIS; NEUTROPENIA AB Background. Invasive fungal diseases are important causes of morbidity and mortality. Clarity and uniformity in defining these infections are important factors in improving the quality of clinical studies. A standard set of definitions strengthens the consistency and reproducibility of such studies. Methods. After the introduction of the original European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group definitions, advances in diagnostic technology and the recognition of areas in need of improvement led to a revision of this document. The revision process started with a meeting of participants in 2003, to decide on the process and to draft the proposal. This was followed by several rounds of consultation until a final draft was approved in 2005. This was made available for 6 months to allow public comment, and then the manuscript was prepared and approved. Results. The revised definitions retain the original classifications of "proven," " probable," and "possible" invasive fungal disease, but the definition of "probable" has been expanded, whereas the scope of the category "possible" has been diminished. The category of proven invasive fungal disease can apply to any patient, regardless of whether the patient is immunocompromised, whereas the probable and possible categories are proposed for immunocompromised patients only. Conclusions. These revised definitions of invasive fungal disease are intended to advance clinical and epidemiological research and may serve as a useful model for defining other infections in high-risk patients. C1 [Donnelly, J. Peter] Radboud Univ Nijmegen, Med Ctr, Dept Hematol, NL-6525 GA Nijmegen, Netherlands. [De Pauw, Ben] Radboud Univ Nijmegen, Med Ctr, Dept Blood Transfus Serv & Transplant Immunol, NL-6525 GA Nijmegen, Netherlands. [Kullberg, Bart Jan] Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, NL-6525 GA Nijmegen, Netherlands. [Bennett, John E.] NIAID, Clin Mycol Sect, Clin Invest Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. [Walsh, Thomas J.] NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. [Stevens, David A.] Stanford Univ, Santa Clara Valley Med Ctr, Palo Alto, CA 94304 USA. [Edwards, John E.] Univ Calif Los Angeles, Med Ctr, Los Angeles Biomed Res Inst Harbor, Torrance, CA 90509 USA. [Pappas, Peter G.; Dismukes, William E.] Univ Alabama, Dept Med, Div Infect Dis, Birmingham, AL 35294 USA. [Kauffman, Carol A.] Univ Michigan, Sch Med,Ann Arbor Vet Affairs Healthcare Syst, Dept Internal Med, Div Infect Dis, Ann Arbor, MI USA. [Patterson, Thomas F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med & Infect Dis, San Antonio, TX 78229 USA. [Marr, Kieren A.] Oregon Hlth & Sci Univ, Div Infect Dis, Portland, OR USA. [Perfect, John R.] Duke Univ, Med Ctr, Dept Med, Div Infect Dis, Durham, NC 27710 USA. [Segal, Brahm H.] SUNY Buffalo, Dept Med, Roswell Pk Canc Inst, Buffalo, NY 14260 USA. [Sobel, Jack D.] Wayne State Univ, Sch Med, Dept Med, Detroit, MI 48201 USA. [Wingard, John R.] Univ Florida, Div Hematol & Oncol, Shands Canc Ctr, Gainesville, FL USA. [Zaoutis, Theoklis] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Calandra, Thierry] CHU Vaudois, Infect Dis Serv, Dept Internal Med, Lausanne, Switzerland. [Bille, Jacques] CHU Vaudois, Clin Microbiol Lab, Lausanne, Switzerland. [Maertens, Johan] Univ Hosp Gasthuisberg, Dept Hematol, B-3000 Louvain, Belgium. [Lortholary, Olivier] Hop Necker Enfants Malad, Serv Malad Infect & Trop, Paris, France. [Herbrecht, Raoul] Univ Hosp Strasbourg, Dept Hematol & Oncol, Strasbourg, France. [Hope, William W.] Univ Manchester, Manchester, Lancs, England. [Denning, David W.] Wythenshawe Hosp, Educ & Res Ctr, Manchester M23 9LT, Lancs, England. [Kibbler, Christopher C.] Royal Free Hosp, Dept Med Microbiol, London NW3 2QG, England. [Odds, Frank C.] Univ Aberdeen, Aberdeen Fungal Grp, Inst Med Sci, Aberdeen, Scotland. [Maschmeyer, Georg] Klinikum Ernst Von Bergmann, Abt Hamatol & Onkol, Med Klin, Potsdam, Germany. [Ruhnke, Markus] Charite Univ Med Berlin, Campus Charite Mitte, Med Klin & Poliklin 2, D-13353 Berlin, Germany. [Munoz, Patricia] Univ Madrid, Dept Clin Microbiol & Infect Dis, Hosp Gen Univ Gregorio Maranon, Madrid 3, Spain. [Restrepo, Angela] Corp Invest Biol, Carrera, Medellin, Colombia. [Sorrell, Tania C.] Univ Sydney, Westmead Millennium Inst, Ctr Infect Dis & Microbiol, Sydney, NSW 2006, Australia. [Sorrell, Tania C.] Univ Sydney, Westmead Millennium Inst, Natl Hlth & Med Res Councils Ctr Clin Res Excelle, Sydney, NSW 2006, Australia. [Viscoli, Claudio] Univ Genoa, Genoa, Italy. [Viscoli, Claudio] San Martino Univ Hosp, Genoa, Italy. RP Donnelly, JP (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Haematol, Geert Grootepl Zuid 8, NL-6525 GA Nijmegen, Netherlands. EM p.donnelly@usa.net RI Herbrecht, Raoul/D-3471-2013; Kullberg, Bart Jan/C-8520-2013; Calandra, Thierry/D-9017-2015 OI Calandra, Thierry/0000-0003-3051-1285 FU Intramural NIH HHS [Z01 AI000654-16] NR 27 TC 1801 Z9 1822 U1 14 U2 93 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUN 15 PY 2008 VL 46 IS 12 BP 1813 EP 1821 DI 10.1086/588660 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 303MP UT WOS:000256044900007 PM 18462102 ER PT J AU Bowman, NM Kawai, V Levy, MZ del Carpio, JGC Cabrera, L Delgado, F Malaga, F Benzaquen, EC Pinedo, VV Steurer, F Seitz, AE Gilman, RH Bern, C AF Bowman, Natalie M. Kawai, Vivian Levy, Michael Z. del Carpio, Juan Geny Cornejo Cabrera, Lilia Delgado, F. Malaga, Francisco Benzaquen, Eleazar Cordova Pinedo, Viviana V. Steurer, Francis Seitz, Amy E. Gilman, Robert H. Bern, Caryn TI Chagas disease transmission in periurban communities of Arequipa, Peru SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID TRYPANOSOMA-CRUZI INFECTION; TRIATOMA-INFESTANS; RISK-FACTORS; ARGENTINA; CHILDREN; SEROPREVALENCE; BENZNIDAZOLE; AREA AB Background. Chagas disease, caused by Trypanosoma cruzi infection, is an urban problem in Arequipa, Peru, and the epidemiology of Chagas disease is likely to be quite different in this area, compared with in rural zones. Methods. We conducted a serosurvey of 1615 children <18 years old in periurban districts that included hillside shantytowns and slightly more affluent low-lying communities. In addition, 639 adult residents of 1 shantytown were surveyed to provide data across the age spectrum for this community. Results. Of 1615 children, 75 (4.7%) were infected with Trypanosoma cruzi. Infection risk increased by 12% per year of age, and children living in hillside shantytowns were 2.5 times as likely to be infected as were those living in lower-lying communities. However, age-prevalence data from 1 shantytown demonstrated that adults were no more likely to be seropositive than were teenagers; the results of maximum likelihood modeling suggest that T. cruzi transmission began in this community <20 years ago. Conclusions. The problem of Chagas disease in periurban settings, such as those around Arequipa, must be addressed to achieve elimination of vector-borne T. cruzi transmission. Identification of infected children, vector-control efforts, and education to avoid modifiable risk factors are necessary to decrease the burden of Chagas disease. C1 [Levy, Michael Z.; Steurer, Francis; Seitz, Amy E.; Bern, Caryn] CDC, Div Parasit Dis F22, NCID, Atlanta, GA 30341 USA. [Bowman, Natalie M.; Kawai, Vivian; Cabrera, Lilia; Pinedo, Viviana V.; Gilman, Robert H.] Salud, Asociac Benef Proyectos Informat, Lima, Peru. [Benzaquen, Eleazar Cordova] Univ Nacl San Agustin, Arequipa, Peru. [del Carpio, Juan Geny Cornejo; Delgado, F.; Malaga, Francisco] Arequipa Minist Hlth, Arequipa, Peru. [Levy, Michael Z.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Gilman, Robert H.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. RP Bern, C (reprint author), CDC, Div Parasit Dis F22, NCID, 4770 Buford Hwy NE, Atlanta, GA 30341 USA. EM Cbern@cdc.gov FU Howard Hughes Medical Institute; NIAID NIH HHS [5T35-AI-007646-03, U19 AI033061, U19-AI-33061] NR 30 TC 28 Z9 29 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUN 15 PY 2008 VL 46 IS 12 BP 1822 EP 1828 DI 10.1086/588299 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 303MP UT WOS:000256044900008 PM 18462104 ER PT J AU Anderson, MJ Pham, VN Vogel, AM Weinstein, BM Roman, BL AF Anderson, Matthew J. Pham, Van N. Vogel, Andreas M. Weinstein, Brant M. Roman, Beth L. TI Loss of unc45a precipitates arteriovenous shunting in the aortic arches SO DEVELOPMENTAL BIOLOGY LA English DT Article DE aortic arches; pharyngeal arches; unc45a; zebrafish; arteriovenous malformation; kurzschluss ID CAENORHABDITIS-ELEGANS; VASCULAR DEVELOPMENT; DIGEORGE-SYNDROME; MICE DEFICIENT; NOTCH PATHWAY; DANIO-RERIO; ZEBRAFISH; UNC-45; MYOSIN; ARTERIAL AB Aortic arch malformations are common congenital disorders that are frequently of unknown etiology. To gain insight into the factors that guide branchial aortic arch development, we examined the process by which these vessels assemble in wild type zebrafish embryos and in kurzschluss(tr12) (kus (tr12)) mutants. In wild type embryos, each branchial aortic arch first appears as an island of angioblasts in the lateral pharyngeal mesoderm, then elaborates by angiogenesis to connect to the lateral dorsal aorta and ventral aorta. In kus(tr12) mutants, angioblast formation and initial sprouting are normal, but aortic arches 5 and 6 fail to form a lumenized connection to the lateral dorsal aorta. Blood enters these blind-ending vessels from the ventral aorta, distending the arteries and precipitating fusion with an adjacent vein. This arteriovenous malformation (AVM), which shunts nearly all blood directly back to the heart, is not exclusively genetically programmed, as its formation correlates with blood flow and aortic arch enlargement. By positional cloning, we have identified a nonsense mutation in unc45a in kus (tr12) mutants. Our results are the first to ascribe a role for Unc45a, a putative myosin chaperone, in vertebrate development, and identify a novel mechanism by which an AVM can form. (C) 2008 Elsevier Inc. All rights reserved. C1 [Roman, Beth L.] Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15260 USA. [Anderson, Matthew J.; Roman, Beth L.] Georgetown Univ, Med Ctr, Tumor Biol Training Program, Washington, DC 20057 USA. [Pham, Van N.; Vogel, Andreas M.; Weinstein, Brant M.] NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. [Roman, Beth L.] Georgetown Univ, Med Ctr, Dept Biochem Mol & Cellular Biol, Washington, DC 20057 USA. RP Roman, BL (reprint author), Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15260 USA. EM romanb@pitt.edu OI Roman, Beth/0000-0002-1250-1705 FU Intramural NIH HHS NR 53 TC 26 Z9 26 U1 2 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 15 PY 2008 VL 318 IS 2 BP 258 EP 267 DI 10.1016/j.ydbio.2008.03.022 PG 10 WC Developmental Biology SC Developmental Biology GA 312EI UT WOS:000256651500005 PM 18462713 ER PT J AU Aamar, E Dawid, IB AF Aamar, Emil Dawid, Igor B. TI Protocadherin-18a has a role in cell adhesion, behavior and migration in zebrafish development SO DEVELOPMENTAL BIOLOGY LA English DT Article DE adhesion; migration; protocadherin; gastrulation; hatching gland; cell dissociation ID CENTRAL-NERVOUS-SYSTEM; CADHERIN SUPERFAMILY; PARAXIAL PROTOCADHERIN; MOUSE-BRAIN; GASTRULATION MOVEMENTS; CONVERGENT EXTENSION; DELTA-PROTOCADHERINS; GENOMIC STRUCTURE; STRUCTURAL BASIS; EXPRESSION AB Protocadherin-18a (Pcdh18a) belongs to the 62-protocadherins, which constitute the largest subgroup within the cadherin superfamily. Here we present isolation of a full-length zebrafish cDNA that encodes a protein highly similar to human and mouse Pcdh18. Zebrafish pcdh18a is expressed in a complex and dynamic pattern in the nervous system from gastrula stages onward, with lesser expression in mesodermal derivatives. Pcdh18a-eGFP fusion protein is expressed in a punctate manner on the membranes between cells. Overexpression of pcdh18a in embryos caused cyclopia, mislocalization of hatching gland tissue, and duplication or splitting of the neural tube. Most neural markers tested were expressed in an approximately correct A-P pattern. By cell transplantation we showed that overexpression of pcdh18a causes diminished cell migration and reduced cell protrusions, resulting in a tendency of cells to stay more firmly aggregated, probably due to increased cell adhesion. In contrast, knockdown of pcdh18a by a morpholino oligonucleotide caused defects in epiboly, and led to reduced cell adhesion as shown by cell dissociation, sorting and transplantation experiments. These results suggest a role for Pcdh18a in cell adhesion, migration and behavior but not cell specification during gastrula and segmentation stages of development. (C) 2008 Published by Elsevier Inc. C1 [Aamar, Emil; Dawid, Igor B.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Mol Genet Lab, NIH, Bethesda, MD USA. RP Dawid, IB (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Mol Genet Lab, NIH, Bldg 6B,Room 413, Bethesda, MD USA. EM idawid@nih.gov FU Intramural NIH HHS NR 78 TC 29 Z9 30 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 15 PY 2008 VL 318 IS 2 BP 335 EP 346 DI 10.1016/j.ydbio.2008.03.040 PG 12 WC Developmental Biology SC Developmental Biology GA 312EI UT WOS:000256651500012 PM 18468594 ER PT J AU Suen, DF Norris, KL Youle, RJ AF Suen, Der-Fen Norris, Kristi L. Youle, Richard J. TI Mitochondrial dynamics and apoptosis SO GENES & DEVELOPMENT LA English DT Review DE Bax; Bcl-2; Drp1; Mfn2; OPA1; fission ID PROGRAMMED CELL-DEATH; CYTOCHROME-C RELEASE; OUTER-MEMBRANE PERMEABILIZATION; DEPENDENT PROTEIN-KINASE; MARIE-TOOTH-DISEASE; FISSION MACHINERY; MAMMALIAN-CELLS; PROTEOLYTIC CLEAVAGE; LOCALIZED INHIBITOR; MOLECULAR MACHINERY AB In healthy cells, mitochondria continually divide and fuse to form a dynamic interconnecting network. The molecular machinery that mediates this organelle fission and fusion is necessary to maintain mitochondrial integrity, perhaps by facilitating DNA or protein quality control. This network disintegrates during apoptosis at the time of cytochrome c release and prior to caspase activation, yielding more numerous and smaller mitochondria. Recent work shows that proteins involved in mitochondrial fission and fusion also actively participate in apoptosis induction. This review will cover the recent advances and presents competing models on how the mitochondrial fission and fusion machinery may intersect apoptosis pathways. C1 [Suen, Der-Fen; Norris, Kristi L.; Youle, Richard J.] NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Youle, RJ (reprint author), NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. EM youler@ninds.nih.gov NR 122 TC 517 Z9 539 U1 11 U2 90 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JUN 15 PY 2008 VL 22 IS 12 BP 1577 EP 1590 DI 10.1101/gad.1658508 PG 14 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 314GG UT WOS:000256797300004 PM 18559474 ER PT J AU Miller, HI AF Miller, Henry I. TI No member of Congress left behind SO GENETIC ENGINEERING & BIOTECHNOLOGY NEWS LA English DT Editorial Material C1 [Miller, Henry I.] Stanford Univ, Hoover Inst, Stanford, CA 94305 USA. [Miller, Henry I.] NIH, Bethesda, MD 20892 USA. [Miller, Henry I.] US FDA, Rockville, MD 20857 USA. RP Miller, HI (reprint author), Stanford Univ, Hoover Inst, Stanford, CA 94305 USA. EM miller@boover.stanford.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1935-472X EI 1937-8661 J9 GENET ENG BIOTECHN N JI Genet. Eng. Biotechnol. News PD JUN 15 PY 2008 VL 28 IS 12 BP 6 EP 7 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 315JB UT WOS:000256873600003 ER PT J AU Guzman, VB Yambartsev, A Goncalves-Primo, A Silva, IDCG Carvalho, CRN Ribalta, JCL Goulart, LR Shulzhenko, N Gerbase-DeLima, M Morgun, A AF Guzman, Valeska B. Yambartsev, Anatoly Goncalves-Primo, Amador Silva, Ismael D. C. G. Carvalho, Carmen R. N. Ribalta, Julisa C. L. Goulart, Luiz Ricardo Shulzhenko, Natalia Gerbase-DeLima, Maria Morgun, Andrey TI New approach reveals CD28 and IFNG gene interaction in the susceptibility to cervical cancer SO HUMAN MOLECULAR GENETICS LA English DT Article ID HUMAN-PAPILLOMAVIRUS INFECTION; INTRAEPITHELIAL NEOPLASIA; GAMMA PRODUCTION; UTERINE CERVIX; HUMAN-DISEASES; CLASS-I; POLYMORPHISM; RISK; WOMEN; CARCINOMA AB Cervical cancer is a complex disease with multiple environmental and genetic determinants. In this study, we sought an association between polymorphisms in immune response genes and cervical cancer using both single-locus and multi-locus analysis approaches. A total of 14 single nucleotide polymorphisms (SNPs) distributed in CD28 , CTLA4 , ICOS , PDCD1 , FAS , TNFA , IL6 , IFNG , TGFB1 and IL10 genes were determined in patients and healthy individuals from three independent case/control sets. The first two sets comprised White individuals (one group with 82 cases and 85 controls, the other with 83 cases and 85 controls) and the third was constituted by non-white individuals (64 cases and 75 controls). The multi-locus analysis revealed higher frequencies in cancer patients of three three-genotype combinations [CD28 +17(TT)/ IFNG +874(AA)/ TNFA -308(GG), CD28 +17(TT)/ IFN+ 847(AA)/ PDCD1 +7785(CT), and CD28 +17(TT)/ IFNG +874(AA)/ ICOS +1564(TT)] (P < 0.01, Monte Carlo simulation). We hypothesized that this two-genotype [CD28 (TT) and IFNG (AA)] combination could have a major contribution to the observed association. To address this question, we analyzed the frequency of the CD28 (TT), IFNG (AA) genotype combination in the three groups combined, and observed its increase in patients (P = 0.0011 by Fisher's exact test). The contribution of a third polymorphism did not reach statistical significance (P = 0.1). Further analysis suggested that gene-gene interaction between CD28 and IFNG might contribute to susceptibility to cervical cancer. Our results showed an epistatic effect between CD28 and IFNG genes in susceptibility to cervical cancer, a finding that might be relevant for a better understanding of the disease pathogenesis. In addition, the novel analytical approach herein proposed might be useful for increasing the statistical power of future genome-wide multi-locus studies. C1 [Shulzhenko, Natalia; Morgun, Andrey] NIAID, TCMTS Ghost Lab, LCMI, NIH, Bethesda, MD 20892 USA. [Guzman, Valeska B.; Goncalves-Primo, Amador; Shulzhenko, Natalia; Morgun, Andrey] Univ Fed Sao Paulo, Div Immunogenet, Dept Pediat, Sao Paulo, Brazil. [Yambartsev, Anatoly] Univ Sao Paulo, Math & Stat Inst, BR-05508 Sao Paulo, Brazil. [Silva, Ismael D. C. G.; Carvalho, Carmen R. N.; Ribalta, Julisa C. L.] Univ Fed Sao Paulo, Dept Gynecol, Sao Paulo, Brazil. [Goulart, Luiz Ricardo] Univ Fed Uberlandia, Dept Genet, Uberlandia, MG, Brazil. [Shulzhenko, Natalia; Morgun, Andrey] NIAID, TCMTS Ghost Lab, LCMI, NIH, Bethesda, MD 20892 USA. RP Morgun, A (reprint author), NIAID, TCMTS Ghost Lab, LCMI, NIH, 9000 Rockville Pike,Bldg 4,Room 111, Bethesda, MD 20892 USA. EM anemorgun@hotmail.com RI Ribalta, Julisa/F-4287-2012; Gerbase-DeLima, Maria/K-2515-2015; Goulart, Luiz/G-7357-2012 OI Goulart, Luiz/0000-0002-1803-4861 FU Intramural NIH HHS [Z01 AI000581-19] NR 57 TC 22 Z9 24 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUN 15 PY 2008 VL 17 IS 12 BP 1838 EP 1844 DI 10.1093/hmg/ddn077 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 306VJ UT WOS:000256275600015 PM 18337305 ER PT J AU Rosenberg, HF Domachowske, JB AF Rosenberg, Helene F. Domachowske, Joseph B. TI Pneumonia virus of mice: severe respiratory infection in a natural host SO IMMUNOLOGY LETTERS LA English DT Review DE inflammation; granulocyte; chemokine; lymphocyte; epithelial ID TOLL-LIKE RECEPTOR-4; SYNCYTIAL-VIRUS; PNEUMOVIRUS INFECTION; PARAMYXOVIRUS INFECTION; INFLAMMATORY RESPONSES; IN-VIVO; GENE; SEQUENCE; TRACT; PVM AB Pneumonia virus of mice (PVM; family Paramyxoviridae, genus Pneumovirus) is a natural mouse pathogen that is closely related to human and bovine respiratory syncytial viruses. Among the prominent features of this infection, robust replication of PVM takes place in bronchial epithelial cells in response to a minimal virus inoculum. Virus replication in situ results in local production of proinflammatory cytokines (MIP-1 alpha, MIP-2, MCP-1 and IFN gamma) and granulocyte recruitment to the lung. If left unchecked, PVM infection and the ensuing inflammatory response ultimately lead to pulmonary edema, respiratory compromise and death. In this review, we consider the recent studies using the PVM model that have provided important insights into the role of the inflammatory response in the pathogenesis of severe respiratory virus infection. We also highlight several works that have elucidated acquired immune responses to this pathogen, including T cell responses and the development of humoral immunity. Finally, we consider several immunomodulatory strategies that have been used successfully to reduce morbidity and mortality when administered to PVM-infected, symptomatic mice, and thus hold promise as realistic therapeutic strategies for severe respiratory virus infections in human subjects. (c) 2008 Elsevier B.V. All rights reserved. C1 [Rosenberg, Helene F.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. [Domachowske, Joseph B.] SUNY Upstate Med Univ, Dept Pediat, Syracuse, NY 13210 USA. RP Rosenberg, HF (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Room 11C215,9000 Rockville Pike, Bethesda, MD 20892 USA. EM hrosenberg@niaid.nih.gov FU Intramural NIH HHS [Z01 AI000943-04, Z99 AI999999, Z01 AI000941-04, Z01 AI000942-04] NR 51 TC 53 Z9 53 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2478 J9 IMMUNOL LETT JI Immunol. Lett. PD JUN 15 PY 2008 VL 118 IS 1 BP 6 EP 12 DI 10.1016/j.imlet.2008.03.013 PG 7 WC Immunology SC Immunology GA 317DU UT WOS:000257000700002 PM 18471897 ER PT J AU Halwani, R Boyer, JD Yassine-Diab, B Haddad, EK Robinson, TM Kumar, S Parkinson, R Wu, L Sidbu, MK Phillipson-Weiner, R Pavlakis, GN Felber, BK Lewis, MG Shen, A Siliciano, RF Weiner, DB Sekaly, RP AF Halwani, Rabih Boyer, Jean D. Yassine-Diab, Bader Haddad, Elias K. Robinson, Tara M. Kumar, Sanjeev Parkinson, Rose Wu, Ling Sidbu, Maninder K. Phillipson-Weiner, Rebecca Pavlakis, George N. Felber, Barbara K. Lewis, Mark G. Shen, Anding Siliciano, Robert F. Weiner, David B. Sekaly, Rafick-Pierre TI Therapeutic vaccination with simian immunodeficiency virus (SIV)-DNA+IL-12 or IL-15 induces distinct CD8 memory subsets in SIV-infected macaques SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL RESPONSES; PLASMID DNA VACCINE; STRUCTURED TREATMENT INTERRUPTIONS; ACTIVE ANTIRETROVIRAL THERAPY; IMMUNE-RESPONSES; IN-VIVO; RHESUS MACAQUES; HOMEOSTATIC PROLIFERATION; DISEASE PROGRESSION; INTERLEUKIN-12 C1 [Halwani, Rabih; Yassine-Diab, Bader; Haddad, Elias K.; Sekaly, Rafick-Pierre] Univ Montreal, Immunol Lab, Ctr Rech, Ctr Hosp Univ Montreal St Luc, Montreal, PQ, Canada. [Halwani, Rabih; Yassine-Diab, Bader; Haddad, Elias K.; Sekaly, Rafick-Pierre] Univ Montreal, Immunol Lab, Dept Microbiol & Immunol, Montreal, PQ, Canada. [Halwani, Rabih; Yassine-Diab, Bader; Haddad, Elias K.; Sekaly, Rafick-Pierre] Univ Montreal, INSERM, Ctr Rech, U743,Ctr Hosp Univ Montreal, Montreal, PQ, Canada. [Sekaly, Rafick-Pierre] McGill Univ, Dept Microbiol & Immunol, Montreal, PQ, Canada. [Boyer, Jean D.; Robinson, Tara M.; Kumar, Sanjeev; Parkinson, Rose; Wu, Ling; Phillipson-Weiner, Rebecca; Weiner, David B.] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Wyeth Lederle, Vaccine Discovery, Pearl River, NY 10965 USA. [Pavlakis, George N.; Felber, Barbara K.] Natl Canc Inst, Human Retrovirus Pathogenesis Sect, Ctr Canc Res, Frederick, MD 21702 USA. [Lewis, Mark G.] BIOQUAL, Rockville, MD 20850 USA. [Shen, Anding; Siliciano, Robert F.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21218 USA. RP Sekaly, RP (reprint author), Ctr Hosp Univ Montreal, Hop St Luc, Ctr Rech, 264 Rene Levesque Est,Bur 1317, Montreal, PQ H2X 1P1, Canada. EM rafick-pierre.sekaly@umontreal.ca RI Weiner, David/H-8579-2014 NR 79 TC 47 Z9 48 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 JUN 15 PY 2008 VL 180 IS 12 BP 7969 EP 7979 PG 11 WC Immunology SC Immunology GA 322VY UT WOS:000257404600021 PM 18523260 ER PT J AU Araki, Y Fann, M Wersto, R Weng, NP AF Araki, Yasuto Fann, Monchou Wersto, Robert Weng, Nan-ping TI Histone acetylation facilitates rapid and robust memory CD8 T cell response through differential expression of effector molecules (eomesodermin and its targets: perforin and granzyme B) SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IFN-GAMMA LOCI; GENE-EXPRESSION; DNA METHYLATION; CHROMATIN; TRANSCRIPTION; BET AB To understand the mechanism regulating the effector function of memory CD8 T cells, we examined expression and chromatin state of a key transcription factor (eomesodermin, EOMES) and two of its targets: perforin (PRF1) and granzyme B (GZMB). Accessible chromatin associated histone 3 lysine 9 acetylation (H3K9Ac) was found significantly higher at the proximal promoter and the first exon region of all three genes in memory CD8 T cells than in naive CD8 T cells. Correspondingly, EOMES and PRF1 were constitutively higher expressed in memory CD8 T cells than in naive CD8 T cells at resting and activated states. In contrast, higher expression of GZMB was induced in memory CD8 T cells than in naive CD8 T cells only after activation. Regardless of their constitutive or inducible expression, decreased H3K9Ac levels after treatment with a histone acetyltransferase inhibitor (Curcumin) led to decreased expression of all three genes in activated memory CD8 T cells. These findings suggest that H3K9Ac associated accessible chromatin state serves as a corner stone for the differentially high expression of these effector genes in memory CD8 T cells. Thus, epigenetic changes mediated via histone acetylation may provide a chromatin "memory" for the rapid and robust transcriptional response of memory CD8 T cells. C1 [Araki, Yasuto; Fann, Monchou; Weng, Nan-ping] NIA, Immunol Lab, NIH, Baltimore, MD 21224 USA. [Wersto, Robert] NIA, Flow Cytometry Unit, NIH, Baltimore, MD 21224 USA. RP Weng, NP (reprint author), 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM wengn@mail.nih.gov FU Intramural NIH HHS [Z01 AG000757-10] NR 26 TC 78 Z9 81 U1 1 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 2008 VL 180 IS 12 BP 8102 EP 8108 PG 7 WC Immunology SC Immunology GA 322VY UT WOS:000257404600035 PM 18523274 ER PT J AU Ishmael, FT Fang, X Galdiero, MR Atasoy, U Rigby, WFC Gorospe, M Cheadle, C Stellato, C AF Ishmael, Faoud T. Fang, Xi Galdiero, Maria Rosaria Atasoy, Ulus Rigby, William F. C. Gorospe, Myriam Cheadle, Chris Stellato, Cristiana TI Role of the RNA-binding protein tristetraprolin in glucocorticoid-mediated gene regulation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ZINC-FINGER PROTEINS; COLONY-STIMULATING FACTOR; EARLY GROWTH RESPONSE-1; FACTOR MESSENGER-RNA; AU-RICH ELEMENTS; NF-KAPPA-B; EPITHELIAL-CELLS; HNRNP PROTEINS; 3'-UNTRANSLATED REGION; ACTIVATED MACROPHAGES AB Glucocorticoids (GCs) are the mainstay of anti-inflammatory therapy. Modulation of posttranscriptional regulation (PTR) of gene expression by GCs is a relevant yet poorly characterized mechanism of their action. The RNA-binding protein tristetraprolin (TTP) plays a central role in PTR by binding to AU-rich elements in the 3'-untranslated region of proinflammatory transcripts and accelerating their decay. We found that GCs induce TTP expression in primary and immortalized human bronchial epithelial cells. To investigate the importance of PTR and the role of TTP in GC function, we compared the effect of GC treatment on genome-wide gene expression using mouse embryonic fibroblasts (MEFs) obtained from wild-type and TTP-/- mice. We confirmed that GCs induce TTP in MEFs and observed in TTP-/- MEFs a striking loss of up to 85 % of GC-mediated gene expression. Gene regulation by TNF-alpha was similarly affected, as was the antagonistic effect of GC on TNF-alpha-induced response. Inflammatory genes, including cytokines and chemokines, were among the genes whose sensitivity to GCs was affected by lack of TTP. Silencing of TTP in WT MEFs by small interfering RNA confirmed loss of GC response in selected targets. Immunoprecipitation of ribonucleoprotein complexes revealed binding of TTP to several validated transcripts. Changes in the rate of transcript degradation studied by actinomycin D were documented for only a subset of transcripts bound to TTP. These results reveal a strong and previously unrecognized contribution of PTR to the anti-inflammatory action of GCs and point at TTP as a key factor mediating this process through a complex mechanism of action. C1 [Ishmael, Faoud T.; Fang, Xi; Galdiero, Maria Rosaria; Cheadle, Chris; Stellato, Cristiana] Johns Hopkins Univ, Div Clin Immunol & Allergy, Johns Hopkins Asthma & Allergy Ctr, Baltimore, MD 21224 USA. [Rigby, William F. C.] Dartmouth Med Sch, Lebanon, NH 03755 USA. [Atasoy, Ulus] Univ Missouri, Dept Surg, Columbia, MO 65212 USA. [Atasoy, Ulus] Univ Missouri, Dept Mol Microbiol & Immunol, Columbia, MO 65212 USA. [Gorospe, Myriam] NIA, Cellular & Mol Biol Lab, NIH, Baltimore, MD 21224 USA. RP Stellato, C (reprint author), Johns Hopkins Univ, Div Clin Immunol & Allergy, Johns Hopkins Asthma & Allergy Ctr, 5501 Hopkins Bayview Circle,Room 1A-12A, Baltimore, MD 21224 USA. EM stellato@jhmi.edu RI Stellato, Cristiana/P-3001-2015 OI Stellato, Cristiana/0000-0002-1294-8355 FU Intramural NIH HHS [Z01 AG000511-10]; NIAID NIH HHS [R01 AI 060990-01A1, R01 AI060990, R01 AI060990-04] NR 68 TC 49 Z9 50 U1 0 U2 8 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 2008 VL 180 IS 12 BP 8342 EP 8353 PG 12 WC Immunology SC Immunology GA 322VY UT WOS:000257404600062 PM 18523301 ER PT J AU Dang, Q Goeken, RM Brown, CR Plishka, RJ Buckler-White, A Byrum, R Foley, BT Hirsch, VM AF Dang, Que Goeken, Robert M. Brown, Charles R. Plishka, Ronald J. Buckler-White, Alicia Byrum, Russell Foley, Brian T. Hirsch, Vanessa M. TI Adaptive evolution of simian immunodeficiency viruses isolated from 2 conventional-progressor macaques with encephalitis SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID IN-VITRO; BRAIN; REPLICATION; INFECTION; CELLS; VIVO AB Simian immunodeficiency virus-infected macaques may develop encephalitis, a feature more commonly observed in macaques with rapid progressive disease than in those with conventional disease. In this report, an analysis of 2 conventional progressors with encephalitis is described. Phylogenetic analyses of viruses isolated from the cerebrospinal fluid and plasma of both macaques demonstrated compartmentalization. Furthermore, these viruses appear to have undergone adaptive evolution to preferentially replicate in their respective cell targets of monocyte-derived macrophages and peripheral blood mononuclear cells. A statistically significant loss of potential N-linked glycosylation sites in glycoprotein 160 was observed in viruses isolated from the central nervous system. C1 [Dang, Que; Goeken, Robert M.; Brown, Charles R.; Plishka, Ronald J.; Buckler-White, Alicia; Hirsch, Vanessa M.] NIAID, Mol Microbiol Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. [Byrum, Russell] Bioqual Inc, Rockville, MD USA. [Foley, Brian T.] Los Alamos Natl Lab, Grp T10, Los Alamos, NM USA. RP Hirsch, VM (reprint author), NIAID, Mol Microbiol Lab, Natl Inst Hlth, Bldg 4,Rm B1-41,4 Ctr Dr, Bethesda, MD 20892 USA. EM vhirsch@niaid.nih.gov OI Foley, Brian/0000-0002-1086-0296 FU Intramural NIH HHS [Z01 AI000370-25, Z99 AI999999] NR 20 TC 6 Z9 6 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 JUN 15 PY 2008 VL 197 IS 12 BP 1695 EP 1700 DI 10.1086/588671 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 307JN UT WOS:000256315300009 PM 18454679 ER PT J AU Chio, A Traynor, BJ Swingler, R Mitchell, D Hardiman, O Mora, G Beghi, E Logroscino, G AF Chio, Adriano Traynor, Bryan J. Swingler, Robert Mitchell, Douglas Hardiman, Orla Mora, Gabriele Beghi, Ettore Logroscino, Giancarlo CA EURALS Consortium TI Amyotrophic lateral sclerosis and soccer: A different epidemiological approach strengthen the previous findings SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Letter ID PLAYERS C1 [Chio, Adriano] Univ Turin, Dept Neurosci, I-10126 Turin, Italy. [Traynor, Bryan J.] NIMH, Sect Dev Genet Epidemiol, NIH, Bethesda, MD USA. [Swingler, Robert] Univ Dundee, Ninewells Hosp & Med Sch, Dept Neurol, Dundee DD1 9SY, Scotland. [Mitchell, Douglas] Royal Preston Hosp, Preston MND Care & Res Ctr, Preston, Lancs, England. [Hardiman, Orla] Royal Coll Surgeons Ireland, Dublin 2, Ireland. [Hardiman, Orla] Beaumont Hosp, Dept Neurol, Dublin 9, Ireland. [Mora, Gabriele] Salvatore Maugeri Fdn, Dept Neurorehabil, Inst Sci, Pavia, Italy. [Beghi, Ettore] Ist Ric Farmacol Mario Negri, I-20157 Milan, Italy. [Logroscino, Giancarlo] Harvard Univ, Dept Epidemiol HSPH, Boston, MA 02115 USA. RP Chio, A (reprint author), Univ Turin, Dept Neurosci, Via Cherasco 15, I-10126 Turin, Italy. EM achio@usa.net RI Traynor, Bryan/G-5690-2010; LOGROSCINO, GIANCARLO/K-5148-2016; OI LOGROSCINO, GIANCARLO/0000-0003-0423-3242; Chio, Adriano/0000-0001-9579-5341; Hardiman, Orla/0000-0003-2610-1291 NR 5 TC 8 Z9 8 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD JUN 15 PY 2008 VL 269 IS 1-2 BP 187 EP 188 DI 10.1016/j.jns.2007.10.005 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 305WM UT WOS:000256208500032 PM 17996254 ER PT J AU Lemer, A Bagic, A AF Lemer, Alicja Bagic, Anto TI Olfactory pathogenesis of idiopathic Parkinson disease revisited SO MOVEMENT DISORDERS LA English DT Article DE Parkinson disease; olfactory pathogenesis; prions; synucleins ID ALPHA-SYNUCLEIN FIBRILLOGENESIS; NEURODEGENERATIVE DISEASES; AFFERENT-PROJECTIONS; SUBSTANTIA-NIGRA; LOCUS-COERULEUS; DORSAL RAPHE; PARAHIPPOCAMPAL CORTICES; ALZHEIMERS-DISEASE; FUTURE-RESEARCH; NERVOUS-SYSTEM AB Idiopathic Parkinson disease (PD) is traditionally considered a movement disorder with hallmark lesions located in the substantia nigra pars compacta (SNpc). However, recent histopathological studies of some PD cases suggest the possibility of a multisystem disorder which progresses in a predictable sequence as described in Braak's staging criteria. The disease process starts in the dorsal motor nucleus of the vagus (dmX) and anterior olfactory nucleus and bulb, and from there, spreads through the brain-stem nuclei to ultimately reach the SNpc, which then presents as symptomatic PD. In this article, we would like to revisit the olfactory pathogenesis of PD based on Braak's staging system and review anatomical pathways supporting such a possibility. We also suggest some biomarkers for early stages of PD. Additionally, we present and discuss the possibility that a prion-like process underlies the neurodegenerative changes in PD. (C) 2008 Movement Disorder Society. C1 [Lemer, Alicja] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. [Bagic, Anto] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA USA. RP Lemer, A (reprint author), NINDS, Human Motor Control Sect, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM lemera@mail.nih.gov NR 71 TC 12 Z9 13 U1 0 U2 2 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 JUN 15 PY 2008 VL 23 IS 8 BP 1076 EP 1084 DI 10.1002/mds.22066 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 322PR UT WOS:000257388300002 PM 18442121 ER PT J AU Galpern, WR AF Galpern, Wendy R. TI Inhibitors of tau phosphorylation SO MOVEMENT DISORDERS LA English DT Meeting Abstract CT 6th International Medical Workshop of the Progressive-Supranuclear-Palsy-Association CY 2007 CL London, ENGLAND SP Progressive Supranuclear Palsy Assoc C1 [Galpern, Wendy R.] Natl Inst Neurol Disorders & Stroke, Natl Inst Hlth, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD JUN 15 PY 2008 VL 23 IS 8 BP 1197 EP 1197 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 322PR UT WOS:000257388300029 ER PT J AU Schepers, RJF Mahoney, JL Shippenberg, TS AF Schepers, Raf Jan-Filip Mahoney, Janet Lynn Shippenberg, Toni Shaun TI Inflammation-induced changes in rostral ventromedial medulla mu and kappa opioid receptor mediated antinociception SO PAIN LA English DT Article DE mu opioid receptor; kappa opioid receptor; descending modulation; inflammation; complete Freund's adjuvant; rostral ventromedial medulla ID MICRO-INJECTION TECHNIQUE; PAIN MODULATING NEURONS; NUCLEUS RAPHE MAGNUS; DORSAL-ROOT GANGLIA; RAT SPINAL-CORD; PERIAQUEDUCTAL GRAY; BRAIN-STEM; PERIPHERAL INFLAMMATION; DESCENDING MODULATION; SUPRASPINAL MU AB Acute microinjection of mu-, delta-, or kappa-opioid receptor (MOPr, DOPr, KOPr) agonists into the rostral ventromedial medulla (RVM) produces antinociception. Thermal antinociception produced by MOPr and DOPr agonists is potentiated during inflammation [Hurley RW, Hammond DL. The analgesic effects of supraspinal mu and delta opioid receptor agonists are potentiated during persistent inflammation. J Neurosci 2000;20:1249-59]. Whether this potentiation extends to other stimulus modalities or to KOPr agonists is unknown. To examine these issues, rats received a unilateral intraplantar injection of complete Freund's adjuvant (CFA). Antinociception produced by RVM infusion of the KOPr agonist, U69593, and the MOPr agonist, DAMGO, was tested 4 h-2 weeks thereafter. Thermal paw withdrawal latencies (PWLs) were assessed using the Hargreaves method. Mechanical thresholds were determined with the Von Frey and Randall-Selitto method. PWLs of the inflamed paw were reduced 4 h-2 weeks after CFA injection. Infusion of either U69593 or DAMGO increased PWLs in CFA treated rats. A bilateral enhancement of the response to both agonists was observed 2 weeks relative to 4 h post-CFA injection. Mechanical thresholds of the inflamed paw were decreased for >2 weeks post-CFA injection. Infusion of either agonist elevated thresholds of the inflamed and non-inflamed paws of CFA-treated rats. The magnitude of these effects was greater 2 weeks post-CFA injection for DAMGO and increased progressively for U69593. These data demonstrate that RVM infusion of MOPr or KOPr agonists attenuates CFA-evoked thermal and tactile allodynia and that these effects increase during prolonged inflammation. The augmented response of the non-inflamed paw to agonists suggests that inflammation induces centrally-mediated neuroplastic changes which enhance MOPr- and KOPr-mediated antinociception. (C) 2008 Published by Elsevier B.V. on behalf of International Association for the Study of Pain. C1 [Schepers, Raf Jan-Filip; Mahoney, Janet Lynn; Shippenberg, Toni Shaun] Natl Inst Drug Abuse, Natl Inst Hlth, Intramural Res Program, Integrat Neurosci Sect,Behav Neurosci Branch, Baltimore, MD 21224 USA. [Schepers, Raf Jan-Filip] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. RP Shippenberg, TS (reprint author), Natl Inst Drug Abuse, Natl Inst Hlth, Intramural Res Program, Integrat Neurosci Sect,Behav Neurosci Branch, 333 Cassell Dr, Baltimore, MD 21224 USA. EM tshippen@mail.nih.gov FU Intramural NIH HHS NR 69 TC 14 Z9 15 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD JUN 15 PY 2008 VL 136 IS 3 BP 320 EP 330 DI 10.1016/j.pain.2007.07.010 PG 11 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 318PX UT WOS:000257105200013 PM 17764840 ER PT J AU Berezhkovskii, AM Coppey, M Sealfon, SC Shvartsman, S AF Berezhkovskii, Alexander M. Coppey, Mathieu Sealfon, Stuart C. Shvartsman, Stanislav TI Cell-to-cell communication: Time and length scales of ligand internalization in cultures of suspended cells SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID STATIC TRAPS; DIFFUSION; AUTOCRINE; SIGNALS AB A problem of cell-to-cell communication by diffusible ligands is analyzed for the case when cells are distributed in three dimensions and diffusible ligands are secreted by cells and reversibly bind to cell surface receptors. Following its binding to a receptor, the ligand can either dissociate and be released back in the medium or be absorbed by the cell in a process that is called internalization. Using an effective medium approximation, we derive analytical expressions that characterize the time and length scales associated with the ligand trajectories leading to internalization. We discuss the applicability of our approximation and illustrate the application of our results to a specific cellular system. (C) 2008 American Institute of Physics. C1 [Berezhkovskii, Alexander M.] NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. [Coppey, Mathieu; Shvartsman, Stanislav] Princeton Univ, Dept Chem Engn, Princeton, NJ 08540 USA. [Coppey, Mathieu; Shvartsman, Stanislav] Princeton Univ, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08540 USA. [Sealfon, Stuart C.] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. [Sealfon, Stuart C.] Mt Sinai Sch Med, Ctr Translat Syst Biol, New York, NY 10029 USA. RP Shvartsman, S (reprint author), NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA. EM stas@princeton.edu FU Intramural NIH HHS [Z99 CT999999]; NIAID NIH HHS [N01AI50021]; PHS HHS [HHSN266200500021C] NR 18 TC 0 Z9 0 U1 0 U2 1 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD JUN 14 PY 2008 VL 128 IS 22 AR 225102 DI 10.1063/1.2936845 PG 6 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 312XS UT WOS:000256706300062 PM 18554059 ER PT J AU Ayme, S Kole, A Groft, S AF Ayme, Segolene Kole, Anna Groft, Stephen TI Empowerment of patients: lessons from the rare diseases community SO LANCET LA English DT Article ID FACIO-CUTANEOUS SYNDROME; PATIENTS ASSOCIATIONS; EXPERT PATIENT; MUTATIONS; INTERNET; FRANCE C1 [Ayme, Segolene; Kole, Anna] INSERM, F-75014 Paris, France. [Groft, Stephen] NIH, Office Rare Dis, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Ayme, S (reprint author), INSERM, SC11,102 Rue Didot, F-75014 Paris, France. EM ayme@orpha.net NR 24 TC 61 Z9 61 U1 1 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD JUN 14 PY 2008 VL 371 IS 9629 BP 2048 EP 2051 DI 10.1016/S0140-6736(08)60875-2 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 312YY UT WOS:000256709500034 PM 18555918 ER PT J AU Ivanov, SV Ivanova, AV Salnikow, K Timofeeva, O Subramaniam, M Lerman, MI AF Ivanov, Sergey V. Ivanova, Alla V. Salnikow, Konstantin Timofeeva, Olga Subramaniam, Malayannan Lerman, Michael I. TI Two novel VHL targets, TGFBl (BIGH3) and its transactivator KLF10, are up-regulated in renal clear cell carcinoma and other tumors SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE VHL; TGFBI; KLF10; TGF-beta; ECM; HIF-1; VHL targets; clear cell carcinoma; BIGH3; keratoepithelin; oncogenic survival ID GROWTH-FACTOR-BETA; TRANSMEMBRANE CARBONIC-ANHYDRASES; MATRIX PROTEIN BETA-IG-H3; SUPPRESSOR GENE; CANCER-CELLS; ARRAY ANALYSIS; LUNG-CANCER; CYCLIN D1; HYPOXIA; EXPRESSION AB Mutations in the VHL gene are associated with highly vascular tumors of kidney, brain, retina, and adrenal gland. The inability of the mutant VHL protein to destabilize HIF-1 plays a crucial role in malignant angiogenesis. VHL is also associated with ECM assembly but the molecular mechanisms of this activity remain unclear. We used expression arrays and cell lines with different VHL status to identify ECM-associated genes controlled by VHL. One of them, adhesion-associated TGFBI, was repressed by VHL and overexpressed in renal, gastrointestinal, brain, and other tumors. Analyzing the mechanism of TGFBI up-regulation in clear cell carcinoma, we identified a novel VHL target, a Kruppel-like transcriptional factor 10 (KLF10). The TGFBI promoter, which we isolated and studied in Luc-reporter assay, was induced by KLF10 but not hypoxia. These data provide the molecular basis for the observed VHL effect on TGFBI and stimulate further research into the KLF10 and TGFBI roles in cancer. Published by Elsevier Inc. C1 [Ivanov, Sergey V.; Ivanova, Alla V.] SAIC Frederick Inc, Bellevue Hosp, Basic Res Program, New York, NY 10016 USA. [Salnikow, Konstantin; Timofeeva, Olga; Lerman, Michael I.] NCI, NIH, Frederick, MD 21702 USA. [Subramaniam, Malayannan] Mayo Clin, Coll Med, Dept Biochem & Mol Biol, Rochester, MN 55905 USA. RP Ivanov, SV (reprint author), SAIC Frederick Inc, Bellevue Hosp, Basic Res Program, 462 1st Ave,Room 15N20, New York, NY 10016 USA. EM Sergey.Ivanov@med.nyu.edu FU Intramural NIH HHS [Z01 BC008579-14]; NCI NIH HHS [N01-CO-56000] NR 46 TC 31 Z9 34 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 13 PY 2008 VL 370 IS 4 BP 536 EP 540 DI 10.1016/j.bbrc.2008.03.066 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 301GH UT WOS:000255883900002 PM 18359287 ER PT J AU O'Brien, SJ AF O'Brien, Stephen J. TI The platypus genome unraveled SO CELL LA English DT Editorial Material ID EVOLUTION AB The genome of the platypus has been sequenced, assembled, and annotated by an international genomics team. Like the animal itself the platypus genome contains an amalgam of mammal, reptile, and bird-like features. C1 NCI, Lab Gen Divers, Frederick, MD 21702 USA. RP O'Brien, SJ (reprint author), NCI, Lab Gen Divers, Frederick, MD 21702 USA. EM obrien@ncifcrf.gov NR 10 TC 7 Z9 7 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD JUN 13 PY 2008 VL 133 IS 6 BP 953 EP 955 DI 10.1016/j.cell.2008.05.038 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 312TJ UT WOS:000256693400011 PM 18555772 ER PT J AU Basto, R Brunk, K Vinadogrova, T Peel, N Franz, A Khodjakov, A Raff, JW AF Basto, Renata Brunk, Kathrin Vinadogrova, Tatiana Peel, Nina Franz, Anna Khodjakov, Alexey Raff, Jordan W. TI Centrosome amplification can initiate tumorigenesis in flies SO CELL LA English DT Article ID ASYMMETRIC CELL-DIVISION; REGULATES SPINDLE ORIENTATION; NEUROBLAST SELF-RENEWAL; NEURAL STEM-CELLS; CENTRIOLE DUPLICATION; TUMOR-SUPPRESSOR; DROSOPHILA-MELANOGASTER; CHROMOSOME INSTABILITY; CYCLE PROGRESSION; CORTICAL POLARITY AB Centrosome amplification is a common feature of many cancer cells, and it has been previously proposed that centrosome amplification can drive genetic instability and so tumorigenesis. To test this hypothesis, we generated Drosophila lines that have extra centrosomes in similar to 60% of their somatic cells. Many cells with extra centrosomes initially form multipolar spindles, but these spindles ultimately become bipolar. This requires a delay in mitosis that is mediated by the spindle assembly checkpoint (SAC). As a result of this delay, there is no dramatic increase in genetic instability in flies with extra centrosomes, and these flies maintain a stable diploid genome over many generations. The asymmetric division of the larval neural stem cells, however, is compromised in the presence of extra centrosomes, and larval brain cells with extra centrosomes can generate metastatic tumors when transplanted into the abdomens of wild-type hosts. Thus, centrosome amplification can initiate tumorigenesis in flies. C1 [Basto, Renata; Brunk, Kathrin; Peel, Nina; Franz, Anna; Raff, Jordan W.] Gurdon Inst, Cambridge CB2 1QN, England. [Vinadogrova, Tatiana; Khodjakov, Alexey] New York State Dept Hlth, Wadsworth Ctr, Albany, NY 12201 USA. [Vinadogrova, Tatiana; Khodjakov, Alexey] SUNY Albany, Dept Biomed Sci, Albany, NY 12222 USA. [Peel, Nina] NIDDK, NIH, Lab Biochem & Genet, Bethesda, MD 20892 USA. RP Basto, R (reprint author), Inst Curie, CNRS, UMR 144, 26 Rue Ulm, Paris 05, France. EM renata.basto@curie.fr; j.raff@gurdon.cam.ac.uk OI Peel, Nina/0000-0002-4277-4106 FU Cancer Research UK; NIGMS NIH HHS [R01 GM059363, R01 GM059363-10]; Wellcome Trust NR 61 TC 262 Z9 267 U1 1 U2 10 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD JUN 13 PY 2008 VL 133 IS 6 BP 1032 EP 1042 DI 10.1016/j.cell.2008.05.039 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 312TJ UT WOS:000256693400018 PM 18555779 ER PT J AU Patterson, GH Hirschberg, K Polishchuk, RS Gerlich, D Phair, RD Lippincott-Schwartz, J AF Patterson, George H. Hirschberg, Koret Polishchuk, Roman S. Gerlich, Daniel Phair, Robert D. Lippincott-Schwartz, Jennifer TI Transport through the Golgi apparatus by rapid partitioning within a two-phase membrane system SO CELL LA English DT Article ID CISTERNAL MATURATION; FLUORESCENT PROTEIN; PLASMA-MEMBRANE; COMPLEX; CELLS; STACK; CHOLESTEROL; CONTINUITIES; MECHANISM; DYNAMICS AB The prevailing view of intra-Golgi transport is cisternal progression, which has a key prediction-that newly arrived cargo exhibits a lag or transit time before exiting the Golgi. Instead, we find that cargo molecules exit at an exponential rate proportional to their total Golgi abundance with no lag. Incoming cargo molecules rapidly mix with those already in the system and exit from partitioned domains with no cargo privileged for export based on its time of entry into the system. Given these results, we constructed a new model of intra-Golgi transport that involves rapid partitioning of enzymes and transmembrane cargo between two lipid phases combined with relatively rapid exchange among cisternae. Simulation and experimental testing of this rapid partitioning model reproduced all the key characteristics of the Golgi apparatus, including polarized lipid and protein gradients, exponential cargo export kinetics, and cargo waves. C1 [Patterson, George H.; Lippincott-Schwartz, Jennifer] NIH, Cell Biol & Metab Program, Bethesda, MD 20892 USA. [Phair, Robert D.] Integrat Bioinformat, Los Altos, CA 94024 USA. [Hirschberg, Koret] Tel Aviv Univ, Sackler Sch Med, Dept Pathol, IL-69978 Tel Aviv, Israel. [Polishchuk, Roman S.] Consorzio Mario Negri Sud Santa Maria Imbaro, Dept Cell Biol & Oncol, I-66030 Chieti, Italy. [Gerlich, Daniel] ETH, Inst Biochem, CH-8093 Zurich, Switzerland. RP Lippincott-Schwartz, J (reprint author), NIH, Cell Biol & Metab Program, Bldg 18T,Room 101,18 Lib Dr, Bethesda, MD 20892 USA. EM lippincj@mail.nih.gov FU Intramural NIH HHS [Z01 HD001609-14, Z99 EB999999]; NIGMS NIH HHS [R01 GM079305, R01 GM079305-01A1, R01GM079305, R43 GM066611, R43GM066611, R44 GM066611, R44GM066611] NR 37 TC 148 Z9 148 U1 1 U2 43 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD JUN 13 PY 2008 VL 133 IS 6 BP 1055 EP 1067 DI 10.1016/j.cell.2008.04.044 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 312TJ UT WOS:000256693400020 PM 18555781 ER PT J AU Costanzi, S Neumann, S Gershengorn, MC AF Costanzi, Stefano Neumann, Susanne Gershengorn, Marvin C. TI Seven transmembrane-spanning receptors for free fatty acids as therapeutic targets for diabetes mellitus: Pharmacological, phylogenetic, and drug discovery aspects SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID PROTEIN-COUPLED RECEPTORS; PANCREATIC BETA-CELLS; INSULIN-SECRETION; AGONIST RECOGNITION; IN-VIVO; GPR40; IDENTIFICATION C1 [Neumann, Susanne; Gershengorn, Marvin C.] NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. [Costanzi, Stefano] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA. RP Gershengorn, MC (reprint author), NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. EM marving@intra.niddk.nih.gov RI Costanzi, Stefano/G-8990-2013; OI Costanzi, Stefano/0000-0003-3183-7332 FU Intramural NIH HHS NR 39 TC 37 Z9 42 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 13 PY 2008 VL 283 IS 24 BP 16269 EP 16273 DI 10.1074/jbc.R800014200 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 309YW UT WOS:000256497100001 PM 18385136 ER PT J AU Wang, D Guo, MX Hu, HM Zhao, ZZ Qiu, HL Shao, HJ Zhu, CG Xue, L Shi, YB Li, WX AF Wang, Di Guo, Ming-Xiong Hu, Hai-Ming Zhao, Zhou-Zhou Qiu, Hong-Ling Shao, Huan-Jie Zhu, Chen-Gang Xue, Lu Shi, Yun-Bo Li, Wen-Xin TI Human T-cell leukemia virus type 1 oncoprotein Tax represses ZNF268 expression through the cAMP-responsive element-binding protein/activating transcription factor pathway SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROENKEPHALIN GENE PROMOTER; ZINC-FINGER GENE; 21-BASE-PAIR REPEATS; PROTEIN; HTLV-1; TRANSACTIVATION; IMMORTALIZATION; IDENTIFICATION; LYMPHOCYTES; INDUCTION AB Expression of the human T-cell leukemia virus type 1 (HTLV-1) oncoprotein Tax is correlated with cellular transformation, contributing to the development of adult T-cell leukemia. In this study, we investigated the role of Tax in the regulation of the ZNF268 gene, which plays a role in the differentiation of blood cells and the pathogenesis of leukemia. We demonstrated that ZNF268 mRNA was repressed in HTLV-1-infected cells. We also showed that stable and transient expression of HTLV-1 Tax led to repression of ZNF268. In addition, by using reporter constructs that bear the human ZNF268 promoter and its mutants, we showed that Tax repressed ZNF268 promoter in a process dependent on a functional cAMP-responsive element. By using Tax, cAMP-responsive element-binding protein (CREB)-1, CREB-2, and their mutants, we further showed that Tax repressed ZNF268 through the CREB/activating transcription factor pathway. Electrophoretic mobility shift assays and chromatin immunoprecipitation demonstrated the formation of the complex of Tax(.)CREB-1 directly at the cAMP-responsive element both in vitro and in vivo. These findings suggest a role for ZNF268 in aberrant T-cell proliferation observed in HTLV-1-associated diseases. C1 [Wang, Di; Guo, Ming-Xiong; Hu, Hai-Ming; Zhao, Zhou-Zhou; Qiu, Hong-Ling; Shao, Huan-Jie; Zhu, Chen-Gang; Xue, Lu; Li, Wen-Xin] Wuhan Univ, State Key Lab Virol, Coll Life Sci, Wuhan 430072, Peoples R China. [Shi, Yun-Bo] NICHD, Sect Mol Morphogenesis, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Li, WX (reprint author), Wuhan Univ, State Key Lab Virol, Coll Life Sci, Wuhan 430072, Peoples R China. EM liwxlab@whu.edu.cn FU Intramural NIH HHS NR 34 TC 12 Z9 14 U1 2 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 13 PY 2008 VL 283 IS 24 BP 16299 EP 16308 DI 10.1074/jbc.M706426200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 309YW UT WOS:000256497100006 PM 18375384 ER PT J AU Joo, JH Jetten, AM AF Joo, Joung Hyuck Jetten, Anton M. TI NF-kappa Beta-dependent transcriptional activation in lung carcinoma cells by farnesol involves p65/RelA(Ser(276)) phosphorylation via the MEK-MSK1 signaling pathway SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ENDOPLASMIC-RETICULUM STRESS; UNFOLDED PROTEIN RESPONSE; ISOPRENOIDS PERILLYL ALCOHOL; B P65 SUBUNIT; INDUCED APOPTOSIS; SACCHAROMYCES-CEREVISIAE; ADENOCARCINOMA CELLS; NSC 641066; ER STRESS; CANCER AB In this study, we demonstrate that treatment of human lung adenocarcinoma H460 cells with farnesol induces the expression of a number of immune response and inflammatory genes, including IL-6, CXCL3, IL-1 alpha, and COX-2. This response was dependent on the activation of the NF-kappa B signaling pathway. Farnesol treatment reduces the level of I kappa B alpha and induces translocation of p65/RelA to the nucleus, its phosphorylation at Ser(276), and transactivation of NF-kappa B-dependent transcription. Moreover, overexpression of I kappa B alpha or treatment with the NF-kappa B inhibitor caffeic acid phenethyl ester greatly diminishes the induction of inflammatory gene expression by farnesol. We provide evidence indicating that the farnesol-induced phosphorylation of p65/RelA at Ser(276) is important for optimal transcriptional activity of NF-kappa B. The MEK1/2 inhibitor U0126 and knockdown of MEK1/2 expression with small interfering RNAs effectively blocked the phosphorylation of p65/RelA(Ser(276)) but not that of Ser(536), suggesting that this phosphorylation is dependent on the activation of the MEK1/2-ERK1/2 pathway. We further show that inhibition of MSK1, a kinase acting downstream of MEK1/2-ERK1/2, by H89 or knockdown of MSK1 expression also inhibited phosphorylation of p65/RelA(Ser(276)), suggesting that this phosphorylation is dependent on MSK1. Knockdown of MEK1/2 or MSK1 expression inhibits farnesol-induced expression of CXCL3, IL-1 alpha, and COX-2 mRNA. Our results indicate that the induction of inflammatory genes by farnesol is mediated by the activation of the NF-kappa B pathway and involves MEK1/2-ERK1/2-MSK1-dependent phosphorylation of p65/RelA(Ser(276)). The activation of the NF-kappa B pathway by farnesol might be part of a prosurvival response during farnesol-induced ER stress. C1 [Joo, Joung Hyuck; Jetten, Anton M.] NIEHS, Cell Biol Sect, LRB, Div Intramural Res,Natl Inst Hlth, Res Triangle Pk, NC 27709 USA. RP Jetten, AM (reprint author), NIEHS, Cell Biol Sect, LRB, Div Intramural Res,Natl Inst Hlth, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM jetten@niehs.nih.gov FU Intramural NIH HHS NR 50 TC 38 Z9 41 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 13 PY 2008 VL 283 IS 24 BP 16391 EP 16399 DI 10.1074/jbc.M800945200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 309YW UT WOS:000256497100015 PM 18424438 ER PT J AU Tone, Y Pedersen, LC Yamamoto, T Izumikawa, T Kitagawa, H Nishihara, J Tamura, J Negishi, M Sugahara, K AF Tone, Yuko Pedersen, Lars C. Yamamoto, Tomoko Izumikawa, Tomomi Kitagawa, Hiroshi Nishihara, Junko Tamura, Jun-ichi Negishi, Masahiko Sugahara, Kazuyuki TI 2-O-phosphorylation of xylose and 6-O-sulfation of galactose in the protein linkage region of Glycosaminoglycans influence the glucuronyltransferase-I activity involved in the linkage region synthesis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SULFATE HYBRID CHAINS; CHONDROITIN-POLYMERIZING FACTOR; GLAND EPITHELIAL-CELLS; EMBRYONIC PIG BRAIN; HEPARAN-SULFATE; MOLECULAR-CLONING; GROWTH-FACTOR; TETRASACCHARIDE SEQUENCE; NEURITOGENIC ACTIVITY; TUMOR SUPPRESSORS AB Sulfated glycosaminoglycans (GAGs), including heparan sulfate and chondroitin sulfate, are synthesized on the so-called common GAG-protein linkage region (GlcUA beta 1-3Gal beta 1-3Gal beta 1-4Xyl beta 1-O-Ser) of core proteins, which is formed by the stepwise addition of monosaccharide residues by the respective specific glycosyltransferases. Glucuronyltransferase-I (GlcAT-I) is the key enzyme that completes the synthesis of this linkage region, which is a prerequisite for the conversion of core proteins to functional proteoglycans bearing GAGs. The Xyl and Gal residues in the linkage region can be modified by phosphorylation and sulfation, respectively, although the biological significance of these modifications remains to be clarified. Here we present evidence that these modifications can significantly influence the catalytic activity of GlcAT-I. Enzyme assays showed that the synthetic substrates, Gal-Gal-Xyl(2-O-phosphate)O-Ser and Gal-Gal(6-O-sulfate)-Xyl(2-O-phosphate)O-Ser, served as better substrates than the unmodified compound, whereas Gal(6-O-sulfate)-Gal-Xyl(2-O-phosphate)-O-Ser exhibited no acceptor activity. The crystal structure of the catalytic domain of GlcAT-I with UDP and Gal-Gal(6-O-sulfate)Xyl(2-O-phosphate)-O-Ser bound revealed that the Xyl(2-O-phosphate)O-Ser is disordered and the 6-O-sulfate forms interactions with Gln(318) from the second GlcAT-I monomer in the dimeric enzyme. The results indicate the possible involvement of these modifications in the processing and maturation of the growing linkage region oligosaccharide required for the assembly of GAG chains. C1 [Sugahara, Kazuyuki] Hokkaido Univ, Fac Adv Life Sci, Frontier Res Ctr Post Gen Sci & Technol, Grad Sch Life Sci,Lab Proteoglycan Signaling & Th, Sapporo, Hokkaido 0010021, Japan. [Tone, Yuko; Yamamoto, Tomoko; Izumikawa, Tomomi; Kitagawa, Hiroshi; Sugahara, Kazuyuki] Kobe Pharmaceut Univ, Dept Biochem, Higashinada Ku, Kobe, Hyogo 6588558, Japan. [Negishi, Masahiko] NIEHS, NIH, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. [Pedersen, Lars C.; Negishi, Masahiko] NIEHS, NIH, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. [Nishihara, Junko; Tamura, Jun-ichi] Tottori Univ, Fac Reg Sci, Dept Reg Environm, Tottori 6808551, Japan. RP Sugahara, K (reprint author), Hokkaido Univ, Fac Adv Life Sci, Frontier Res Ctr Post Gen Sci & Technol, Grad Sch Life Sci,Lab Proteoglycan Signaling & Th, Sapporo, Hokkaido 0010021, Japan. EM k-sugar@sci.hokudai.ac.jp FU Intramural NIH HHS NR 56 TC 34 Z9 36 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 13 PY 2008 VL 283 IS 24 BP 16801 EP 16807 DI 10.1074/jbc.M709556200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 309YW UT WOS:000256497100057 PM 18400750 ER PT J AU Greggio, E Zambrano, I Kaganovich, A Beilina, A Taymans, JM Daniels, V Lewis, P Jain, S Ding, J Syed, A Thomas, KJ Baekelandt, V Cookson, MR AF Greggio, Elisa Zambrano, Ibardo Kaganovich, Alice Beilina, Alexandra Taymans, Jean-Marc Daniels, Veronique Lewis, Patrick Jain, Shushant Ding, Jinhui Syed, Ali Thomas, Kelly J. Baekelandt, Veerle Cookson, Mark R. TI The Parkinson disease-associated leucine-rich repeat kinase 2 (LRRK2) is a dimer that undergoes intramolecular autophosphorylation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE ACTIVITY; NEURONAL TOXICITY; GTP-BINDING; ROC DOMAIN; MUTATIONS; G2019S; ACTIVATION; LRRK2/DARDARIN; GENE; LOOP AB Mutations in leucine-rich repeat kinase 2 (LRRK2) are a common cause of familial and apparently sporadic Parkinson disease. LRRK2 is a multidomain protein kinase with autophosphorylation activity. It has previously been shown that the kinase activity of LRRK2 is required for neuronal toxicity, suggesting that understanding the mechanism of kinase activation and regulation may be important for the development of specific kinase inhibitors for Parkinson disease treatment. Here, we show that LRRK2 predominantly exists as a dimer under native conditions, a state that appears to be stabilized by multiple domain-domain interactions. Furthermore, an intact C terminus, but not N terminus, is required for autophosphorylation activity. We identify two residues in the activation loop that contribute to the regulation of LRRK2 autophosphorylation. Finally, we demonstrate that LRRK2 undergoes intramolecular autophosphorylation. Together, these results provide insight into the mechanism and regulation of LRRK2 kinase activity. C1 [Greggio, Elisa; Ding, Jinhui] NIA, NIH, Neurogenet Lab, Bioinformat Facil, Bethesda, MD 20982 USA. [Greggio, Elisa; Zambrano, Ibardo; Kaganovich, Alice; Beilina, Alexandra; Lewis, Patrick; Jain, Shushant; Syed, Ali; Thomas, Kelly J.; Cookson, Mark R.] NIA, NIH, Cell Biol & Genen Express Unit, Bethesda, MD 20982 USA. [Daniels, Veronique; Baekelandt, Veerle] Katholieke Univ Leuven, Dept Mol & Cellular Med, Div Mol Med, Lab Neurobiol & Gene Therapy, B-3000 Louvain, Belgium. RP Greggio, E (reprint author), NIA, NIH, Neurogenet Lab, Bioinformat Facil, Bldg 35,Rm 1A1012,MSC 3707,35 Convent Dr, Bethesda, MD 20982 USA. EM greggio@mail.nih.gov RI Lewis , Patrick/C-3674-2009; Greggio, Elisa/H-6119-2013; OI Greggio, Elisa/0000-0002-8172-3598; Taymans, Jean-Marc/0000-0001-5503-5524; Lewis, Patrick/0000-0003-4537-0489 FU Intramural NIH HHS NR 34 TC 163 Z9 164 U1 0 U2 9 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 13 PY 2008 VL 283 IS 24 BP 16906 EP 16914 DI 10.1074/jbc.M708718200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 309YW UT WOS:000256497100068 PM 18397888 ER PT J AU Levitin, F Weiss, M Hahn, Y Stern, O Papke, RL Matusik, R Nandana, SR Ziv, R Pichinuk, E Salame, S Bera, T Vincent, J Lee, B Pastan, I Wreschner, DH AF Levitin, Fiana Weiss, Mordechai Hahn, Yoonsoo Stern, Omer Papke, Roger L. Matusik, Robert Nandana, Srinivas R. Ziv, Ravit Pichinuk, Edward Salame, Sharbel Bera, Tapan Vincent, James Lee, Byungkook Pastan, Ira Wreschner, Daniel H. TI PATE gene clusters code for multiple, secreted TFP/Ly-6/uPAR proteins that are expressed in reproductive and neuron-rich tissues and possess neuromodulatory activity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NICOTINIC ACETYLCHOLINE-RECEPTOR; VENOM ALPHA-NEUROTOXINS; ACROSOME REACTION; HUMAN SPERM; PLASMINOGEN-ACTIVATOR; SEQUENCE ALIGNMENT; SEMINAL-VESICLE; HUMAN SP-10; SNAKE; TOXINS AB We report here syntenic loci in humans and mice incorporating gene clusters coding for secreted proteins each comprising 10 cysteine residues. These conform to three-fingered protein/Ly-6/urokinase-type plasminogen activator receptor (uPAR) domains that shape three-fingered proteins (TFPs). The founding gene is PATE, expressed primarily in prostate and less in testis. We have identified additional human PATE-like genes (PATE-M, PATE-DJ, and PATE-B) that co-localize with the PATE locus, code for novel secreted PATE-like proteins, and show selective expression in prostate and/ or testis. Anti-PATE-B-specific antibodies demonstrated the presence of PATE-B in the region of the sperm acrosome and at high levels on malignant prostatic epithelial cells. The syntenic mouse Pate-like locus encompasses 14 active genes coding for secreted proteins, which are all, except for Pate-P and Pate-Q, expressed primarily in prostate and/ or testis. Pate-P and Pate-Q are expressed solely in placental tissue. Castration up-regulates prostate expression of mouse Pate-Band Pate-E, whereas testosterone ablates this induced expression. The sequence similarity between TFP/Ly-6/uPAR proteins that modulate activity of nicotinic acetylcholine receptors and the PATE (Pate)-like proteins stimulated us to see whether these proteins possess analogous activity. Pharmacological studies showed significant modulation of the nicotinic acetylcholines by the PATE-B, Pate-C, and Pate-P proteins. In concert with these findings, certain PATE (Pate)-like genes were extensively expressed in neuron-rich tissues. Taken together, our findings indicate that in addition to participation of the PATE (Pate)-like genes in functions related to fertility and reproduction, some of them likely act as important modulators of neural transmission. C1 [Levitin, Fiana; Stern, Omer; Ziv, Ravit; Pichinuk, Edward; Salame, Sharbel; Wreschner, Daniel H.] Tel Aviv Univ, Dept Cell Res & Immunol, IL-69978 Ramat Aviv, Israel. [Weiss, Mordechai] Assaf Harofeh Med Ctr, Dept Endocrinol, IL-70300 Zerifin, Israel. [Papke, Roger L.] Univ Florida, Dept Pharmacol & Therapeut, Gainesville, FL 32610 USA. [Hahn, Yoonsoo; Bera, Tapan; Vincent, James; Lee, Byungkook; Pastan, Ira; Wreschner, Daniel H.] NCI, NIH, Bethesda, MD 20892 USA. [Matusik, Robert; Nandana, Srinivas R.] Vanderbilt Univ, Med Ctr, Nashville, TN 37232 USA. [Wreschner, Daniel H.] Geneswitch Technol LLC, Waban, MA 02468 USA. RP Wreschner, DH (reprint author), Tel Aviv Univ, Dept Cell Res & Immunol, IL-69978 Ramat Aviv, Israel. EM danielhw@post.tau.ac.il FU Intramural NIH HHS [Z01 BC010298-10]; NIGMS NIH HHS [R01 GM057481] NR 34 TC 35 Z9 42 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 13 PY 2008 VL 283 IS 24 BP 16928 EP 16939 DI 10.1074/jbc.M801454200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 309YW UT WOS:000256497100070 PM 18387948 ER PT J AU Kovac, S Yang, XL Huang, FL Hixson, D Josic, D AF Kovac, Spomenka Yang, Xinli Huang, Feilei Hixson, Douglas Josic, Djuro TI Proteomics as a tool for optimization of human plasma protein separation SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article; Proceedings Paper CT 27th International Symposium on the Separation and Analysis of Proteins, Peptides and Polynucleotides CY OCT 21-24, 2007 CL Orlando, FL DE human plasma proteins; proteomics; chromatographic separation; process design ID ALPHA INHIBITOR PROTEINS; VON-WILLEBRAND-FACTOR; CLOTTING FACTOR-VIII; FACTOR-IX; PURIFICATION; CHROMATOGRAPHY; FRACTIONATION; STRATIFIN; CLUSTERIN; MEMBRANES AB The application of proteomics technology in purification of proteins from human plasma and for characterization of plasma-derived therapeutics has been recently discussed. However, until now, the impact of this technology on the plasma protein fractionation and analysis of the final product has not been realized. In the present work, we demonstrate the use of proteomic techniques the monitoring of the first step of the plasma fractionation by use of anion-exchange chromatography. This chromatographic method is frequently used in the purification scheme for isolation of vitamin K dependent clotting factors II, VII, IX and X, and clotting inhibitors protein C and protein S, as well as inter-alpha inhibitor proteins (IaIp). After the removal of immunoglobulin G and non-binding proteins in the flow-through fraction, albumin and weakly bound proteins were eluted with low concentration of sodium chloride. The proteins that strongly bind to the anion-exchange column were eluted by higher salt concentrations. The fractions of interest were analyzed, and proteins were identified by LC-ESI-MS/MS. By use of this method, not only candidates for therapeutic concentrates, but also some potentially harmful components were identified. This strategy was very helpful for further process optimization, fast identification of target proteins with relatively low abundance, and for the design of subsequent steps in their removal or purification. Published by Elsevier B.V. C1 [Yang, Xinli; Huang, Feilei; Hixson, Douglas; Josic, Djuro] Brown Univ, Providence, RI 02912 USA. [Yang, Xinli; Huang, Feilei; Hixson, Douglas; Josic, Djuro] Rhode Isl Hosp, Ctr Canc Res Dev, COBRE, Providence, RI 02904 USA. [Kovac, Spomenka] JJ Strossmayer Univ Osijek, Dept Chem, HR-31000 Osijek, Croatia. RP Josic, D (reprint author), Rhode Isl Hosp, Ctr Canc Res Dev, COBRE, 1 Hoppin St,Core W 4, Providence, RI 02904 USA. EM Djuro_Josic@brown.edu NR 39 TC 16 Z9 16 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD JUN 13 PY 2008 VL 1194 IS 1 BP 38 EP 47 DI 10.1016/j.chroma.2008.04.026 PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 315DV UT WOS:000256859000006 PM 18486944 ER PT J AU Cano, OD Neurauter, G Fuchs, D Shearer, GM Boasso, A AF Cano, Oscar D. Neurauter, Gabriele Fuchs, Dietmar Shearer, Gene M. Boasso, Adriano TI Differential effect of type I and type II interferons on neopterin production and amino acid metabolism in human astrocyte-derived cells SO NEUROSCIENCE LETTERS LA English DT Article DE astrocyte-derived cells; neopterin; indoleamine (2,3)-dioxygenase; interferon; amino acids; HIV ID PLASMACYTOID DENDRITIC CELLS; CD4(+) T-CELLS; INDOLEAMINE 2,3-DIOXYGENASE; TRYPTOPHAN; GAMMA; HIV-1; INACTIVATION; INFECTION; PROTEINS; INDOLEAMINE-2,3-DIOXYGENASE AB Intrathecal production of neopterin, a pteridine produced by interferon (IFN)-gamma-stimulated monocyte-derived macrophages, is associated with neurological disorders and infections. We investigated whether IFN-alpha/beta, IFN-gamma, or human immunodeficiency virus (HIV) induce neopterin production by human astroglioma cells. IFN-alpha/beta and IFN-gamma, but not HIV, induced neopterin. Interestingly, IFN-gamma, but not IFN-alpha/beta, increased expression and activity of the tryptophan-catabolizing enzyme indoleamine (2,3)-dioxygenase. In contrast, IFN-alpha/beta, but not IFN-gamma, reduced the uptake of three aromatic amino acids in U87MG and U138 astroglioma cells. Thus type I and type II IFN stimulate astrocyte-derived cells to produce neopterin and exert differential effects on amino acid metabolism. (C) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Cano, Oscar D.; Shearer, Gene M.; Boasso, Adriano] NCI, NIH, Expt Immunol Branch, Bethesda, MD 20892 USA. [Neurauter, Gabriele; Fuchs, Dietmar] Innsbruck Med Univ, Div Biol Chem, A-6020 Innsbruck, Austria. RP Boasso, A (reprint author), Univ London Imperial Coll Sci Technol & Med, Chelsea & Westminster Hosp, Fac Med, Dept Immunol,Div Investigat Sci, 369 Fulham Rd, London SW10 9NH, England. EM a.boasso@imperial.ac.uk OI Boasso, Adriano/0000-0001-9673-6319 FU Intramural NIH HHS NR 25 TC 13 Z9 14 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 EI 1872-7972 J9 NEUROSCI LETT JI Neurosci. Lett. PD JUN 13 PY 2008 VL 438 IS 1 BP 22 EP 25 DI 10.1016/j.neulet.2008.04.046 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 319GL UT WOS:000257152000006 PM 18457922 ER PT J AU Giacobini, P Wray, S AF Giacobini, Paolo Wray, Susan TI Prenatal expression of cholecystokinin (CCK) in the central nervous system (CNS) of mouse SO NEUROSCIENCE LETTERS LA English DT Article DE CCK; in situ hybridization; development; GnRH-1; median eminence ID IN-SITU HYBRIDIZATION; IMMUNOHISTOCHEMICAL ANALYSIS; GENE-EXPRESSION; MESSENGER-RNA; GONADOTROPIN; HORMONE; NEURONS; RAT; CELLS; RECEPTOR AB Cholecystokinin (CCK) is a peptide found in both gut and brain. Although numerous studies address the role of brain CCK postnatally, relatively little is known about the ontogeny of CCK expression in the central nervous system (CNS). Recent work revealed that CCK modulates olfactory axon outgrowth and gonadotropin-releasing hormone-1 (GnRH-1) neuronal migration, suggesting that CCK may be an important factor during CNS development. To further characterize the developmental expression of CCK in the nervous system, in situ hybridization experiments were performed. CCK mRNA expression was widely distributed in the developing mouse brain. As early as E12.5, robust CCK expression is detected in the thalamus and spinal cord. By E17.5, cells in the cortex, hippocampus, thalamus and hypothalamus express CCK. In addition, CCK mRNA was also detected in the external zone of the median eminence where axons of the neuroendocrine hypophysiotropic systems terminate. Our study demonstrates that CCK mRNA is expressed prenatally in multiple areas of the CNS, many of which maintain CCK mRNA expression postnatally into adult life. In addition, we provide evidence that regions of the CNS known to integrate hormonal and sensory information associated with reproduction and the GnRH-1 system, expressed CCK already during prenatal development. Published by Elsevier Ireland Ltd. C1 [Giacobini, Paolo; Wray, Susan] NINDS, Natl Inst Hlth, Cellular & Dev Neurobiol Sect, Bethesda, MD 20892 USA. [Giacobini, Paolo] Univ Turin, Dept Human & Anim Biol, Neurobiol Lab, I-10124 Turin, Italy. RP Wray, S (reprint author), NINDS, Natl Inst Hlth, Cellular & Dev Neurobiol Sect, Bldg 35,Room 3A-1012, Bethesda, MD 20892 USA. EM wrays@ninds.nih.gov RI Giacobini, Paolo/P-5451-2015; OI Giacobini, Paolo/0000-0002-3075-1441; wray, susan/0000-0001-7670-3915 FU Intramural NIH HHS [Z01 NS002824-17] NR 30 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD JUN 13 PY 2008 VL 438 IS 1 BP 96 EP 101 DI 10.1016/j.neulet.2008.04.042 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 319GL UT WOS:000257152000022 PM 18462884 ER PT J AU Soutoglou, E Misteli, T AF Soutoglou, Evi Misteli, Tom TI Activation of the cellular DNA damage response in the absence of DNA lesions SO SCIENCE LA English DT Article ID DOUBLE-STRAND BREAKS; HISTONE H2AX; MDC1; CHECKPOINT; ATM; PHOSPHORYLATION; 53BP1; RECOGNITION; MACHINERY; RETENTION AB The cellular DNA damage response (DDR) is initiated by the rapid recruitment of repair factors to the site of DNA damage to form a multiprotein repair complex. How the repair complex senses damaged DNA and then activates the DDR is not well understood. We show that prolonged binding of DNA repair factors to chromatin can elicit the DDR in an ATM (ataxia telangiectasia mutated)- and DNAPK (DNA-dependent protein kinase)-dependent manner in the absence of DNA damage. Targeting of single repair factors to chromatin revealed a hierarchy of protein interactions within the repair complex and suggests amplification of the damage signal. We conclude that activation of the DDR does not require DNA damage and stable association of repair factors with chromatin is likely a critical step in triggering, amplifying, and maintaining the DDR signal. C1 [Soutoglou, Evi; Misteli, Tom] NCI, NIH, Bethesda, MD 20892 USA. RP Soutoglou, E (reprint author), NCI, NIH, Bethesda, MD 20892 USA. EM soutogle@mail.nih.gov; mistelit@mail.nih.gov FU Intramural NIH HHS [Z01 BC010309-09] NR 21 TC 184 Z9 186 U1 0 U2 10 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUN 13 PY 2008 VL 320 IS 5882 BP 1507 EP 1510 DI 10.1126/science.1159051 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 312MV UT WOS:000256676400048 PM 18483401 ER PT J AU Boedigheimer, MJ Wolfinger, RD Bass, MB Bushel, PR Chou, JW Cooper, M Corton, JC Fostel, J Hester, S Lee, JS Liu, FL Liu, J Qian, HR Quackenbush, J Pettit, S Thompson, KL AF Boedigheimer, Michael J. Wolfinger, Russell D. Bass, Michael B. Bushel, Pierre R. Chou, Jeff W. Cooper, Matthew Corton, J. Christopher Fostel, Jennifer Hester, Susan Lee, Janice S. Liu, Fenglong Liu, Jie Qian, Hui-Rong Quackenbush, John Pettit, Syril Thompson, Karol L. TI Sources of variation in baseline gene expression levels from toxicogenomics study control animals across multiple laboratories SO BMC GENOMICS LA English DT Article ID RAT-LIVER; KIDNEY; TRANSCRIPTOME; PROFILES; PATTERNS; ARRAYS; BLOOD; MODEL AB Background: The use of gene expression profiling in both clinical and laboratory settings would be enhanced by better characterization of variance due to individual, environmental, and technical factors. Meta-analysis of microarray data from untreated or vehicle-treated animals within the control arm of toxicogenomics studies could yield useful information on baseline fluctuations in gene expression, although control animal data has not been available on a scale and in a form best served for data-mining. Results: A dataset of control animal microarray expression data was assembled by a working group of the Health and Environmental Sciences Institute's Technical Committee on the Application of Genomics in Mechanism Based Risk Assessment in order to provide a public resource for assessments of variability in baseline gene expression. Data from over 500 Affymetrix microarrays from control rat liver and kidney were collected from 16 different institutions. Thirty-five biological and technical factors were obtained for each animal, describing a wide range of study characteristics, and a subset were evaluated in detail for their contribution to total variability using multivariate statistical and graphical techniques. Conclusion: The study factors that emerged as key sources of variability included gender, organ section, strain, and fasting state. These and other study factors were identified as key descriptors that should be included in the minimal information about a toxicogenomics study needed for interpretation of results by an independent source. Genes that are the most and least variable, gender-selective, or altered by fasting were also identified and functionally categorized. Better characterization of gene expression variability in control animals will aid in the design of toxicogenomics studies and in the interpretation of their results. C1 [Thompson, Karol L.] US FDA, CDER, Silver Spring, MD 20993 USA. [Boedigheimer, Michael J.; Bass, Michael B.] Amgen Inc, Thousand Oaks, CA 91320 USA. [Wolfinger, Russell D.] SAS Inst Inc, Cary, NC 27513 USA. [Bushel, Pierre R.; Chou, Jeff W.; Fostel, Jennifer] NIEHS, Res Triangle Pk, NC 27709 USA. [Cooper, Matthew] Roche Palo Alto LLC, Palo Alto, CA 94304 USA. [Corton, J. Christopher; Hester, Susan; Lee, Janice S.] US EPA, Res Triangle Pk, NC 27711 USA. [Liu, Fenglong; Quackenbush, John] Dana Farber Canc Inst, Boston, MA 02115 USA. [Liu, Jie] NIEHS, NCI, ICS, Res Triangle Pk, NC 27709 USA. [Qian, Hui-Rong] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Quackenbush, John] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Pettit, Syril] ILSI HESI, Washington, DC 20005 USA. RP Thompson, KL (reprint author), US FDA, CDER, Silver Spring, MD 20993 USA. EM mboedigh@amgen.com; Russ.Wolfinger@jmp.com; mbass@amgen.com; bushel@niehs.nih.gov; chou@niehs.nih.gov; matthew.cooper.mc1@roche.com; Corton.Chris@epamail.epa.gov; fostel@niehs.nih.gov; hester.susan@epa.gov; lee.janices@epa.gov; fliu@jimmy.harvard.edu; liu6@niehs.nih.gov; QIAN_HUI-RONG@LILLY.COM; johnq@jimmy.harvard.edu; spettit@ilsi.org; karol.thompson@fda.hhs.gov NR 32 TC 32 Z9 32 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD JUN 12 PY 2008 VL 9 AR 285 DI 10.1186/1471-2164-9-285 PG 16 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 327PR UT WOS:000257741500001 PM 18549499 ER PT J AU Mckay, R Kittappa, R AF McKay, Ron Kittappa, Raja TI Will stem cell biology generate new therapies for Parkinson's disease? SO NEURON LA English DT Editorial Material ID DOPAMINE NEURONS; DEGENERATION; PATHOLOGY; MICE AB Three papers recently published in Nature Medicine provide the most detailed analyses of fetal midbrain grafts in patients with Parkinson's disease. Some of the results are surprising and suggest a new wave of questions aimed at both the value of cell therapy and the nature of the disease itself. C1 [McKay, Ron; Kittappa, Raja] Natl Inst Neurol Disorders & Stroke, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Mckay, R (reprint author), Natl Inst Neurol Disorders & Stroke, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM ronmckay@mail.nih.gov NR 14 TC 23 Z9 24 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD JUN 12 PY 2008 VL 58 IS 5 BP 659 EP 661 DI 10.1016/j.neuron.2008.05.016 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 315IA UT WOS:000256870800004 PM 18549778 ER PT J AU Plested, AJR Vijayan, R Biggin, PC Mayer, ML AF Plested, Andrew J. R. Vijayan, Ranjit Biggin, Philip C. Mayer, Mark L. TI Molecular basis of kainate receptor modulation by sodium SO NEURON LA English DT Article ID LIGAND-BINDING CORE; GLUTAMATE-RECEPTOR; CRYSTAL-STRUCTURES; ION CHANNELS; MECHANISMS; ACTIVATION; SITES; AMPA; NA+; DESENSITIZATION AB Membrane proteins function in a polarized ionic environment with sodium-rich extracellular and potassium-rich intracellular solutions. Glutamate receptors that mediate excitatory synaptic transmission in the brain show unusual sensitivity to external ions, resulting in an apparent requirement for sodium in order for glutamate to activate kainate receptors. Here, we solve the structure of the Na+-binding sites and determine the mechanism by which allosteric anions and cations. regulate ligand-binding dimer stability, and hence the rate of desensitization and receptor availability for gating by glutamate. We establish a stoichiometry for binding of 2 Na+ to 1 Cl- and show that allosteric anions and cations bind at physically discrete sites with strong electric fields, that the binding sites are not saturated in CSF, and that the requirement of kainate receptors for Na+ occurs simply because other cations bind with lower affinity and have lower efficacy compared to Na+. C1 [Plested, Andrew J. R.; Mayer, Mark L.] NICHD, Lab Cellular & Mol Neurophysiol, Porter Neurosci Res Ctr, NIH,DHHS, Bethesda, MD 20892 USA. [Vijayan, Ranjit; Biggin, Philip C.] Univ Oxford, Dept Biochem, Oxford OX1 3QU, England. [Vijayan, Ranjit] Life Sci Interface Doctoral Training Ctr, Oxford OX1 3QD, England. RP Mayer, ML (reprint author), NICHD, Lab Cellular & Mol Neurophysiol, Porter Neurosci Res Ctr, NIH,DHHS, Bethesda, MD 20892 USA. EM mlm@helix.nih.gov RI Mayer, Mark/H-5500-2013; OI Vijayan, Ranjit/0000-0002-3830-7409; Plested, Andrew/0000-0001-6062-0832 FU Intramural NIH HHS [Z01 HD000707-23]; Wellcome Trust NR 43 TC 55 Z9 56 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD JUN 12 PY 2008 VL 58 IS 5 BP 720 EP 735 DI 10.1016/j.neuron.2008.04.001 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 315IA UT WOS:000256870800010 PM 18549784 ER PT J AU Suh, YH Pelkey, KA Lavezzari, G Roche, PA Huganir, RL McBain, CJ Roche, KW AF Suh, Young Ho Pelkey, Kenneth A. Lavezzari, Gabriela Roche, Paul A. Huganir, Richard L. McBain, Chris J. Roche, Katherine W. TI Corequirement of PICK1 binding and PKC phosphorylation for stable surface expression of the metabotropic glutamate receptor mGluR7 SO NEURON LA English DT Article ID LONG-TERM DEPRESSION; FIBER-INTERNEURON SYNAPSES; DOMAIN-CONTAINING PROTEINS; KINASE-C-ALPHA; AMPA RECEPTORS; CA2+-DEPENDENT INACTIVATION; PRESYNAPTIC LOCALIZATION; SYNAPTIC-TRANSMISSION; CALMODULIN-BINDING; COUPLED RECEPTORS AB The presynaptic metabotropic glutamate receptor (mGluR) mGluR7 modulates excitatory neurotransmission by regulating neurotransmitter release and plays a critical role in certain forms of synaptic plasticity. Although the dynamic regulation of mGluR7 surface expression governs a form of metaplasticity in the hippocampus, little is known about the molecular mechanisms regulating mGluR7 trafficking. We now show that mGluR7 surface expression is stabilized by both PKC phosphorylation and by receptor binding to the PDZ domain-containing protein PICK1. Phosphorylation of mGluR7 on serine 862 (S862) inhibits CaM binding, thereby increasing mGluR7 surface expression and receptor binding to PICK1. Furthermore, in mice lacking PICK1, PKC-dependent increases in mGluR7 phosphorylation and surface expression are diminished, and mGluR7-dependent plasticity at mossy fiber-interneuron hippocampal synapses is impaired. These data support a model in which PICK1 binding and PKC phosphorylation act together to stabilize mGluR7 on the cell surface in vivo. C1 [Suh, Young Ho; Lavezzari, Gabriela; Roche, Katherine W.] Natl Inst Neurol Disorders & Stroke, Bethesda, MD 20892 USA. [Suh, Young Ho; Roche, Paul A.] NCI, Bethesda, MD 20892 USA. [Pelkey, Kenneth A.; McBain, Chris J.] NICHHD, Lab Cellular & Synapt Neurophysiol, NIH, Bethesda, MD 20892 USA. [Huganir, Richard L.] Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21205 USA. RP Roche, KW (reprint author), Natl Inst Neurol Disorders & Stroke, Bethesda, MD 20892 USA. EM rochek@ninds.nih.gov OI Roche, Katherine/0000-0001-7282-6539 FU Intramural NIH HHS [Z01 NS003036-01, Z99 NS999999] NR 68 TC 43 Z9 43 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD JUN 12 PY 2008 VL 58 IS 5 BP 736 EP 748 DI 10.1016/j.neuron.2008.03.028 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 315IA UT WOS:000256870800011 PM 18549785 ER PT J AU Gerstein, HC Miller, ME Byington, RP Goff, DC Bigger, JT Buse, JB Cushman, WC Genuth, S Ismail-Beigi, F Grimm, RH Probstfield, JL Simons-Morton, DG Friedewald, WT AF Gerstein, Hertzel C. Miller, Michael E. Byington, Robert P. Goff, David C., Jr. Bigger, J. Thomas Buse, John B. Cushman, William C. Genuth, Saul Ismail-Beigi, Faramarz Grimm, Richard H., Jr. Probstfield, Jeffrey L. Simons-Morton, Denise G. Friedewald, William T. CA Act Control Cardiovasc Risk Diabet TI Effects of intensive glucose lowering in type 2 diabetes SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CONTROL CARDIOVASCULAR RISK; ACCORD TRIAL; GLYCEMIC CONTROL; MELLITUS; DESIGN; COMPLICATIONS; DISEASE; RATIONALE; ASSOCIATION; PREVENTION AB Background: Epidemiologic studies have shown a relationship between glycated hemoglobin levels and cardiovascular events in patients with type 2 diabetes. We investigated whether intensive therapy to target normal glycated hemoglobin levels would reduce cardiovascular events in patients with type 2 diabetes who had either established cardiovascular disease or additional cardiovascular risk factors. Methods: In this randomized study, 10,251 patients (mean age, 62.2 years) with a median glycated hemoglobin level of 8.1% were assigned to receive intensive therapy (targeting a glycated hemoglobin level below 6.0%) or standard therapy (targeting a level from 7.0 to 7.9%). Of these patients, 38% were women, and 35% had had a previous cardiovascular event. The primary outcome was a composite of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. The finding of higher mortality in the intensive-therapy group led to a discontinuation of intensive therapy after a mean of 3.5 years of follow-up. Results: At 1 year, stable median glycated hemoglobin levels of 6.4% and 7.5% were achieved in the intensive-therapy group and the standard-therapy group, respectively. During follow-up, the primary outcome occurred in 352 patients in the intensive-therapy group, as compared with 371 in the standard-therapy group (hazard ratio, 0.90; 95% confidence interval [CI], 0.78 to 1.04; P=0.16). At the same time, 257 patients in the intensive-therapy group died, as compared with 203 patients in the standard-therapy group (hazard ratio, 1.22; 95% CI, 1.01 to 1.46; P=0.04). Hypoglycemia requiring assistance and weight gain of more than 10 kg were more frequent in the intensive-therapy group (P<0.001). Conclusions: As compared with standard therapy, the use of intensive therapy to target normal glycated hemoglobin levels for 3.5 years increased mortality and did not significantly reduce major cardiovascular events. These findings identify a previously unrecognized harm of intensive glucose lowering in high-risk patients with type 2 diabetes. (ClinicalTrials.gov number, NCT00000620.). C1 [Miller, Michael E.; Byington, Robert P.; Goff, David C., Jr.] Wake Forest Univ, Sch Med, Div Publ Hlth Sci, Winston Salem, NC 27157 USA. [Gerstein, Hertzel C.] McMaster Univ, Hamilton, ON, Canada. [Gerstein, Hertzel C.] Hamilton Hlth Sci Populat Hlth Res Inst, Hamilton, ON, Canada. [Bigger, J. Thomas] Columbia Univ, Coll Phys & Surg, New York, NY USA. [Buse, John B.] Univ N Carolina, Sch Med, Chapel Hill, NC USA. [Cushman, William C.] Vet Affairs Med Ctr, Memphis, TN USA. [Genuth, Saul; Ismail-Beigi, Faramarz] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Grimm, Richard H., Jr.] Berman Ctr Outcomes & Clin Res, Minneapolis, MN USA. [Probstfield, Jeffrey L.] Univ Washington, Seattle, WA 98195 USA. [Simons-Morton, Denise G.] NHLBI, Bethesda, MD 20892 USA. [Friedewald, William T.] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. RP Byington, RP (reprint author), Wake Forest Univ, Sch Med, Div Publ Hlth Sci, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM bbyingto@wfubmc.edu RI Friedewald, William/C-8034-2011 NR 25 TC 3195 Z9 3303 U1 28 U2 218 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 12 PY 2008 VL 358 IS 24 BP 2545 EP 2559 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA 311IJ UT WOS:000256593600003 ER PT J AU Malozowski, S Nelson, L Calis, KA AF Malozowski, Saul Nelson, Lawrence Calis, Karim Anton TI More on ovarian insufficiency with imatinib SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Malozowski, Saul] NIDDKD, Bethesda, MD 20892 USA. [Nelson, Lawrence] NICHHD, Bethesda, MD 20892 USA. [Calis, Karim Anton] Mark O Hatfield Clin Res Ctr, Bethesda, MD 20892 USA. RP Malozowski, S (reprint author), NIDDKD, Bethesda, MD 20892 USA. EM sm87j@nih.gov NR 4 TC 6 Z9 6 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 12 PY 2008 VL 358 IS 24 BP 2648 EP 2648 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 311IJ UT WOS:000256593600038 PM 18550885 ER PT J AU Tetievsky, A Cohen, O Eli-Berchoer, L Gerstenblith, G Stern, MD Wapinski, I Friedman, N Horowitz, M AF Tetievsky, Anna Cohen, Omer Eli-Berchoer, Luba Gerstenblith, Gary Stern, Michael D. Wapinski, Ilan Friedman, Nir Horowitz, Michal TI Physiological and molecular evidence of heat acclimation memory: a lesson from thermal responses and ischemic cross-tolerance in the heart SO PHYSIOLOGICAL GENOMICS LA English DT Article DE cellular memory; cytoprotection; stress proteins; deacclimation; reacclimation ID SHOCK TRANSCRIPTION FACTOR; HYPOHYDRATION STRESS; NITRIC-OXIDE; RAT; PROTEINS; YEAST; GENE; PHOSPHORYLATION; EXPRESSION; ELEMENT AB Sporadic findings in humans suggest that reinduction of heat acclimation (AC) after its loss occurs markedly faster than that during the initial AC session. Animal studies substantiated that the underlying acclimatory processes are molecular. Here we test the hypothesis that faster reinduction of AC (ReAC) implicates "molecular memory." In vivo measurements of colonic temperature profiles during heat stress and ex vivo assessment of cross-tolerance to ischemia-reperfusion or anoxia insults in the heart demonstrated that ReAC only needs 2 days vs. the 30 days required for the initial development of AC. Stress gene profiling in the experimental groups highlighted clusters of transcriptionally activated genes (37%), which included heat shock protein (HSP) genes, antiapoptotic genes, and chromatin remodeling genes. Despite a return of the physiological phenotype to its preacclimation state, after a 1 mo deacclimation (DeAC) period, the gene transcripts did not resume their preacclimation levels, suggesting a dichotomy between genotype and phenotype in this system. Individual detection of hsp70 and hsf1 transcripts agreed with these findings. HSP72, HSF1/P-HSF1, and Bcl-xL protein profiles followed the observed dichotomized genomic response. In contrast, HSP90, an essential cytoprotective component mismatched transcriptional activation upon DeAC. The uniform activation of the similarly responding gene clusters upon De-/ReAC implies that reacclimatory phenotypic plasticity is associated with upstream denominators. During AC, DeAC, and ReAC, the maintenance of elevated/phosphorylated HSF1 protein levels and transcriptionally active chromatin remodeling genes implies that chromatin remodeling plays a pivotal role in the transcriptome profile and in preconditioning to rapid cytoprotective acclimatory memory. C1 [Tetievsky, Anna; Cohen, Omer; Eli-Berchoer, Luba; Horowitz, Michal] Hebrew Univ Jerusalem, Fac Med Dent, Environm Physiol Lab, IL-91120 Jerusalem, Israel. [Wapinski, Ilan; Friedman, Nir] Hebrew Univ Jerusalem, Sch Engn & Comp Sci, IL-91120 Jerusalem, Israel. [Gerstenblith, Gary] Johns Hopkins Univ, Dept Med Cardiol, Baltimore, MD USA. [Stern, Michael D.] NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. RP Horowitz, M (reprint author), Hebrew Univ Jerusalem, Fac Med Dent, Environm Physiol Lab, POB 12272, IL-91120 Jerusalem, Israel. EM horowitz@cc.huji.ac.il FU Intramural NIH HHS NR 45 TC 30 Z9 31 U1 2 U2 13 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 EI 1531-2267 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD JUN 12 PY 2008 VL 34 IS 1 BP 78 EP 87 DI 10.1152/physiolgenomics.00215.2007 PG 10 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 314OT UT WOS:000256819400009 PM 18430807 ER PT J AU Bethard, S Lu, ZY Martin, JH Hunter, L AF Bethard, Steven Lu, Zhiyong Martin, James H. Hunter, Lawrence TI Semantic role labeling for protein transport predicates SO BMC BIOINFORMATICS LA English DT Article ID INFORMATION; TEXT AB Background: Automatic semantic role labeling (SRL) is a natural language processing (NLP) technique that maps sentences to semantic representations. This technique has been widely studied in the recent years, but mostly with data in newswire domains. Here, we report on a SRL model for identifying the semantic roles of biomedical predicates describing protein transport in GeneRIFs - manually curated sentences focusing on gene functions. To avoid the computational cost of syntactic parsing, and because the boundaries of our protein transport roles often did not match up with syntactic phrase boundaries, we approached this problem with a word-chunking paradigm and trained support vector machine classifiers to classify words as being at the beginning, inside or outside of a protein transport role. Results: We collected a set of 837 GeneRIFs describing movements of proteins between cellular components, whose predicates were annotated for the semantic roles AGENT, PATIENT, ORIGIN and DESTINATION. We trained these models with the features of previous word-chunking models, features adapted from phrase-chunking models, and features derived from an analysis of our data. Our models were able to label protein transport semantic roles with 87.6% precision and 79.0% recall when using manually annotated protein boundaries, and 87.0% precision and 74.5% recall when using automatically identified ones. Conclusion: We successfully adapted the word-chunking classification paradigm to semantic role labeling, applying it to a new domain with predicates completely absent from any previous studies. By combining the traditional word and phrasal role labeling features with biomedical features like protein boundaries and MEDPOST part of speech tags, we were able to address the challenges posed by the new domain data and subsequently build robust models that achieved F-measures as high as 83.1. This system for extracting protein transport information from GeneRIFs performs well even with proteins identified automatically, and is therefore more robust than the rule-based methods previously used to extract protein transport roles. C1 [Lu, Zhiyong] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. [Bethard, Steven; Martin, James H.] Univ Colorado, Dept Comp Sci, Boulder, CO 80309 USA. [Hunter, Lawrence] Univ Colorado, Sch Med, Ctr Computat Pharmacol, Aurora, CO USA. RP Lu, ZY (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. EM steven.bethard@colorado.edu; luzh@ncbi.nlm.nih.gov; james.martin@colorado.edu; larry.hunter@uchsc.edu OI Hunter, Lawrence/0000-0003-1455-3370 FU Intramural NIH HHS; NLM NIH HHS [R01 LM008111, 5R01LM008111-03, R01 LM009254, R01LM009254] NR 56 TC 11 Z9 12 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD JUN 11 PY 2008 VL 9 AR 277 DI 10.1186/1471-2105-9-277 PG 15 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 328XS UT WOS:000257832100001 PM 18547432 ER PT J AU Ducut, E Liu, F Fontelo, P AF Ducut, Erick Liu, Fang Fontelo, Paul TI An update on Uniform Resource Locator (URL) decay in MEDLINE abstracts and measures for its mitigation SO BMC MEDICAL INFORMATICS AND DECISION MAKING LA English DT Article ID RESEARCH ARTICLES; READING HABITS; ACCURACY; JOURNALS AB Background: For years, Uniform Resource Locator (URL) decay or "link rot" has been a growing concern in the field of biomedical sciences. This paper addresses this issue by examining the status of the URLs published in MEDLINE abstracts, establishing current availability and estimating URL decay in these records from 1994 to 2006. We also reviewed the information provided by the URL to determine if the context that the author cited in writing the paper is the same information presently available in the URL. Lastly, with all the documented recommended methods to preserve URL links, we determined which among them have gained acceptance among authors and publishers. Methods: MEDLINE records from 1994 to 2006 from the National Library of Medicine in Extensible Mark-up Language (XML) format were processed yielding 10,208 URL addresses. These were accessed once daily at random times for 30 days. Titles and abstracts were also searched for the presence of archival tools such as WebCite, Persistent URL (PURL) and Digital Object Identifier (DOI). Results: Results showed that the average URL length ranged from 13 to 425 characters with a mean length of 35 characters [Standard Deviation (SD) = 13.51; 95% confidence interval (CI) 13.25 to 13.77]. The most common top-level domains were ".org" and ".edu", each with 34%. About 81% of the URL pool was available 90% to 100% of the time, but only 78% of these contained the actual information mentioned in the MEDLINE record. "Dead" URLs constituted 16% of the total. Finally, a survey of archival tool usage showed that since its introduction in 1998, only 519 of all abstracts reviewed had incorporated DOI addresses in their MEDLINE abstracts. Conclusion: URL persistence parallels previous studies which showed approximately 81% general availability during the 1-month study period. As peer-reviewed literature remains to be the main source of information in biomedicine, we need to ensure the accuracy and preservation of these links. C1 [Ducut, Erick; Liu, Fang; Fontelo, Paul] Natl Inst Hlth, Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20892 USA. RP Ducut, E (reprint author), Natl Inst Hlth, Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20892 USA. EM ducute@mail.nih.gov; fliu@mail.nih.gov; pfontelo@mail.nih.gov FU Intramural NIH HHS NR 14 TC 8 Z9 8 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6947 J9 BMC MED INFORM DECIS JI BMC Med. Inform. Decis. Mak. PD JUN 11 PY 2008 VL 8 AR 23 DI 10.1186/1472-6947-8-23 PG 8 WC Medical Informatics SC Medical Informatics GA 317BH UT WOS:000256993600001 PM 18547428 ER PT J AU Stiles, AR Qian, X Shears, SB Grabau, EA AF Stiles, Amanda R. Qian, Xun Shears, Stephen B. Grabau, Elizabeth A. TI Metabolic and signaling properties of an Itpk gene family in Glycine max SO FEBS LETTERS LA English DT Article DE phytate; InsP(6); soybean; ITPK; inositol; tetrakisphosphate ID INOSITOL 1,3,4-TRISPHOSPHATE 5/6-KINASE; SPIRODELA-POLYRHIZA L; PHOSPHATE KINASE; ARABIDOPSIS; PHYTATE; 3,4,5,6-TETRAKISPHOSPHATE; POLYPHOSPHATES; EXPRESSION; SEEDS; RICE AB We have cloned and characterized four Itpk genes from soybean. All four recombinant Itpk proteins showed canonical Ins(1,3,4)P-3 5/6-kinase activity, but a kinetic analysis raised questions about its biological significance. Instead, we provide evidence that one alternative biological role for soybean Itpks is to interconvert the Cl- channel inhibitor, Ins(3,4,5,6)P-4, and its metabolic precursor, Ins(I,3,4,5,6)P-5, within a substrate cycle. The soybean Itpks also phosphorylated Ins(3,4,6)P-3 to Ins(1,3,4,6)P-4 which was further phosphorylated to Ins(1,3,4,5,6)P-5 by soybean Ipk2. Thus, soybean Itpks may participate in an inositol lipid-independent pathway Of InsP(6) synthesis. (c) 2008 Federation of European Biochemical Societies. All rights reserved. C1 [Stiles, Amanda R.; Grabau, Elizabeth A.] Virginia Polytech Inst & State Univ, Dept Plant Pathol Physiol & Weed Sci, Blacksburg, VA 24061 USA. [Qian, Xun; Shears, Stephen B.] NIEHS, Lab Signal Transduct, NIH, DHSS, Res Triangle Pk, NC 27709 USA. RP Grabau, EA (reprint author), Virginia Polytech Inst & State Univ, Dept Plant Pathol Physiol & Weed Sci, 413 Price Hall, Blacksburg, VA 24061 USA. EM egrabau@vt.edu FU Intramural NIH HHS [Z01 ES080046-19] NR 26 TC 8 Z9 11 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JUN 11 PY 2008 VL 582 IS 13 BP 1853 EP 1858 DI 10.1016/j.febslet.2008.04.054 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 318EG UT WOS:000257073800012 PM 18474240 ER PT J AU Schetter, AJ Harris, CC AF Schetter, Aaron J. Harris, Curtis C. TI MicroRNA expression in colon adenocarcinoma - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID CANCER C1 [Schetter, Aaron J.; Harris, Curtis C.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. RP Schetter, AJ (reprint author), NCI, Ctr Canc Res, Bethesda, MD 20892 USA. EM curtis_harris@nih.gov NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 11 PY 2008 VL 299 IS 22 BP 2628 EP 2629 DI 10.1001/jama.299.22.2628-b PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 311FN UT WOS:000256586200017 ER PT J AU Alvarez, RP Biggs, A Chen, G Pine, DS Grillon, C AF Alvarez, Ruben P. Biggs, Arter Chen, Gang Pine, Daniel S. Grillon, Christian TI Contextual fear conditioning in humans: Cortical-hippocampal and amygdala contributions SO JOURNAL OF NEUROSCIENCE LA English DT Article DE classical conditioning; pavlovian conditioning; context conditioning; fMRI; psychophysiology; anxiety ID MEDIAL PREFRONTAL CORTEX; MACAQUE MONKEYS; POTENTIATED STARTLE; INSULAR CORTICES; EXTINCTION; FMRI; BRAIN; CONNECTIONS; RATS; INFORMATION AB Functional imaging studies of cued fear conditioning in humans have mostly confirmed findings in animals, but it is unclear whether the brain mechanisms that underlie contextual fear conditioning in animals are also preserved in humans. We investigated this issue using functional magnetic resonance imaging and virtual reality contexts. Subjects underwent differential context conditioning in which they were repeatedly exposed to two contexts (CXT+ and CXT-) in semirandom order, with contexts counterbalanced across participants. An unsignaled footshock was consistently paired with the CXT+, and no shock was ever delivered in the CXT-. Evidence for context conditioning was established using skin conductance and anxiety ratings. Consistent with animal models centrally implicating the hippocampus and amygdala in a network supporting context conditioning, CXT+ compared with CXT-significantly activated right anterior hippocampus and bilateral amygdala. In addition, context conditioning was associated with activation in posterior orbitofrontal cortex, medial dorsal thalamus, anterior insula, subgenual anterior cingulate, and parahippocampal, inferior frontal, and parietal cortices. Structural equation modeling was used to assess interactions among the core brain regions mediating context conditioning. The derived model indicated that medial amygdala was the source of key efferent and afferent connections including input from orbitofrontal cortex. These results provide evidence that similar brain mechanisms may underlie contextual fear conditioning across species. C1 [Alvarez, Ruben P.; Biggs, Arter; Pine, Daniel S.; Grillon, Christian] NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. RP Alvarez, RP (reprint author), NIMH, Mood & Anxiety Disorders Program, NIH, 15K North Dr,MSC 2670, Bethesda, MD 20892 USA. EM alvarezr@mail.nih.gov FU Intramural NIH HHS [Z99 MH999999] NR 66 TC 139 Z9 139 U1 6 U2 29 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUN 11 PY 2008 VL 28 IS 24 BP 6211 EP 6219 DI 10.1523/JNEUROSCI.1246-08.2008 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 312JU UT WOS:000256668500016 PM 18550763 ER PT J AU Bonsi, P Martella, G Cuomo, D Platania, P Sciamanna, G Bernardi, G Wess, J Pisani, A AF Bonsi, Paola Martella, Giuseppina Cuomo, Dario Platania, Paola Sciamanna, Giuseppe Bernardi, Giorgio Wess, Juergen Pisani, Antonio TI Loss of muscarinic autoreceptor function impairs long-term depression but not long-term potentiation in the striatum SO JOURNAL OF NEUROSCIENCE LA English DT Article DE cholinergic interneuron; long-term depression; long-term potentiation; striatal slices; electrophysiology; muscarine ID RECEPTOR KNOCKOUT MICE; MEDIUM SPINY NEURONS; NEOSTRIATAL CHOLINERGIC INTERNEURONS; SYNAPTIC DEPRESSION; RAT NEOSTRIATUM; ACETYLCHOLINE-RECEPTORS; MEDIATED MODULATION; CA2+ CURRENTS; N-TYPE; P-TYPE AB Muscarinic autoreceptors regulate cholinergic tone in the striatum. We investigated the functional consequences of genetic deletion of striatal muscarinic autoreceptors by means of electrophysiological recordings from either medium spiny neurons (MSNs) or cholinergic interneurons (ChIs) in slices from single M-4 or double M-2/M-4 muscarinic acetylcholine receptor (mAChR) knock-out (-/-) mice. In control ChIs, the muscarinic agonist oxotremorine (300 nM) produced a self-inhibitory outward current that was mostly reduced in M-4(-/)-and abolished in M-2/M-4(-/)-mice, suggesting an involvement of both M-2 and M-4 autoreceptors. In MSNs from both M-4(-/)-and M-2/M-4(-/)-mice, muscarine caused a membrane depolarization that was prevented by the M-1 receptor-preferring antagonist pirenzepine (100 nM), suggesting that M-1 receptor function was unaltered. Acetylcholine has been involved in striatal long-term potentiation (LTP) or long-term depression (LTD) induction. Loss of muscarinic autoreceptor function is predicted to affect synaptic plasticity by modifying striatal cholinergic tone. Indeed, high-frequency stimulation of glutamatergic afferents failed to induce LTD in MSNs from both M-4(-/)-and M-2/M-4(-/)-mice, as well as in wild-type mice pretreated with the M-2/M-4 antagonist AF-DX384 (11-[[2-[(diethylamino)methyl]-1-piperidinyl] acetyl]-5,1 1-dihydro-6H-pyrido[2,3b][ 1,4] benzodiazepin-6-one). Interestingly, LTD could be restored by either pirenzepine (100 nM) or hemicholinium-3 (10 mu M), a depletor of endogenous ACh. Conversely, LTP induction did not show any difference among the three mouse strains and was prevented by pirenzepine. These results demonstrate that M-2/M-4 muscarinic autoreceptors regulate ACh release from striatal ChIs. As a consequence, endogenous ACh drives the polarity of bidirectional synaptic plasticity. C1 [Martella, Giuseppina; Cuomo, Dario; Platania, Paola; Sciamanna, Giuseppe; Bernardi, Giorgio; Pisani, Antonio] Univ Roma Tor Vergata, Dept Neurosci, I-00133 Rome, Italy. [Bonsi, Paola; Sciamanna, Giuseppe; Bernardi, Giorgio; Pisani, Antonio] Fdn Santa Lucia, Inst Ricovero & Cura Carattere Sci, I-00146 Rome, Italy. [Wess, Juergen] NIDDK, Mol Signaling Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Pisani, A (reprint author), Univ Roma Tor Vergata, Dept Neurosci, Via Montpellier 1, I-00133 Rome, Italy. EM pisani@uniroma2.it RI Sciamanna, Giuseppe/B-6553-2013; yu, yan/C-2322-2012; Bonsi, Paola/K-4688-2012 OI Sciamanna, Giuseppe/0000-0002-0070-1638; Bonsi, Paola/0000-0001-5940-9028 FU Intramural NIH HHS NR 35 TC 39 Z9 39 U1 0 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUN 11 PY 2008 VL 28 IS 24 BP 6258 EP 6263 DI 10.1523/JNEUROSCI.1678-08.2008 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 312JU UT WOS:000256668500021 PM 18550768 ER PT J AU Nunez, J Celi, FS Ng, L Forrest, D AF Nunez, Jacques Celi, Francesco S. Ng, Lily Forrest, Douglas TI Multigenic control of thyroid hormone functions in the nervous system SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Review DE thyroid hormone receptor; deiodinase; neuronal differentiation; central nervous system; retina; cochlea ID TYPE-2 IODOTHYRONINE DEIODINASE; MICROTUBULE-ASSOCIATED PROTEINS; NEONATAL-RAT-BRAIN; IMPAIRS SYNAPTIC-TRANSMISSION; CEREBRAL GLUCOSE-UTILIZATION; DEPENDENT GENE-EXPRESSION; TRANSGENIC MICE BEARING; HERNDON-DUDLEY-SYNDROME; EMBRYONIC STEM-CELLS; KNOCK-IN MOUSE AB Thyroid hormone (TH) has a remarkable range of actions in the development and function of the nervous system. A multigenic picture is emerging of the mechanisms that specify these diverse functions in target tissues. Distinct responses are mediated by alpha and beta isoforms of TH receptor which act as ligand-regulated transcription factors. Receptor activity can be regulated at several levels including that of uptake of TH ligand and the activation or inactivation of ligand by deiodinase enzymes in target tissues. Processes under the control of TH range from learning and anxiety-like behaviour to sensory function. At the cellular level, TH controls events as diverse as axonal outgrowth, hippocampal synaptic activity and the patterning of opsin photopigments necessary for colour vision. Overall, TH coordinates this variety of events in both central and sensory systems to promote the function of the nervous system as a complete entity. Published by Elsevier Ireland Ltd. C1 [Nunez, Jacques; Celi, Francesco S.; Ng, Lily; Forrest, Douglas] NIDDK, NIH, Clin Endocrinol Branch, Bethesda, MD 20892 USA. RP Forrest, D (reprint author), NIDDK, NIH, Clin Endocrinol Branch, 10 Ctr Dr,Bldg 10,Room 8N307, Bethesda, MD 20892 USA. EM jnunez@mail.nih.gov; fc93a@nih.gov; ngl@niddk.nih.gov; forrestd@niddk.nih.gov FU Intramural NIH HHS [Z01 DK047043-01] NR 198 TC 41 Z9 44 U1 1 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD JUN 11 PY 2008 VL 287 IS 1-2 BP 1 EP 12 DI 10.1016/j.mce.2008.03.006 PG 12 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 316XD UT WOS:000256982100001 PM 18448240 ER PT J AU Zhao, MH Sharma, V Wei, HY Birge, RR Stuart, JA Papadimitrakopoulos, F Huey, BD AF Zhao, Minhua Sharma, Vaneet Wei, Haoyan Birge, Robert R. Stuart, Jeffrey A. Papadimitrakopoulos, Fotios Huey, Bryan D. TI Ultrasharp and high aspect ratio carbon nanotube atomic force microscopy probes for enhanced surface potential imaging SO NANOTECHNOLOGY LA English DT Article ID SELF-ASSEMBLED MONOLAYERS; KELVIN PROBE; ULTRAHIGH-VACUUM; SCALE VARIATIONS; RESOLUTION; DEPOSITION; INTERFACE; TIP; AFM; BACTERIORHODOPSIN AB The resolution of scanning surface potential microscopy (SSPM) is mainly limited by non-local electrostatic interactions due to the finite probe size. Here we present high resolution surface potential imaging with ultrasharp and high aspect ratio carbon nanotube (CNT) atomic force microscopy (AFM) probes fabricated via dielectrophoresis. Enhancement of surface potential contrast by several factors is reported for integrated circuit structures and purple membrane fragments for these CNT AFM probes as compared to conventional probes. In particular, ultrahigh lateral resolution (similar to 2 nm) surface potential images of self- assembled bacteriorhodopsin proteins are reported at ambient conditions, with the implication of label- free protein detection by SSPM techniques. C1 [Zhao, Minhua; Sharma, Vaneet; Wei, Haoyan; Birge, Robert R.; Stuart, Jeffrey A.; Papadimitrakopoulos, Fotios; Huey, Bryan D.] Univ Connecticut, Inst Mat Sci, Storrs, CT USA. RP Zhao, MH (reprint author), NIST, Natl Res Council, NIH, Joint Res Associateship Programs, Bethesda, MD 20892 USA. EM minhua.zhao@nist.gov; bhuey@ims.uconn.edu RI Zhao, Minhua/A-6678-2009; Wei, Haoyan/B-3779-2008; Huey, Bryan/G-7512-2014 OI Zhao, Minhua/0000-0003-4880-1010; Huey, Bryan/0000-0002-1441-1180 NR 47 TC 26 Z9 26 U1 0 U2 17 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0957-4484 EI 1361-6528 J9 NANOTECHNOLOGY JI Nanotechnology PD JUN 11 PY 2008 VL 19 IS 23 AR 235704 DI 10.1088/0957-4484/19/23/235704 PG 7 WC Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied SC Science & Technology - Other Topics; Materials Science; Physics GA 298BZ UT WOS:000255662700028 PM 21825803 ER PT J AU Agarwal, V Kommaddi, RP Valli, K Ryder, D Hyde, TM Kleinman, JE Strobel, HW Ravindranath, V AF Agarwal, Varsha Kommaddi, Reddy P. Valli, Khader Ryder, Daniel Hyde, Thomas M. Kleinman, Joel E. Strobel, Henry W. Ravindranath, Vijayalakshmi TI Drug Metabolism in Human Brain: High Levels of Cytochrome P4503A43 in Brain and Metabolism of Anti-Anxiety Drug Alprazolam to Its Active Metabolite SO PLOS ONE LA English DT Article AB Cytochrome P450 (P450) is a super-family of drug metabolizing enzymes. P450 enzymes have dual function; they can metabolize drugs to pharmacologically inactive metabolites facilitating their excretion or biotransform them to pharmacologically active metabolites which may have longer half-life than the parent drug. The variable pharmacological response to psychoactive drugs typically seen in population groups is often not accountable by considering dissimilarities in hepatic metabolism. Metabolism in brain specific nuclei may play a role in pharmacological modulation of drugs acting on the CNS and help explain some of the diverse response to these drugs seen in patient population. P450 enzymes are also present in brain where drug metabolism can take place and modify therapeutic action of drugs at the site of action. We have earlier demonstrated an intrinsic difference in the biotransformation of alprazolam (ALP) in brain and liver, relatively more alpha-hydroxy alprazolam (alpha-OHALP) is formed in brain as compared to liver. In the present study we show that recombinant CYP3A43 metabolizes ALP to both alpha-OHALP and 4-hydroxy alprazolam (4-OHALP) while CYP3A4 metabolizes ALP predominantly to its inactive metabolite, 4-OHALP. The expression of CYP3A43 mRNA in human brain samples correlates with formation of relatively higher levels of alpha-OH ALP indicating that individuals who express higher levels of CYP3A43 in the brain would generate larger amounts of alpha-OHALP. Further, the expression of CYP3A43 was relatively higher in brain as compared to liver across different ethnic populations. Since CYP3A enzymes play a prominent role in the metabolism of drugs, the higher expression of CYP3A43 would generate metabolite profile of drugs differentially in human brain and thus impact the pharmacodynamics of psychoactive drugs at the site of action. C1 [Agarwal, Varsha; Kommaddi, Reddy P.; Valli, Khader; Ravindranath, Vijayalakshmi] Natl Brain Res Ctr, Div Mol & Cellular Neurosci, Nainwal Mode, Manesar, India. [Ryder, Daniel; Strobel, Henry W.] Univ Texas, Med Sch, Dept Biochem & Mol Biol, Houston, TX USA. [Hyde, Thomas M.; Kleinman, Joel E.] NIMH, NIH, DIRP, Sect Neuropathol,Clin Brain Disorders Branch, Bethesda, MD USA. RP Agarwal, V (reprint author), Natl Brain Res Ctr, Div Mol & Cellular Neurosci, Nainwal Mode, Manesar, India. EM vijir@nbrc.ac.in FU National Institutes of Health [MH 70054] FX This work was supported by National Institutes of Health grant MH 70054 to HWS and VR. NR 27 TC 27 Z9 30 U1 1 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 11 PY 2008 VL 3 IS 6 AR e2337 DI 10.1371/journal.pone.0002337 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 405UD UT WOS:000263248800007 PM 18545703 ER PT J AU Braun, A McArdle, J Jones, J Nechaev, V Zalewski, C Brewer, C Drayna, D AF Braun, Allen McArdle, Joe Jones, Jennifer Nechaev, Vladimir Zalewski, Christopher Brewer, Carmen Drayna, Dennis TI Tune Deafness: Processing Melodic Errors Outside of Conscious Awareness as Reflected by Components of the Auditory ERP SO PLOS ONE LA English DT Article ID CONGENITAL AMUSIA; TONE-DEAFNESS; FREQUENCY; CORTEX; RECOGNITION; KNOWLEDGE; GENETICS; HEARING; BRAIN; P300 AB Tune deafness (TD) is a central auditory processing disorder characterized by the inability to discriminate pitch, reproduce melodies or to recognize deviations in melodic structure, in spite of normal hearing. The cause of the disorder is unknown. To identify a pathophysiological marker, we ascertained a group of severely affected TD patients using the Distorted Tunes Test, an ecologically valid task with a longstanding history, and used electrophysiological methods to characterize the brain's responses to correct and incorrect melodic sequences. As expected, we identified a neural correlate of patients' unawareness of melodic distortions: deviant notes modulated long-latency auditory evoked potentials and elicited a mismatch negativity in controls but not in affected subjects. However a robust P300 was elicited by deviant notes, suggesting that, as in blindsight, TD subjects process stimuli that they cannot consciously perceive. Given the high heritability of TD, these patients may make it possible to use genetic methods to study cellular and molecular mechanisms underlying conscious awareness. C1 [Braun, Allen; McArdle, Joe; Nechaev, Vladimir] Natl Inst Deafness & Other Commun Disorders, Language Sect, NIH, Bethesda, MD USA. [Jones, Jennifer; Drayna, Dennis] NIH, National Inst Deafness & Other Commun Disorders, Sect Syst Biol Commun Disorders, Bethesda, MD USA. [Zalewski, Christopher; Brewer, Carmen] NIH, Natl Inst Deafness & Other Commun Disorders, Audiol Unit, Bethesda, MD USA. RP Braun, A (reprint author), Natl Inst Deafness & Other Commun Disorders, Language Sect, NIH, Bethesda, MD USA. EM brauna@nidcd.nih.gov FU Intramural Program of the National Institute on Deafness and other Communications Disroders FX This work was supported by the Intramural Program of the National Institute on Deafness and other Communications Disroders. NR 29 TC 9 Z9 9 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 11 PY 2008 VL 3 IS 6 AR e2349 DI 10.1371/journal.pone.0002349 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 405UD UT WOS:000263248800010 PM 18545651 ER PT J AU Greene, JM Burwitz, BJ Blasky, AJ Mattila, TL Hong, JJ Rakasz, EG Wiseman, RW Hasenkrug, KJ Skinner, PJ O'Connor, SL O'Connor, DH AF Greene, Justin M. Burwitz, Benjamin J. Blasky, Alex J. Mattila, Teresa L. Hong, Jung Joo Rakasz, Eva G. Wiseman, Roger W. Hasenkrug, Kim J. Skinner, Pamela J. O'Connor, Shelby L. O'Connor, David H. TI Allogeneic Lymphocytes Persist and Traffic in Feral MHC-Matched Mauritian Cynomolgus Macaques SO PLOS ONE LA English DT Article AB Background: Thus far, live attenuated SIV has been the most successful method for vaccinating macaques against pathogenic SIV challenge; however, it is not clear what mechanisms are responsible for this protection. Adoptive transfer studies in mice have been integral to understanding live attenuated vaccine protection in models like Friend virus. Previous adoptive transfers in primates have failed as transferred cells are typically cleared within hours after transfer. Methodology/Principal Findings: Here we describe adoptive transfer studies in Mauritian origin cynomolgus macaques (MCM), a non-human primate model with limited MHC diversity. Cells transferred between unrelated MHC-matched macaques persist for at least fourteen days but are rejected within 36 hours in MHC-mismatched macaques. Cells trafficked from the blood to peripheral lymphoid tissues within 12 hours of transfer. Conclusions/Significance: MHC-matched MCM provide the first viable primate model for adoptive transfer studies. Because macaques infected with SIV are the best model for HIV/AIDS pathogenesis, we can now directly study the correlates of protective immune responses to AIDS viruses. For example, plasma viral loads following pathogenic SIV challenge are reduced by several orders of magnitude in macaques previously immunized with attenuated SIV. Adoptive transfer of lymphocyte subpopulations from vaccinated donors into SIV-naive animals may define the immune mechanisms responsible for protection and guide future vaccine development. C1 [Greene, Justin M.; Burwitz, Benjamin J.; O'Connor, Shelby L.; O'Connor, David H.] Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53706 USA. [Blasky, Alex J.; Rakasz, Eva G.; Wiseman, Roger W.; O'Connor, David H.] Univ Wisconsin, Wisconsin Natl Primate Res Ctr, Madison, WI USA. [Mattila, Teresa L.; Hong, Jung Joo; Skinner, Pamela J.] Univ Minnesota, Dept Vet & Biomed Sci, St Paul, MN USA. [Hasenkrug, Kim J.] NIH, NIAID, Rocky Mountain Lab, Lab Persistent Viral Dis, Hamilton, MT USA. RP Greene, JM (reprint author), Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53706 USA. EM doconnor@primate.wisc.edu OI o'connor, david/0000-0003-2139-470X; Skinner, Pamela/0000-0003-3388-1687 FU International AIDS Vaccine Initiative (IAVI) [133-JH10]; NIH [1R21AI068488-01A2, RR021745-01A1]; National Center for Research Resources (NCRR) [P51 RR000167] FX This work was supported by International AIDS Vaccine Initiative (IAVI) grant 133-JH10; and NIH grants 1R21AI068488-01A2 and RR021745-01A1. This publication was made possible in part by grant number P51 RR000167 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), to the Wisconsin National Primate Research Center, University of Wisconsin-Madison. This research was conducted in part at a facility constructed with support from Research Facilities Improvement Program grant numbers RR15459-01 and RR020141-01. NR 47 TC 16 Z9 16 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 11 PY 2008 VL 3 IS 6 AR e2384 DI 10.1371/journal.pone.0002384 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 405UD UT WOS:000263248800023 PM 18545705 ER PT J AU Guerreiro, RJ Schymick, JC Crews, C Singleton, A Hardy, J Traynor, BJ AF Guerreiro, Rita J. Schymick, Jennifer C. Crews, Cynthia Singleton, Andrew Hardy, John Traynor, Bryan J. TI TDP-43 Is Not a Common Cause of Sporadic Amyotrophic Lateral Sclerosis SO PLOS ONE LA English DT Article AB Background: TAR DNA binding protein, encoded by TARDBP, was shown to be a central component of ubiquitin-positive, tau-negative inclusions in frontotemporal lobar degeneration (FTLD-U) and amyotrophic lateral sclerosis (ALS). Recently, mutations in TARDBP have been linked to familial and sporadic ALS. Methodology/Principal Findings: To further examine the frequency of mutations in TARDBP in sporadic ALS, 279 ALS cases and 806 neurologically normal control individuals of European descent were screened for sequence variants, copy number variants, genetic and haplotype association with disease. An additional 173 African samples from the Human Gene Diversity Panel were sequenced as this population had the highest likelihood of finding changes. No mutations were found in the ALS cases. Several genetic variants were identified in controls, which were considered as non-pathogenic changes. Furthermore, pathogenic structural variants were not observed in the cases and there was no genetic or haplotype association with disease status across the TARDBP locus. Conclusions: Our data indicate that genetic variation in TARDBP is not a common cause of sporadic ALS in North American. C1 [Guerreiro, Rita J.; Schymick, Jennifer C.; Crews, Cynthia; Singleton, Andrew; Traynor, Bryan J.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Guerreiro, Rita J.] Univ Coimbra, Ctr Neurosci & Cell Biol, Coimbra, Portugal. [Schymick, Jennifer C.] Univ Oxford, Dept Physiol, Anat & Genet, Oxford, England. [Hardy, John] Inst Neurol, Dept Mol Neurosci, Reta Lila Weston Inst, London, England. [Hardy, John] Inst Neurol, Dept Neurodegen Dis, Reta Lila Weston Inst, London, England. [Traynor, Bryan J.] NIH, NINDS, Neurogenet Branch, Bethesda, MD USA. RP Guerreiro, RJ (reprint author), NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. EM portalegrer@nia.nih.gov RI Singleton, Andrew/C-3010-2009; Guerreiro, Rita/A-1327-2011; Traynor, Bryan/G-5690-2010 FU ALS Association; Packard Center for ALS Research at Hopkins; NIA [1 Z01 AG000951-06]; NINDS; Fundacao para a Ciencia e Tecnologia, Portugal [SFRH/BD/27442/2006] FX This study was supported by grants from the ALS Association, the Packard Center for ALS Research at Hopkins, the intramural programs of NIA (1 Z01 AG000951-06) and NINDS and grant #SFRH/BD/27442/2006 from Fundacao para a Ciencia e Tecnologia, Portugal. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 30 TC 50 Z9 52 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 11 PY 2008 VL 3 IS 6 AR e2450 DI 10.1371/journal.pone.0002450 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 405UD UT WOS:000263248800058 PM 18545701 ER PT J AU Martin, B Pearson, M Brenneman, R Golden, E Keselman, A Iyun, T Carlson, OD Egan, JM Becker, KG Wood, W Prabhu, V de Cabo, R Maudsley, S Mattson, MP AF Martin, Bronwen Pearson, Michele Brenneman, Randall Golden, Erin Keselman, Alex Iyun, Titilola Carlson, Olga D. Egan, Josephine M. Becker, Kevin G. Wood, William, III Prabhu, Vinayakumar de Cabo, Rafael Maudsley, Stuart Mattson, Mark P. TI Conserved and Differential Effects of Dietary Energy Intake on the Hippocampal Transcriptomes of Females and Males SO PLOS ONE LA English DT Article AB The level of dietary energy intake influences metabolism, reproductive function, the development of age-related diseases, and even cognitive behavior. Because males and females typically play different roles in the acquisition and allocation of energy resources, we reasoned that dietary energy intake might differentially affect the brains of males and females at the molecular level. To test this hypothesis, we performed a gene array analysis of the hippocampus in male and female rats that had been maintained for 6 months on either ad libitum (control), 20% caloric restriction (CR), 40% CR, intermittent fasting (IF) or high fat/high glucose (HFG) diets. These diets resulted in expected changes in body weight, and circulating levels of glucose, insulin and leptin. However, the CR diets significantly increased the size of the hippocampus of females, but not males. Multiple genes were regulated coherently in response to energy restriction diets in females, but not in males. Functional physiological pathway analyses showed that the 20% CR diet down-regulated genes involved in glycolysis and mitochondrial ATP production in males, whereas these metabolic pathways were up-regulated in females. The 40% CR diet up-regulated genes involved in glycolysis, protein deacetylation, PGC-1 alpha and mTor pathways in both sexes. IF down-regulated many genes in males including those involved in protein degradation and apoptosis, but up-regulated many genes in females including those involved in cellular energy metabolism, cell cycle regulation and protein deacetylation. Genes involved in energy metabolism, oxidative stress responses and cell death were affected by the HFG diet in both males and females. The gender-specific molecular genetic responses of hippocampal cells to variations in dietary energy intake identified in this study may mediate differential behavioral responses of males and females to differences in energy availability. C1 [Martin, Bronwen; Pearson, Michele; Brenneman, Randall; Golden, Erin; Keselman, Alex; Iyun, Titilola; Maudsley, Stuart; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. [Carlson, Olga D.; Egan, Josephine M.] NIA, Lab Clin Invest, Intramural Res Program, Baltimore, MD USA. [Becker, Kevin G.; Wood, William, III; Prabhu, Vinayakumar] NIA, Gene Expression & Genom Unit, Intramural Res Program, Baltimore, MD USA. [de Cabo, Rafael] NIA, Lab Expt Gerontol, Intramural Res Program, Baltimore, MD USA. [Mattson, Mark P.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD USA. RP Martin, B (reprint author), NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. EM martinbro@grc.nia.nih.gov RI de Cabo, Rafael/E-7996-2010; Mattson, Mark/F-6038-2012; de Cabo, Rafael/J-5230-2016; OI de Cabo, Rafael/0000-0002-3354-2442; Becker, Kevin/0000-0002-6794-6656; , rafael/0000-0003-2830-5693 FU Intramural Research Program of the National Institute on Aging FX This work was supported by the Intramural Research Program of the National Institute on Aging. NR 44 TC 36 Z9 36 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 11 PY 2008 VL 3 IS 6 AR e2398 DI 10.1371/journal.pone.0002398 PG 18 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 405UD UT WOS:000263248800036 PM 18545695 ER PT J AU Gonzalez, FM Shiva, S Vincent, PS Ringwood, LA Hsu, LY Hon, YY Aletras, AH Cannon, RO Gladwin, MT Arai, AE AF Gonzalez, Felix M. Shiva, Sruti Vincent, Pamela S. Ringwood, Lorna A. Hsu, Li-Yueh Hon, Yuen Yi Aletras, Anthony H. Cannon, Richard O., III Gladwin, Mark T. Arai, Andrew E. TI Nitrite anion provides potent cytoprotective and antiapoptotic effects as adjunctive therapy to reperfusion for acute myocardial infarction SO CIRCULATION LA English DT Article DE apoptosis; ischemia; magnetic resonance imaging; myocardial infarction; nitric oxide ID FATTY-ACID TRANSDUCTION; REGIONAL BLOOD-FLOW; IN-VIVO; ISCHEMIA/REPERFUSION INJURY; ISCHEMIA-REPERFUSION; NITROLINOLEIC ACID; HYPOXIC CONDITIONS; HUMAN CIRCULATION; N-NITROSO; OXIDE AB Background - Accumulating evidence suggests that the ubiquitous anion nitrite (NO2-) is a physiological signaling molecule, with roles in intravascular endocrine nitric oxide transport, hypoxic vasodilation, signaling, and cytoprotection. Thus, nitrite could enhance the efficacy of reperfusion therapy for acute myocardial infarction. The specific aims of this study were (1) to assess the efficacy of nitrite in reducing necrosis and apoptosis in canine myocardial infarction and (2) to determine the relative role of nitrite versus chemical intermediates, such as S-nitrosothiols. Methods and Results - We evaluated infarct size, microvascular perfusion, and left ventricular function by histopathology, microspheres, and magnetic resonance imaging in 27 canines subjected to 120 minutes of coronary artery occlusion. This was a blinded, prospective study comparing a saline control group (n = 9) with intravenous nitrite during the last 60 minutes of ischemia (n = 9) and during the last 5 minutes of ischemia (n = 9). In saline-treated control animals, 70 +/- 10% of the area at risk was infarcted compared with 23 +/- 5% in animals treated with a 60-minute nitrite infusion. Remarkably, a nitrite infusion in the last 5 minutes of ischemia also limited the extent of infarction (36 +/- 8% of area at risk). Nitrite improved microvascular perfusion, reduced apoptosis, and improved contractile function. S-Nitrosothiol and iron-nitrosyl-protein adducts did not accumulate in the 5-minute nitrite infusion, suggesting that nitrite is the bioactive intravascular nitric oxide species accounting for cardioprotection. Conclusions - Nitrite has significant potential as adjunctive therapy to enhance the efficacy of reperfusion therapy for acute myocardial infarction. C1 [Gonzalez, Felix M.; Vincent, Pamela S.; Hsu, Li-Yueh; Aletras, Anthony H.; Cannon, Richard O., III; Arai, Andrew E.] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA. [Shiva, Sruti; Ringwood, Lorna A.; Gladwin, Mark T.] NHLBI, Pulm Vasc Med Branch, Bethesda, MD 20892 USA. [Shiva, Sruti; Ringwood, Lorna A.; Gladwin, Mark T.] Natl Inst Hlth, Dept Crit Care Med, Bethesda, MD USA. [Hon, Yuen Yi] Natl Inst Hlth, Ctr Clin, Dept Pharm, Bethesda, MD USA. [Gonzalez, Felix M.] Natl Inst Hlth, Res Scholars Program, Howard Hughes Med Inst, Bethesda, MD USA. RP Arai, AE (reprint author), NHLBI, Translat Med Branch, NIH, Bldg 10,Room B1D416,MSC 1061,10 Ctr Dr, Bethesda, MD 20892 USA. EM araia@nih.gov OI Aletras, Anthony/0000-0002-3786-3817 FU Intramural NIH HHS [Z99 HL999999, Z01 HL004607-09, ZIA HL005111-05, ZIA HL005111-06, ZIA HL005112-05, ZIA HL006136-01] NR 47 TC 113 Z9 122 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 10 PY 2008 VL 117 IS 23 BP 2986 EP 2994 DI 10.1161/CIRCULATIONAHA.107.748814 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 311CB UT WOS:000256576600005 PM 18519850 ER PT J AU Terashvili, M Wu, HE Schwasinger, ET Hung, KC Hong, JS Tseng, LF AF Terashvili, Maia Wu, Hsiang-En Schwasinger, Emma T. Hung, Kuei-Chun Hong, Jau-Shyong Tseng, Leon F. TI (+)-Morphine attenuates the (-)-morphine-produced conditioned place preference and the g-opioid receptor-mediated dopamine increase in the posterior nucleus accumbens of the rat SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE addiction; mesolimbic system; dopamine; morphine; opioid; (Rat) ID VENTRAL TEGMENTAL AREA; SENSITIVE SIGMA-RECEPTOR; IN-VIVO MICRODIALYSIS; DEXTRO-MORPHINE; BRAIN; SHELL; INVOLVEMENT; RELEASE; COCAINE; DELTA AB An unbiased conditioned place preference paradigm and the microdialysis technique was used to evaluate the effect of (+)-morphine pretreatment on the conditioned place preference produced by (-)-morphine and the increased release of the dopamine produced by P-opioid ligand endomorphin-1, respectively, in the posterior nucleus accumbens shell of the male CD rat. (-)-Morphine (2.5-10 mu g) microinjected into the posterior nucleus accumbens shell dose-dependently produced the conditioned place preference. Pretreatment with (+)-morphine (0.1-10 pg) given into the posterior accumbens shell for 45 min dose-dependently attenuated the conditioned place preference produced by (-)-morphine (5 mu g) given into the same posterior accumbens shell. However, higher doses of (+)-morphine (0.1 and 1 ng) were less effective in attenuating the (-)-morphine-produced conditioned place preference. Thus, like given systemically, (+)-morphine given into the posterior nucleus accumbens shell also induces a U-shaped dose-response curve for attenuating the (-)-morphine-produced conditioned place preference. Microinjection of mu-opioid agonist endomorphin-1 (1-10 mu g) given into the ventral tegmental area dose-dependently increased the release of the extracellular dopamine in the posterior nucleus accumbens shell in the urethane-anesthetized rats. The increased dopamine caused by endomorphin-1 (10 mu g) was completed blocked by the (+)-morphine (10 pg) pretreatment given into ventral tegmental area. It is concluded that (+)-morphine attenuates the (-)-morphine-produced conditioned place preference and the p-opioid receptor-mediated increase of extracellular dopamine in the posterior nucleus accumbens shell of the rat. (c) 2008 Elsevier B.V. All rights reserved. C1 [Terashvili, Maia; Wu, Hsiang-En; Schwasinger, Emma T.; Hung, Kuei-Chun; Tseng, Leon F.] Med Coll Wisconsin, Dept Anesthesiol, Milwaukee, WI 53226 USA. [Hong, Jau-Shyong] NIEHS, NIH, Lab Pharmacol & Chem, Neuropharmacol Sect, Res Triangle Pk, NC 27709 USA. RP Tseng, LF (reprint author), Med Coll Wisconsin, Dept Anesthesiol, 8701 Watertown Planck Rd, Milwaukee, WI 53226 USA. EM ltseng@wi.rr.com FU Intramural NIH HHS; NIDA NIH HHS [DA12588, R01 DA012588-01A2, R01 DA012588, K01 DA024751] NR 37 TC 12 Z9 12 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD JUN 10 PY 2008 VL 587 IS 1-3 BP 147 EP 154 DI 10.1016/j.ejphar.2008.03.020 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 314PR UT WOS:000256821800022 PM 18448094 ER PT J AU Cole, NB DiEuliis, D Leo, P Mitchell, DC Nussbaum, RL AF Cole, Nelson B. DiEuliis, Diane Leo, Paul Mitchell, Drake C. Nussbaum, Robert L. TI Mitochondrial translocation of alpha-synuclein is promoted by intracellular acidification SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE alpha-synuclein; mitochondria; pH; Parkinson's disease; oxidative stress; metabolic dysfunction ID DROSOPHILA-PARKIN MUTANTS; OXIDATIVE STRESS; CELL-DEATH; COMPLEX-I; NEURODEGENERATIVE DISEASES; CYTOSOLIC ACIDIFICATION; ENDOPLASMIC-RETICULUM; INDUCED APOPTOSIS; TRANSGENIC MICE; TUMOR-CELLS AB Mitochondrial dysfunction plays a central role in the selective vulnerability of dopaminergic neurons in Parkinson's disease (PD) and is influenced by both environmental and genetic factors. Expression of the PD protein alpha-synuclein or its familial mutants often sensitizes neurons to oxidative stress and to damage by mitochondrial toxins. This effect is thought to be indirect, since little evidence physically linking alpha-synuclein to mitochondria has been reported. Here, we show that the distribution of a-synuclein within neuronal and non-neuronal cells is dependent on intracellular pH. Cytosolic acidification induces translocation of a-synuclein from the cytosol onto the surface of mitochondria. Translocation occurs rapidly under artificially-induced low pH conditions and as a result of pH changes during oxidative or metabolic stress. Binding is likely facilitated by low pH-induced exposure of the mitochondria-specific lipid cardiolipin. These results imply a direct role for alpha-synuclein in mitochondrial physiology, especially under pathological conditions, and in principle, link alpha-synuclein to other PD genes in regulating mitochondrial homeostasis. Published by Elsevier Inc. C1 [Cole, Nelson B.; Leo, Paul; Nussbaum, Robert L.] NHGRI, Natl Inst Hlth, Genet Dis Res Branch, Bethesda, MD 20892 USA. [DiEuliis, Diane] NINDS, Div Extramural Activ, Bethesda, MD 20892 USA. [Mitchell, Drake C.] NIAAA, LMBB, Sect Fluorescent Studies, Rockville, MD 20852 USA. RP Cole, NB (reprint author), NHLBI, Biochem Lab, 50 S Dr MSC 8012, Bethesda, MD 20892 USA. EM ncole@mail.nih.gov RI Leo, Paul/B-3470-2011 OI Leo, Paul/0000-0001-8325-4134 FU Intramural NIH HHS [Z99 HL999999] NR 71 TC 76 Z9 77 U1 0 U2 7 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD JUN 10 PY 2008 VL 314 IS 10 BP 2076 EP 2089 DI 10.1016/j.yexcr.2008.03.012 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 312AI UT WOS:000256641100009 PM 18440504 ER PT J AU Szekely, CA Green, RC Breitner, JCS Ostbye, T Beiser, AS Corrada, MM Dodge, HH Ganguli, M Kawas, CH Kuller, LH Psaty, BM Resnick, SM Wolf, PA Zonderman, AB Welsh-Bohmer, KA Zandi, PP AF Szekely, C. A. Green, R. C. Breitner, J. C. S. Ostbye, T. Beiser, A. S. Corrada, M. M. Dodge, H. H. Ganguli, M. Kawas, C. H. Kuller, L. H. Psaty, B. M. Resnick, S. M. Wolf, P. A. Zonderman, A. B. Welsh-Bohmer, K. A. Zandi, P. P. TI No advantage of A beta(42)-lowering NSAIDs for prevention of Alzheimer dementia in six pooled cohort studies SO NEUROLOGY LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; RANDOMIZED CONTROLLED-TRIAL; GAMMA-SECRETASE; CACHE COUNTY; DOUBLE-BLIND; DISEASE; RISK; POPULATION; ROFECOXIB; HEALTH AB Introduction: Observational studies show reduced incidence of Alzheimer dementia (AD) in users of nonsteroidal anti-inflammatory drugs (NSAIDs). One hypothesis holds that the subset of NSAIDs known as selective A beta(42)-lowering agents (SALAs) is responsible for this apparent reduction in AD risk. Methods: We pooled individual-level data from six prospective studies to obtain a sufficient sample to examine AD risk in users of SALA vs non-SALA NSAIDs. Results: Of 13,499 initially dementia-free participants (70,863 person-years), 820 developed incident AD. Users of NSAIDs (29.6%) showed reduced risk of AD (adjusted hazard ratio [aHR] 0.77, 95% CI 0.65-0.91). The point estimates were similar for SALAs (aHR 0.87, CI 0.72-1.04) and non-SALAs (aHR 0.75, CI 0.56-1.01). Because 573 NSAID users (14.5%) reported taking both a SALA and non-SALA, we examined their use alone and in combination. Resulting aHRs were 0.82 (CI 0.67-0.99) for SALA only, 0.60 (CI 0.40-0.90) for non-SALA only, and 0.87 (CI 0.57-1.33) for both NSAIDs (Wald test for differences, p = 0.32). The 40.7% of participants who used aspirin also showed reduced risk of AD, even when they used no other NSAIDs (aHR 0.78, CI 0.66-0.92). By contrast, there was no association with use of acetaminophen (aHR 0.93, CI 0.76-1.13). Conclusions: In this pooled dataset, nonsteroidal anti-inflammatory drug (NSAID) use reduced the risk of Alzheimer dementia (AD). However, there was no apparent advantage in AD risk reduction for the subset of NSAIDs shown to selectively lower A beta(42), suggesting that all conventional NSAIDs including aspirin have a similar protective effect in humans. C1 [Szekely, C. A.; Zandi, P. P.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. [Szekely, C. A.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Green, R. C.; Wolf, P. A.] Boston Univ, Sch Med, Boston, MA 02215 USA. [Green, R. C.; Beiser, A. S.] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Breitner, J. C. S.] VA Puget Sound Hlth Care System, Seattle, WA USA. [Psaty, B. M.] Univ Washington, Sch Med, Seattle, WA 98195 USA. [Ostbye, T.; Welsh-Bohmer, K. A.] Duke Univ, Med Ctr, Durham, NC USA. [Ostbye, T.] Duke NUS Grad Med Sch Singapore, Singapore, Singapore. [Corrada, M. M.; Kawas, C. H.] Univ Calif Irvine, Sch Med, Corvallis, OR USA. [Dodge, H. H.] Oregon State Univ, Coll Hlth & Human Serv, Corvallis, OR 97331 USA. [Dodge, H. H.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. [Ganguli, M.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. [Psaty, B. M.] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA. [Resnick, S. M.; Zonderman, A. B.] NIA, Intramural Res Program, Baltimore, MD 21224 USA. RP Zandi, PP (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Hampton House Room 857,624 N Broadway, Baltimore, MD 21205 USA. EM pzandi@jhsph.edu RI Szekely, Christine/C-1342-2009; Ganguli, Mary/A-3638-2013; MORAN, CATHERINE/C-9539-2015 FU Intramural NIH HHS [Z01 AG000185-18]; NHGRI NIH HHS [R01 HG002213, R01-HG02213]; NHLBI NIH HHS [N01HC85079, N01 HC-55222, N01 HC015103, N01 HC025195, N01 HC035129, N01 HC045133, N01 HC055222, N01 HC075150, N01 HC085079, N01 HC085080, N01 HC085081, N01 HC085082, N01 HC085083, N01 HC085084, N01 HC085085, N01 HC085086, N01-HC-75150, N01-HC-85079, N01-HC-85080, N01-HC-85081, N01-HC-85082, N01-HC-85083, N01-HC-85086, N01-HC25195, N01HC25195, N01HC55222, N01HC75150, N01HC85086, U01 HL080295, U01 HL080295-01, U01 HL080295-02, U01 HL080295-03, U01 HL080295-04, U01-HL080295]; NIA NIH HHS [AG13846, K01 AG023014, K01 AG023014-01, K01 AG023014-02, K01 AG023014-03, K01 AG023014-04, K01 AG023014-05, K01 AG023014-06, K01-AG023014, K24 AG022035, K24 AG022035-01, K24 AG027841, K24 AG027841-01A1, K24-AG022035, K24-AG027841, P30 AG013846, P30 AG013846-04, R01 AG008122, R01 AG008122-07, R01 AG008325, R01 AG008325-10, R01 AG008325-11, R01 AG009029, R01 AG009029-09, R01 AG009556, R01 AG009556-05, R01 AG009556-06A2, R01 AG009556-07, R01 AG009556-08, R01 AG009556-09, R01 AG011380, R01 AG011380-06, R01 AG011380-07, R01 AG011380-08, R01 AG011380-09, R01 AG011380-10, R01 AG011380-10S1, R01 AG011380-11, R01 AG011380-11S1, R01 AG011380-12, R01 AG011380-12S1, R01 AG011380-13, R01 AG011380-13S1, R01 AG015928, R01 AG015928-02, R01 AG016495, R01-AG-09556, R01-AG07562, R01-AG08122, R01-AG08325, R01-AG09029, R01-AG11380, R01-AG15928, R01-AG16495, R01-AG85477, R01-AG88930] NR 44 TC 74 Z9 78 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN 10 PY 2008 VL 70 IS 24 BP 2291 EP 2298 DI 10.1212/01.wnl.0000313933.17796.f6 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 317ZS UT WOS:000257060000006 PM 18509093 ER PT J AU Antignani, A Youle, RJ AF Antignani, Antonella Youle, Richard J. TI Endosome fusion induced by diphtheria toxin translocation domain SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE early endosomes; Rab5; Rab7 ID INHIBITS MEMBRANE TRANSLOCATION; T-DOMAIN; LOW PH; ESCHERICHIA-COLI; CATALYTIC DOMAIN; CELL-DEATH; ENTRY; PROTEINS; MUTANT; ORGANIZATION AB Endosomal cargo travels through a dynamic vesicle network en route to degradation by lysosomes or recycling through the Golgi apparatus back to the cell surface. Rab5 is a key determinant of the early endosomes by organizing effector proteins in specific subdomains and mediating early endosome fusion. We find that early endosome morphogenesis and maturation is disrupted by diphtheria toxin (DT). Rab5 bound endosomes increase in size and in Rab5 content due to luminal toxin exposure, whereas Rab7 positive endosomes are not detectably altered. These changes appear to be caused by an activity of the toxin entry domain (T domain) as mutations inactivating either the receptor binding (CRM107) or ADP-ribosyl transferase (CRM197) activities do not inhibit the effect of DT on endosome morphogenesis. In contrast, mutations in the T domain or diminishing the endosomal pH gradient, which prevents T domain membrane insertion, inhibit these endosome changes. The change in size appears to be due to changing the early endosome fission-fusion equilibrium. The Rab5 membrane exchange rate, assessed with photoactivatable GFP-Rab5, decreases in the presence of DT. These changes to endosomes may reflect activities of the T domain that mediate toxin entry to the cytosol. The nontoxic mutant DT, CRM197, yields a new tool to manipulate endosome dynamics in living cells. C1 [Antignani, Antonella; Youle, Richard J.] NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Youle, RJ (reprint author), NINDS, Biochem Sect, Surg Neurol Branch, NIH, 35 Convent Dr,MSC 3704, Bethesda, MD 20892 USA. EM youler@ninds.nih.gov NR 39 TC 8 Z9 8 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 10 PY 2008 VL 105 IS 23 BP 8020 EP 8025 DI 10.1073/pnas.0711707105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 314AT UT WOS:000256781800023 PM 18539770 ER PT J AU Palmer, DC Chan, CC Gattinoni, L Wrzesinski, C Paulos, CM Hinrichs, CS Powell, DJ Klebanoff, CA Finkelstein, SE Fariss, RN Yu, ZY Nussenblatt, RB Rosenberg, SA Restifo, NP AF Palmer, Douglas C. Chan, Chi-Chao Gattinoni, Luca Wrzesinski, Claudia Paulos, Chrystal M. Hinrichs, Christian S. Powell, Daniel J., Jr. Klebanoff, Christopher A. Finkelstein, Steven E. Fariss, Robert N. Yu, Zhiya Nussenblatt, Robert B. Rosenberg, Steven A. Restifo, Nicholas P. TI Effective tumor treatment targeting a melanoma/melanocyte-associated antigen triggers severe ocular autoimmunity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cancer; immunotherapy; vaccine; adoptive cell transfer; IFN-gamma ID CD8(+) T-CELLS; CANCER-IMMUNOTHERAPY; METASTATIC MELANOMA; DENDRITIC CELLS; CLASS-I; LYMPHOCYTES; DESTRUCTION; VITILIGO; AFFINITY; IMMUNITY AB Nonmutated tissue differentiation antigens expressed by tumors are attractive targets for cancer immunotherapy, but the consequences of a highly effective antitumor immune response on self-tissue have not been fully characterized. We found that the infusion of ex vivo expanded adoptively transferred melanoma/melanocyte-specific CD8(+) T cells that mediated robust tumor killing also induced autoimmune destruction of melanocytes in the eye. This severe autoimmunity was associated with the upregulation of MHC class I molecules in the eye and high levels of IFN-gamma derived-from both adoptively transferred CD8(+) T cells and host cells. Furthermore, ocular autoimmunity required the presence of the IFN-gamma receptor on target tissues. Data compiled from >200 eyes and tumors in 10 independently performed experiments revealed a highly significant correlation (P < 0.0001) between the efficacy of tumor immunotherapy and the severity of ocular autoimmunity. Administration of high doses of steroids locally mitigated ocular autoimmunity without impairing the antitumor effect. These findings have particular importance for immunotherapies directed against self-antigens and highlight the need for targeting unique tumor antigens not expressed in critical tissues. C1 [Palmer, Douglas C.; Gattinoni, Luca; Wrzesinski, Claudia; Paulos, Chrystal M.; Hinrichs, Christian S.; Powell, Daniel J., Jr.; Klebanoff, Christopher A.; Finkelstein, Steven E.; Yu, Zhiya; Rosenberg, Steven A.; Restifo, Nicholas P.] NCI, NIH, Bethesda, MD 20892 USA. [Klebanoff, Christopher A.] NIH, Howard Hughes Med Inst, Bethesda, MD 20814 USA. [Chan, Chi-Chao; Fariss, Robert N.; Nussenblatt, Robert B.] NEI, NIH, Bethesda, MD 20892 USA. RP Palmer, DC (reprint author), NCI, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM palmerd@mail.nih.gov RI Gattinoni, Luca/A-2281-2008; Klebanoff, Christopher/B-8088-2008; Palmer, Douglas/B-9454-2008; Restifo, Nicholas/A-5713-2008; Klebanoff, Christopher/D-9581-2011; OI Gattinoni, Luca/0000-0003-2239-3282; Palmer, Douglas/0000-0001-5018-5734; Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS NR 37 TC 77 Z9 76 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 10 PY 2008 VL 105 IS 23 BP 8061 EP 8066 DI 10.1073/pnas.0710929105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 314AT UT WOS:000256781800030 PM 18523011 ER PT J AU Sun, YC Hinnebusch, BJ Darby, C AF Sun, Yi-Cheng Hinnebusch, B. Joseph Darby, Creg TI Experimental evidence for negative selection in the evolution of a Yersinia pestis pseudogene SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE biofilm; flea; bubonic plague; phosphorelay; Caenorhabditis elegans ID EARLY-PHASE TRANSMISSION; ESCHERICHIA-COLI; RCS PHOSPHORELAY; BIOFILM FORMATION; FLEA VECTOR; MULTISTEP PHOSPHORELAY; CAENORHABDITIS-ELEGANS; SIGNAL-TRANSDUCTION; GENETIC-ANALYSIS; UNBLOCKED FLEAS AB Yersinia pestis, the agent of bubonic plague, evolved from the enteric pathogen Yersinia pseudo tuberculosis within the past 20,000 years. Because ancestor and descendant both exist, it is possible to infer steps in molecular evolution by direct experimental approaches. The Y. pestis life cycle includes establishment of a biofilm within its vector, the flea. Although Y. pseudotuberculosis makes biofilms in other environments, it fails to do so in the insect. We show that rcsA, a negative regulator of biofilms that is functional in Y. pseudotuberculosis, is a pseudogene in Y. pestis. Replacement of the pseudogene with the functional Y. pseudotuberculosis rcsA allele strongly represses biofilm formation and essentially abolishes flea biofilms. The conversion of rcsA to a pseudogene during Y. pestis evolution, therefore, was a case of negative selection rather than neutral genetic drift. C1 [Sun, Yi-Cheng; Darby, Creg] Univ Calif San Francisco, Dept Cell & Tissue Biol, Program Microbiol Pathogenesis, San Francisco, CA 94143 USA. [Hinnebusch, B. Joseph] NIAID, Rocky Mt Labs, Hamilton, MT 59840 USA. RP Darby, C (reprint author), Univ Calif San Francisco, Dept Cell & Tissue Biol, Program Microbiol Pathogenesis, San Francisco, CA 94143 USA. EM creg.darby@ucsf.edu FU NIAID NIH HHS [AI057512, R01 AI057512, R56 AI057512] NR 35 TC 62 Z9 69 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 10 PY 2008 VL 105 IS 23 BP 8097 EP 8101 DI 10.1073/pnas.0803525105 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 314AT UT WOS:000256781800036 PM 18523005 ER PT J AU Elkins, JG Podar, M Graham, DE Makarova, KS Wolf, Y Randau, L Hedlund, BP Brochier-Armanet, C Kunin, V Anderson, I Lapidus, A Goltsman, E Barry, K Koonin, EV Hugenholtz, P Kyrpides, N Wanner, G Richardson, P Keller, M Stetter, KO AF Elkins, James G. Podar, Mircea Graham, David E. Makarova, Kira S. Wolf, Yuri Randau, Lennart Hedlund, Brian P. Brochier-Armanet, Celine Kunin, Victor Anderson, Iain Lapidus, Alla Goltsman, Eugene Barry, Kerrie Koonin, Eugene V. Hugenholtz, Phil Kyrpides, Nikos Wanner, Gerhard Richardson, Paul Keller, Martin Stetter, Karl O. TI A korarchaeal genome reveals insights into the evolution of the Archaea SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE microbial cultivation; genomics; hyperthermophiles; Korarchaeota; phylogeny ID YELLOWSTONE-NATIONAL-PARK; TRANSFER-RNA GENES; PYROCOCCUS-FURIOSUS; FERREDOXIN OXIDOREDUCTASE; MICROBIAL DIVERSITY; SPECIES COMPOSITION; CELL-DIVISION; SEQUENCE; BACTERIA; SEA AB The candidate division Korarchaeota comprises a group of uncultivated microorganisms that, by their small subunit rRNA phylogeny, may have diverged early from the major archaeal phyla Crenarchaeota and Euryarchaeota. Here, we report the initial characterization of a member of the Korarchaeota with the proposed name, "Candidatus Korarchaeum cryptofilum," which exhibits an ultrathin filamentous morphology. To investigate possible ancestral relationships between deep-branching Korarchaeota and other phyla, we used whole-genome shotgun sequencing to construct a complete composite korarchaeal genome from enriched cells. The genome was assembled into a single contig 1.59 Mb in length with a G + C content of 49%. Of the 1,617 predicted protein-coding genes, 1,382,(85%) could be assigned to a revised set of archaeal Clusters of Orthologous Groups (COGs). The predicted gene functions suggest that the organism relies on a simple mode of peptide fermentation for carbon and energy and lacks the ability to synthesize de novo purines, CoA, and several other cofactors. Phylogenetic analyses based on conserved single genes and concatenated protein sequences positioned the korarchaeote as a deep archaeal lineage with an apparent affinity to the Crenarchaeota. However, the predicted gene content revealed that several conserved cellular systems, such as cell division, DNA replication, and tRNA maturation, resemble the counterparts in the Euryarchaeota. In light of the known composition of archaeal genomes, the Korarchaeota might have retained a set of cellular features that represents the ancestral archaeal form. C1 [Elkins, James G.; Stetter, Karl O.] Univ Regensburg, Lehrstuhl Mikrobiol & Archaeenzentrum, D-93053 Regensburg, Germany. [Podar, Mircea; Keller, Martin] Oak Ridge Natl Lab, Biosci Div, Oak Ridge, TN 37831 USA. [Graham, David E.] Univ Texas Austin, Dept Chem & Biochem, Austin, TX 78712 USA. [Makarova, Kira S.; Wolf, Yuri; Koonin, Eugene V.] Natl Inst Hlth, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [Randau, Lennart] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA. [Hedlund, Brian P.] Univ Nevada, Sch Life Sci, Las Vegas, NV 89154 USA. [Brochier-Armanet, Celine] Univ Aix Marseille 1, CNRS, Chim Bacterienne Lab, Unite Propre Rech 9043, F-13331 Marseille 3, France. [Kunin, Victor; Anderson, Iain; Lapidus, Alla; Goltsman, Eugene; Barry, Kerrie; Hugenholtz, Phil; Kyrpides, Nikos; Wanner, Gerhard; Richardson, Paul] US DOE, Joint Genome Inst, Walnut Creek, CA 94598 USA. [Wanner, Gerhard] Univ Munich, Inst Bot, D-80638 Munich, Germany. [Stetter, Karl O.] Univ Calif Los Angeles, Inst Geophys & Planetary Phys, Los Angeles, CA 90095 USA. [Elkins, James G.; Stetter, Karl O.] Univ Regensburg, Archaeenzentrum, D-93053 Regensburg, Germany. RP Stetter, KO (reprint author), Univ Regensburg, Lehrstuhl Mikrobiol, Univ Str 31, D-93343 Regensburg, Germany. EM karl.stetter@biologie.uni-regensburg.de RI Graham, David/F-8578-2010; Hugenholtz, Philip/G-9608-2011; Keller, Martin/C-4416-2012; Elkins, James/A-6199-2011; Kyrpides, Nikos/A-6305-2014; Lapidus, Alla/I-4348-2013; OI Graham, David/0000-0001-8968-7344; Elkins, James/0000-0002-8052-5688; Kyrpides, Nikos/0000-0002-6131-0462; Lapidus, Alla/0000-0003-0427-8731; Podar, Mircea/0000-0003-2776-0205; hugenholtz, philip/0000-0001-5386-7925 NR 52 TC 135 Z9 220 U1 2 U2 34 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 10 PY 2008 VL 105 IS 23 BP 8102 EP 8107 DI 10.1073/pnas.0801980105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 314AT UT WOS:000256781800037 PM 18535141 ER PT J AU Ravindran, A Lao, QZ Harry, JB Abrahimi, P Kobrinsky, E Soldatov, NM AF Ravindran, Arippa Lao, Qi Zong Harry, Jo Beth Abrahimi, Parwiz Kobrinsky, Evgeny Soldatov, Nikolai M. TI Calmodulin-dependent gating of Ca(v)1.2 calcium channels in the absence of Ca-v beta subunits SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE plasma-membrane targeting; voltage gating ID CA2+-DEPENDENT INACTIVATION; ALPHA(1C) SUBUNIT; MOLECULAR DETERMINANTS; EXONS 40-42; MOTIF; MODULATION; COMPLEX; LINKER; DOMAIN; TAILS AB It is generally accepted that to generate calcium currents in response to depolarization, Ca(v)1.2 calcium channels require association of the pore-forming alpha(1c) subunit with accessory Ca-v beta and alpha(2)delta subunits. A single calmodulin (CaM) molecule is tethered to the C-terminal alpha(1c)-LA/IQ region and mediates Ca2+-dependent inactivation of the channel. Ca-v beta subunits are stably associated with the alpha(1c)-interaction domain site of the cytoplasmic linker between internal repeats I and II and also interact dynamically, in a Ca2+-dependent manner, with the alpha(1c)-IQ region. Here, we describe a surprising discovery that coexpression of exogenous CaM (CaMex) with alpha(1c)/alpha(2)delta in COS1 cells in the absence of Ca-v beta subunits stimulates the plasma membrane targeting of alpha(1c), facilitates calcium channel gating, and supports Ca2+-dependent inactivation. Neither real-time PCR with primers, complementary to monkey Ca-v beta subunits nor coimmunoprecipitation analysis with exogenous alpha(1c) revealed an induction of endogenous Ca-v beta subunits that could be linked to the effect of CaMex. Coexpression of a calcium-insensitive CaM mutant CaM1234 also facilitated gating of Ca-v beta-free Ca(v)1.2 channels but did not support Ca2+-dependent inactivation. Our results show there is a functional matchup between CaMex and Ca-v beta subunits that, in the absence of Ca-v beta, renders Ca2+ channel gating facilitated by CaM molecules other than the one tethered to LA/IQ to support Ca2+-dependent inactivation. Thus, coexpression of CaMex creates conditions when the channel gating, voltage- and Ca2+-dependent inactivation, and plasma-membrane targeting occur in the absence of Ca-v beta. We suggest that CaMex affects specific Ca-v beta-free conformations of the channel that are not available to endogenous CaM. C1 [Ravindran, Arippa; Lao, Qi Zong; Harry, Jo Beth; Abrahimi, Parwiz; Kobrinsky, Evgeny; Soldatov, Nikolai M.] NIA, NIH, Baltimore, MD 21224 USA. RP Soldatov, NM (reprint author), NIA, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM soldatovn@grc.nia.nih.gov FU Intramural NIH HHS; NIA NIH HHS [Z01 AG000294, Z01 AG000294-08] NR 32 TC 17 Z9 17 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 10 PY 2008 VL 105 IS 23 BP 8154 EP 8159 DI 10.1073/pnas.0711624105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 314AT UT WOS:000256781800046 PM 18535142 ER PT J AU Hong, JS AF Hong, Jau-Shyong TI Role of inflammation in the pathogenesis of Parkinson's disease: Models, mechanisms, and therapeutic interventions SO EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Meeting Abstract CT 19th Helsinki Drug Research CY JUN 09-11, 2008 CL Helsinki, FINLAND SP Univ Helsinki, Fac Pharm, Finnish Pharmaceut Soc C1 [Hong, Jau-Shyong] NIEHS, Lab Pharmacol & Chem, Neuropharmacol Sect, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0928-0987 J9 EUR J PHARM SCI JI Eur. J. Pharm. Sci. PD JUN 9 PY 2008 VL 34 IS 1 SU S BP S5 EP S5 DI 10.1016/j.ejps.2008.02.012 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 305VU UT WOS:000256206700002 ER PT J AU Qian, L Hong, JS Flood, PM AF Qian, L. Hong, J. -S. Flood, P. M. TI Salmeterol, a long-acting beta 2-adrenergic receptor agonist, is neuroprotective through inhibition of microglial NADPH oxidase SO EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Meeting Abstract CT 19th Helsinki Drug Research CY JUN 09-11, 2008 CL Helsinki, FINLAND SP Univ Helsinki, Fac Pharm, Finnish Pharmaceut Soc C1 [Qian, L.; Flood, P. M.] Univ N Carolina, Comprehens Ctr Inflammatory Disorders, Chapel Hill, NC 27515 USA. [Qian, L.; Hong, J. -S.] NIH, Neuropharmacol Sect, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0928-0987 J9 EUR J PHARM SCI JI Eur. J. Pharm. Sci. PD JUN 9 PY 2008 VL 34 IS 1 SU S BP S33 EP S33 DI 10.1016/j.ejps.2008.02.089 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 305VU UT WOS:000256206700076 ER PT J AU Holdener, M Hintermann, E Bayer, M Rhode, A Rodrigo, E Hintereder, G Johnson, EF Gonzalez, FJ Pfeilschifter, J Manns, MP Herrath, MV Christen, U AF Holdener, Martin Hintermann, Edith Bayer, Monika Rhode, Antje Rodrigo, Evelyn Hintereder, Gudrun Johnson, Eric F. Gonzalez, Frank J. Pfeilschifter, Josef Manns, Michael P. Herrath, Matthias von G. Christen, Urs TI Breaking tolerance to the natural human liver autoantigen cytochrome P450 2D6 by virus infection SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID HEPATITIS-C VIRUS; KIDNEY MICROSOMAL AUTOANTIBODY; TYPE-2 AUTOIMMUNE HEPATITIS; PRIMARY BILIARY-CIRRHOSIS; CHRONIC ACTIVE HEPATITIS; CD8(+) T-CELLS; MOLECULAR MIMICRY; IN-VIVO; ANTIGENIC SITES; TRANSGENIC MICE AB Autoimmune liver diseases, such as autoimmune hepatitis (AIH) and primary biliary cirrhosis, often have severe consequences for the patient. Because of a lack of appropriate animal models, not much is known about their potential viral etiology. Infection by liver-tropic viruses is one possibility for the breakdown of self-tolerance. Therefore, we infected mice with adenovirus Ad5 expressing human cytochrome P450 2D6 (Ad-2D6). Ad-2D6-infected mice developed persistent autoimmune liver disease, apparent by cellular infiltration, hepatic fibrosis, "fused" liver lobules, and necrosis. Similar to type 2 AIH patients, Ad-2D6 infected mice generated type 1 liver kidney microsomal-like antibodies recognizing the immunodominant epitope WDPAQPPRD of cytochrome P450 2D6 (CYP2D6). Interestingly, Ad-2D6-infected wild-type FVB/N mice displayed exacerbated liver damage when compared with transgenic mice expressing the identical human CYP2D6 protein in the liver, indicating the presence of a stronger immunological tolerance in CYP2D6 mice. We demonstrate for the first time that infection with a virus expressing a natural human autoantigen breaks tolerance, resulting in a chronic form of severe, autoimmune liver damage. Our novel model system should be instrumental for studying mechanisms involved in the initiation, propagation, and precipitation of virus-induced autoimmune liver diseases. C1 [Holdener, Martin; Hintermann, Edith; Bayer, Monika; Pfeilschifter, Josef; Christen, Urs] Univ Frankfurt, Pharmazentrum Frankfurt, Zentrum Arzneimittelforsch Entwicklung & Sicherhe, D-60590 Frankfurt, Germany. [Rhode, Antje; Rodrigo, Evelyn; Herrath, Matthias von G.] La Jolla Inst Allergy & Immunol, La Jolla, CA 92037 USA. [Johnson, Eric F.] Scripps Res Inst, La Jolla, CA 92037 USA. [Gonzalez, Frank J.] NCI, NIH, Bethesda, MD 20892 USA. [Manns, Michael P.] Hannover Med Sch, D-30623 Hannover, Germany. RP Christen, U (reprint author), Univ Frankfurt, Pharmazentrum Frankfurt, Zentrum Arzneimittelforsch Entwicklung & Sicherhe, D-60590 Frankfurt, Germany. EM christen@med.uni-frankfurt.de RI Christen, Urs/A-7338-2009 FU NIDDK NIH HHS [R21 DK071577] NR 64 TC 91 Z9 94 U1 1 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUN 9 PY 2008 VL 205 IS 6 BP 1409 EP 1422 DI 10.1084/jem.20071859 PG 14 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 317EG UT WOS:000257002000017 PM 18474629 ER PT J AU Gerosa, F Baldani-Guerra, B Lyakh, LA Batoni, G Esin, S Winkler-Pickett, RT Consolaro, MR De Marchi, M Giachino, D Robbiano, A Astegiano, M Sambataro, A Kastelein, RA Carra, G Trinchieri, G AF Gerosa, Franca Baldani-Guerra, Barbara Lyakh, Lyudmila A. Batoni, Giovanna Esin, Semih Winkler-Pickett, Robin T. Consolaro, Maria Rita De Marchi, Mario Giachino, Daniela Robbiano, Angela Astegiano, Marco Sambataro, Angela Kastelein, Robert A. Carra, Giuseppe Trinchieri, Giorgio TI Differential regulation of interleukin 12 and interleukin 23 production in human dendritic cells SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID TOLL-LIKE RECEPTOR-2; BLOOD MONONUCLEAR-CELLS; T-HELPER-CELLS; CANDIDA-ALBICANS; MYCOBACTERIUM-TUBERCULOSIS; INNATE IMMUNITY; AUTOIMMUNE INFLAMMATION; INTERFERON-GAMMA; HOST-DEFENSE; IN-VIVO AB We analyzed interleukin (IL) 12 and IL-23 production by monocyte-derived dendritic cells (mono-DCs). Mycobacterium tuberculosis H37Rv and zymosan preferentially induced IL-23. IL-23 but not IL-12 was efficiently induced by the combination of nucleotide-binding oligodimerization domain and Toll-like receptor (TLR) 2 ligands, which mimics activation by M. tuberculosis, or by the human dectin-1 ligand beta-glucan alone or in combination with TLR2 ligands, mimicking induction by zymosan. TLR2 ligands inhibited IL-12 and increased IL-23 production. DC priming with interferon (IFN) gamma strongly increased IL-12 production, but was not required for IL-23 production and inhibited IL-23 production induced by beta-glucan. The pattern of IL-12 and IL-23 induction was reflected in accumulation of the IL-12p35 and IL-23p19 transcripts, respectively, but not IL-12/23p40. Although IL-23, transforming growth factor beta, and IL-6 contained in the supernatants of activated mono-DCs played a role in the induction of IL-17 by human CD4(+) T cells, IL-1 beta, in combination with one or more of those factors, was required for IL-17 production, and its production determined the differential ability of the stimuli used to elicit mono-DCs to produce soluble factors directing IL-17 production. Thus, the differential ability of pathogens to induce antigen-presenting cells to produce cytokines regulates the immune response to infection. C1 [Gerosa, Franca; Baldani-Guerra, Barbara; Consolaro, Maria Rita; Carra, Giuseppe] Univ Verona, Immunol Sect, Dept Pathol, I-37134 Verona, Italy. [Lyakh, Lyudmila A.; Winkler-Pickett, Robin T.; Trinchieri, Giorgio] NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA. [Batoni, Giovanna; Esin, Semih] Univ Pisa, Dept Expt Pathol Med Biotechnol Infectivol & Epid, I-56126 Pisa, Italy. [De Marchi, Mario; Giachino, Daniela; Robbiano, Angela] Univ Turin, Dept Clin & Biol Sci, I-10043 Orbassano, Italy. [Astegiano, Marco] Azienda Sanit Osped San Giovanni Battista, Gastroenterol Unit, I-10126 Turin, Italy. [Sambataro, Angela] Azienda Sanit Osped San Luigi, Gastroenterol Unit, I-10043 Orbassano, Italy. [Kastelein, Robert A.] Schering Plough Biopharma, Discovery Res, Palo Alto, CA 94305 USA. RP Gerosa, F (reprint author), Univ Verona, Immunol Sect, Dept Pathol, I-37134 Verona, Italy. EM franca.gerosa@univr.it RI De Marchi, Mario/G-7558-2011; OI Batoni, Giovanna/0000-0002-4448-2385 FU Intramural NIH HHS NR 68 TC 172 Z9 175 U1 0 U2 15 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUN 9 PY 2008 VL 205 IS 6 BP 1447 EP 1461 DI 10.1084/jem.20071450 PG 15 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 317EG UT WOS:000257002000020 PM 18490488 ER PT J AU Boasso, A Shearer, GM Clerici, M AF Boasso, Adriano Shearer, Gene M. Clerici, Mario TI The hunt for an HIV vaccine: time to rethink recent failures SO LANCET LA English DT Editorial Material ID INFECTION C1 [Clerici, Mario] Univ Milan, Dept Biomed Sci & Technol, I-20100 Milan, Italy. [Clerici, Mario] Fdn Don C Gnocchi, I-20100 Milan, Italy. [Boasso, Adriano] Univ London Imperial Coll Sci Technol & Med, Chelsea & Westminster Hosp, Dept Immunol, London, England. [Shearer, Gene M.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Clerici, M (reprint author), Univ Milan, Dept Biomed Sci & Technol, I-20100 Milan, Italy. EM mario.clerici@unimi.it OI Boasso, Adriano/0000-0001-9673-6319 NR 10 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD JUN 7 PY 2008 VL 371 IS 9628 BP 1897 EP 1898 DI 10.1016/S0140-6736(08)60812-0 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 310OI UT WOS:000256538500009 PM 18539209 ER PT J AU Wang, HS Feng, JX Qi, CF Morse, HC AF Wang, Hongsheng Feng, Jianxun Qi, Chenfeng Morse, Herbert C., III TI An ENU-induced mutation in the lymphotoxin alpha gene impairs organogenesis of lymphoid tissues in C57BL/6 mice SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE lymph organogenesis; lymph node; spleen; marginal zone; leukocytosis; B1B; bone marrow; thymus; ENU ID TUMOR-NECROSIS-FACTOR; KNOCKOUT MICE; CELL-DEVELOPMENT; DEFICIENT MICE; BETA-GENE; LT-ALPHA; EXPRESSION; FOLLICLES; RECEPTOR; ORGANS AB The TNF family is critical for development of lymphoid organs and plays significant roles in regulation of innate and adoptive immune responses. Here, we describe a novel N-ethyl-N-nitrosourea (ENU)-induced mutant strain, HLB382, with a point mutation in the Lta gene, which encodes lymphotoxin (LT) a, a member of the TNF family. Mutant mice had no lymph nodes and no Peyer's patches. Microscopically, the spleens had disordered follicles and no germinal centers or discernible marginal zones (MZ). While the development of T cells and follicular B cells was normal, the numbers of NK and MZ B cells were significantly reduced. Interestingly, the numbers of peritoneal B1b cells were significantly increased. Genomic DNA sequences revealed a single base pair insertion in the coding region of Lta resulting in a frame shift and a premature stop codon. This new strain provides opportunities for understanding the full range of Lta gene function on a pure C578L/6 background. Published by Elsevier Inc. C1 [Wang, Hongsheng; Feng, Jianxun; Qi, Chenfeng; Morse, Herbert C., III] NIAID, Immunopathol Lab, NIH, Rockville, MD 20852 USA. RP Wang, HS (reprint author), NIAID, Immunopathol Lab, NIH, 5640 Fisheries LN,TB1,Rm 1518, Rockville, MD 20852 USA. EM wanghongs@niaid.nih.gov OI Morse, Herbert/0000-0002-9331-3705 FU Intramural NIH HHS [Z01 AI001024-01, Z99 AI999999]; NHLBI NIH HHS [U01 HL066611, HL66611] NR 27 TC 4 Z9 4 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 6 PY 2008 VL 370 IS 3 BP 461 EP 467 DI 10.1016/j.bbrc.2008.03.118 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 298CT UT WOS:000255664700016 PM 18384745 ER PT J AU Lin, J AF Lin, Jimmy TI PageRank without hyperlinks: Reranking with PubMed related article networks for biomedical text retrieval SO BMC BIOINFORMATICS LA English DT Article AB Background: Graph analysis algorithms such as PageRank and HITS have been successful in Web environments because they are able to extract important inter-document relationships from manually-created hyperlinks. We consider the application of these techniques to biomedical text retrieval. In the current PubMed (R) search interface, a MEDLINE (R) citation is connected to a number of related citations, which are in turn connected to other citations. Thus, a MEDLINE record represents a node in a vast content-similarity network. This article explores the hypothesis that these networks can be exploited for text retrieval, in the same manner as hyperlink graphs on the Web. Results: We conducted a number of reranking experiments using the TREC 2005 genomics track test collection in which scores extracted from PageRank and HITS analysis were combined with scores returned by an off-the-shelf retrieval engine. Experiments demonstrate that incorporating PageRank scores yields significant improvements in terms of standard ranked-retrieval metrics. Conclusion: The link structure of content-similarity networks can be exploited to improve the effectiveness of information retrieval systems. These results generalize the applicability of graph analysis algorithms to text retrieval in the biomedical domain. C1 [Lin, Jimmy] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. [Lin, Jimmy] Univ Maryland, The iSch, College Pk, MD 20742 USA. RP Lin, J (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. EM jimmylin@umd.edu FU Intramural NIH HHS NR 25 TC 11 Z9 11 U1 1 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD JUN 6 PY 2008 VL 9 AR 270 DI 10.1186/1471-2105-9-270 PG 12 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 326JC UT WOS:000257653500002 PM 18538027 ER PT J AU Landi, MT Consonni, D Rotunno, M Bergen, AW Goldstein, AM Lubin, JH Goldin, L Alavanja, M Morgan, G Subar, AF Linnoila, I Previdi, F Corno, M Rubagotti, M Marinelli, B Albetti, B Colombi, A Tucker, M Wacholder, S Pesatori, AC Caporaso, NE Bertazzi, PA AF Landi, Maria Teresa Consonni, Dario Rotunno, Melissa Bergen, Andrew W. Goldstein, Alisa M. Lubin, Jay H. Goldin, Lynn Alavanja, Michael Morgan, Glen Subar, Amy F. Linnoila, Ilona Previdi, Fabrizio Corno, Massimo Rubagotti, Maurizia Marinelli, Barbara Albetti, Benedetta Colombi, Antonio Tucker, Margaret Wacholder, Sholom Pesatori, Angela C. Caporaso, Neil E. Bertazzi, Pier Alberto TI Environment And Genetics in Lung cancer Etiology (EAGLE) study: An integrative population-based case-control study of lung cancer SO BMC PUBLIC HEALTH LA English DT Article ID SCALE; GENES; RISK AB Background: Lung cancer is the leading cause of cancer mortality worldwide. Tobacco smoking is its primary cause, and yet the precise molecular alterations induced by smoking in lung tissue that lead to lung cancer and impact survival have remained obscure. A new framework of research is needed to address the challenges offered by this complex disease. Methods/Design: We designed a large population-based case-control study that combines a traditional molecular epidemiology design with a more integrative approach to investigate the dynamic process that begins with smoking initiation, proceeds through dependency/smoking persistence, continues with lung cancer development and ends with progression to disseminated disease or response to therapy and survival. The study allows the integration of data from multiple sources in the same subjects (risk factors, germline variation, genomic alterations in tumors, and clinical endpoints) to tackle the disease etiology from different angles. Before beginning the study, we conducted a phone survey and pilot investigations to identify the best approach to ensure an acceptable participation in the study from cases and controls. Between 2002 and 2005, we enrolled 2101 incident primary lung cancer cases and 2120 population controls, with 86.6% and 72.4% participation rate, respectively, from a catchment area including 216 municipalities in the Lombardy region of Italy. Lung cancer cases were enrolled in 13 hospitals and population controls were randomly sampled from the area to match the cases by age, gender and residence. Detailed epidemiological information and biospecimens were collected from each participant, and clinical data and tissue specimens from the cases. Collection of follow-up data on treatment and survival is ongoing. Discussion: EAGLE is a new population-based case-control study that explores the full spectrum of lung cancer etiology, from smoking addiction to lung cancer outcome, through examination of epidemiological, molecular, and clinical data. We have provided a detailed description of the study design, field activities, management, and opportunities for research following this integrative approach, which allows a sharper and more comprehensive vision of the complex nature of this disease. The study is poised to accelerate the emergence of new preventive and therapeutic strategies with potentially enormous impact on public health. C1 [Landi, Maria Teresa; Rotunno, Melissa; Bergen, Andrew W.; Goldstein, Alisa M.; Lubin, Jay H.; Goldin, Lynn; Alavanja, Michael; Tucker, Margaret; Wacholder, Sholom; Caporaso, Neil E.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Consonni, Dario; Previdi, Fabrizio; Corno, Massimo; Rubagotti, Maurizia; Marinelli, Barbara; Albetti, Benedetta; Colombi, Antonio; Pesatori, Angela C.; Bertazzi, Pier Alberto] Univ Milan, EPOCA, Epidemiol Res Ctr, Mangiagalli Regina Elena, Italy. [Consonni, Dario; Previdi, Fabrizio; Corno, Massimo; Rubagotti, Maurizia; Marinelli, Barbara; Albetti, Benedetta; Colombi, Antonio; Pesatori, Angela C.; Bertazzi, Pier Alberto] Osped Maggiore Policlin, Fdn IRCCS, Mangiagalli Regina Elena, Italy. [Morgan, Glen; Subar, Amy F.] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Linnoila, Ilona] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Landi, MT (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. EM landim@mail.nih.gov; dario.consonni@unimi.it; rotunnom@mail.nih.gov; andrew.bergen@sri.com; goldstea@mail.nih.gov; lubinj@mail.nih.gov; goldinl@mail.nih.gov; alavanjam@mail.nih.gov; gmorgan@mail.nih.gov; subara@mail.nih.gov; linnoila@mail.nih.gov; fprevidi@craon.it; mcorno@impresaedilemariani.it; maurizia.rubagotti@unimi.it; barbara.marinelli@unimi.it; benedetta.albetti@unimi.it; antonio.colombi@unimi.it; tuckerp@mail.nih.gov; wacholders@mail.nih.gov; angela.pesatori@unimi.it; caporasn@mail.nih.gov; pieralberto.bertazzi@unimi.it RI Tucker, Margaret/B-4297-2015; bertazzi, pietro alberto/D-5039-2017; OI bertazzi, pietro alberto/0000-0003-3475-2449; Bergen, Andrew/0000-0002-1237-7644; pesatori, angela/0000-0002-0261-3252 FU Intramural NIH HHS NR 22 TC 64 Z9 65 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2458 J9 BMC PUBLIC HEALTH JI BMC Public Health PD JUN 6 PY 2008 VL 8 AR 203 DI 10.1186/1471-2458-8-203 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 328MJ UT WOS:000257802200001 PM 18538025 ER PT J AU Bilski, P Zhao, BZ Chignell, CF AF Bilski, Piotr Zhao, Baozhong Chignell, Colin F. TI Singlet oxygen phosphorescence photosensitized in nano-aggregates of C(60) buckminsterfullerene is insensitive to solvent and quenchers and strongly red-shifted indicating highly polarizable interior SO CHEMICAL PHYSICS LETTERS LA English DT Article ID MOLECULAR-OXYGEN; SPECTRAL SHIFTS; LUMINESCENCE; O-2((1)DELTA(G)); A(1)DELTA(G); FULLERENES; TRANSITION; MIXTURES; EMISSION; DECAY AB We investigated the strongly red-shifted singlet oxygen ((1)O(2)) phosphorescence spectra in an aqueous preparation of C(60) buckminsterfullerene. The similar to 10 nm red shift was associated with H(2)O dispersions of C(60) nanoaggregates (C(60)) n that can photosensitize (1)O(2) in their polarizable cores. In contrast to (1)O(2) produced by the water-soluble C(60)-(c-cyclodextrin) 2 complex, (1)O(2) trapped inside (C(60)) n was short-lived (similar to 2 -3 mu s), insensitive to solvent and (1)O(2) quenchers, and did not induce photocytotoxicity. To our knowledge, (1)O(2) spectrum from (C(60)) n is the most red-shifted (1)O(2) spectrum recorded to date and it may be used to probe the inner polarizability of carbon (nano) aggregates. Published by Elsevier B.V. C1 [Bilski, Piotr; Zhao, Baozhong; Chignell, Colin F.] NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Bilski, P (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, Res Triangle Pk, NC 27709 USA. EM bilski@niehs.nih.gov RI Zhao, Baozhong/B-5865-2011 NR 19 TC 17 Z9 17 U1 1 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-2614 J9 CHEM PHYS LETT JI Chem. Phys. Lett. PD JUN 6 PY 2008 VL 458 IS 1-3 BP 157 EP 160 DI 10.1016/j.cplett.2008.04.085 PG 4 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 306YR UT WOS:000256284900033 ER PT J AU Lule, D Hacker, S Ludolph, A Birbaumer, N Kubler, A AF Lule, Dorothee Haecker, Sonja Ludolph, Albert Birbaumer, Niels Kuebler, Andrea TI Depression and Quality of Life in Patients With Amyotrophic Lateral Sclerosis SO DEUTSCHES ARZTEBLATT INTERNATIONAL LA English DT Article DE depression; respiratory insufficiency; amyotrophic lateral sclerosis; assisted suicide; quality of life ID PHYSICIAN-ASSISTED SUICIDE; MULTIPLE-SCLEROSIS; CANCER-PATIENTS; STAGE ALS; DISORDERS; DEATH; VENTILATION; PREVALENCE; MANAGEMENT; DIAGNOSIS AB Introduction: There is increasing debate on the issue of whether to facilitate the end-of-life decisions of severely disabled patients with diseases such as amyotrophic lateral sclerosis (ALS). Our two studies were intended to explore the emotional state and quality of life of patients with ALS. Methods: Two studies were performed to investigate depression and the quality of life in ALS patients: one was a longitudinal study, the other a comparison of ALS patients to normal control subjects. Results: These studies found no correlation between physical disability in ALS and either depression or the quality of life. The severity of depression was found to be inversely related to educational status. In ALS patients the quality of life was comparable with healthy controls. Discussion: The rationale for not providing life-sustaining treatment to severely disabled patients is that a poor quality of life is expected after such treatment. Our studies have shown, however, that ALS patients can experience a satisfactory quality of life without depressive manifestations even if they are severely physically impaired, including in the terminal phase. Dtsch Arztebl Int 2008; 105(23): 397-403 DOI: 10.3238/arztebl.2008.0397 C1 [Lule, Dorothee; Ludolph, Albert] Univ Ulm, Abt Neurol, D-89081 Ulm, Germany. [Lule, Dorothee; Haecker, Sonja; Birbaumer, Niels; Kuebler, Andrea] Univ Tubingen, Inst Med Psychol & Verhaltensneurobiol, D-72074 Tubingen, Germany. [Birbaumer, Niels] NINDS, NIH, Bethesda, MD 20892 USA. [Kuebler, Andrea] Roehampton Univ, Sch Human & Life Sci, Clin & Hlth Psychol Res Ctr, London, England. RP Ludolph, A (reprint author), Univ Ulm, RKU, Neurol Klin, Oberer Eselsberg 45, D-89081 Ulm, Germany. EM albert.ludolph@rku.de OI Kubler, Andrea/0000-0003-4876-0415 NR 47 TC 39 Z9 39 U1 0 U2 2 PU DEUTSCHER AERZTE-VERLAG GMBH PI COLOGNE PA DIESELSTRABE 2, POSTFACH 400265, D-50859 COLOGNE, GERMANY SN 1866-0452 J9 DTSCH ARZTEBL INT JI Dtsch. Arztebl. Int. PD JUN 6 PY 2008 VL 105 IS 23 BP 397 EP I DI 10.3238/arztebl.2008.0397 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 476DV UT WOS:000268419100002 PM 19626161 ER PT J AU Lao, QZ Kobrinsky, E Harry, JB Ravindran, A Soldatov, NM AF Lao, Qi Zong Kobrinsky, Evgeny Harry, Jo Beth Ravindran, Arippa Soldatov, Nikolai M. TI New determinant for the Ca-v beta(2) subunit modulation of the Ca(v)1.2 calcium channel SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GATED CA2+ CHANNELS; BETA-SUBUNIT; FUNCTIONAL-PROPERTIES; MOLECULAR DETERMINANTS; ALPHA(1C) SUBUNIT; SPLICE VARIANTS; SKELETAL-MUSCLE; HUMAN HEART; VOLTAGE; INACTIVATION AB Ca-v beta subunits support voltage gating of Ca(v)1.2 calcium channels and play important role in excitation-contraction coupling. The common central membrane-associated guanylate kinase (MAGUK) region of Ca-v beta binds to the alpha-interaction domain (AID) and the IQ motif of the pore-forming alpha(1C) subunit, but these two interactions do not explain why the cardiac Ca-v beta(2) subunit splice variants differentially modulate inactivation of Ca2+ currents (I-Ca). Previously we described beta(2 Delta g), a functionally active splice variant of human Ca-v beta(2) lacking MAGUK. By deletion analysis of beta(2 Delta g), we have now identified a 41-amino acid C-terminal essential determinant (beta 2CED) that stimulates ICa in the absence of Ca-v beta subunits and conveys a +20-mV shift in the peak of the I-Ca-voltage relationship. The beta 2CED is targeted by alpha(1C) to the plasma membrane, forms a complex with alpha(1C) but does not bind to AID. Electrophysiology and binding studies point to the calmodulin-interacting LA/IQ region in the alpha(1C) subunit C terminus as a functionally relevant beta 2CED binding site. The beta 2CED interacts with LA/IQ in a Ca2+- and calmodulin-independent manner and need LA, but not IQ, to activate the channel. Deletion/mutation analyses indicated that each of the three Ca-v beta(2)/alpha(1C) interactions is sufficient to support I-Ca. However, beta 2CED does not support Ca2+-dependent inactivation, suggesting that interactions of MAGUK with AID and IQ are crucial for Ca2+-induced inactivation. The beta 2CED is conserved only in Ca-v beta(2) subunits. Thus, beta 2CED constitutes a previously unknown integrative part of the multifactorial mechanism of Ca-v beta(2)-subunit differential modulation of the Ca(v)1.2 calcium channel that in beta(2 Delta g) occurs without MAGUK. C1 [Lao, Qi Zong; Kobrinsky, Evgeny; Harry, Jo Beth; Ravindran, Arippa; Soldatov, Nikolai M.] NIA, Natl Inst Hlth, Baltimore, MD 21224 USA. RP Soldatov, NM (reprint author), 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM soldatovN@grc.nia.nih.gov FU Intramural NIH HHS [Z01 AG000294-08] NR 40 TC 14 Z9 14 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 6 PY 2008 VL 283 IS 23 BP 15577 EP 15588 DI 10.1074/jbc.M802035200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 307QD UT WOS:000256332500011 PM 18411278 ER PT J AU Ebina, H Chatterjee, AG Judson, RL Levin, HL AF Ebina, Hirotaka Chatterjee, Atreyi Ghatak Judson, Robert L. Levin, Henry L. TI The GP(Y/F) domain of TF1 integrase multimerizes when present in a fragment, and substitutions in this domain reduce enzymatic activity of the full-length protein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TERMINAL REPEAT-RETROTRANSPOSON; RETROVIRAL DNA INTEGRATION; TYPE-1 INTEGRASE; HIV-1 INTEGRASE; FISSION YEAST; CONCERTED INTEGRATION; FUNCTIONAL DOMAINS; CATALYTIC DOMAIN; SELF-ASSOCIATION AB Integrases (INs) of retroviruses and long terminal repeat retrotransposons possess a C-terminal domain with DNA binding activity. Other than this binding activity, little is known about how the C-terminal domain contributes to integration. A stretch of conserved amino acids called the GP(Y/F) domain has been identified within the C-terminal IN domains of two distantly related families, the gamma-retroviruses and the metavirus retrotransposons. To enhance understanding of the C-terminal domain, we examined the function of the GP(Y/F) domain in the IN of Tf1, a long terminal repeat retrotransposon of Schizosaccharomyces pombe. The activities of recombinant IN were measured with an assay that modeled the reverse of integration called disintegration. Although deletion of the entire C-terminal domain disrupted disintegration activity, an alanine substitution (P365A) in a conserved amino acid of the GP(Y/ F) domain did not significantly reduce disintegration. When assayed for the ability to join two molecules of DNA in a reaction that modeled forward integration, the P365A substitution disrupted activity. UV cross-linking experiments detected DNA binding activity in the C-terminal domain and found that this activity was not reduced by substitutions in two conserved amino acids of the GP(Y/F) domain, G364A and P365A. Gel filtration and cross-linking of a 71-amino acid fragment containing the GP(Y/F) domain revealed a surprising ability to form dimers, trimers, and tetramers that was disrupted by the G364A and P365A substitutions. These results suggest that the GP(Y/F) residues may play roles in promoting multimerization and intermolecular strand joining. C1 [Ebina, Hirotaka; Chatterjee, Atreyi Ghatak; Judson, Robert L.; Levin, Henry L.] NICHD, Sect Eukaryot Transposable Elements, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Levin, HL (reprint author), NICHD, Sect Eukaryot Transposable Elements, Lab Gene Regulat & Dev, NIH, 18 Lib Dr, Bethesda, MD 20892 USA. EM henry_levin@nih.gov FU Intramural NIH HHS NR 41 TC 4 Z9 4 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 6 PY 2008 VL 283 IS 23 BP 15965 EP 15974 DI 10.1074/jbc.M801354200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 307QD UT WOS:000256332500055 PM 18397885 ER PT J AU Pace, JM Wiese, M Drenguis, AS Kuznetsova, N Leikin, S Schwarze, U Chen, D Mooney, SH Unger, S Byers, PH AF Pace, James M. Wiese, Mary Drenguis, Andrea S. Kuznetsova, Natalia Leikin, Sergey Schwarze, Ulrike Chen, Diana Mooney, Suzanne H. Unger, Sheila Byers, Peter H. TI Defective C-propeptides of the pro alpha 2(I) chain of type I procollagen impede molecular assembly and result in osteogenesis imperfecta SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CARBOXYL-TERMINAL PROPEPTIDE; COLLAGEN MUTATION DATABASE; FRAMESHIFT MUTATION; LETHAL VARIANT; ALPHA-1 CHAIN; TRIPLE-HELIX; GENE; SUBSTITUTION; DISRUPTION; CYSTEINE AB Type I procollagen is a heterotrimer composed of two pro alpha 1(I) chains and one pro alpha 2(I) chain, encoded by the COL1A1 and COL1A2 genes, respectively. Mutations in these genes usually lead to dominantly inherited forms of osteogenesis imperfecta (OI) by altering the triple helical domains, but a few affect sequences in the pro alpha 1(I) C-terminal propeptide (C-propeptide), and one, which has a phenotype only in homozygotes, alters the pro alpha 2(I) C-propeptide. Here we describe four dominant mutations in the COL1A2 gene that alter sequences of the pro alpha 2(I) C-propeptide in individuals with clinical features of a milder form of the disease, OI type IV. Three of the four appear to interfere with disulfide bonds that stabilize the C-propeptide conformation and its interaction with other chains in the trimer. Cultured cells synthesized pro alpha 2(I) chains that were slow to assemble with pro alpha 1(I) chains to form heterotrimers and that were retained intracellularly. Some alterations led to the uncharacteristic formation of pro alpha 1(I) homotrimers. These findings show that the C-propeptide of pro alpha 2(I), like that of the pro alpha 1(I) C-propeptide, is essential for efficient assembly of type I procollagen heterotrimers. The milder OI phenotypes likely reflect a diminished amount of normal type I procollagen, small populations of overmodified heterotrimers, and pro alpha 1(I) homotrimers that are compatible with normal skeletal growth. C1 [Pace, James M.; Wiese, Mary; Drenguis, Andrea S.; Schwarze, Ulrike; Chen, Diana; Mooney, Suzanne H.; Byers, Peter H.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Kuznetsova, Natalia; Leikin, Sergey] NICHD, Sect Phys Biochem, NIH, Bethesda, MD 20892 USA. [Unger, Sheila] Univ Freiburg, Inst Human Genet, D-79085 Freiburg, Germany. [Byers, Peter H.] Univ Washington, Dept Med, Seattle, WA 98195 USA. RP Byers, PH (reprint author), Univ Washington, Dept Pathol, Box 357470, Seattle, WA 98195 USA. EM pbyers@u.washington.edu RI Leikin, Sergey/A-5518-2008; unger, sheila/E-9177-2015 OI Leikin, Sergey/0000-0001-7095-0739; FU NIAMS NIH HHS [5R01AR041223-13] NR 35 TC 29 Z9 30 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 6 PY 2008 VL 283 IS 23 BP 16061 EP 16067 DI 10.1074/jbc.M801982200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 307QD UT WOS:000256332500064 PM 18375391 ER PT J AU Nechaev, S Geiduschek, EP AF Nechaev, Sergei Geiduschek, E. Peter TI Dissection of the bacteriophage T4 late promoter complex SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE RNA polymerase; promoter; gene regulation; phage T4; sliding clamp ID COLI RNA-POLYMERASE; ESCHERICHIA-COLI; SLIDING-CLAMP; DNA-POLYMERASE; TRANSCRIPTIONAL ACTIVATION; RECOGNITION ELEMENT; ACCESSORY PROTEINS; PRIMER-TEMPLATE; ALPHA-SUBUNIT; CORE GENOME AB Activated transcription of the bacteriophage T4 late genes is generated by a mechanism that stands apart from the common modalities of transcriptional regulation: the activator is gp45, the viral replisome's sliding clamp; two sliding-clamp-binding proteins, gp33 and gp55, replace the host RNA polymerase (RNAP) a subunit. We have mutagenized, reconfigured and selectively disrupted individual interactions of the sliding clamp with gp33 and gp55 and have monitored effects on transcription. The C-terminal sliding-clamp-binding epitopes of gp33 and gp55 are perfectly interchangeable, but the functions of these two RNAP-sliding clamp connections differ: only the gp33-gp45 linkage is essential for activation, while loss of the gh55-gP45 linkage impairs but does not abolish activation. Formation of transcription-ready promoter complexes by the sliding-clamp-activated wild-type T4 RNAP resists competition by high concentrations of the polyanion heparin. This avid formation of promoter complexes requires both linkages of the T4 late RNAP to the sliding clamp. Preopening the promoter compensates for loss of the gp55-gp45 but not the gp33-gp45 linkage. We interpret the relationship of these findings and our prior analysis to the common model of transcriptional initiation in bacteria in terms of two parallel pathways, with two RNAP holoenzymes and two DNA templates: (1) gp55-RNAP and the T4 late promoter execute basal transcription; (2) gp55-gp33-RNAP and the T4 late promoter with its mobile enhancer, the T4 sliding clamp, execute activated transcription. gp55 and gp33 perform (J-like functions, gp55 in promoter recognition and gp33 (as well as gp55) in enhancer recognition. gp33 operates the switch between these two pathways by repressing basal transcription. (c) 2008 Elsevier Ltd. All rights reserved. C1 Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA. Univ Calif San Diego, Ctr Mol Genet, La Jolla, CA 92093 USA. RP Nechaev, S (reprint author), NIEHS, Mol Carcinogenesis Lab, 11 TW Alexander Dr,Room D434, Res Triangle Pk, NC 27709 USA. EM nechaevs@niehs.nih.gov; epg@biomail.ucsd.edu FU NIGMS NIH HHS [R01 GM018386-38] NR 39 TC 11 Z9 12 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JUN 6 PY 2008 VL 379 IS 3 BP 402 EP 413 DI 10.1016/j.jmb.2008.03.071 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 311FQ UT WOS:000256586500002 PM 18455735 ER PT J AU Casanovas, J Nussinov, R Aleman, C AF Casanovas, Jordi Nussinov, Ruth Aleman, Carlos TI Intrinsic conformational preferences of C-alpha,C-alpha-dibenzylglycine SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID ALPHA-AMINOISOBUTYRIC-ACID; PREFERRED CONFORMATION; DISUBSTITUTED GLYCINES; SYSTEMATIC EVALUATION; CYCLOPROPANE ANALOG; SOLVATION MODEL; SIDE-CHAIN; PEPTIDES; PHENYLALANINE; RESIDUES AB [GRAPHICS] The intrinsic conformational preferences of C-alpha,C-alpha-dibenzylglycine, a symmetric alpha,alpha-dialkyiated amino acid bearing two benzyl substituents on the alpha-carbon atom, have been determined using quantum chemical calculations at the B3LYP/6-31 +G(d,p) level. A total of 46 minimum energy conformations were found for the N-acetyl-M-niethylamide derivative, even though only nine of them showed a relative energy lower than 5.0 kcal/mol. The latter involves C-7, C-5, and alpha' backbone conformations stabilized by intramolecular hydrogen bonds and/or N-H center dot center dot center dot pi interactions. Calculation of the conformational free energies in different environments (gas-phase, carbon tetrachloride, chloroform, methanol, and water solutions) indicates that four different minima (two C-5 and two C-7) are energetically accessible at room temperature in the gas phase, while in methanol and aqueous solutions one such minimum (C-5) becomes the only significant conformation. Comparison with results recently reported for C-alpha,C-alpha-diphenylglycine indicates that substitution of phenyl side groups by benzyl enhances the conformational flexibility leading to (i) a reduction of the strain of the peptide backbone and (ii) alleviating the repulsive interactions between the T electron density of the phenyl groups and the lone pairs of the carbonyl oxygen atoms. C1 [Casanovas, Jordi] Univ Lleida, Escola Politecn Super, Dept Quim, E-25001 Lleida, Spain. [Nussinov, Ruth] NCI, Ctr Canc, Res Nanobiol Program, SAIC Frederick Inc,Basic Res Program, Frederick, MD 21702 USA. [Nussinov, Ruth] Tel Aviv Univ, Sch Med, Dept Human Genet Sackler, IL-69978 Tel Aviv, Israel. [Aleman, Carlos] Univ Politecn Cataluna, ETS Engn Ind Barcelona, Dept Engn Quim, E-08028 Barcelona, Spain. RP Casanovas, J (reprint author), Univ Lleida, Escola Politecn Super, Dept Quim, C Jaume 2 69, E-25001 Lleida, Spain. EM jcasanovas@quimica.udl.cat RI Casanovas, Jordi/B-5435-2013 OI Casanovas, Jordi/0000-0002-4914-9194 FU Intramural NIH HHS [Z01 BC010440-06]; NCI NIH HHS [N01 CO012400, N01CO12400] NR 50 TC 9 Z9 9 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD JUN 6 PY 2008 VL 73 IS 11 BP 4205 EP 4211 DI 10.1021/jo8005528 PG 7 WC Chemistry, Organic SC Chemistry GA 307MR UT WOS:000256323500028 PM 18465898 ER PT J AU Fang, ZL Song, YL Sarkar, T Hamel, E Fogler, WE Agoston, GE Fanwick, PE Cushman, M AF Fang, Zhenglai Song, Yunlong Sarkar, Taradas Hamel, Ernest Fogler, William E. Agoston, Gregory E. Fanwick, Phillip E. Cushman, Mark TI Stereoselective synthesis of 3,3-diarylacrylonitriles as tubulin polymerization inhibitors SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID STATHMIN-LIKE DOMAIN; CONJUGATE ADDITION; ALPHA,BETA-ACETYLENIC ESTERS; COPPER(I) CHLORIDE; CHEMISTRY; SYSTEMS; TRANSMETALATION; COLCHICINE; REAGENTS; THERAPY AB A series of 3,3-diarylacrylonitriles were synthesized stercoselectively as tubulin polymerization inhibitors for potential use in cancer chemotherapy. This synthetic route features stannylcupration and palladium-catalyzed Stille cross-coupling chemistry, allowing both E and Z isomers of 3,3-diarylacrylonitriles to be prepared in a very short sequence of reactions. C1 [Fang, Zhenglai; Song, Yunlong; Cushman, Mark] Purdue Univ, Sch Pharm & Pharmaceut Sci, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. [Fang, Zhenglai; Song, Yunlong; Cushman, Mark] Purdue Univ, Purdue Canc Ctr, W Lafayette, IN 47907 USA. [Sarkar, Taradas; Hamel, Ernest] Natl Inst Hlth, Natl Canc Inst, Div Canc Treatment & Diag, Dev Therapeut Program,Toxicol & Pharmacol Branch, Frederick, MD 21702 USA. [Fogler, William E.; Agoston, Gregory E.] EntreMed Inc, Rockville, MD 20850 USA. [Fanwick, Phillip E.] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. RP Cushman, M (reprint author), Purdue Univ, Sch Pharm & Pharmaceut Sci, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. EM cushman@pharmacy.purdue.edu RI Fanwick, Phillip/A-8625-2009 NR 41 TC 13 Z9 13 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD JUN 6 PY 2008 VL 73 IS 11 BP 4241 EP 4244 DI 10.1021/jo800428b PG 4 WC Chemistry, Organic SC Chemistry GA 307MR UT WOS:000256323500035 PM 18447388 ER PT J AU Kireeva, ML Nedialkov, YA Cremona, GH Purtov, YA Lubkowska, L Malagon, F Burton, ZF Strathern, JN Kashlev, M AF Kireeva, Maria L. Nedialkov, Yuri A. Cremona, Gina H. Purtov, Yuri A. Lubkowska, Lucyna Malagon, Francisco Burton, Zachary F. Strathern, Jeffrey N. Kashlev, Mikhail TI Transient reversal of RNA polymerase II active site closing controls fidelity of transcription elongation SO MOLECULAR CELL LA English DT Article ID STATE KINETIC-ANALYSIS; STRUCTURAL BASIS; DEPENDENT RNA-POLYMERASE-(3D(POL)); SACCHAROMYCES-CEREVISIAE; ESCHERICHIA-COLI; RIBONUCLEOTIDE INCORPORATION; NUCLEOSIDE TRIPHOSPHATES; CLEAVAGE ACTIVITY; TRIGGER LOOP; IN-VIVO AB To study fidelity of RNA polymerase II (Pol II), we analyzed properties of the 6-azauracil-sensitive and TFIIS-dependent E1103G mutant of rbpl (rpo21), the gene encoding the catalytic subunit of Pol II in Saccharomyces cerevisiae. Using an in vivo retro-transposition-based transcription fidelity assay, we observed that rpb1-E1103G causes a 3-fold increase in transcription errors. This mutant showed a 10-fold decrease in fidelity of transcription elongation in vitro. The mutation does not appear to significantly affect translocation state equilibrium of Pol II in a stalled elongation complex. Primarily, it promotes NTP sequestration in the polymerase active center. Furthermore, pre-steady-state analyses revealed that the E1103G mutation shifted the equilibrium between the closed and the open active center conformations toward the closed form. Thus, open conformation of the active center emerges as an intermediate essential for preincorporation fidelity control. Similar mechanisms may control fidelity of DNA-dependent DNA polymerases and RNA-dependent RNA polymerases. C1 [Kireeva, Maria L.; Nedialkov, Yuri A.; Cremona, Gina H.; Purtov, Yuri A.; Lubkowska, Lucyna; Malagon, Francisco; Strathern, Jeffrey N.; Kashlev, Mikhail] NCI, Ctr Canc Res, Ft Detrick, MD 21702 USA. [Nedialkov, Yuri A.; Burton, Zachary F.] Michigan State Univ, Dept Biochem & Mol Biol, E Lansing, MI 48824 USA. RP Kashlev, M (reprint author), NCI, Ctr Canc Res, Ft Detrick, MD 21702 USA. EM mkashlev@mail.ncifcrf.gov RI Malagon, Francisco/A-7059-2013 NR 52 TC 85 Z9 86 U1 1 U2 7 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD JUN 6 PY 2008 VL 30 IS 5 BP 557 EP 566 DI 10.1016/j.molcel.2008.04.017 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 312BM UT WOS:000256644100006 PM 18538654 ER PT J AU Kaiser, J Collins, F AF Kaiser, Jocelyn Collins, Francis TI Departing U.S. Genome Institute director takes stock of personalized medicine SO SCIENCE LA English DT Editorial Material C1 [Collins, Francis] NHGRI, Bethesda, MD 20892 USA. NR 0 TC 11 Z9 12 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUN 6 PY 2008 VL 320 IS 5881 BP 1272 EP 1272 DI 10.1126/science.320.5881.1272 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 309DO UT WOS:000256441100005 ER PT J AU Hutcheson, HB Lautenberger, JA Nelson, GW Pontius, JU Kessing, BD Winkler, CA Smith, MW Johnson, R Stephens, R Phair, J Goedert, JJ Donfield, S O'Brien, SJ AF Hutcheson, H. B. Lautenberger, J. A. Nelson, G. W. Pontius, J. U. Kessing, B. D. Winkler, C. A. Smith, M. W. Johnson, R. Stephens, R. Phair, J. Goedert, J. J. Donfield, S. O'Brien, S. J. TI Detecting AIDS restriction genes: From candidate genes to genome-wide association discovery SO VACCINE LA English DT Article; Proceedings Paper CT 1st International Symposium on Genetic and Immune Correlates of HIV Infection and Vaccine-Induced Immunity CY JUN 10-13, 2007 CL Budapest, HUNGARY DE aIDS restriction genes (ARGs) ID IMMUNODEFICIENCY-VIRUS TYPE-1; PROMOTER POLYMORPHISM; HIV-1 INFECTION; DISEASE; RANTES; SUSCEPTIBILITY; VARIANTS; PROGRESSION; RECEPTOR; RISK AB The screening of common genetic polymorphisms among candidate genes for AIDS pathology in HIV exposed cohort populations has led to the description of 20 AIDS restriction genes (ARGs), variants that affect susceptibility to HIV infection or to AIDS progression. The combination of high-throughput genotyping platforms and the recent HapMap annotation of some 3 mithon human SNP variants has been developed for and applied to gene discovery in complex and mutti-factoriat diseases. Here, we explore novel computational approaches to ARG discovery which consider interacting anaLytical modeLs, various genetic influences, and SNP-haptotype/LD structure in AIDS cohort populations to determine if these ARGs could have been discovered using an unbiased genome-wide association approach. The procedures were evaluated by tracking the performance of haplotypes and SNPs within ARG regions to detect genetic association in the same AIDS cohort populations in which the ARGs were originally discovered. The methodology captures the signats of muttiple non-independent AIDS-genetic association tests of different disease stages and uses association signal strength (odds ratio or relative hazard), statistical significance (p-vatues), gene influence, internal reptication, and hapLotype structure together as a mutti-facetted approach to identifying important genetic associations within a deLuge of genotyping/test data. The complementary approaches perform rather well. and predict the detection of a variety of undiscovered ARGs that affect different stages of HIV/AIDS pathogenesis using genome-wide association anatyses. Pubtished by Etsevier Ltd. C1 [Hutcheson, H. B.; Lautenberger, J. A.; O'Brien, S. J.] Natl Canc Inst, Lab Genom Div, Frederick, MD 21702 USA. [Nelson, G. W.; Pontius, J. U.; Kessing, B. D.; Winkler, C. A.; Smith, M. W.; Johnson, R.] NCI, SAIC Frederick Inc, Lab Genom Div Basic Res Program, Frederick, MD 21702 USA. [Stephens, R.] SAIC Frederick, Adv Biomed Comp Ctr, Frederick, MD 21702 USA. [Phair, J.] NW Univ Med Sch, Div Infect Dis, Chicago, IL 60611 USA. [Goedert, J. J.] Natl Canc Inst, Viral Epidemiol Branch, Rockville, MD 20852 USA. [Donfield, S.] Rho Inc, Chapel Hill, NC 27514 USA. RP O'Brien, SJ (reprint author), Natl Canc Inst, Lab Genom Div, Frederick, MD 21702 USA. EM obrien@ncifcrf.gov RI Smith, Michael/B-5341-2012; Johnson, Randall/B-1517-2014 OI Johnson, Randall/0000-0001-7754-0847 FU NCI NIH HHS [N01-CO-12400] NR 52 TC 12 Z9 12 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD JUN 6 PY 2008 VL 26 IS 24 BP 2951 EP 2965 DI 10.1016/j.vaccine.2007.12.054 PG 15 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 323WW UT WOS:000257480100002 PM 18325640 ER PT J AU Jacobs, A Garg, H Viard, M Raviv, Y Puri, A Blumenthal, R AF Jacobs, Amy Garg, Himanshu Viard, Mathias Raviv, Yossef Puri, Anu Blumenthal, Robert TI HIV-1 envelope glycoprotein-mediated fusion and pathogenesis: Implications for therapy and vaccine development SO VACCINE LA English DT Article; Proceedings Paper CT 1st International Symposium on Genetic and Immune Correlates of HIV Infection and Vaccine-Induced Immunity CY JUN 10-13, 2007 CL Budapest, HUNGARY DE HIV; membrane fusion; membrane rafts; FRAP; lateral mobility; CD4; chemokine receptors; HIV gp120; HIV gp41; cholesterol; sphingomyelin; glycosphingolipids; six-helix bundle ID VIRUS TYPE-1 ENVELOPE; 6-HELIX BUNDLE FORMATION; MEMBRANE-FUSION; ANTIRETROVIRAL THERAPY; CONFORMATIONAL-CHANGES; BIOLOGICAL-MEMBRANES; SYNTHETIC PEPTIDE; T-CELLS; GP41; CD4 AB Our overall goal is to understand how viral envelope proteins mediate membrane fusion and pathogenesis. Membrane fusion is a crucial step in the delivery of the viral genome into the cell resulting in infection. On the other hand, fusion activity of viral envelope glycoproteins expressed in infected cells may cause the demise of uninfected bystander cells by apoptosis. Our general approach is to kinetically resolve steps in the pathway of viral. envelope glycoprotein-mediated membrane fusion and to uncover physical parameters undertying those steps using a variety of biochemical, biophysical, virological, and molecular and cell biotogical. techniques. Since HIV fusion involves a comptex cascade of interactions of the envelope glycoprotein with two receptors, membrane organization plays an important rote and interfering with it may modulate entry. To study this phenomenon, we have either examined cell, lines with differential expression of sphingolipids (such as GM3), or altered membrane organization by modifying levels of cholesterol, ceramides, or gtycosphingolipids. We show that the localized plasma membrane lipid microenvironment (and not the specific membrane lipids) in the vicinity of CD4 controls receptor mobitity and HIV-1 fusion. The complex cascade of C1 [Jacobs, Amy; Garg, Himanshu; Viard, Mathias; Raviv, Yossef; Puri, Anu; Blumenthal, Robert] Natl Canc Inst, Ctr Canc Res Nanobiol Program, Ctr Canc Res, NIH, Frederick, MD 21702 USA. [Viard, Mathias; Raviv, Yossef] NCI, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Blumenthal, R (reprint author), Natl Canc Inst, Ctr Canc Res Nanobiol Program, Ctr Canc Res, NIH, POB B, Frederick, MD 21702 USA. EM blumenthalr@mail.nih.gov FU Intramural NIH HHS [Z01 BC008303-35, Z01 BC010652-03, Z99 CA999999]; NCI NIH HHS [N01CO12400, N01-CO-12400] NR 59 TC 16 Z9 16 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD JUN 6 PY 2008 VL 26 IS 24 BP 3026 EP 3035 DI 10.1016/j.vaccine.2007.12.026 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 323WW UT WOS:000257480100009 PM 18242797 ER PT J AU Borkowsky, W Yogev, R Muresan, P McFarland, E Frenkel, L Fenton, T Capparelli, E Moye, J Harding, P Ellis, N Heckman, B Kraimer, J AF Borkowsky, William Yogev, Ram Muresan, Petronella McFarland, Elizabeth Frenkel, Lisa Fenton, Terry Capparelli, Edmond Moye, Jack Harding, Paul Ellis, Nina Heckman, Barbara Kraimer, Joyce TI Structured treatment interruptions (STIs) in HIV-1 infected pediatric populations increases interferon gamma production and reduces viremia SO VACCINE LA English DT Article; Proceedings Paper CT 1st International Symposium on Genetic and Immune Correlates of HIV Infection and Vaccine-Induced Immunity CY JUN 10-13, 2007 CL Budapest, HUNGARY AB We assessed the effect of progressively longer antiretroviral structured treatment interruptions (STIs) starting with 3 days, increasing by 2 days in length each cycle on HIV-specific immune responses. As welt, we correlated these responses with control of HIV viremia. Eight individuals became viremic and reached cycle 13 with an STI of >= 27 days. HIV-specific gammainterferon production to inactivated HIV and vaccinia vectors expressing gag, env, nef, and pot increased (> 10-fold in six of eight subjects. Median plasma RNA levels peaked @ cycle 7 and declined to Levels < 10(4)cp/mlaftercycle 10. In a subset of five who reached cycle 17, HIV-specific IFN-gamma frequencies increased from cycle 8 to cycle 17 with evidence of improved virologic control over comparable periods off antiretrovirat therapy. This allowed us to conclude that exposure to autologous virus increased HIV-specific immune responses and decreased HIV RNA were seen in those who have had > 13 interruptions, with STI intervals that exceeded 27 days. (c) 2008 Published by Elsevier Ltd. C1 [Borkowsky, William] NYU, Sch Med, New York, NY 10016 USA. [Yogev, Ram] Chicago Childrens Mem Hosp, Chicago, IL USA. [Muresan, Petronella; Fenton, Terry] Harvard Univ, Sch Publ Hlth, FSTRF, Boston, MA 02115 USA. [McFarland, Elizabeth; Harding, Paul] Univ Colorado, Hlth Sci Ctr, Denver, CO USA. [Frenkel, Lisa; Ellis, Nina] Univ Washington, Seattle, WA 98195 USA. [Capparelli, Edmond] Univ Calif San Diego, La Jolla, CA 92093 USA. [Moye, Jack] NICHD, NIH, Bethesda, MD USA. [Heckman, Barbara] FSTRF Data Management Ctr, Amherst, NY USA. [Kraimer, Joyce] Social & Sci Syst Inc, Silver Spring, MD USA. RP Borkowsky, W (reprint author), NYU, Sch Med, 550 1st Ave, New York, NY 10016 USA. EM borkow01@gcrc.med.nyu.edu OI moye, john/0000-0001-9976-8586 FU NCRR NIH HHS [M01 RR000096, RR00096, M01 RR000069, M01 RR00069]; NIAID NIH HHS [U01 AI027553] NR 5 TC 3 Z9 3 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD JUN 6 PY 2008 VL 26 IS 24 BP 3086 EP 3089 DI 10.1016/j.vaccine.2007.12.017 PG 4 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 323WW UT WOS:000257480100016 PM 18472197 ER PT J AU Roohi, J Tegay, DH Pomeroy, JC Burkett, S Stone, G Stanyon, R Hatchwell, E AF Roohi, Jasmin Tegay, David H. Pomeroy, John C. Burkett, Sandra Stone, Gary Stanyon, Roscoe Hatchwell, Eli TI A de novo apparently balanced translocation [46AY,t(2;9)(p13;p24)] interrupting RAB11FIP5 identifies a potential candidate gene for autism spectrum disorder SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE autism; translocation, genetic; RAB11 family interacting protein 5 (class I), human; doublestranded DNA break; type I DNA topoisomerase ID RAB11-INTERACTING PROTEINS; RECYCLING ENDOSOMES; TRAFFICKING; DNA; SEQUENCES; LINKAGE; MOTIFS; FAMILY AB Autism spectrum disorder (ASD) is a severe developmental disorder of the central nervous system characterized by impairments in social interaction, communication, and range of interests and behaviors. The syndrome's prevalence is estimated to be as high as 1 in 150 American children yet its etiology remains largely unknown. Examination of observed cytogenetic variants in individuals with ASD may identify genes involved in its pathogenesis. As part of a multidisciplinary study, an apparently balanced de novo translocation between chromosomes 2 and 9 [46,X-Y,t(2;9)(p13;p24)] was identified in a subject with pervasive developmental disorder not otherwise specified (PDD-NOS), and no distinctive dysmorphic features. Molecular characterization of the rearrangement revealed direct interruption of the RAB11 family interacting protein 5 (RAB11FIP5) gene. RAB11FIP5 is a Rab effector involved in protein trafficking from apical recycling endosomes to the apical plasma membrane. It is ubiquitously expressed and reported to contribute to both neurotransmitter release and neurotransmitter uptake at the synaptic junction. Detailed analysis of the rearrangement breakpoints suggests that the reciprocal translocation may have formed secondary to incorrect repair of double strand breaks (DSBs) by nonhomologous end-joining (NHEJ). (c) 2008 Wiley-Liss, Inc. C1 [Hatchwell, Eli] SUNY Stony Brook, Dept Pathol, Stony Brook, NY 11794 USA. [Roohi, Jasmin; Hatchwell, Eli] SUNY Stony Brook, Dept Genet, Stony Brook, NY 11794 USA. [Tegay, David H.; Pomeroy, John C.] SUNY Stony Brook, Dept Pediat, Med Ctr, Stony Brook, NY 11794 USA. [Tegay, David H.] New York Coll Osteopath Med, Dept Med & Med Genet, Old Westbury, NY USA. [Burkett, Sandra; Stone, Gary; Stanyon, Roscoe] NCI, Frederick, MD 21701 USA. [Stanyon, Roscoe] Univ Florence, Dept Anim Biol & Genet, Florence, Italy. RP Hatchwell, E (reprint author), SUNY Stony Brook, Dept Pathol, BST-9, Stony Brook, NY 11794 USA. EM eli.hatchwell@stonybrook.edu FU Intramural NIH HHS; NCRR NIH HHS [M01 RR010710, MO1RR10710]; NIGMS NIH HHS [T32 GM008444] NR 34 TC 7 Z9 7 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD JUN 5 PY 2008 VL 147B IS 4 BP 411 EP 417 DI 10.1002/ajmg.b.30755 PG 7 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 307PO UT WOS:000256331000001 PM 18384058 ER PT J AU Zheng, J Jang, H Ma, B Nussinov, R AF Zheng, Jie Jang, Hyunbum Ma, Buyong Nussinov, Ruth TI Annular structures as intermediates in fibril formation of Alzheimer A beta(17-42) SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID AMYLOID-BETA-PROTEIN; MOLECULAR-DYNAMICS SIMULATIONS; SOLID-STATE NMR; ION CHANNELS; PEPTIDE AGGREGATION; MISFOLDING DISEASES; 3D STRUCTURE; OLIGOMERS; TOXICITY; SEQUENCE AB We report all-atom molecular dynamics simulations of annular beta-amyloid (17-42) structures, single- and double-layered, in solution. We assess the structural stability and association force of A beta annular oligomers associated through different interfaces, with a mutated sequence (M35A), and with the oxidation state (M35O). Simulation results show that single-layered annular models display inherent structural instability: one is broken down into linear-like oligomers, and the other collapses. On the other hand, a double-layered annular structure where the two layers interact through their C-termini to form an NC-CN interface (where N and C are the N and C termini, respectively) exhibits high structural stability over the simulation time due to strong hydrophobic interactions and geometrical constraints induced by the closed circular shape. The observed dimensions and molecular weight of the oligomers from atomic force microscopy (AFM) experiments are found to correspond well. to our stable double-layered model with the NC-CN interface. Comparison with K3 annular structures derived from the beta(2)-microglobulin suggests that the driving force for amyloid formation is sequence specific, strongly dependent on side-chain packing arrangements, structural morphologies, sequence composition, and residue positions. Combined with our previous simulations of linear-like A beta, K3 peptide, and sup35-derived GNNQQNY peptide, the annular structures provide useful insight into oligomeric structures and driving forces that are critical in amyloid fibril formation. C1 [Zheng, Jie] Univ Akron, Dept Chem & Biomol Engn, Akron, OH 44325 USA. [Jang, Hyunbum; Ma, Buyong; Nussinov, Ruth] NCI, Ctr Canc Res Nanobiol Program, SAIC Frederick Inc, Basic Res Program, Frederick, MD 21702 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel. RP Zheng, J (reprint author), Univ Akron, Dept Chem & Biomol Engn, Akron, OH 44325 USA. EM zhengj@uakron.edu; ruthn@ncifcrf.gov RI Ma, Buyong/F-9491-2011; Zheng, Jie/B-5057-2013 OI Ma, Buyong/0000-0002-7383-719X; Zheng, Jie/0000-0003-1547-3612 FU Intramural NIH HHS [Z01 BC010440-06]; NCI NIH HHS [N01-CO-12400, N01CO12400] NR 53 TC 53 Z9 53 U1 2 U2 21 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-6106 J9 J PHYS CHEM B JI J. Phys. Chem. B PD JUN 5 PY 2008 VL 112 IS 22 BP 6856 EP 6865 DI 10.1021/jp711335b PG 10 WC Chemistry, Physical SC Chemistry GA 306RH UT WOS:000256265000016 PM 18457440 ER PT J AU Graves, AR Curran, PK Smith, CL Mindell, JA AF Graves, Austin R. Curran, Patricia K. Smith, Carolyn L. Mindell, Joseph A. TI The Cl(-)/H(+) antiporter ClC-7 is the primary chloride permeation pathway in lysosomes SO NATURE LA English DT Article ID OSTEOPETROSIS TYPE-II; FUNCTIONAL RECONSTITUTION; TORPEDO-CALIFORNICA; PROTON PUMP; CHANNEL; PROTEINS; MUTATION; DISEASE; LEADS AB Lysosomes are the stomachs of the cell - terminal organelles on the endocytic pathway where internalized macromolecules are degraded. Containing a wide range of hydrolytic enzymes, lysosomes depend on maintaining acidic luminal pH values for efficient function. Although acidification is mediated by a V- type proton ATPase, a parallel anion pathway is essential to allow bulk proton transport(1,2). The molecular identity of this anion transporter remains unknown. Recent results of knockout experiments raise the possibility that ClC- 7, a member of the CLC family of anion channels and transporters, is a contributor to this pathway in an osteoclast lysosome- like compartment, with loss of ClC- 7 function causing osteopetrosis(3). Several mammalian members of the CLC family have been characterized in detail; some ( including ClC- 0, ClC- 1 and ClC- 2) function as Cl(-) -conducting ion channels(4), whereas others act as Cl(-)/H(+) antiporters ( ClC- 4 and ClC-5) (5,6). However, previous attempts at heterologous expression of ClC- 7 have failed to yield evidence of functional protein, so it is unclear whether ClC- 7 has an important function in lysosomal biology, and also whether this protein functions as a Cl(-) channel, a Cl(-)/H(+) antiporter, or as something else entirely. Here we directly demonstrate an anion transport pathway in lysosomes that has the defining characteristics of a CLC Cl(-)/H(+) antiporter and show that this transporter is the predominant route for Cl(-) through the lysosomal membrane. Furthermore, knockdown of ClC- 7 expression by short interfering RNA can essentially ablate this lysosomal Cl(-)/H(+) antiport activity and can strongly diminish the ability of lysosomes to acidify in vivo, demonstrating that ClC- 7 is a Cl(-)/H(+) antiporter, that it constitutes the major Cl(-) permeability of lysosomes, and that it is important in lysosomal acidification. C1 [Graves, Austin R.; Curran, Patricia K.; Mindell, Joseph A.] Natl Inst Neurol Disorders & Stroke, Membrane Transport Biophys Unit, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA. [Smith, Carolyn L.] Natl Inst Neurol Disorders & Stroke, Light Microscopy Facil, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA. RP Mindell, JA (reprint author), Natl Inst Neurol Disorders & Stroke, Membrane Transport Biophys Unit, Porter Neurosci Res Ctr, NIH, 35 Convent Dr,Bldg 35,MSC 3701, Bethesda, MD 20892 USA. EM mindellj@ninds.nih.gov OI Mindell, Joseph/0000-0002-6952-8247 FU Intramural NIH HHS NR 22 TC 162 Z9 169 U1 0 U2 12 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUN 5 PY 2008 VL 453 IS 7196 BP 788 EP 792 DI 10.1038/nature06907 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 308UK UT WOS:000256415300045 PM 18449189 ER PT J AU Zhou, G Xie, TX Zhao, M Jasser, SA Younes, MN Sano, D Lin, J Kupferman, ME Santillan, AA Patel, V Gutkind, JS Ei-Naggar, AK Emberley, ED Watson, PH Matsuzawa, SI Reed, JC Myers, JN AF Zhou, G. Xie, T-X Zhao, M. Jasser, S. A. Younes, M. N. Sano, D. Lin, J. Kupferman, M. E. Santillan, A. A. Patel, V. Gutkind, J. S. Ei-Naggar, A. K. Emberley, E. D. Watson, P. H. Matsuzawa, S-I Reed, J. C. Myers, J. N. TI Reciprocal negative regulation between S100A7/psoriasin and beta-catenin signaling plays an important role in tumor progression of squamous cell carcinoma of oral cavity SO ONCOGENE LA English DT Article DE S100A7; psoriasin; beta-catenin; oral squamous cell carcinoma; head and neck squamous cell carcinoma ID F-BOX PROTEIN; PSORIASIN S100A7; BREAST-CANCER; DEGRADATION PATHWAY; COLORECTAL-CANCER; HUMAN SKIN; IN-VITRO; C-MYC; EXPRESSION; COMPLEX AB Overexpression of S100A7 (psoriasin), a small calcium-binding protein, has been associated with the development of psoriasis and carcinomas in different types of epithelia, but its precise functions are still unknown. Using human tissue specimens, cultured cell lines, and a mouse model, we found that S100A7 is highly expressed in preinvasive, well-differentiated and early staged human squamous cell carcinoma of the oral cavity (SCCOC), but little or no expression was found in poorly differentiated, later-staged invasive tumors. Interestingly, our results showed that S100A7 inhibits both SCCOC cell proliferation in vitro and tumor growth/invasion in vivo. Furthermore, we demonstrated that S100A7 is associated with the beta-catenin complex, and inhibits beta-catenin signaling by targeting beta-catenin degradation via a noncanonical mechanism that is independent of GSK3 beta-mediated phosphorylation. More importantly, our results also indicated that beta-catenin signaling negatively regulates S100A7 expression. Thus, this reciprocal negative regulation between S100A7 and beta-catenin signaling implies their important roles in tumor development and progression. Despite its high levels of expression in early stage SCCOC tumorigenesis, S100A7 actually inhibits SCCOC tumor growth/invasion as well as tumor progression. Downregulation of S100A7 in later stages of tumorigenesis increases beta-catenin signaling, leading to promotion of tumor growth and tumor progression. C1 [Zhou, G.; Xie, T-X; Zhao, M.; Jasser, S. A.; Younes, M. N.; Sano, D.; Lin, J.; Kupferman, M. E.; Santillan, A. A.; Myers, J. N.] Univ Texas MD Anderson Canc Ctr, Dept Head & Neck Surg, Houston, TX 77030 USA. [Patel, V.; Gutkind, J. S.] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA. [Ei-Naggar, A. K.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Emberley, E. D.; Watson, P. H.] BC Canc Agcy, Deeley Res Ctr, Victoria, BC, Canada. [Matsuzawa, S-I; Reed, J. C.] Burnham Inst Med Res, La Jolla, CA USA. [Myers, J. N.] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA. RP Myers, JN (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Head & Neck Surg, 1515 Holcombe Blvd,Unit 441, Houston, TX 77030 USA. EM jmyers@mdanderson.org RI Gutkind, J. Silvio/A-1053-2009; Lin, Jing /I-3889-2013 OI Lin, Jing /0000-0002-2563-5083 FU NCI NIH HHS [CA16672, CA69381, P30 CA016672]; NIDCR NIH HHS [R01DE01461301] NR 37 TC 29 Z9 29 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN 5 PY 2008 VL 27 IS 25 BP 3527 EP 3538 DI 10.1038/sj.onc.1211015 PG 12 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 309NW UT WOS:000256468500004 PM 18223693 ER PT J AU Das, AT Klaver, B Centlivre, M Harwig, A Ooms, M Page, M Almond, N Yuan, F Piatak, M Lifson, JD Berkhout, B AF Das, Atze T. Klaver, Bep Centlivre, Mireille Harwig, Alex Ooms, Marcel Page, Mark Almond, Neil Yuan, Fang Piatak, Mike, Jr. Lifson, Jeffrey D. Berkhout, Ben TI Optimization of the doxycycline-dependent simian immunodeficiency virus through in vitro evolution SO RETROVIROLOGY LA English DT Article ID REGULATED GENE-EXPRESSION; ATTENUATED HIV VACCINES; PROTECTIVE IMMUNITY; VIRAL REPLICATION; TYPE-1 VACCINE; LEADER RNA; EX-VIVO; LIVE; SYSTEM; TET AB Background: Vaccination of macaques with live attenuated simian immunodeficiency virus (SIV) provides significant protection against the wild-type virus. The use of a live attenuated human immunodeficiency virus (HIV) as AIDS vaccine in humans is however considered unsafe because of the risk that the attenuated virus may accumulate genetic changes during persistence and evolve to a pathogenic variant. We earlier presented a conditionally live HIV-1 variant that replicates exclusively in the presence of doxycycline (dox). Replication of this vaccine strain can be limited to the time that is needed to provide full protection through transient dox administration. Since the effectiveness and safety of such a conditionally live virus vaccine should be tested in macaques, we constructed a similar dox-dependent SIV variant. The Tat-TAR transcription control mechanism in this virus was inactivated through mutation and functionally replaced by the dox-inducible Tet-On regulatory system. This SIV-rtTA variant replicated in a dox-dependent manner in T cell lines, but not as efficiently as the parental SIVmac239 strain. Since macaque studies will likely require an efficiently replicating variant, we set out to optimize SIV-rtTA through in vitro viral evolution. Results: Upon long-term culturing of SIV-rtTA, additional nucleotide substitutions were observed in TAR that affect the structure of this RNA element but that do not restore Tat binding. We demonstrate that the bulge and loop mutations that we had introduced in the TAR element of SIV-rtTA to inactivate the Tat-TAR mechanism, shifted the equilibrium between two alternative conformations of TAR. The additional TAR mutations observed in the evolved variants partially or completely restored this equilibrium, which suggests that the balance between the two TAR conformations is important for efficient viral replication. Moreover, SIV-rtTA acquired mutations in the U3 promoter region. We demonstrate that these TAR and U3 changes improve viral replication in T-cell lines and macaque peripheral blood mononuclear cells (PBMC) but do not affect dox-control. Conclusion: The dox-dependent SIV-rtTA variant was optimized by viral evolution, yielding variants that can be used to test the conditionally live virus vaccine approach and as a tool in SIV biology studies and vaccine research. C1 [Das, Atze T.; Klaver, Bep; Centlivre, Mireille; Harwig, Alex; Ooms, Marcel; Berkhout, Ben] Univ Amsterdam, Acad Med Ctr, CINIMA, Dept Med Microbiol,Lab Expt Virol, NL-1012 WX Amsterdam, Netherlands. [Page, Mark; Almond, Neil] Natl Inst Biol Stand & Controls, Div Retrovirol, Potters Bar EN6 3QG, Herts, England. [Yuan, Fang; Piatak, Mike, Jr.; Lifson, Jeffrey D.] NCI, AIDS Vaccine Program, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Das, AT (reprint author), Univ Amsterdam, Acad Med Ctr, CINIMA, Dept Med Microbiol,Lab Expt Virol, NL-1012 WX Amsterdam, Netherlands. EM a.t.das@amc.uva.nl; g.p.klaver@amc.uva.nl; m.centlivre@amc.uva.nl; a.harwig@amc.uva.nl; engelooms@yahoo.com; mpage@nibsc.ac.uk; nalmond@nibsc.ac.uk; yuanf@ncicrf.gov; piatakm@ncicrf.gov; lifson@ncicrf.gov; b.berkhout@amc.uva.nl RI Centlivre, Mireille/A-3449-2011; OI Harwig, Alex/0000-0002-1117-9216 FU Medical Research Council [G0601201, G0600007]; NCI NIH HHS [N01-CO-12400, N01CO12400] NR 44 TC 21 Z9 21 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD JUN 5 PY 2008 VL 5 AR 44 DI 10.1186/1742-4690-5-44 PG 14 WC Virology SC Virology GA 326HZ UT WOS:000257650500001 PM 18533993 ER PT J AU Polonis, VR Brown, BK Borges, AR Zolla-Pazner, S Dimitrov, DS Zhang, MY Barnett, SW Ruprecht, RM Scarlatti, G Fenyo, EM Montefiori, DC McCutchan, FE Michael, NL AF Polonis, Victoria R. Brown, Bruce K. Borges, Andrew Rosa Zolla-Pazner, Susan Dimitrov, Dimiter S. Zhang, Mei-Yun Barnett, Susan W. Ruprecht, Ruth M. Scarlatti, Gabriella Fenyoe, Eva-Maria Montefiori, David C. McCutchan, Francine E. Michael, Nelson L. TI Recent advances in the characterization of HIV-1 neutralization assays for standardized evaluation of the antibody response to infection and vaccination SO VIROLOGY LA English DT Review DE human immunodeficiency virus type I (HIV-1); antibodies; neutralization assays; pseudovirus; vaccine immune assessment; standardization ID IMMUNODEFICIENCY-VIRUS TYPE-1; MONOCLONAL-ANTIBODIES; ENVELOPE GLYCOPROTEIN; VACCINES; EPITOPES; BINDING; FUSION; PANEL AB In AIDS vaccine development the pendulum has swung towards a renewed emphasis on the potential role for neutralizing antibodies in a successful global vaccine. It is recognized that vaccine-induced antibody performance, as assessed in the available neutralization assays, may well serve as a "gatekeeper" for HIV-1 subunit vaccine prioritization and advancement. As a result, development of a standardized platform for reproducible measurement of neutralizing antibodies has received considerable attention. Here we review current advancements in our knowledge of the performance of different types of antibodies in a traditional primary cell neutralization assay and the newer, more standardized TZM-bl reporter cell line assay. In light of recently revealed differences (see accompanying article) in the results obtained in these two neutralization formats, parallel evaluation with both platforms should be contemplated as an interim solution until a better understanding of immune correlates of protection is achieved. Published by Elsevier Inc. C1 [Polonis, Victoria R.; Michael, Nelson L.] Walter Reed Army Med Ctr, Walter Reed Army Inst Res, Washington, DC 20307 USA. [Brown, Bruce K.; Borges, Andrew Rosa; McCutchan, Francine E.] Henry M Jackson Fdn, Rockville, MD USA. [Zolla-Pazner, Susan] NYU, Sch Med, New York, NY USA. [Zolla-Pazner, Susan] VA Hosp, New York, NY USA. [Dimitrov, Dimiter S.; Zhang, Mei-Yun] NCI, US NIH, Frederick, MD 21701 USA. [Barnett, Susan W.] Novartis Vaccines & Diagnost Inc, Emeryville, CA USA. [Ruprecht, Ruth M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Ruprecht, Ruth M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Scarlatti, Gabriella] Ist Sci San Raffaele, I-20132 Milan, IT, Italy. [Fenyoe, Eva-Maria] Lund Univ, Lund, Sweden. [Montefiori, David C.] Duke Univ, Durham, NC USA. RP Polonis, VR (reprint author), WRAIR, 13 Taft Court, Rockville, MD 20850 USA. EM vpolonis@hivresearch.org FU Intramural NIH HHS; NCI NIH HHS [N01 CO 12400] NR 21 TC 84 Z9 86 U1 0 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JUN 5 PY 2008 VL 375 IS 2 BP 315 EP 320 DI 10.1016/j.virol.2008.02.007 PG 6 WC Virology SC Virology GA 304JQ UT WOS:000256106200001 PM 18367229 ER PT J AU Nikolaitchik, OA Gorelick, RJ Leavitt, MG Pathak, VK Hu, WS AF Nikolaitchik, Olga A. Gorelick, Robert J. Leavitt, Maria G. Pathak, Vinay K. Hu, Wei-Shau TI Functional complementation of nucleocapsid and late domain PTAP mutants of human immunodeficiency virus type 1 during replication SO VIROLOGY LA English DT Article DE HIV; nucleocapsid; PTAP late domain; complementation; replication ID ROUS-SARCOMA-VIRUS; MURINE LEUKEMIA-VIRUS; ACID-CHAPERONE ACTIVITY; GP41 CYTOPLASMIC TAIL; MAJOR HOMOLOGY REGION; PROTEIN ZINC-FINGER; IN-VITRO; REVERSE TRANSCRIPTION; GAG PROTEINS; RNA ENCAPSIDATION AB During human immunodeficiency virus type 1 (HIV-1) assembly, the nucleocapsid (NC) and the PTAP motif in p6 of Gag play important roles in RNA encapsidation and virus release, respectively. We have previously demonstrated that functional complementation occurs between an NC mutant and a PTAP mutant to rescue viral replication. In this report, we examined the amounts of functional NC and PTAP motif that are required during virus replication. When NC and PTAP mutants were coexpressed at 5:1, 5:5, and 1:5 ratios, virus titers were rescued at 5%, 51%, and 86% of the wild-type level, respectively. These results indicate that HIV-1 requires a small amount of functional PTAP motif but far more functional NC to complete efficient replication. Further analyses reveal that RNA packaging can be significantly rescued in viruses containing a small amount of functional NC. However, most of the NC proteins must be functional to generate the wild-type level of R-U5 DNA product. Once the R-U5 product is generated, viruses containing half of the functional NC can complete reverse transcription and DNA integration at near-wild-type efficiency. These results define the quantitative requirements of NC and p6 during HIV-1 replication and provide insights into the requirement for the development of anti-HIV strategies using NC and p6 as targets. Published by Elsevier Inc. C1 [Nikolaitchik, Olga A.; Leavitt, Maria G.; Pathak, Vinay K.; Hu, Wei-Shau] NCI Frederick, HIV Drug Resistance Program, Frederick, MD 21702 USA. [Gorelick, Robert J.] SAIC Frederick Inc, Natl Canc Inst, Basic Res Program, Frederick, MD 21702 USA. RP Hu, WS (reprint author), NCI Frederick, HIV Drug Resistance Program, POB B,Bldg 535,Room 336, Frederick, MD 21702 USA. EM whu@ncifcrf.gov FU Intramural NIH HHS [Z01 BC010506-05, Z01 BC010814-01, Z01 BC010504-05, Z01 BC010533-05]; NCI NIH HHS [N01 CO 12400, N01CO12400] NR 84 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JUN 5 PY 2008 VL 375 IS 2 BP 539 EP 549 DI 10.1016/j.virol.2008.02.026 PG 11 WC Virology SC Virology GA 304JQ UT WOS:000256106200023 PM 18353416 ER PT J AU Kim, NK Tharakaraman, K Marino-Ramirez, L Spouge, JL AF Kim, Nak-Kyeong Tharakaraman, Kannan Marino-Ramirez, Leonardo Spouge, John L. TI Finding sequence motifs with Bayesian models incorporating positional information: an application to transcription factor binding sites SO BMC BIOINFORMATICS LA English DT Article ID REGULATORY ELEMENTS; DNA-SEQUENCES; START SITES; ALIGNMENT; IDENTIFICATION; DISCOVERY; TRANSFAC(R); EUKARYOTES; EVOLUTION; PATTERNS AB Background: Biologically active sequence motifs often have positional preferences with respect to a genomic landmark. For example, many known transcription factor binding sites ( TFBSs) occur within an interval [- 300, 0] bases upstream of a transcription start site ( TSS). Although some programs for identifying sequence motifs exploit positional information, most of them model it only implicitly and with ad hoc methods, making them unsuitable for general motif searches. Results: A- GLAM, a user- friendly computer program for identifying sequence motifs, now incorporates a Bayesian model systematically combining sequence and positional information. AGLAM's predictions with and without positional information were compared on two human TFBS datasets, each containing sequences corresponding to the interval [- 2000, 0] bases upstream of a known TSS. A rigorous statistical analysis showed that positional information significantly improved the prediction of sequence motifs, and an extensive cross- validation study showed that A- GLAM's model was robust against mild misspecification of its parameters. As expected, when sequences in the datasets were successively truncated to the intervals [- 1000, 0], [- 500, 0] and [- 250, 0], positional information aided motif prediction less and less, but never hurt it significantly. Conclusion: Although sequence truncation is a viable strategy when searching for biologically active motifs with a positional preference, a probabilistic model ( used reasonably) generally provides a superior and more robust strategy, particularly when the sequence motifs' positional preferences are not well characterized. C1 [Kim, Nak-Kyeong; Tharakaraman, Kannan; Marino-Ramirez, Leonardo; Spouge, John L.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Spouge, JL (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM kimnak@ncbi.nlm.nih.gov; tharakar@ncbi.nlm.nih.gov; marino@ncbi.nlm.nih.gov; spouge@ncbi.nlm.nih.gov RI Marino-Ramirez, Leonardo/I-5759-2013 OI Marino-Ramirez, Leonardo/0000-0002-5716-8512 FU Intramural NIH HHS [Z99 LM999999] NR 34 TC 24 Z9 25 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD JUN 4 PY 2008 VL 9 AR 262 DI 10.1186/1471-2105-9-262 PG 11 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 319JK UT WOS:000257159700001 PM 18533028 ER PT J AU Frikke-Schmidt, R Nordestgaard, BG Stene, MCA Sethi, AA Remaley, AT Schnohr, P Grande, P Tybjaerg-Hansen, A AF Frikke-Schmidt, Ruth Nordestgaard, Borge G. Stene, Maria C. A. Sethi, Amar A. Remaley, Alan T. Schnohr, Peter Grande, Peer Tybjaerg-Hansen, Anne TI Association of loss-of-function mutations in the ABCA1 gene with high-density lipoprotein cholesterol levels and risk of ischemic heart disease SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ESTER TRANSFER PROTEIN; CORONARY-ARTERY-DISEASE; HDL CHOLESTEROL; MENDELIAN RANDOMIZATION; MYOCARDIAL-INFARCTION; TAQIB POLYMORPHISM; TANGIER-DISEASE; CARDIOVASCULAR-DISEASE; SELECTIVE RETENTION; LIPASE MUTATIONS AB Context Low levels of high- density lipoprotein ( HDL) cholesterol are inversely related to cardiovascular risk. Whether this is a causal effect is unclear. Objective To determine whether genetically reduced HDL cholesterol due to heterozygosity for 4 loss- of- function mutations in ABCA1 cause increased risk of ischemic heart disease ( IHD). Design, Setting, and Participants Three studies of white individuals from Copenhagen, Denmark, were used: the Copenhagen City Heart Study ( CCHS), a 31-year prospective general population study ( n= 9022; 28 heterozygotes); the Copenhagen General Population Study ( CGPS), a cross- sectional general population study ( n= 31 241; 76 heterozygotes); and the Copenhagen Ischemic Heart Disease Study ( CIHDS), a case- control study ( n= 16 623; 44 heterozygotes). End points in all 3 studies were recorded during the period of January 1, 1976, through July 9, 2007. Main Outcome Measures Levels of HDL cholesterol in the general population, cellular cholesterol efflux, and the association between IHD and HDL cholesterol and genotype. Results Heterozygotes vs noncarriers for 4 ABCA1 mutations ( P1065S, G1216V, N1800H, R2144X) had HDL cholesterol levels of 41 mg/ dL ( interquartile range, 31- 50 mg/ dL) vs 58 mg/ dL ( interquartile range, 46- 73 mg/ dL), corresponding to a reduction in HDL cholesterol of 17 mg/ dL ( P <. 001). A 17- mg/ dL lower HDL cholesterol level in the CCHS was associated with a multifactorially adjusted hazard ratio for IHD of 1.70 ( 95% confidence interval [ CI], 1.57- 1.85). However, for IHD in heterozygotes vs noncarriers, the multifactorially adjusted hazard ratio was 0.67 ( 95% CI, 0.28-1.61; 1741 IHD events) in the CCHS, the multifactorially adjusted odds ratio was 0.82 ( 95% CI, 0.34- 1.96; 2427 IHD events) in the CGPS, and the multifactorially adjusted odds ratio was 0.86 ( 95% CI, 0.32- 2.32; 2498 IHD cases) in the CIHDS. The corresponding odds ratio for IHD in heterozygotes vs noncarriers for the combined studies ( n= 41 961; 6666 cases; 109 heterozygotes) was 0.93 ( 95% CI, 0.53- 1.62). Conclusion Lower plasma levels of HDL cholesterol due to heterozygosity for loss-of-function mutations in ABCA1 were not associated with an increased risk of IHD. C1 [Frikke-Schmidt, Ruth; Stene, Maria C. A.; Tybjaerg-Hansen, Anne] Univ Copenhagen Hosp, Dept Clin Biochem, Mol Genet Sect, Rigshosp, DK-2100 Copenhagen O, Denmark. [Grande, Peer] Rigshosp, Dept Cardiol, DK-2100 Copenhagen, Denmark. [Frikke-Schmidt, Ruth; Nordestgaard, Borge G.; Tybjaerg-Hansen, Anne] Herlev Hosp, Dept Clin Biochem, Copenhagen Gen Populat Study, DK-2730 Herlev, Denmark. [Nordestgaard, Borge G.; Schnohr, Peter; Tybjaerg-Hansen, Anne] Bispebjerg Hosp, Copenhagen City Heart Study, DK-2400 Copenhagen, Denmark. [Sethi, Amar A.; Remaley, Alan T.] Univ Copenhagen Hosp, Fac Hlth Sci, DK-2100 Copenhagen, Denmark. [Sethi, Amar A.; Remaley, Alan T.] NHLBI, Lipoprot Metab Sect, Vasc Med Branch, NIH, Bethesda, MD 20892 USA. RP Tybjaerg-Hansen, A (reprint author), Univ Copenhagen Hosp, Dept Clin Biochem, Mol Genet Sect, Rigshosp, KB3011,Blegdamsvej 9, DK-2100 Copenhagen O, Denmark. EM at-h@rh.regionh.dk NR 59 TC 231 Z9 232 U1 1 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 4 PY 2008 VL 299 IS 21 BP 2524 EP 2532 DI 10.1001/jama.299.21.2524 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 308AR UT WOS:000256361200024 PM 18523221 ER PT J AU Jost, TS Emanuel, EJ AF Jost, Timothy Stoltzfus Emanuel, Ezekiel J. TI Legal reforms necessary to promote delivery system innovation SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID MEDICAL-CARE; QUALITY C1 [Emanuel, Ezekiel J.] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA. [Jost, Timothy Stoltzfus] Washington & Lee Univ, Sch Law, Lexington, VA 24450 USA. RP Emanuel, EJ (reprint author), NIH, Dept Bioeth, Ctr Clin, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM eemanuel@nih.gov NR 11 TC 7 Z9 7 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 4 PY 2008 VL 299 IS 21 BP 2561 EP 2563 DI 10.1001/jama.299.21.2561 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 308AR UT WOS:000256361200029 PM 18523225 ER PT J AU Cornwell, BR Johnson, LL Holroyd, T Carver, FW Grillon, C AF Cornwell, Brian R. Johnson, Linda L. Holroyd, Tom Carver, Frederick W. Grillon, Christian TI Human hippocampal and parahippocampal theta during goal-directed spatial navigation predicts performance on a virtual Morris water maze SO JOURNAL OF NEUROSCIENCE LA English DT Article DE hippocampus; magnetoencephalography; Morris water maze; spatial memory; synthetic aperture magnetometry; theta; rhythm ID WORKING-MEMORY TASK; EPISODIC MEMORY; OSCILLATIONS; BRAIN; MAGNETOENCEPHALOGRAPHY; ACTIVATION; DEFICITS; RHYTHM; FMRI; EEG AB The hippocampus and parahippocampal cortices exhibit theta oscillations during spatial navigation in animals and humans, and in the former are thought to mediate spatial memory formation. Functional specificity of human hippocampal theta, however, is unclear. Neuromagnetic activity was recorded with a whole-head 275-channel magnetoencephalographic (MEG) system as healthy participants navigated to a hidden platform in a virtual reality Morris water maze. MEG data were analyzed for underlying oscillatory sources in the 4-8 Hz band using a spatial filtering technique (i.e., synthetic aperture magnetometry). Source analyses revealed greater theta activity in the left anterior hippocampus and parahippocampal cortices during goal-directed navigation relative to aimless movements in a sensorimotor control condition. Additional analyses showed that left anterior hippocampal activity was predominantly observed during the first one-half of training, pointing to a role for this region in early learning. Moreover, posterior hippocampal theta was highly correlated with navigation performance, with the former accounting for 76% of the variance of the latter. Our findings suggest human spatial learning is dependent on hippocampal and parahippocampal theta oscillations, extending to humans a significant body of research demonstrating such a pivotal role for hippocampal theta in animal navigation. C1 [Cornwell, Brian R.; Johnson, Linda L.; Grillon, Christian] NIMH, Mood Anxiety Disorders Program, Bethesda, MD 20892 USA. [Holroyd, Tom; Carver, Frederick W.] NIMH, Magnetoencephalog Core Facil, Bethesda, MD 20892 USA. RP Cornwell, BR (reprint author), NIMH, Mood Anxiety Disorders Program, 15K N Dr,MSC 2670, Bethesda, MD 20892 USA. EM cornwellb@mail.nih.gov FU Intramural NIH HHS [Z99 MH999999] NR 50 TC 97 Z9 99 U1 1 U2 14 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUN 4 PY 2008 VL 28 IS 23 BP 5983 EP 5990 DI 10.1523/JNEUROSCI.5001-07.2008 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 308QF UT WOS:000256404400013 PM 18524903 ER PT J AU Lee, JC Gray, HB Winkler, JR AF Lee, Jennifer C. Gray, Harry B. Winkler, Jay R. TI Copper(II) binding to alpha-synuclein, the Parkinson's protein SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; PRION PROTEIN; OXIDATIVE STRESS; DISEASE; AGGREGATION; MUTATION; METALS; PATHOGENESIS; FIBRILLATION; ALZHEIMERS AB Variations in tryptophan fluorescence intensities confirm that copper(II) interacts with a-synuclein, a protein implicated in Parkinson's disease. Trp4 fluorescence ;decay kinetics measured for the F4W protein show that Cu(II) binds tightly (K-d similar to 100 nM) near the N-terminus at pH 7. Work on a F4W/H50S mutant indicates that a histidine imidazole is not a ligand in this high-affinity site. C1 [Lee, Jennifer C.] NHLBI, NIH, Lab Mol Biophys, Bethesda, MD 20892 USA. [Gray, Harry B.; Winkler, Jay R.] CALTECH, Beckman Inst, Pasadena, CA 91125 USA. RP Lee, JC (reprint author), NHLBI, NIH, Lab Mol Biophys, Bldg 10, Bethesda, MD 20892 USA. EM leej4@mail.nih.gov RI Lee, Jennifer/E-9658-2015 OI Lee, Jennifer/0000-0003-0506-8349 FU Intramural NIH HHS [Z01 HL001055-01]; NIDDK NIH HHS [DK19038, R01 DK019038, R37 DK019038]; NIGMS NIH HHS [GM068461, R01 GM068461] NR 31 TC 102 Z9 106 U1 2 U2 16 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD JUN 4 PY 2008 VL 130 IS 22 BP 6898 EP + DI 10.1021/ja711415b PG 3 WC Chemistry, Multidisciplinary SC Chemistry GA 307EQ UT WOS:000256301200003 PM 18465859 ER PT J AU Ahn, J Peters, U Albanes, D Purdue, MP Abnet, CC Chatterjee, N Horst, RL Hollis, BW Huang, WY Shikany, JM Hayes, RB AF Ahn, Jiyoung Peters, Ulrike Albanes, Demetrius Purdue, Mark P. Abnet, Christian C. Chatterjee, Nilanjan Horst, Ronald L. Hollis, Bruce W. Huang, Wen-Yi Shikany, James M. Hayes, Richard B. CA Prostate Lung Colorectal Ovarian C TI Serum vitamin D concentration and prostate cancer risk: A nested case-control study SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID SUBSEQUENT DEVELOPMENT; ULTRAVIOLET-RADIATION; GENE POLYMORPHISMS; D METABOLITES; 1,25-DIHYDROXYVITAMIN-D; 25-HYDROXYVITAMIN-D; PLASMA; EXPOSURE; ASSOCIATION; ESOPHAGEAL AB Background Epidemiological studies have yielded inconsistent associations between vitamin D status and prostate cancer risk, and few studies have evaluated whether the associations vary by disease aggressiveness. We investigated the association between vitamin D status, as determined by serum 25-hydroxyvitamin D [25(OH)D] level, and risk of prostate cancer in a case-control study nested within the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Methods The study included 749 case patients with incident prostate cancer who were diagnosed 1-8 years after blood draw and 781 control subjects who were frequency matched by age at cohort entry, time since initial screening, and calendar year of cohort entry. All study participants were selected from the trial screening arm (which includes annual standardized prostate cancer screening). Conditional logistic regression was used to estimate adjusted odds ratios (ORs) with 95% confidence intervals (CIs) by quintile of season-standardized serum 25(OH)D concentration. Statistical tests were two-sided. Results No statistically significant trend in overall prostate cancer risk was observed with increasing season-standardized serum 25(OH)D level. However, serum 25(OH)D concentrations greater than the lowest quintile (Q1) were associated with increased risk of aggressive (Gleason sum >= 7 or clinical stage III or IV) disease (in a model adjusting for matching factors, study center, and history of diabetes, ORs for Q2 vs Q1 = 1.20, 95% CI = 0.80 to 1.81, for Q3 vs Q1 =1.96, 95% CI = 1.34 to 2.87, for Q4 vs Q1 = 1.61, 95% CI = 1.09 to 2.38, and for Q5 vs Q1 = 1.37, 95% CI = 0.92 to 2.05; P-trend = .05). The rates of aggressive prostate cancer for increasing quintiles of serum 25(OH)D were 406, 479, 780, 633, and 544 per 100 000 person-years. In exploratory analyses, these associations with aggressive disease were consistent across subgroups defined by age, family history of prostate cancer, diabetes, body mass index, vigorous physical activity, calcium intake, study center, season of blood collection, and assay batch. Conclusion The findings of this large prospective study do not support the hypothesis that vitamin D is associated with decreased risk of prostate cancer; indeed, higher circulating 25(OH)D concentrations may be associated with increased risk of aggressive disease. C1 [Ahn, Jiyoung; Albanes, Demetrius; Purdue, Mark P.; Abnet, Christian C.; Chatterjee, Nilanjan; Huang, Wen-Yi; Hayes, Richard B.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Peters, Ulrike] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98104 USA. [Peters, Ulrike] Univ Washington, Dept Epidemiol, Sch Publ Hlth, Seattle, WA 98195 USA. [Horst, Ronald L.; Hollis, Bruce W.] Heartland Assays, Ames, IA USA. [Shikany, James M.] Univ Alabama, Sch Med, Div Prevent Med, Birmingham, AL USA. RP Ahn, J (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM Ahnj@mail.nih.gov RI Albanes, Demetrius/B-9749-2015; Abnet, Christian/C-4111-2015; Purdue, Mark/C-9228-2016 OI Hayes, Richard/0000-0002-0918-661X; Abnet, Christian/0000-0002-3008-7843; Purdue, Mark/0000-0003-1177-3108 FU Intramural NIH HHS [ZIA CP010221-02] NR 34 TC 144 Z9 146 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 4 PY 2008 VL 100 IS 11 BP 796 EP 804 DI 10.1093/jnci/djn152 PG 9 WC Oncology SC Oncology GA 310IU UT WOS:000256522900010 PM 18505967 ER PT J AU Freedman, DM Looker, AC Chang, SC Graubard, BI AF Freedman, D. Michal Looker, Anne C. Chang, Shih-Chen Graubard, Barry I. TI Re: Prospective study of vitamin D and cancer mortality in the United States - Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 [Freedman, D. Michal; Chang, Shih-Chen; Graubard, Barry I.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Looker, Anne C.] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. [Chang, Shih-Chen] AstraZeneca Int, Wilmington, DE USA. RP Freedman, DM (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, EPS Rm 7036,6120 Execut Blvd, Bethesda, MD 20892 USA. EM mf101e@nih.gov NR 1 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 4 PY 2008 VL 100 IS 11 BP 827 EP 828 DI 10.1093/jnci/djn042 PG 2 WC Oncology SC Oncology GA 310IU UT WOS:000256522900014 ER PT J AU Li, HJ Smolen, GA Beers, LF Xia, L Gerald, W Wang, J Haber, DA Lee, SB AF Li, Hongjie Smolen, Gromoslaw A. Beers, Lisa F. Xia, Li Gerald, William Wang, Joanne Haber, Daniel A. Lee, Sean Bong TI Adenosine Transporter ENT4 Is a Direct Target of EWS/WT1 Translocation Product and Is Highly Expressed in Desmoplastic Small Round Cell Tumor SO PLOS ONE LA English DT Article AB Background: Desmoplastic Small Round Cell Tumor (DSRCT) is a highly aggressive malignancy that affects mainly adolescents and young adults. A defining characteristic of DSRCT is a specific chromosomal translocation, t(11;22)(p13;q12), that fuses EWS with WT1, leading to a production of two isoforms of chimeric transcription factor, EWS/WT1(-KTS) and EWS/WT1(+KTS). The chimeric proteins are thought to play critical roles in various stages of oncogenesis through aberrant transcription of different genes, but only a few of these genes have been identified. Methodology/Principal Findings: We report the identification of a new target of EWS/WT1, ENT4 (equilibrative nucleoside transporter 4) which encodes a pH-dependent adenosine transporter. ENT4 is transcriptionally activated by both isoforms of EWS/WT1 as evidenced by promoter-reporter and chromatin immunoprecipitation (ChIP) analyses. Furthermore, ENT4 is highly and specifically expressed in primary tumors of DSRCT as well as in a DSRCT cell line, JN-DSRCT-1. Treatment of JN-DSRCT1 cells with adenosine analogs, such as 2-chloro-2'-deoxyadenosine (2-CdA), resulted in an increased cytotoxic response in dose- and pH-dependent manner. Conclusions/Significance: Our detailed analyses of a novel target of EWS/WT1 in DSRCT reveal an insight into the oncogenic mechanism of EWS-fusion chromosomal translocation gene products and provide a new marker for DSRCT. Furthermore, identification of ENT4 as a highly expressed transcript in DSRCT may represent an attractive pathway for targeting chemotherapeutic drugs into DSRCT. C1 [Li, Hongjie; Beers, Lisa F.; Lee, Sean Bong] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20824 USA. [Smolen, Gromoslaw A.; Haber, Daniel A.] Massachusetts Gen Hosp Canc Ctr, Harvard Med Sch, Charlestown, MA USA. [Xia, Li; Wang, Joanne] Univ Washington, Dept Pharmaceut, Seattle, WA USA. [Gerald, William] Memorial Sloan Kettering Canc Ctr, Dept Pathol, New York, NY USA. RP Li, HJ (reprint author), NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20824 USA. EM seanL@intra.niddk.nih.gov FU Intramural Research Program of the NIH, NIDDK FX This research was supported by the Intramural Research Program of the NIH, NIDDK (S.B.L.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript NR 45 TC 21 Z9 21 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 4 PY 2008 VL 3 IS 6 AR e2353 DI 10.1371/journal.pone.0002353 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 396TO UT WOS:000262614300041 PM 18523561 ER PT J AU Levy, MM Rapoport, J Lemeshow, S Chalfin, DB Phillips, G Danis, M AF Levy, Mitchell M. Rapoport, John Lemeshow, Stanley Chalfin, Donald B. Phillips, Gary Danis, Marion TI Association between critical care physician management and patient mortality in the intensive care unit SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID DESCRIPTIVE ANALYSIS; RESOURCE UTILIZATION; FULL-TIME; IMPACT; OUTCOMES; STATES; EFFICIENCY; LENGTH; STAY; ICU AB Background: Critically ill patients admitted to intensive care units (ICUs) are thought to gain an added survival benefit from management by critical care physicians, but evidence of this benefit is scant. Objective: To examine the association between hospital mortality in critically ill patients and management by critical care physicians. Design: Retrospective analysis of a large, prospectively collected database of critically ill patients. Setting: 123 ICUs in 100 U. S. hospitals. Patients: 101 832 critically ill adults. Measurements: Through use of a random-effects logistic regression, investigators compared hospital mortality between patients cared for entirely by critical care physicians and patients cared for entirely by non-critical care physicians. An expanded Simplified Acute Physiology Score was used to adjust for severity of illness, and a propensity score was used to adjust for differences in the probability of selective referral of patients to critical care physicians. Results: Patients who received critical care management (CCM) were generally sicker, received more procedures, and had higher hospital mortality rates than those who did not receive CCM. After adjustment for severity of illness and propensity score, hospital mortality rates were higher for patients who received CCM than for those who did not. The difference in adjusted hospital mortality rates was less for patients who were sicker and who were predicted by propensity score to receive CCM. Limitation: Residual confounders for illness severity and selection biases for CCM might exist that were inadequately assessed or recognized. Conclusion: In a large sample of ICU patients in the United States, the odds of hospital mortality were higher for patients managed by critical care physicians than those who were not. Additional studies are needed to further evaluate these results and clarify the mechanisms by which they might occur. C1 Brown Univ, Providence, RI 02912 USA. Mt Holyoke Coll, S Hadley, MA 01075 USA. Ohio State Univ, Coll Hlth, Columbus, OH 43210 USA. Albert Einstein Coll Med, New York, NY USA. NIH, Bethesda, MD 20892 USA. RP Levy, MM (reprint author), Rhode Isl Hosp, 593 Eddy St, Providence, RI 02903 USA. EM Mitchell_Levy@brown.edu FU Intramural NIH HHS [ZIA MH002240-23] NR 26 TC 133 Z9 139 U1 0 U2 8 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUN 3 PY 2008 VL 148 IS 11 BP 801 EP U10 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 308CG UT WOS:000256365300001 PM 18519926 ER PT J AU Martin, GG Hostetler, HA McIntosh, AL Tichy, SE Williams, BJ Russell, DH Berg, JM Spencer, TA Ball, J Kier, AB Schroeder, F AF Martin, Gregory G. Hostetler, Heather A. McIntosh, Avery L. Tichy, Shane E. Williams, Brad J. Russell, David H. Berg, Jeremy M. Spencer, Thomas A. Ball, Judith Kier, Ann B. Schroeder, Friedhelm TI Structure and function of the sterol carrier protein-2 N-terminal presequence SO BIOCHEMISTRY LA English DT Article ID LIPID-TRANSFER PROTEIN; IMPORT RECEPTOR PEX5P; VERY-LONG-CHAIN; SECONDARY STRUCTURE; BINDING PROTEIN; HIGH-AFFINITY; RECOGNITION; PEROXISOMES; INTERACTS; ACCURACY AB Although sterol carrier protein-2 (SCP-2) is encoded as a precursor protein (proSCP-2), little is known regarding the structure and function of the 20-amino acid N-terminal presequence. As shown herein, the presequence contains significant secondary structure and alters SCP-2: (i) secondary structure (CD), (ii) tertiary structure (aqueous exposure of Trp shown by UV absorbance, fluorescence, and fluorescence quenching), (iii) ligand binding site [Trp response to ligands, peptide cross-linked by photoactivatable free cholesterol (FCBP)], (iv) selectivity for interaction with anionic phospholipid-rich membranes, (v) interaction with a peroxisomal import protein [FRET studies of Pex5p(C) binding], the N-terminal presequence increased SCP-2's affinity for Pex5p(C) by 10-fold, and (vi) intracellular targeting in living and fixed cells (confocal microscopy). Nearly 5-fold more SCP-2 than proSCP-2 colocalized with plasma membrane lipid rafts and caveolae (AF488-CTB); 2.8-fold more SCP-2 than proSCP-2 colocalized with a mitochondrial marker (Mitotracker), but nearly 2-fold less SCP-2 than proSCP-2 colocalized with peroxisomes (AF488 antibody to PMP70). These data indicate the importance of the N-terminal presequence in regulating SCP-2 structure, cholesterol localization within the ligand binding site, membrane association, and, potentially, intracellular targeting. C1 [Martin, Gregory G.; Hostetler, Heather A.; McIntosh, Avery L.; Schroeder, Friedhelm] Texas A&M Univ, Dept Physiol & Pharmacol, TVMC, College Stn, TX 77843 USA. [Tichy, Shane E.; Williams, Brad J.; Russell, David H.] Texas A&M Univ, Dept Chem, College Stn, TX 77843 USA. [Berg, Jeremy M.] NIDDK, NIH, Mol Biol Lab, Bethesda, MD 20892 USA. [Spencer, Thomas A.] Dartmouth Coll, Dept Chem, Hanover, NH 03755 USA. [Ball, Judith; Kier, Ann B.] Texas A&M Univ, Dept Pathobiol, College Stn, TX 77843 USA. RP Schroeder, F (reprint author), Texas A&M Univ, Dept Physiol & Pharmacol, TVMC, College Stn, TX 77843 USA. EM f.schroeder@cvm.tamu.edu RI Russell, David/C-3618-2015; OI Russell, David/0000-0003-0830-3914; Berg, Jeremy/0000-0003-3022-0963 FU NIDDK NIH HHS [R01 DK041402, DK077573, DK41402, K99 DK077573, K99 DK077573-02, R00 DK077573, R01 DK041402-20]; NIGMS NIH HHS [GM31651, GM63236, R01 GM031651, R01 GM031651-25, R01 GM062326-05] NR 53 TC 30 Z9 30 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 3 PY 2008 VL 47 IS 22 BP 5915 EP 5934 DI 10.1021/bi800251e PG 20 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 306NX UT WOS:000256256200004 PM 18465878 ER PT J AU Jain, A Fisher, LW Fedarko, NS AF Jain, Alka Fisher, Larry W. Fedarko, Neal S. TI Bone sialoprotein binding to matrix metalloproteinase-2 alters enzyme inhibition kinetics SO BIOCHEMISTRY LA English DT Article ID COMPLEMENT-MEDIATED ATTACK; TISSUE INHIBITOR; BREAST-CANCER; GELATINASE-A; DOMAIN INTERACTIONS; SIBLING PROTEINS; TERMINAL DOMAIN; LUNG-CANCER; OSTEOPONTIN; EXPRESSION AB Bone sialoprotein (BSP) is a secreted glycophosphoprotein normally restricted in expression to skeletal tissue that is also induced by multiple neoplasms in vivo. Previous work has shown that BSP can bind to matrix metalloproteinase-2 (MMP-2). Because of MMP-2 activity in promoting tumor progression, potential therapeutic inhibitors were developed, but clinical trials have been disappointing. The effect of BSP on MMP-2 modulation by inhibitors was determined with purified components and in cell culture. Enzyme inhibition kinetics were studied using a low-molecular weight freely diffusable substrate and purified MMP-2, BSP, and natural (tissue inhibitor of matrix metalloproteinase-2) and synthetic (ilomastat and oleoyl-N-hydroxylamide) inhibitors. We determined parameters of enzyme kinetics by varying substrate concentrations at different fixed inhibitor concentrations added to MMP-2 alone, MMP-2 and BSP, or preformed MMP-2-BSP complexes and solving a general linear mixed inhibition rate equation with a global curve fitting program. Two in vitro angiogenesis model systems employing human umbilical vein endothelial cells (HUVECs) were used to follow BSP modulation of MMP-2 inhibition and tubule formation. The presence of BSP increased the competitive K-I values between 15- and 47-fold for natural and synthetic inhibitors. The extent of tubule formation by HUVECs cocultured with dermal fibroblasts was reduced in the presence of inhibitors, while the addition of BSP restored vessel formation. A second HUVEC culture system demonstrated that tubule formation by cells expressing BSP could be inhibited by an activity blocking antibody against MMP-2. BSP modulation of MMP-2 activity and inhibition may define its biological role in promoting tumor progression. C1 [Jain, Alka; Fedarko, Neal S.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21224 USA. [Fisher, Larry W.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. RP Fedarko, NS (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, Room 5A-64 JHAAC,5501 Hopkins Bayview Circle, Baltimore, MD 21224 USA. EM ndarko@jhmi.edu FU Intramural NIH HHS; NCI NIH HHS [R01 CA113865, CA113865, R01 CA113865-02] NR 37 TC 13 Z9 13 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 3 PY 2008 VL 47 IS 22 BP 5986 EP 5995 DI 10.1021/bi800133n PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 306NX UT WOS:000256256200010 PM 18465841 ER PT J AU Sharov, AA Falco, G Piao, Y Poosala, S Becker, KG Zonderman, AB Longo, DL Schlessinger, D Ko, MSH AF Sharov, Alexei A. Falco, Geppino Piao, Yulan Poosala, Suresh Becker, Kevin G. Zonderman, Alan B. Longo, Dan L. Schlessinger, David Ko, Minoru S. H. TI Effects of aging and calorie restriction on the global gene expression profiles of mouse testis and ovary SO BMC BIOLOGY LA English DT Article ID GRANULOSA-CELLS; DIETARY RESTRICTION; FOLLICULAR-GROWTH; ADIPOSE-TISSUE; KNOCKOUT MICE; ENERGY-INTAKE; MUTANT MICE; LIFE-SPAN; AGE; FOLLICLES AB Background: The aging of reproductive organs is not only a major social issue, but of special interest in aging research. A long-standing view of 'immortal germ line versus mortal soma' poses an important question of whether the reproductive tissues age in similar ways to the somatic tissues. As a first step to understand this phenomenon, we examine global changes in gene expression patterns by DNA microarrays in ovaries and testes of C57BL/6 mice at 1, 6, 16, and 24 months of age. In addition, we compared a group of mice on ad libitum (AL) feeding with a group on lifespan-extending 40% calorie restriction (CR). Results: We found that gene expression changes occurred in aging gonads, but were generally different from those in somatic organs during aging. For example, only two functional categories of genes previously associated with aging in muscle, kidney, and brain were confirmed in ovary: genes associated with complement activation were upregulated, and genes associated with mitochondrial electron transport were downregulated. The bulk of the changes in gonads were mostly related to gonad-specific functions. Ovaries showed extensive gene expression changes with age, especially in the period when ovulation ceases (from 6 to 16 months), whereas testes showed only limited age-related changes. The same trend was seen for the effects of CR: CR-mediated reversal of age-associated gene expression changes, reported in somatic organs previously, was limited to a small number of genes in gonads. Instead, in both ovary and testis, CR caused small and mostly gonad-specific effects: suppression of ovulation in ovary and activation of testis-specific genes in testis. Conclusion: Overall, the results are consistent with unique modes of aging and its modification by CR in testis and ovary. C1 [Sharov, Alexei A.; Falco, Geppino; Schlessinger, David; Ko, Minoru S. H.] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. [Poosala, Suresh; Becker, Kevin G.; Zonderman, Alan B.] NIA, Res Resources Branch, NIH, Baltimore, MD 21224 USA. [Longo, Dan L.] NIA, Immunol Lab, NIH, Baltimore, MD 21224 USA. RP Ko, MSH (reprint author), NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. EM SharovAl@grc.nia.nih.gov; falcoge@grc.nia.nih.gov; PiaoY@grc.nia.nih.gov; PoosalaSu@grc.nia.nih.gov; BeckerK@grc.nia.nih.gov; Zonderman@nih.gov; LongoD@grc.nia.nih.gov; SchlessingerD@grc.nia.nih.gov; kom@grc.nia.nih.gov RI Ko, Minoru/B-7969-2009; OI Ko, Minoru/0000-0002-3530-3015; Becker, Kevin/0000-0002-6794-6656; Zonderman, Alan B/0000-0002-6523-4778 FU Intramural NIH HHS NR 82 TC 23 Z9 23 U1 2 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1741-7007 J9 BMC BIOL JI BMC Biol. PD JUN 3 PY 2008 VL 6 AR 24 DI 10.1186/1741-7007-6-24 PG 16 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 315AA UT WOS:000256849100001 PM 18522719 ER PT J AU Sharov, AA Masui, S Sharova, LV Piao, Y Aiba, K Matoba, R Xin, L Niwa, H Ko, MSH AF Sharov, Alexei A. Masui, Shinji Sharova, Lioudmila V. Piao, Yulan Aiba, Kazuhiro Matoba, Ryo Xin, Li Niwa, Hitoshi Ko, Minoru S. H. TI Identification of Pou5f1, Sox2, and Nanog downstream target genes with statistical confidence by applying a novel algorithm to time course microarray and genome-wide chromatin immunoprecipitation data SO BMC GENOMICS LA English DT Article ID EMBRYONIC STEM-CELLS; ZINC-FINGER PROTEINS; SELF-RENEWAL; TRANSCRIPTIONAL REGULATION; EXPRESSION DATA; ES CELLS; MOUSE; PLURIPOTENCY; DIFFERENTIATION; OCT3/4 AB Background: Target genes of a transcription factor (TF) Pou5f1 (Oct3/4 or Oct4), which is essential for pluripotency maintenance and self-renewal of embryonic stem (ES) cells, have previously been identified based on their response to Pou5f1 manipulation and occurrence of Chromatin-immunoprecipitation (ChIP)-binding sites in promoters. However, many responding genes with binding sites may not be direct targets because response may be mediated by other genes and ChIP-binding site may not be functional in terms of transcription regulation. Results: To reduce the number of false positives, we propose to separate responding genes into groups according to direction, magnitude, and time of response, and to apply the false discovery rate (FDR) criterion to each group individually. Using this novel algorithm with stringent statistical criteria (FDR < 0.2) to a compendium of published and new microarray data (3, 6, 12, and 24 hr after Pou5f1 suppression) and published ChIP data, we identified 420 tentative target genes (TTGs) for Pou5f1. The majority of TTGs (372) were down-regulated after Pou5f1 suppression, indicating that the Pou5f1 functions as an activator of gene expression when it binds to promoters. Interestingly, many activated genes are potent suppressors of transcription, which include polycomb genes, zinc finger TFs, chromatin remodeling factors, and suppressors of signaling. Similar analysis showed that Sox2 and Nanog also function mostly as transcription activators in cooperation with Pou5f1. Conclusion: We have identified the most reliable sets of direct target genes for key pluripotency genes - Pou5f1, Sox2, and Nanog, and found that they predominantly function as activators of downstream gene expression. Thus, most genes related to cell differentiation are suppressed indirectly. C1 [Sharov, Alexei A.; Sharova, Lioudmila V.; Piao, Yulan; Aiba, Kazuhiro; Matoba, Ryo; Xin, Li; Ko, Minoru S. H.] NIA, Dev Genom & Aging Sect, Genet Lab, NIH, Baltimore, MD 21224 USA. [Masui, Shinji; Niwa, Hitoshi] RIKEN, Ctr Dev Biol, Lab Pluripotent Cell Studies, Kobe, Hyogo 6500047, Japan. RP Ko, MSH (reprint author), NIA, Dev Genom & Aging Sect, Genet Lab, NIH, Baltimore, MD 21224 USA. EM sharoval@mail.nih.gov; masui@ri.imcj.go.jp; sharovali@mail.nih.gov; PiaoY@mail.nih.gov; aiba@scdi.or.jp; matoba@dna-chip.co.jp; lxin@nia.nih.gov; niwa@cdb.riken.jp; kom@mail.nih.gov RI Ko, Minoru/B-7969-2009 OI Ko, Minoru/0000-0002-3530-3015 FU Intramural NIH HHS; NIA NIH HHS [Z01 AG000656] NR 59 TC 106 Z9 108 U1 1 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD JUN 3 PY 2008 VL 9 AR 269 DI 10.1186/1471-2164-9-269 PG 19 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 316AL UT WOS:000256921200002 PM 18522731 ER PT J AU Kottgen, A Kao, WHL Hwang, SJ Boerwinkle, E Yang, Q Levy, D Benjamin, EJ Larson, MG Astor, BC Coresh, J Fox, CS AF Kottgen, Anna Kao, Wen Hong L. Hwang, Shih-Jen Boerwinkle, Eric Yang, Qiong Levy, Daniel Benjamin, Emelia J. Larson, Martin G. Astor, Brad C. Coresh, Josef Fox, Caroline S. TI Genome-wide association study for renal traits in the Framingham Heart and Atherosclerosis Risk in Communities Studies SO BMC MEDICAL GENETICS LA English DT Article ID GLOMERULAR-FILTRATION-RATE; CHRONIC KIDNEY-DISEASE; CARDIOVASCULAR-DISEASE; SERUM CREATININE; MUTATIONS; FAMILIES; GENES; LOCI; COMPLEX; CLONING AB Background: The Framingham Heart Study (FHS) recently obtained initial results from the first genome-wide association scan for renal traits. The study of 70,987 single nucleotide polymorphisms (SNPs) in 1,010 FHS participants provides a list of SNPs showing the strongest associations with renal traits which need to be verified in independent study samples. Methods: Sixteen SNPs were selected for replication based on the most promising associations with chronic kidney disease (CKD), estimated glomerular filtration rate (eGFR), and serum cystatin C in FHS. These SNPs were genotyped in 15,747 participants of the Atherosclerosis in Communities (ARIC) Study and evaluated for association using multivariable adjusted regression analyses. Primary outcomes in ARIC were CKD and eGFR. Secondary prospective analyses were conducted for association with kidney disease progression using multivariable adjusted Cox proportional hazards regression. The definition of the outcomes, all covariates, and the use of an additive genetic model was consistent with the original analyses in FHS. Results: The intronic SNP rs6495446 in the gene MTHFS was significantly associated with CKD among white ARIC participants at visit 4: the odds ratio per each C allele was 1.24 (95% CI 1.09 - 1.41, p = 0.001). Borderline significant associations of rs6495446 were observed with CKD at study visit 1 ( p = 0.024), eGFR at study visits 1 ( p = 0.073) and 4 ( lower mean eGFR per C allele by 0.6 ml/min/1.73 m(2), p = 0.043) and kidney disease progression ( hazard ratio 1.13 per each C allele, 95% CI 1.00 - 1.26, p = 0.041). Another SNP, rs3779748 in EYAI, was significantly associated with CKD at ARIC visit 1 ( odds ratio per each T allele 1.22, p = 0.01), but only with eGFR and cystatin C in FHS. Conclusion: This genome-wide association study provides unbiased information implicating MTHFS as a candidate gene for kidney disease. Our findings highlight the importance of replication to identify common SNPs associated with renal traits. C1 [Kottgen, Anna; Kao, Wen Hong L.; Astor, Brad C.; Coresh, Josef] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD 21218 USA. [Kottgen, Anna; Kao, Wen Hong L.; Astor, Brad C.; Coresh, Josef] Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA. [Kao, Wen Hong L.; Astor, Brad C.; Coresh, Josef] Johns Hopkins Univ, Dept Med, Sch Med, Baltimore, MD USA. [Hwang, Shih-Jen; Levy, Daniel; Benjamin, Emelia J.; Larson, Martin G.; Fox, Caroline S.] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Hwang, Shih-Jen; Levy, Daniel; Benjamin, Emelia J.; Larson, Martin G.; Fox, Caroline S.] NHLBIs Framingham Heart Study, Framingham, MA USA. [Boerwinkle, Eric] Univ Texas Houston, Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA. [Boerwinkle, Eric] Univ Texas Houston, Hlth Sci Ctr, Inst Mol Med, Houston, TX USA. [Yang, Qiong] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Benjamin, Emelia J.] Boston Univ, Div Cardiol, Boston, MA USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Dept Prevent Med,Sch Med, Boston, MA USA. [Coresh, Josef] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol Hypertens & Metab, Boston, MA 02115 USA. [Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA. RP Coresh, J (reprint author), Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD 21218 USA. EM akottgen@jhsph.edu; wkao@jhsph.edu; hwangs2@nhlbi.nih.gov; Eric.Boerwinkle@uth.tmc.edu; qyang@bu.edu; levyd@nih.gov; emelia@bu.edu; mlarson@bu.edu; bastor@jhsph.edu; coresh@jhu.edu; foxca@nhlbi.nih.gov RI Kottgen, Anna/D-2920-2012; Yang, Qiong/G-5438-2014; OI Larson, Martin/0000-0002-9631-1254; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [N01 HC055016, N01 HC055018, N01 HC055019, N01-HC-25195, N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, N01HC25195, N01HC55015, N01HC55016, N01HC55018, N01HC55019, N01HC55020, N01HC55021, N01HC55022]; NIDDK NIH HHS [K01 DK067207, K01DK067207] NR 39 TC 24 Z9 25 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2350 J9 BMC MED GENET JI BMC Med. Genet. PD JUN 3 PY 2008 VL 9 AR 49 DI 10.1186/1471-2350-9-49 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 317AR UT WOS:000256992000001 PM 18522750 ER PT J AU Kwon, GP Schroeder, JL Amar, MJ Remaley, AT Balaban, RS AF Kwon, Gina P. Schroeder, Jamie L. Amar, Marcelo J. Remaley, Alan T. Balaban, Robert S. TI Contribution of macromolecular structure to the retention of low-density lipoprotein at arterial branch points SO CIRCULATION LA English DT Article DE aorta; atherosclerosis; collagen; imaging; lipoproteins; pathology ID SHEAR-STRESS; CARDIOVASCULAR-DISEASE; MECHANICAL-PROPERTIES; ENDOTHELIAL-CELLS; WALL STRESS; ATHEROSCLEROSIS; ATHEROGENESIS; PROTEOGLYCAN; INITIATION; COLLAGEN AB Background-Extracellular deposition of low-density lipoprotein (LDL) in the arterial wall is an essential early step in atherosclerosis. This process preferentially occurs at arterial branch points, reflecting a regional variation in lipoprotein-arterial wall interactions. In this study, we characterized the submicron microstructure of arterial wall collagen and elastin to evaluate its potential role in regional LDL deposition. Methods and Results-With 2-photon microscopy, we used the intrinsic optical properties of collagen and elastin to determine the arterial wall macromolecular microstructure in fresh porcine and murine arteries. This optical approach generated unique nondestructive en face 3-dimensional views of the wall. The collagen/elastin microstructure was found to vary with the topology of the arterial bed. A nearly confluent elastin surface layer was present throughout but was missing at atherosclerosis-susceptible branch points, exposing dense collagen-proteoglycan complexes. In LDL binding studies, this luminal elastin layer limited LDL penetration, whereas its absence at the branches resulted in extensive LDL binding. Furthermore, LDL colocalized with proteoglycans with a sigmoidal dose dependence (inflection point, approximate to 130 mg LDL/dL). Ionic strength and competing anions studies were consistent with the initial interaction of LDL with proteoglycans to be electrostatic in nature. Conclusions-This optical sectioning approach provided a robust 3-dimensional collagen/elastin microstructure of the arterial wall in fresh samples. At atherosclerosis-susceptible vascular branch points, the absence of a luminal elastin barrier and the presence of a dense collagen/proteoglycan matrix contribute to increased retention of LDL. C1 [Kwon, Gina P.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Schroeder, Jamie L.; Balaban, Robert S.] NHLBI, Dept Hlth & Human Serv, Natl Inst Hlth, Cardiac Energet Lab, Bethesda, MD 20892 USA. [Amar, Marcelo J.; Remaley, Alan T.] NHLBI, Dept Hlth & Human Serv, Natl Inst Hlth, Vasc Med Branch, Bethesda, MD 20892 USA. RP Balaban, RS (reprint author), NHLBI, Dept Hlth & Human Serv, Natl Inst Hlth, Cardiac Energet Lab, Bldg 10,Room B1D416, Bethesda, MD 20892 USA. EM rsb@nih.gov FU Howard Hughes Medical Institute; Intramural NIH HHS [ZIA HL004610-02, Z01 HL004601-20] NR 36 TC 40 Z9 41 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 3 PY 2008 VL 117 IS 22 BP 2919 EP 2927 DI 10.1161/CIRCULATIONAHA.107.754614 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 308GL UT WOS:000256376200011 PM 18506002 ER PT J AU Shnyrova, A Frolov, VA Zimmerberg, J AF Shnyrova, Anna Frolov, Vadim A. Zimmerberg, Joshua TI ER biogenesis: Self-assembly of tubular topology by protein hairpins SO CURRENT BIOLOGY LA English DT Editorial Material ID ENDOPLASMIC-RETICULUM; MEMBRANE-PROTEINS; CURVATURE; DOMAINS; FUSION; BAR AB The structure of the endoplasmic reticulum (ER) depends on members of the reticulon and DP1/Yop1p families. Two of these proteins are sufficient to form tubular membrane networks from pure phospholipid vesicles, thus revealing a new paradigm of ER morphogenesis. C1 [Shnyrova, Anna; Frolov, Vadim A.; Zimmerberg, Joshua] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD 20892 USA. RP Shnyrova, A (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD 20892 USA. EM joshz@helix.nih.gov OI Frolov, Vadim/0000-0002-0653-5669 NR 18 TC 9 Z9 11 U1 0 U2 7 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD JUN 3 PY 2008 VL 18 IS 11 BP R474 EP R476 DI 10.1016/j.cub.2008.04.031 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 308SR UT WOS:000256410800018 PM 18522819 ER PT J AU Vanderver, A Hathout, Y Maletkovic, J Gordon, ES Mintz, M Timmons, M Hoffman, EP Horzinski, L Niel, F Fogli, A Boespflug-Tanguy, O Schiffmann, R AF Vanderver, A. Hathout, Y. Maletkovic, J. Gordon, E. S. Mintz, M. Timmons, M. Hoffman, E. P. Horzinski, L. Niel, F. Fogli, A. Boespflug-Tanguy, O. Schiffmann, R. TI Sensitivity and specificity of decreased CSF asialotransferrin for eIF2B-related disorder SO NEUROLOGY LA English DT Article ID VANISHING WHITE-MATTER; CEREBROSPINAL-FLUID TRANSFERRIN; NERVOUS-SYSTEM HYPOMYELINATION; UNFOLDED PROTEIN RESPONSE; INITIATION-FACTOR EIF2B; CHILDHOOD ATAXIA; OVARIAN DYSGENESIS; TRANSGENIC MICE; LEUKOENCEPHALOPATHY; DISEASE AB Objective: This is a study estimating diagnostic accuracy of CSF asialotransferrin to transferrin ratio measurement in eIF2B related disorders by using clinical evaluation and EIF2B mutation analysis as the reference standard. eIF2B-related disorder is a relatively common leukodystrophy with broad phenotypic variation that is caused by mutations in any of the five EIF2B genes. There is a need for a simple and clinically valid screening tool for physicians evaluating patients with an unclassified leukodystrophy. Methods: CSF two-dimensional gel (2DG) electrophoresis analyses to measure asialotransferrin to transferrin ratios were performed in 60 subjects including 6 patients with documented EIF2B gene mutations, patients with other types of leukodystrophy, and patients with no leukodystrophy. Results: All six patients with mutation proven eIF2B-related disease showed low to nearly undetectable amounts of asialotransferrin in their CSF when compared to 54 unaffected controls by CSF 2DG analyses in this study. eIF2B-like patients, with clinically similar presentations but no mutations in EIF2B1-5, were distinguished from patients with mutations in EIF2B1-5 by this biomarker. Patients with mutations in EIF2B1-5 had asialotransferrin/transferrin ratio levels significantly different from the group as a whole (p < 0.001). Using 8% asialotransferrin/transferrin ratio as a cutoff, this biomarker has a 100% sensitivity (95% CI = 52-100%) and 94% specificity (95% CI = 84-99%). Conclusion: Decreased asialotransferrin/ transferrin ratio in the CSF of patients with eIF2-Brelated disorder is highly sensitive and specific. This rapid (< 48 hours) and inexpensive diagnostic tool for eIF2B-related disorders has the potential to identify patients with likely eIF2B-related disorder for mutation analysis. C1 [Vanderver, A.; Hathout, Y.; Maletkovic, J.; Gordon, E. S.; Mintz, M.; Hoffman, E. P.] Childrens Natl Med Ctr, Childrens Res Inst, Ctr Genet Med, Washington, DC 20010 USA. [Timmons, M.; Schiffmann, R.] NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. [Horzinski, L.; Fogli, A.; Boespflug-Tanguy, O.] INSERM, Fac Med, Clermont Ferrand, France. [Niel, F.; Boespflug-Tanguy, O.] CHU, Clermont Ferrand, France. RP Vanderver, A (reprint author), Childrens Natl Med Ctr, Childrens Res Inst, Ctr Genet Med, 111 Michigan Ave NW, Washington, DC 20010 USA. EM avanderv@cnmc.org FU Intramural NIH HHS; NICHD NIH HHS [1P30HD40677-01, HD-P30-40677, K12 HD001399, K12HD001399, P30 HD040677] NR 48 TC 15 Z9 15 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN 3 PY 2008 VL 70 IS 23 BP 2226 EP 2232 DI 10.1212/01.wnl.0000313857.54398.0e PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 312YH UT WOS:000256707800008 PM 18519871 ER PT J AU Dalakas, MC AF Dalakas, Marinos C. TI Invited article: Inhibition of B cell functions - Implications for neurology SO NEUROLOGY LA English DT Article ID PROGRESSIVE MULTIPLE-SCLEROSIS; CENTRAL-NERVOUS-SYSTEM; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; NEUROMYELITIS-OPTICA; CEREBROSPINAL-FLUID; LUPUS-ERYTHEMATOSUS; THERAPEUTIC TARGETS; ANTIBODY-PRODUCTION; PERIPHERAL-BLOOD; OPEN-LABEL AB B cells are involved in the pathophysiology of many neurologic diseases, either in a causative or contributory role, via production of autoantibodies, cytokine secretion, or by acting as antigen-presenting cells leading to T cell activation. B cells are clonally expanded in various CNS disorders, such as multiple sclerosis (MS), paraneoplastic CNS disorders, or stiff-person syndrome, and are activated to produce pathogenic autoantibodies in demyelinating neuropathies and myasthenia. B cell activating factor (BAFF) and a proliferating inducing ligand (APRIL), key cytokines for B cell survival, are strongly unregulated in MS brain and in muscles of inflammatory myopathies. Modulation of B cell functions using a series of monoclonal antibodies against CD20 + B cells or the molecules that increase B cell survival, such as BAFF/APRIL and their receptors BAFF-R, TACI, and BCMA, provide a rational approach to the treatment of the aforementioned neurologic disorders. In controlled studies, rituximab, a B cell-depleting monoclonal antibody, has been encouraging in MS and paraproteinemic anti-MAG demyelinating neuropathy, exerting long-lasting remissions. In uncontrolled series, benefit has been reported in several disorders. B cell depletion is a well-tolerated therapeutic option currently explored in the treatment of several autoimmune neurologic disorders. C1 [Dalakas, Marinos C.] NINDS, Neuromuscular Dis Sect, NIH, Bethesda, MD 20892 USA. RP Dalakas, MC (reprint author), Thomas Jefferson Univ, 900 Walnut St,Suite 200, Philadelphia, PA 19107 USA. EM marinos.dalakas@jefferson.edu FU Intramural NIH HHS NR 45 TC 57 Z9 58 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN 3 PY 2008 VL 70 IS 23 BP 2252 EP 2260 DI 10.1212/01.wnl.0000313840.27060.bf PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 312YH UT WOS:000256707800012 PM 18519875 ER PT J AU Wang, Y Yabuuchi, A McKinney-Freeman, S Ducharme, DMK Ray, MK Chawengsaksophak, K Archer, TK Daley, GQ AF Wang, Yuan Yabuuchi, Akiko McKinney-Freeman, Shannon Ducharme, Danica M. K. Ray, Manas K. Chawengsaksophak, Kallayanee Archer, Trevor K. Daley, George Q. TI Cdx gene deficiency compromises embryonic hematopoiesis in the mouse SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Hox genes; embryonic stem cell; A-P patterning; development; embryoid body ID ACUTE MYELOID-LEUKEMIA; STEM-CELLS; HOX GENES; DEFINITIVE HEMATOPOIESIS; EXPRESSION; PROGENITORS; MICE; GASTRULATION; ELONGATION; PROTEIN AB Cdx genes (Cdx1, Cdx2, and Cdx4) encode a family of caudal-related transcription factors that mediate anterior-posterior patterning during embryogenesis through Hox gene regulation. Homologues in the zebrafish have been shown to play key roles in blood formation. To define the role of Cdx genes during embryonic hematopoiesis in a mammalian system, we examined the hematopoietic potential of Cdx-deficient mouse embryonic stem cells (ESCs) in vitro and in vivo. Individual Cdx-deficient ESCs exhibited impaired embryonic hematopoietic progenitor formation and altered Hox gene expression, most notably for Cdx2 deficiency. A more severe hematopoietic defect was observed with compound Cdx deficiency than loss of function of any single Cdx gene. Reduced hematopoietic progenitor formation of ESCs deficient in multiple Cdx genes could be rescued by ectopic expression of Cdx4, concomitant with partially restored Hox gene expression. These results reveal an essential and partially redundant role for multiple Calk genes during embryonic hematopoiesis in the mouse. C1 [Wang, Yuan; Archer, Trevor K.] NIEHS, Mol Carcinogenesis Lab, Natl Inst Hlth, Res Triangle Pk, NC 27709 USA. [Ducharme, Danica M. K.] NIEHS, Microarray Grp, Natl Inst Hlth, Res Triangle Pk, NC 27709 USA. [Ray, Manas K.] NIEHS, Reprod & Dev Toxicol Lab, Natl Inst Hlth, Res Triangle Pk, NC 27709 USA. [Yabuuchi, Akiko; McKinney-Freeman, Shannon; Daley, George Q.] Harvard Univ, Sch Med, Div Hematol & Oncol,Howard Hughes Med Inst, Childrens Hosp Boston,Harvard Stem Cell Inst, Boston, MA 02115 USA. [Daley, George Q.] Harvard Univ, Sch Med, Howard Hughes Med Inst,Harvard Stem Cell Inst, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Chawengsaksophak, Kallayanee] Univ Queensland, Inst Mol & Biosci, St Lucia, Qld 4067, Australia. RP Archer, TK (reprint author), NIEHS, Mol Carcinogenesis Lab, Natl Inst Hlth, Res Triangle Pk, NC 27709 USA. EM archer1@niehs.nih.gov; george.daley@childrens.harvard.edu RI Chawengsaksophak, Kallayanee/G-4427-2014 OI Chawengsaksophak, Kallayanee/0000-0001-9401-2122 FU Intramural NIH HHS NR 31 TC 36 Z9 37 U1 1 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 3 PY 2008 VL 105 IS 22 BP 7756 EP 7761 DI 10.1073/pnas.0708951105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 312DF UT WOS:000256648600025 PM 18511567 ER PT J AU Gomes, R Teixeira, C Teixeira, MJ Oliveira, F Menezes, MJ Silva, C de Oliveira, CI Miranda, JC Elnaiem, DE Kamhawi, S Valenzuela, JG Brodskyn, CI AF Gomes, Regis Teixeira, Clarissa Jania Teixeira, Maria Oliveira, Fabiano Jose Menezes, Maria Silva, Claire de Oliveira, Calmila I. Miranda, Jose C. Elnaiem, Dia-Eldin Kamhawi, Shaden Valenzuela, Jesus G. Brodskyn, Claudia I. TI Immunity to a salivary protein of a sand fly vector protects against the fatal outcome of visceral leishmaniasis in a hamster model SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE antisaliva immunity; Leishmania; sand fly saliva; vector-based vaccine ID LUTZOMYIA-LONGIPALPIS; CUTANEOUS LEISHMANIASIS; NITRIC-OXIDE; BORRELIA-BURGDORFERI; CLINICAL EVOLUTION; GOLDEN-HAMSTER; INFECTION; DONOVANI; TRANSMISSION; RESISTANCE AB Visceral leishmaniasis (VL) is a fatal disease for humans, and no vaccine is currently available. Sand fly salivary proteins have been associated with protection against cutaneous leishmaniasis. To test whether vector salivary proteins can protect against VL, a hamster model was developed involving intradermal inoculation in the ears of 100,000 Leishmania infantum chagasi parasites together with Lutzomyia longipalpis saliva to mimic natural transmission by sand flies. Hamsters developed classical signs of VL rapidly, culminating in a fatal outcome 5-6 months postinfection. Saliva had no effect on the course of infection in this model. Immunization with 16 DNA plasmids coding for salivary proteins of Lu. longipalpis resulted in the identification of LJM19, a novel 11-kDa protein, that protected hamsters against the fatal outcome of VL. LJM19-immunized hamsters maintained a low parasite load that correlated with an overall high IFN-gamma/TGF-beta ratio and inducible NOS expression in the spleen and liver up to 5 months postinfection. Importantly, a delayed-type hypersensitivity response with high expression of IFN-gamma was also noted in the skin of LJM19-immunized hamsters 48 h after exposure to uninfected sand fly bites. Induction of IFN-gamma at the site of bite could partly explain the protection observed in the viscera of LJM19-immunized hamsters through direct parasite killing and/or priming of anti-Leishmania immunity. We have shown that immunity to a defined salivary protein (LJM19) confers powerful protection against the fatal outcome of a parasitic disease, which reinforces the concept of using components of arthropod saliva in vaccine strategies against vector-borne diseases. C1 [Gomes, Regis; Teixeira, Clarissa; Oliveira, Fabiano; Elnaiem, Dia-Eldin; Kamhawi, Shaden; Valenzuela, Jesus G.] NIAID, Vector Mol Biol Unit, Lab Malaria & Vector Res, Natl Inst Hlth, Rockville, MD 20852 USA. [Gomes, Regis; Teixeira, Clarissa; Jania Teixeira, Maria; Oliveira, Fabiano; Jose Menezes, Maria; Silva, Claire; de Oliveira, Calmila I.; Miranda, Jose C.; Brodskyn, Claudia I.] Fundacao Oswaldo Cruz, Ctr Pesquisas Goncalo Moniz, BR-40296710 Salvador, BA, Brazil. [Brodskyn, Claudia I.] Inst Invest Imunol, BR-40296710 Salvador, BA, Brazil. RP Valenzuela, JG (reprint author), NIAID, Vector Mol Biol Unit, Lab Malaria & Vector Res, Natl Inst Hlth, 12735 Twinbrook Pkwy, Rockville, MD 20852 USA. EM jvalenzuela@niaid.nih.gov; brodskyn@cpqgm.fiocruz.br RI de Oliveira, Camila/B-4358-2009; Brodskyn, Claudia/A-9970-2010; Oliveira, Fabiano/B-4251-2009; Imunologia, Inct/I-2124-2013 OI de Oliveira, Camila/0000-0002-7868-5164; Oliveira, Fabiano/0000-0002-7924-8038; FU Intramural NIH HHS NR 43 TC 105 Z9 107 U1 2 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 3 PY 2008 VL 105 IS 22 BP 7845 EP 7850 DI 10.1073/pnas.0712153105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 312DF UT WOS:000256648600040 PM 18509051 ER PT J AU Duan, JH Mu, JB Thera, MA Joy, D Pond, SLK Diemert, D Long, C Zhou, H Miura, K Ouattara, A Dolo, A Doumbo, O Su, XZ Miller, L AF Duan, Junhui Mu, Jianbing Thera, Mahamadou Ali Joy, Deirdre Pond, Sergei L. Kosakovsky Diemert, David Long, Carole Zhou, Hong Miura, Kazutoyo Ouattara, Amed Dolo, Amagana Doumbo, Ogobara Su, Xin-Zhuan Miller, Louis TI Population structure of the genes encoding the polymorphic Plasmodium falciparum apical membrane antigen 1: Implications for vaccine design SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MULTILOCUS GENOTYPE DATA; MALARIA; CHLOROQUINE; MONKEYS; AMA1; PROTECTION; DIVERSITY; INFERENCE; SELECTION; INVASION AB Immunization with the highly polymorphic Plasmodium falciparum apical membrane antigen 1 (PfAMA1) induces protection in animals but primarily against parasites that express the same or similar alleles. One strategy to overcome the obstacle of polymorphism is to combine PfAMA1 proteins representing major haplotypes into one vaccine. To determine the minimum number of haplotypes that would confer broad protection, we sequenced the coding region of PfAMA 1 from 97 clones from around the world and 61 isolates from Mali, identifying 150 haplotypes for domains 1 to 3 that included previous sequences. A clustering algorithm grouped the 150 haplotypes into six populations that were independent of geographic location. Each of the six populations contained haplotypes predominantly of that population (predominant haplotypes) and haplotypes that were a mixture of haplotypes represented in other populations (admixed haplotypes). To determine the biological relevance of the populations identified through the clustering algorithm, antibodies induced against one predominant haplotype of population 1 (3D7) and one admixed haplotype of population 5 (FVO) were tested for their ability to block parasite invasion of erythrocytes. Parasites expressing PfAMA1s belonging to population 1 were efficiently inhibited by 3D7-specific antibodies, whereas parasites expressing PfAMA1s belonging to other populations were not. For FVO-specific antibodies, we observed growth inhibition against itself as well as isolates belonging to populations 3 and 6. Our data suggests that the inclusion of PfAMA1 sequences. from each of the six populations may result in a vaccine that induces protective immunity against a broad range of malaria parasites. C1 [Duan, Junhui; Diemert, David; Miura, Kazutoyo; Miller, Louis] NIAID, Malaria Vaccine Dev Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. [Mu, Jianbing; Joy, Deirdre; Long, Carole; Zhou, Hong; Su, Xin-Zhuan] NIAID, Lab Malaria & Vector Res, Natl Inst Hlth, Bethesda, MD 20892 USA. [Pond, Sergei L. Kosakovsky] Univ Calif San Diego, Dept Pathol, San Diego, CA 92103 USA. [Thera, Mahamadou Ali; Ouattara, Amed; Dolo, Amagana] Univ Bamako, Fac Med, Dept Epidemiol & Parasit Dis, Malaria Res & Training Ctr, Bamako, Mali. RP Miller, L (reprint author), NIAID, Malaria Vaccine Dev Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. EM jmu@niaid.nih.gov; lmiller@niaid.nih.gov RI Pond, Sergei/G-9830-2012; OI Pond, Sergei/0000-0003-4817-4029; Diemert, David/0000-0002-2789-0512; Su, Xinzhuan/0000-0003-3246-3248 FU Intramural NIH HHS NR 24 TC 65 Z9 65 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 3 PY 2008 VL 105 IS 22 BP 7857 EP 7862 DI 10.1073/pnas.0802328105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 312DF UT WOS:000256648600042 PM 18515425 ER PT J AU Rericha, EC Parent, CA AF Rericha, Erin C. Parent, Carole A. TI Steering in Quadruplet: The Complex Signaling Pathways Directing Chemotaxis SO SCIENCE SIGNALING LA English DT Article AB Studies in the social amoeba Dictyostelium discoideum reveal that signaling cascades coordinating chemotactic directional sensing and migration are complex, with redundant pathways emerging as cells differentiate. Lack of accumulation of the leading-edge marker phosphatidylinositol-3,4,5-trisphosphate can be compensated by a pathway containing phospholipase A(2) (PLA(2)) in early developed cells and guanylyl cyclase (GC) in later developed, polarized cells. Because numerous signaling networks operational during Dictyostelium chemotaxis are conserved in mammalian cells, PLA(2) and GC pathways may also be effective in higher eukaryotes, providing avenues for future research. C1 [Parent, Carole A.] NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Rericha, Erin C.] Univ Maryland, Inst Res Elect & Appl Phys, College Pk, MD 20742 USA. RP Parent, CA (reprint author), NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM parentc@mail.nih.gov NR 34 TC 13 Z9 13 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1937-9145 J9 SCI SIGNAL JI Sci. Signal. PD JUN 3 PY 2008 VL 1 IS 22 AR pe26 DI 10.1126/scisignal.122pe26 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA V10WB UT WOS:000207493000002 PM 18523238 ER PT J AU Horn, TL Harder, JB Johnson, WD Curry, PT Parchment, RE Morrissey, RL Mellick, PW Calis, KA Gold, PW Rice, KC Contoreggi, C Charney, DS Cizza, G Glaze, ER Tomaszewski, JE McCormick, DL AF Horn, Thomas L. Harder, J. Brooks Johnson, William D. Curry, Patrick T. Parchment, Ralph E. Morrissey, Robert L. Mellick, Paul W. Calis, Karim A. Gold, Philip W. Rice, Kenner C. Contoreggi, Carlo Charney, Dennis S. Cizza, Giovanni Glaze, Elizabeth R. Tomaszewski, Joseph E. McCormick, David L. TI Integration of in vivo and in vitro approaches to characterize the toxicity of Antalarmin, a corticotropin-releasing hormone receptor antagonist SO TOXICOLOGY LA English DT Article DE Antalarmin; corticotropin-releasing hormone receptor antagonist; preclinical toxicology; bone marrow cytotoxicity ID MAJOR DEPRESSION; ACTH RELEASE; STRESS; RESPONSES; MYELOTOXICITY; VASOPRESSIN; PROGENITORS; MURINE; CANINE; TESTS AB Non-clinical studies were conducted to evaluate the toxicity of Antalarmin, a corticotropin-releasing hormone type 1 receptor antagonist being developed for therapy of stress-related pathologies. Antalarmin was not genotoxic in bacterial mutagenesis assays, mammalian cell mutagenesis assays, or in vivo DNA damage assays. In a 14-day range-finding study in rats, Antalarmin doses >= 500mg/kg/day (3000 mg/m(2)/day) induced mortality. In a 90-day toxicity study in rats, no gross toxicity was seen at doses of 30, 100, or 300 mg/kg/day (180, 600, or 1800 mg/m(2)/day, respectively). Antalarmin (300 mg/kg/day) induced mild anemia, increases in serumy-glutamyl transferase activity, and microscopic hepatic pathology (bile duct hyperplasia and epithelial necrosis, periportal inflammation). Microscopic renal changes (cortical necrosis, inflammation, hypertrophy, nephropathy) were observed in rats at all Antalarmin doses. In a 14-day range-finding study in dogs, Antalarmin doses >= 50mg/kg/day (1000mg/m(2)/day) induced repeated emesis and bone marrow suppression. In a 90-day toxicity study in dogs, Antalarmin (4, 8, or 16 mg/kg/day (80, 160, or 320 mg/m(2)/day, respectively)) induced bone marrow and lymphoid depletion, but no gross toxicity. Comparative in vitro studies using rat, dog, and human neutrophil progenitors demonstrated that canine bone marrow cells are highly sensitive to Antalarmin cytotoxicity, while rat and human bone marrow cells are relatively insensitive. As such, the bone marrow toxicity observed in dogs is considered likely to over-predict Antalarmin toxicity in humans. The hepatic and renal toxicities seen in rats exposed to Antalarmin identify those tissues as the most likely targets for Antalarmin toxicity in humans. (C) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Horn, Thomas L.; Harder, J. Brooks; Johnson, William D.; Curry, Patrick T.; McCormick, David L.] IIT, Res Inst, Chicago, IL 60616 USA. [Morrissey, Robert L.] Chales River Labs Inc, Pathol Associates, Chicago, IL 60612 USA. [Mellick, Paul W.] Chales River Labs Inc, Pathol Associates, Kansas City, MO 64137 USA. [Calis, Karim A.; Gold, Philip W.; Rice, Kenner C.; Contoreggi, Carlo; Charney, Dennis S.; Cizza, Giovanni; Glaze, Elizabeth R.; Tomaszewski, Joseph E.] NIH, Bethesda, MD 20892 USA. RP Horn, TL (reprint author), IIT, Res Inst, Chicago, IL 60616 USA. FU Intramural NIH HHS; NCI NIH HHS [N01-CM-87028, N01 CM042202, N01 CM087102, N01CM42202, N01-CM-42202] NR 21 TC 6 Z9 6 U1 0 U2 0 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 JUN 3 PY 2008 VL 248 IS 1 BP 8 EP 17 DI 10.1016/j.tox.2008.03.002 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 310OU UT WOS:000256539700002 PM 18423834 ER PT J AU Nosek, K Dennis, K Andrus, BM Ahmadiyeh, N Baum, AE Woods, LCS Redei, EE AF Nosek, Katarzyna Dennis, Kristen Andrus, Brian M. Ahmadiyeh, Nasim Baum, Amber E. Woods, Leah C. Solberg Redei, Eva E. TI Context and strain-dependent behavioral response to stress SO BEHAVIORAL AND BRAIN FUNCTIONS LA English DT Article ID ELEVATED PLUS-MAZE; WISTAR-KYOTO WKY; INBRED RAT STRAINS; OPEN-FIELD; PLASMA-CORTICOSTERONE; GENETIC-ANALYSIS; ANXIETY; MICE; CHLORDIAZEPOXIDE; EMOTIONALITY AB Background: This study posed the question whether strain differences in stress-reactivity lead to differential behavioral responses in two different tests of anxiety. Strain differences in anxiety-measures are known, but strain differences in the behavioral responses to acute prior stress are not well characterized. Methods: We studied male Fisher 344 (F344) and Wistar Kyoto (WKY) rats basally and immediately after one hour restraint stress. To distinguish between the effects of novelty and prior stress, we also investigated behavior after repeated exposure to the test chamber. Two behavioral tests were explored; the elevated plus maze (EPM) and the open field (OFT), both of which are thought to measure activity, exploration and anxiety-like behaviors. Additionally, rearing, a voluntary behavior, and grooming, a relatively automatic, stress-responsive stereotyped behavior were measured in both tests. Results: Prior exposure to the test environment increased anxiety-related measures regardless of prior stress, reflecting context-dependent learning process in both tests and strains. Activity decreased in response to repeated testing in both tests and both strains, but prior stress decreased activity only in the OFT which was reversed by repeated testing. Prior stress decreased anxiety-related measures in the EPM, only in F344s, while in the OFT, stress led to increased freezing mainly in WKYs. Conclusion: Data suggest that differences in stressfulness of these tests predict the behavior of the two strains of animals according to their stress-reactivity and coping style, but that repeated testing can overcome some of these differences. C1 [Nosek, Katarzyna; Dennis, Kristen; Andrus, Brian M.; Ahmadiyeh, Nasim; Baum, Amber E.; Woods, Leah C. Solberg; Redei, Eva E.] Northwestern Univ, Feinberg Sch Med, Asher Ctr, Dept Psychiat & Behav Sci, Chicago, IL 60611 USA. [Ahmadiyeh, Nasim] Brigham & Womens Hosp, Boston, MA 02115 USA. [Ahmadiyeh, Nasim] Dana Farber Canc Inst, Boston, MA 02115 USA. [Baum, Amber E.] NIH, Bethesda, MD 20892 USA. [Woods, Leah C. Solberg] Med Coll Wisconsin, Milwaukee, WI 53226 USA. RP Redei, EE (reprint author), Northwestern Univ, Feinberg Sch Med, Asher Ctr, Dept Psychiat & Behav Sci, Chicago, IL 60611 USA. EM kmn@uchicago.edu; k-dennis@northwestern.edu; b-andrus@northwestern.edu; nahmadiyeh@partners.org; bauma@mail.nih.gov; lsolberg@mcw.edu; e-redei@northwestern.edu FU NIMH NIH HHS [R21 MH077234] NR 49 TC 29 Z9 30 U1 2 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1744-9081 J9 BEHAV BRAIN FUNCT JI Behav. Brain Funct. PD JUN 2 PY 2008 VL 4 AR 23 DI 10.1186/1744-9081-4-23 PG 8 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 314SB UT WOS:000256828000001 PM 18518967 ER PT J AU Zhang, L Li, H Su, TP Barker, JL Maric, D Fullerton, CS Webster, MJ Hough, CJ Li, XX Ursano, R AF Zhang, L. Li, H. Su, T. P. Barker, J. L. Maric, D. Fullerton, C. S. Webster, M. J. Hough, C. J. Li, X. X. Ursano, R. CA Traumatic Stress Brain Study Grp TI p11 is up-regulated in the forebrain of stressed rats by glucocorticoid acting via two specific glucocorticoid response elements in the p11 promoter SO NEUROSCIENCE LA English DT Article DE posttraumatic stress disorder; glucocorticoid response elements; glucocorticoid receptor; p11; prefrontal cortex ID SUICIDAL-BEHAVIOR; PROTEIN-SYNTHESIS; EPITHELIAL-CELLS; PLASMA-CORTISOL; DISORDER; EXPRESSION; COMORBIDITY; DEPRESSION; CORTICOSTERONE; HIPPOCAMPUS AB Posttraumatic stress disorder (PTSD) is one of the most common psychiatric disorders. Despite the extensive study of the neurobiological correlates of this disorder, the underlying mechanisms of PTSD are still poorly understood. Recently, a study demonstrated that dexamethasone (Dex), a synthetic glucocorticoid, can up-regulate p11, known as S100A10-protein which is down-regulated in patients with depression, (Yao et al., 1999; Huang et al., 2003) a common comorbid disorder in PTSD. These observations led to our hypothesis that traumatic stress may alter expression of p11 mediated through a glucocorticold receptor. Here, we demonstrate that inescapable tail shock increased both prefrontal cortical pi 1 mRNA levels and plasma corticosterone levels in rats. We also found that Dex up-regulated p11 expression in SH-SY5Y cells through glucocorticoid response elements (GREs) within the p11 promoter. This response was attenuated by either RU486, a glucocorticoid receptor (GR) antagonist or mutating two of three glucocorticoid response elements (GRE2 and GRE3) in the p11 promoter. Finally, we showed that p11 mRNA levels were increased in postmortem prefrontal cortical tissue (area 46) of patients with PTSD. The data obtained from our work in a rat model of inescapable tail shock, a p11-transfected cell line and postmortem brain tissue from PTSD patients outline a possible mechanism by which p11 is regulated by glucocorticoids elevated by traumatic stress. Published by Elsevier Ltd on behalf of IBRO. C1 [Zhang, L.; Li, H.; Fullerton, C. S.; Hough, C. J.; Li, X. X.; Ursano, R.] Uniformed Serv Univ Hlth Sci, Dept Psychiat, Ctr Study Traumat Stress, Bethesda, MD 20814 USA. [Su, T. P.] Taipei Vet Gen Hosp, Dept Psychiat, Taipei, Taiwan. [Su, T. P.] Natl Yang Ming Univ, Sch Med, Div Psychiat, Taipei 112, Taiwan. [Barker, J. L.; Maric, D.] Natl Inst Neurol Disorders & Stroke, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. [Webster, M. J.] Stanley Med Res Inst, Chevy Chase, MD 20894 USA. RP Zhang, L (reprint author), Uniformed Serv Univ Hlth Sci, Dept Psychiat, Ctr Study Traumat Stress, Bethesda, MD 20814 USA. EM Lezhang@USUHS.mil RI Osuch, Elizabeth/B-5009-2015 OI Osuch, Elizabeth/0000-0001-5946-1862 NR 33 TC 35 Z9 37 U1 16 U2 17 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD JUN 2 PY 2008 VL 153 IS 4 BP 1126 EP 1134 DI 10.1016/j.neuroscience.2008.03.022 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 313LN UT WOS:000256742200022 PM 18440154 ER PT J AU Arnarsson, A Jonasson, F Eiriksdottir, G Harris, T Launer, L Klein, BE Klein, R Cotch, MF Gudnason, V AF Arnarsson, A. Jonasson, F. Eiriksdottir, G. Harris, T. Launer, L. Klein, B. E. Klein, R. Cotch, M. F. Gudnason, V TI Prevalence of age-related macular degeneration in the ages - Reykjavik study SO ACTA OPHTHALMOLOGICA LA English DT Meeting Abstract C1 [Arnarsson, A.; Jonasson, F.] Landspitali Univ Hosp, Reykjavik, Iceland. [Arnarsson, A.] Univ Akureyri, Akureyri, Iceland. [Eiriksdottir, G.; Gudnason, V] Iceland Heart Assoc, Kopavogur, Iceland. [Harris, T.; Launer, L.] NIA, Intramural Res Program, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Klein, B. E.; Klein, R.] Univ Wisconsin, Madison, WI USA. [Cotch, M. F.] NEI, Div Epidemiol & Clin Res, Bethesda, MD 20892 USA. RI Gudnason, Vilmundur/K-6885-2015 OI Gudnason, Vilmundur/0000-0001-5696-0084 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1755-375X J9 ACTA OPHTHALMOL JI Acta Ophthalmol. PD JUN PY 2008 VL 86 SU 241 BP 3 EP 3 PG 1 WC Ophthalmology SC Ophthalmology GA 305RU UT WOS:000256196300009 ER PT J AU Obladen, M Metze, B Henrich, W Aktas, A Czernik, C Schulz-Baldes, A AF Obladen, Michael Metze, Boris Henrich, Wolfgang Aktas, Ayse Czernik, Christoph Schulz-Baldes, Annette TI Interdisciplinary surveillance of intraventricular haemorrhage associated conditions in infants < 1000 g SO ACTA PAEDIATRICA LA English DT Article DE extremely low birthweight; interdisciplinary quality management; intraventricular haemorrhage; prematurity; prospective surveillance ID BIRTH-WEIGHT INFANTS; ISCHEMIC BRAIN-INJURY; INTENSIVE-CARE-UNIT; PREMATURE-INFANTS; RISK-FACTORS; PRETERM INFANTS; PREVENTION; TERM AB Aim: Intraventricular haemorrhage (IVH) causes some of the most adverse outcomes in infants with birthweight < 1000 g. Incomplete antenatal steroids, acidosis, inflammation, postnatal transfer, delayed surfactant administration, hypothermia, hypotension, hypocapnia, persistent ductus arteriosus and pneumothorax are all associated with IVH. We hypothesized that prospective surveillance of these IVH-associated conditions decreases their frequency and thus the frequency of IVH. Methods: Cranial ultrasound was performed on days 1, 3, 7, 30 after birth and at discharge, and was assessed according to Papile. The incidence of IVH and IVH-associated conditions was monitored prospectively in all infants < 1000 g born in our perinatal centre in 2005/2006, and obstetricians and neonatologists held monthly interdisciplinary review conferences to discuss the preventability of IVH-associated conditions (IVH surveillance). These data were compared to existing prospective data gathered during routine monitoring in 2004. Results: IVH (all grades) occurred in 29/86 extremely low birthweight (ELBW) infants during routine monitoring and in 12/89 ELBW infants during IVH surveillance (p = 0.007). IVH grades 3-4 dropped from 20% to 3.4% (p = 0.0006). There were significant differences in completeness of antenatal steroids (54% vs. 67%, p = 0.04) and timeliness in initial surfactant substitution (45% vs. 71%, p = 0.01). Most other IVH-associated conditions were reduced during IVH surveillance without reaching significance. Conclusions: IVH is not always an inevitable disaster. Obstetricians and neonatologists can reduce its incidence by joint prospective surveillance of IVH-associated conditions. C1 [Obladen, Michael; Aktas, Ayse; Czernik, Christoph] Charite Univ Med Berlin, Dept Neonatol, Campus Virchow Klinikum, D-13353 Berlin, Germany. [Metze, Boris] Charite Univ Med Berlin, Div Qual Management, Berlin, Germany. [Henrich, Wolfgang] Charite Univ Med Berlin, Dept Obstet, Berlin, Germany. [Schulz-Baldes, Annette] NIH, Dept Bioeth, Bethesda, MD 20892 USA. RP Obladen, M (reprint author), Charite Univ Med Berlin, Dept Neonatol, Campus Virchow Klinikum, Augustenburger Pl 1, D-13353 Berlin, Germany. EM michael.obladen@charite.de RI Schulz, Sandra/F-6238-2012 NR 29 TC 7 Z9 7 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0803-5253 J9 ACTA PAEDIATR JI Acta Paediatr. PD JUN PY 2008 VL 97 IS 6 BP 731 EP 737 DI 10.1111/j.1651-2227.2008.00812.x PG 7 WC Pediatrics SC Pediatrics GA 296FJ UT WOS:000255528600013 PM 18460106 ER PT J AU Le Foll, B Forget, B Aubin, HJ Goldberg, SR AF Le Foll, Bernard Forget, Benoit Aubin, Henri-Jean Goldberg, Steven R. TI Blocking cannabinoid CB(1) receptors for the treatment of nicotine dependence: insights from pre-clinical and clinical studies SO ADDICTION BIOLOGY LA English DT Review DE acomplia; behaviour; cannabinoid; drug; nicotine; tobacco dependence ID CONDITIONED PLACE PREFERENCE; MIDBRAIN DOPAMINE NEURONS; COCAINE-SEEKING BEHAVIOR; DIHYDRO-BETA-ERYTHROIDINE; FOOD-REINFORCED BEHAVIOR; FREELY-MOVING RATS; NUCLEUS-ACCUMBENS; SMOKING-CESSATION; PREFRONTAL CORTEX; DRUG-SEEKING AB Tobacco use is one of the leading preventable causes of death in developed countries. Since existing medications are only partially effective in treating tobacco smokers, there is a great need for improved medications for smoking cessation. It has been recently proposed that cannabinoid CB(1) receptor antagonists represent a new class of therapeutic agents for drug dependence, and notably, nicotine dependence. Here, we will review current evidence supporting the use of this class of drugs for smoking cessation treatment. Pre-clinical studies indicate that nicotine exposure produces changes in endocannabinoid content in the brain. In experimental animals, N-piperidinyl-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxamide (rimonabant, SR141716) and N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251), two cannabinoid CB(1) receptor antagonists, block nicotine self-administration behavior, an effect that may be related to the blockade of the dopamine-releasing effects of nicotine in the brain. Rimonabant also seems efficacious in decreasing the influence of nicotine-associated stimuli over behavior, suggesting that it may act on two distinct neuronal pathways, those implicated in drug-taking behavior and those involved in relapse phenomena. The utility of rimonabant has been evaluated in several clinical trials. It seems that rimonabant is an efficacious treatment for smoking cessation, although its efficacy does not exceed that of nicotine-replacement therapy and its use may be limited by emotional side effects (nausea, anxiety and depression, mostly). Rimonabant also appears to decrease relapse rates in smokers. These findings indicate significant, but limited, utility of rimonabant for smoking cessation. C1 [Le Foll, Bernard; Forget, Benoit] Univ Toronto, Ctr Addict & Mental Hlth, Translat Addict Res Lab, Toronto, ON M5S 2S1, Canada. [Aubin, Henri-Jean] INSERM, U669, F-75654 Paris 13, France. [Goldberg, Steven R.] NIDA, Preclin Pharmacol Sect, Behav Neurosci Res Branch, NIH,Dept Hlth & Human Serv, Bethesda, MD USA. RP Le Foll, B (reprint author), Univ Toronto, Ctr Addict & Mental Hlth, Translat Addict Res Lab, 33 Russell St, Toronto, ON M5S 2S1, Canada. EM bernard_lefoll@camh.net RI Le Foll, Bernard/K-2952-2014 OI Le Foll, Bernard/0000-0002-6406-4973 FU Intramural NIH HHS [Z01 DA000001-23, Z01 DA000003-22] NR 132 TC 59 Z9 61 U1 1 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1355-6215 J9 ADDICT BIOL JI Addict. Biol. PD JUN PY 2008 VL 13 IS 2 BP 239 EP 252 DI 10.1111/j.1369-1600.2008.00113.x PG 14 WC Biochemistry & Molecular Biology; Substance Abuse SC Biochemistry & Molecular Biology; Substance Abuse GA 301RP UT WOS:000255913600008 PM 18482433 ER PT J AU Luther, EJ Parzynski, CS Jaszyna-Gasior, M Bagot, KS Royo, MB Leff, MK Moolchan, ET AF Luther, Emily J. Parzynski, Craig S. Jaszyna-Gasior, Maria Bagot, Kara S. Royo, Marc B. Leff, Michelle K. Moolchan, Eric T. TI Does allowing adolescents to smoke at home affect their consumption and dependence? SO ADDICTIVE BEHAVIORS LA English DT Article DE adolescents; smoking; parental allowance; tobacco ID NICOTINE PATCH THERAPY; RESTRICTIONS; BEHAVIORS; HOUSEHOLD AB Negative parental attitudes towards smoking decrease adolescent smoking initiation but limited research explores the relationship between parental attitudes and degree of adolescent smoking among established smokers. The aim of this study was to examine the relationship between parental allowance of smoking in the home and adolescent smoking behavior and level of dependence. Interviews from 408 youths seeking assistance to quit smoking showed that adolescents who were allowed to smoke at home smoked more cigarettes per day and had higher scores on the Fagerstrom Test of Nicotine Dependence than those not allowed to smoke at home. Studies that additionally evaluate parental smoking status and the temporal relationship of parental allowance of smoking with changes in adolescent smoking behavior are warranted to clarify public health implications of parental smoking interdictions. Published by Elsevier Ltd. C1 [Luther, Emily J.; Parzynski, Craig S.; Jaszyna-Gasior, Maria; Bagot, Kara S.; Royo, Marc B.; Leff, Michelle K.; Moolchan, Eric T.] NIDA, Intramural Res Program, Teen Tobacco Addict Treatment Res Clin, Bethesda, MD USA. RP Moolchan, ET (reprint author), 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM emoolcha@intra.nida.nih.gov FU Intramural NIH HHS [Z01 DA000459-05] NR 13 TC 2 Z9 2 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 J9 ADDICT BEHAV JI Addict. Behav. PD JUN PY 2008 VL 33 IS 6 BP 836 EP 840 DI 10.1016/j.addbeh.2008.01.006 PG 5 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 297LX UT WOS:000255619300009 PM 18272294 ER PT J AU Soto-Ramirez, LE Rodriguez-Diaz, R Duran, AS Losso, MH Salomon, H Gomez-Carrillo, M Pampuro, S Harris, DR Duarte, G De Souza, RS Read, JS AF Soto-Ramirez, Luis E. Rodriguez-Diaz, Roberto Duran, Adriana S. Losso, Marcelo H. Salomon, Horacio Gomez-Carrillo, Manuel Pampuro, Sandra Harris, D. Robert Duarte, Geraldo De Souza, Ricardo S. Read, Jennifer S. CA NISDI Perinatal Study Grp TI Antiretroviral resistance among HIV type 1-infected women first exposed to antiretrovirals during pregnancy: Plasma versus PBMCs SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID TO-CHILD TRANSMISSION; BLOOD MONONUCLEAR-CELLS; TREATMENT-EXPERIENCED PATIENTS; IMMUNODEFICIENCY-VIRUS TYPE-1; MATERNAL-INFANT TRANSMISSION; SINGLE-DOSE NEVIRAPINE; DRUG-RESISTANCE; ZIDOVUDINE; MUTATIONS; PREVENTION AB Resistance-associated mutations (RAMs) in plasma samples from HIV-1-infected women who received antiretroviral (ARV) prophylaxis during pregnancy was assessed and correlated with the detection of RAMs in peripheral blood mononuclear cells (PMBCs). The study population was composed of HIV-1-infected women enrolled in a prospective cohort study in Latin America and the Caribbean (NISDI Perinatal Study) as of March 1, 2005, who were diagnosed with HIV-1 infection during the current pregnancy, who received ARVs during pregnancy for prevention of mother-to-child transmission of HIV-1, and who were followed through at least the 6-12 week postpartum visit. Plasma samples collected at enrollment during pregnancy and at 6-12 weeks postpartum were assayed for RAMs. Plasma results were compared to previously described PBMC results from the same study population. Of 819 enrolled subjects, 197 met the eligibility criteria. Nucleic acid amplification was accomplished in 123 plasma samples at enrollment or 6-12 weeks postpartum, and RAMs were detected in 22 (17.9%; 95% CI: 11.7-25.9%). Previous analyses had demonstrated detection of RAMs in PBMCs in 19 (16.1%). There was high concordance between RAMs detected in plasma and PBMC samples, with only eight discordant pairs. The prevalence of RAMs among these pregnant, HIV-1-infected women is high (>15%). Rates of detection of RAMs in plasma and PBMC samples were similar. C1 [Read, Jennifer S.] NICHD, PAMA Branch, CRMC, NIH,DHHS, Bethesda, MD 20892 USA. [Soto-Ramirez, Luis E.; Rodriguez-Diaz, Roberto] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Infect Dis, Mexico City, DF, Mexico. [Duran, Adriana S.; Losso, Marcelo H.] Hosp Gen Agudos Jose Maria Ramos Mejia, Buenos Aires, DF, Argentina. [Salomon, Horacio; Gomez-Carrillo, Manuel; Pampuro, Sandra] Univ Buenos Aires, Sch Med, Dept Microbiol, Natl Reference Ctr AIDS, Buenos Aires, DF, Argentina. [Harris, D. Robert] WESTAT Corp, Rockville, MD 20850 USA. [Duarte, Geraldo] Univ Sao Paulo, BR-14049 Ribeirao Preto, Brazil. [De Souza, Ricardo S.] Univ Caxias do Sul, Lab Pesquisa HIV AIDS, Caxias Do Sul, Brazil. RP Read, JS (reprint author), NICHD, PAMA Branch, CRMC, NIH,DHHS, Execut Bldg,Room 4B11C,6100 Execut Blvd,MSC 7510, Bethesda, MD 20892 USA. EM jennifer_read@nih.gov RI Mussi-Pinhata, Marisa/G-6568-2012; Duarte, Geraldo/J-7906-2012 FU NICHD NIH HHS [HN01-HD-3-3345] NR 21 TC 11 Z9 11 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JUN PY 2008 VL 24 IS 6 BP 797 EP 804 DI 10.1089/aid.2007.0246 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 329FN UT WOS:000257852400006 PM 18507526 ER PT J AU Lee, Y Rowe, J Eskue, K West, JR Maier, SE AF Lee, Youngki Rowe, Julie Eskue, Kyle West, James R. Maier, Susan E. TI Alcohol exposure on postnatal day 5 induces Purkinje cell loss and evidence of Purkinje cell degradation in lobule I of rat cerebellum SO ALCOHOL LA English DT Article DE fetal alcohol syndrome; third trimester; cell death; ethanol; stereology; Fluoro-Jade B ID BRAIN GROWTH SPURT; ETHANOL EXPOSURE; TEMPORAL VULNERABILITY; REGIONAL DIFFERENCES; NEONATAL CEREBELLUM; MOTOR COORDINATION; BINGE EXPOSURE; FLUORO-JADE; ADULT RATS; VITAMIN-E AB The reduction in neuron number in specific brain regions is one of the most destructive aspects of alcohol-induced developmental brain injury, and its occurrence depends on the timing, pattern, and dose of maternal alcohol consumption during pregnancy. The purpose of this investigation was to quantify the dose-response aspect of Purkinje cell loss and rapid cellular degradation indicative of Purkinje cell loss following a single alcohol exposure on postnatal day 5 in lobule 1, a lobule that has been shown to be vulnerable to alcohol-induced injury during cerebellar development. Fluoro-Jade B was used to identify Purkinje cell degeneration in 2-h intervals during the first 24 h following the single alcohol exposure. At the end of 24 h, stereology cell counting techniques were used to estimate the number of Purkinje cells in lobule I of the cerebellum. Significant Fluoro-Jade B labeling of lobule I Purkinje cells began at 12-h postexposure in the 6.0-g/kg group with continued significant expression of the marker at the 16- and 18-h time points. Notably, the magnitude of Fluoro-Jade B expression in the 6.0-g/kg group remained high during the period between 12 and 24 h even though the difference between the 6.0-g/kg group and other groups did not reach statistical significance at the 14-, 20-, and 24-h time points. On postnatal day 6, 24 h following the alcohol exposure, rats exposed to the highest alcohol dose (6.0 g/kg) had lost significantly more Purkinje cells than those in the nutritional or caloric control to the highest dose of alcohol group. These results are suggestive of a unique relationship among the quantity of alcohol, the onset and duration of cell degradation, and the degree of eventual cell loss. Given that cerebellar Purkinje cells (and many developing neurons) are vulnerable to alcohol-induced neuronal loss within hours of a single alcohol insult, women should be counseled to avoid drinking alcohol in a manner that significantly increases blood alcohol levels during pregnancy (e.g., binge drinking). (c) 2008 Elsevier Inc. All rights reserved. C1 [Lee, Youngki] Cheju Natl Univ, Coll Med, Dept Histol, Jeju Si 690756, South Korea. [Rowe, Julie; Eskue, Kyle; West, James R.; Maier, Susan E.] Texas A&M Hlth Sci Ctr, Dept Neurosci & Expt Therapeut, Coll Med, College Stn, TX 77843 USA. RP Maier, SE (reprint author), NIAAA, 5635 Fishers Lane,Room 2017, Bethesda, MD 20892 USA. EM maiers@mail.nih.gov FU NIAAA NIH HHS [AA05523, AA10990] NR 44 TC 14 Z9 16 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-8329 J9 ALCOHOL JI Alcohol PD JUN PY 2008 VL 42 IS 4 BP 295 EP 302 DI 10.1016/j.alcohol.2008.01.010 PG 8 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA 316NN UT WOS:000256956800007 PM 18400452 ER PT J AU Holmes, A AF Holmes, Andrew TI Developing novel mouse models of executive control over reward-seeking SO ALCOHOL LA English DT Meeting Abstract CT Conference on Alcoholism and Stress - A Framework for Future Treatment Strategies CY MAY 06-08, 2008 CL Volterra, ITALY C1 [Holmes, Andrew] NIAAA, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-8329 J9 ALCOHOL JI Alcohol PD JUN PY 2008 VL 42 IS 4 MA S5 BP 308 EP 308 PG 1 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA 316NN UT WOS:000256956800013 ER PT J AU Gehlert, DR Cippitelli, A Thorsell, A Lee, AD Hipskind, PA Hamdouchi, C Lu, J Hembre, EJ Cramer, J Song, M McKinzie, D Morin, M Ciccocioppo, R Heilig, M AF Gehlert, D. R. Cippitelli, A. Thorsell, A. Le, A. D. Hipskind, P. A. Hamdouchi, C. Lu, J. Hembre, E. J. Cramer, J. Song, M. McKinzie, D. Morin, M. Ciccocioppo, R. Heilig, M. TI MTIP: a novel brain penetrant, orally available corticotropin-releasing hormone receptor 1 (CRH-R1) antagonist for treatment of alcoholism SO ALCOHOL LA English DT Meeting Abstract CT Conference on Alcoholism and Stress - A Framework for Future Treatment Strategies CY MAY 06-08, 2008 CL Volterra, ITALY C1 Eli Lilly & Co, Lilly Res Lab, Indianapolis, IN 46285 USA. NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD USA. Univ Toronto, Ctr Addict & Mental Hlth, Toronto, ON, Canada. Univ Camerino, Dept Exp Med & Publ Hlth, I-62032 Camerino, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-8329 J9 ALCOHOL JI Alcohol PD JUN PY 2008 VL 42 IS 4 MA S13 BP 310 EP 310 PG 1 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA 316NN UT WOS:000256956800021 ER PT J AU Thorsell, A Cippitelli, A Heilig, M AF Thorsell, Annika Cippitelli, Andrea Heilig, Markus TI Neuropeptide Y in stress, anxiety, and alcoholism SO ALCOHOL LA English DT Meeting Abstract CT Conference on Alcoholism and Stress - A Framework for Future Treatment Strategies CY MAY 06-08, 2008 CL Volterra, ITALY C1 [Thorsell, Annika; Cippitelli, Andrea; Heilig, Markus] NIAAA, LCTS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-8329 J9 ALCOHOL JI Alcohol PD JUN PY 2008 VL 42 IS 4 MA S15 BP 310 EP 310 PG 1 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA 316NN UT WOS:000256956800023 ER PT J AU George, DT Gilman, J Hersh, J Thorsell, A Gehlert, DR Tauscher, JT Hunt, SP Hommer, D Heilig, M AF George, David T. Gilman, Jodi Hersh, Jacqueline Thorsell, Annika Gehlert, Donald R. Tauscher, Johannes T. Hunt, Stephen P. Hommer, Daniel Heilig, Markus TI Neurokinin 1 (NK1) receptor blockade: A novel anti-stress based mechanisms for treatment of alcoholism SO ALCOHOL LA English DT Meeting Abstract CT Conference on Alcoholism and Stress - A Framework for Future Treatment Strategies CY MAY 06-08, 2008 CL Volterra, ITALY C1 [George, David T.; Gilman, Jodi; Hersh, Jacqueline; Thorsell, Annika; Gehlert, Donald R.; Tauscher, Johannes T.; Hunt, Stephen P.; Hommer, Daniel; Heilig, Markus] NIAAA, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-8329 J9 ALCOHOL JI Alcohol PD JUN PY 2008 VL 42 IS 4 MA S17 BP 311 EP 311 PG 1 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA 316NN UT WOS:000256956800025 ER PT J AU Zakhari, S AF Zakhari, Sam TI Alcohol metabolism in the brain: Significance of acetaldehyde and acetate SO ALCOHOL LA English DT Meeting Abstract CT Conference on Alcoholism and Stress - A Framework for Future Treatment Strategies CY MAY 06-08, 2008 CL Volterra, ITALY C1 [Zakhari, Sam] NIAAA, Div Metab & Hlth Effects, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-8329 J9 ALCOHOL JI Alcohol PD JUN PY 2008 VL 42 IS 4 MA S42 BP 317 EP 317 PG 1 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA 316NN UT WOS:000256956800050 ER PT J AU Shaham, Y AF Shaham, Yavin TI Stress and relapse to drug seeking: an update SO ALCOHOL LA English DT Meeting Abstract CT Conference on Alcoholism and Stress - A Framework for Future Treatment Strategies CY MAY 06-08, 2008 CL Volterra, ITALY C1 [Shaham, Yavin] NIDA, IRP, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-8329 J9 ALCOHOL JI Alcohol PD JUN PY 2008 VL 42 IS 4 MA S53 BP 320 EP 320 PG 1 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA 316NN UT WOS:000256956800061 ER PT J AU Cippitelli, A Damadzic, R Hansson, AC Sommer, WH Thorsell, A Heilig, M AF Cippitelli, A. Damadzic, R. Hansson, A. C. Sommer, W. H. Thorsell, A. Heilig, M. TI Role of Neuropeptide Y (NPY) in relapse to alcohol-seeking SO ALCOHOL LA English DT Meeting Abstract CT Conference on Alcoholism and Stress - A Framework for Future Treatment Strategies CY MAY 06-08, 2008 CL Volterra, ITALY C1 [Cippitelli, A.; Damadzic, R.; Hansson, A. C.; Sommer, W. H.; Thorsell, A.; Heilig, M.] NIAAA, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-8329 J9 ALCOHOL JI Alcohol PD JUN PY 2008 VL 42 IS 4 MA P102 BP 332 EP 332 PG 1 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA 316NN UT WOS:000256956800109 ER PT J AU Holmes, A AF Holmes, Andrew TI Effects of anti-glutamatergic drugs on sensitivity to ethanol's acute intoxicating effects in mice SO ALCOHOL LA English DT Meeting Abstract CT Conference on Alcoholism and Stress - A Framework for Future Treatment Strategies CY MAY 06-08, 2008 CL Volterra, ITALY C1 [Holmes, Andrew] NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosc, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-8329 J9 ALCOHOL JI Alcohol PD JUN PY 2008 VL 42 IS 4 MA Y115 BP 336 EP 336 PG 1 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA 316NN UT WOS:000256956800124 ER PT J AU Gehlert, DR Cippitelli, A Thorsell, A Le, AD Hipskind, PA Hamdouchi, C Lu, J Hembre, EJ Cramer, J Song, M McKinzie, D Morin, M Ciccocioppo, R Heilig, M AF Gehlert, D. R. Cippitelli, A. Thorsell, A. Le, A. D. Hipskind, P. A. Hamdouchi, C. Lu, J. Hembre, E. J. Cramer, J. Song, M. McKinzie, D. Morin, M. Ciccocioppo, R. Heilig, M. TI MTIP: a novel brain penetrant, orally available corticotropin-releasing hormone receptor 1 (CRH-R1) antagonist for treatment of alcoholism SO ALCOHOL LA English DT Meeting Abstract CT Conference on Alcoholism and Stress - A Framework for Future Treatment Strategies CY MAY 06-08, 2008 CL Volterra, ITALY C1 Eli Lilly & Co, Lilly Res Labs, Discovery Res, Indianapolis, IN 46285 USA. NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD USA. Univ Toronto, Ctr Addict & Mental Hlth, Toronto, ON, Canada. Univ Camerino, Dept Exp Med & Publ Hlth, I-62032 Camerino, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-8329 J9 ALCOHOL JI Alcohol PD JUN PY 2008 VL 42 IS 4 MA R122 BP 338 EP 338 PG 1 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA 316NN UT WOS:000256956800131 ER PT J AU Adermark, L Karlsson, RM Holmes, A Lovinger, DM Heilig, M AF Adermark, L. Karlsson, R-M. Holmes, A. Lovinger, D. M. Heilig, M. TI Lack of conditioned place preference to ethanol and abnormal striatal plasticity in glutamate transporter (GLAST) mutant mice SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 NIAAA, NIH, Lab Clin & Translat Studies, Lab Integrat Neurosci, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 12A EP 12A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497200009 ER PT J AU Jeong, WI Park, O Gao, B AF Jeong, W. I. Park, O. Gao, B. TI ADH3 and retinoic acid are essential for proliferation and survival of hepatic stellate cells in mouse liver SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Jeong, W. I.; Park, O.; Gao, B.] NIAAA, Sect Liver Biol, 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 37A EP 37A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497200106 ER PT J AU Song, BJ Moon, KH Olsson, NU Salem, N AF Song, B. J. Moon, K. -H. Olsson, N. U. Salem, N., Jr. TI Prevention of alcoholic fatty liver and mitochondrial dysfunction in the rat by long-chain polyunsaturated fatty acids SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Song, B. J.; Moon, K. -H.; Olsson, N. U.; Salem, N., Jr.] NIAAA, Lab Membrane Biochem & Biophys, 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 38A EP 38A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497200112 ER PT J AU Gilman, JM Ramchandani, VA Davis, MB Bjork, JM Hommer, DW AF Gilman, J. M. Ramchandani, V. A. Davis, M. B. Bjork, J. M. Hommer, D. W. TI Why we like to drink: An fMRI study of the rewarding and anxiolytic effects of alcohol SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism/International-Society-for-Biomedical-Rese arch-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Gilman, J. M.; Ramchandani, V. A.; Davis, M. B.; Bjork, J. M.; Hommer, D. W.] NIAAA, Lab Clin & Translat Studies, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 52A EP 52A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497200168 ER PT J AU Freeman, RC Falk, DE AF Freeman, R. C. Falk, D. E. TI Changes in HIV-related sexual behaviors among drug-using heavy drinkers following treatment SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 NIAAA, Div Epidemiol & Prevent Res, Bethesda, MD 20892 USA. CSR Inc, Arlington, VA 22201 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 57A EP 57A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497200186 ER PT J AU Yi, H Chen, CM Breslow, RA AF Yi, H. Chen, C. M. Breslow, R. A. TI The association of body weight with alcoholic beverage type and drinking location SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Yi, H.; Chen, C. M.] NIAAA, NIH, CSR Inc, Arlington, VA 22201 USA. [Breslow, R. A.] NIAAA, 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 58A EP 58A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497200192 ER PT J AU Hingson, R Heeren, T Edwards, E Rosenbloom, D AF Hingson, R. Heeren, T. Edwards, E. Rosenbloom, D. TI Early age of drinking onset and involvement in motor vehicle crashes, injuries, and physical fights after drinking compared to when not drinking SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 NIAAA, Bethesda, MD 20892 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02118 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 60A EP 60A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497200199 ER PT J AU Snell, LD Pridzun, L Herion, D Heilig, M Tabakoff, B AF Snell, L. D. Pridzun, L. Herion, D. Heilig, M. Tabakoff, B. TI The mysteries of MAO: Is it really a marker for alcoholism? SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 Lohocla Res Corp, Aurora, CO USA. Univ Colorado, Sch Med, Aurora, CO 80045 USA. NIAAA, Lab Clin & Translat Studies, Bethesda, MD 20892 USA. Mediagnost, Reutlingen, Germany. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 67A EP 67A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497200228 ER PT J AU Lopez-Coleman, N Lindell, SG Schwandt, ML Peele, LN Higley, JD Suomi, SJ Goldman, D Heilig, M Barr, CS AF Lopez-Coleman, N. Lindell, S. G. Schwandt, M. L. Peele, L. N. Higley, J. D. Suomi, S. J. Goldman, D. Heilig, M. Barr, C. S. TI OPRM1 gene variation influences HPA axis responding to stress and alcohol in rhesus macaques SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Lopez-Coleman, N.; Lindell, S. G.; Schwandt, M. L.; Peele, L. N.; Higley, J. D.; Suomi, S. J.; Goldman, D.; Heilig, M.; Barr, C. S.] NIAAA, Lab Clin & Translat Studies, NIH, Poolesville, MD 20842 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 77A EP 77A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497200268 ER PT J AU Cippitelli, A Damadzic, R Hansson, AC Sommer, WH Thorsell, A Heilig, M AF Cippitelli, A. Damadzic, R. Hansson, A. C. Sommer, W. H. Thorsell, A. Heilig, M. TI Role of neuropeptide Y (NPY) in relapse to alcohol-seeking SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Cippitelli, A.; Damadzic, R.; Hansson, A. C.; Sommer, W. H.; Thorsell, A.; Heilig, M.] NIAAA, Lab Clin & Translat Studies, 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 78A EP 78A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497200270 ER PT J AU Jerlhag, E Landgren, S Egecioglu, E Heilig, M Moechars, D Steckler, T Dickson, SL Svensson, L Engel, JA AF Jerlhag, E. Landgren, S. Egecioglu, E. Heilig, M. Moechars, D. Steckler, T. Dickson, S. L. Svensson, L. Engel, J. A. TI The orexigenic peptide ghrelin is involved in mediating the rewarding properties of ethanol SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism/International-Society-for-Biomedical-Rese arch-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Jerlhag, E.; Landgren, S.; Egecioglu, E.; Dickson, S. L.; Svensson, L.; Engel, J. A.] Univ Gothenburg, Inst Neurosci & Physiol, Gothenburg, Sweden. [Heilig, M.] NIAAA, Bethesda, MD USA. [Moechars, D.; Steckler, T.] Johnson & Johnson Pharmaceut Res & Dev, Beerse, Belgium. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 79A EP 79A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497200275 ER PT J AU Sommer, WH Lidstrom, J Rimondini, R Bader, M Heilig, M AF Sommer, W. H. Lidstroem, J. Rimondini, R. Bader, M. Heilig, M. TI Plasticity and impact of the central renin-angiotensin system during development of ethanol dependence SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism/International-Society-for-Biomedical-Rese arch-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 NIAAA, NIH, Lab Clin & Translat Studies, I-40126 Bethesda, MD USA. Univ Bologna, Dept Pharmacol, Bologna, Italy. Max Delbruck Ctr Mol Med, Berlin, Germany. RI Horstmann, Britta/C-2154-2008; Rimondini, Roberto/B-2500-2010 OI Rimondini, Roberto/0000-0003-4099-513X NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 82A EP 82A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497200288 ER PT J AU Chen, YC Holmes, A AF Chen, Yi-Chyan Holmes, Andrew TI Effects of anti-glutamatergic and anti-dopaminergic drugs on sensitivity to ethanol's acute intoxicating effects in mice SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism/International-Society-for-Biomedical-Rese arch-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 NDMC, Dept Psychiat, Tri Serv Gen Hosp, Taipei, 20892, Taiwan. [Chen, Yi-Chyan; Holmes, Andrew] NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 84A EP 84A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497200296 ER PT J AU Xiong, W Lovinger, DM Zhang, L AF Xiong, Wei Lovinger, David M. Zhang, Li TI Involvement of glycine receptors in low dose ethanol-induced incoordination in mice SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Xiong, Wei; Lovinger, David M.; Zhang, Li] NIAAA, Lab Integrat Neurosci, NIH, Bethesda, MD 20892 USA. RI Xiong, Wei/F-8251-2011 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 90A EP 90A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497200320 ER PT J AU Feyder, M Davis, MI Grant, SGN Holmes, A AF Feyder, M. Davis, M. I. Grant, S. G. N. Holmes, A. TI Loss of postsynaptic density-95 (PSD-95) potentiates the sedative/hypnotic effects of ethanol SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 NIAAA, Sect Behav Sci & Genet, LIN, NIH, Rockville, MD USA. Wellcome Trust Sanger Inst, Cambridge, England. RI Davis, Margaret/F-4165-2010 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 91A EP 91A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497200321 ER PT J AU Breslow, RA Juan, W Chen, C Guenther, PM AF Breslow, R. A. Juan, W. Chen, C. Guenther, P. M. TI Alcohol consumption and nutrient intakes: Potential for confounding SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Breslow, R. A.; Juan, W.; Chen, C.; Guenther, P. M.] NIAAA, NIH, Div Epidemiol & Prevent Res, 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 128A EP 128A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497200469 ER PT J AU Yoon, J AF Yoon, J. TI The association between perpetrator substance use and physical injuries among adolescent victims SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Yoon, J.] NIAAA, 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 135A EP 135A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497200497 ER PT J AU Albrecht, A Hodgkinson, CA Shen, PH Ducci, F Yuan, Q White, KV Albaugh, B Goldman, D Enoch, MA AF Albrecht, A. Hodgkinson, C. A. Shen, P-H. Ducci, F. Yuan, Q. White, K. V. Albaugh, B. Goldman, D. Enoch, M-A. TI Genomewide linkage scan for resting EEG phenotypes identifies candidate gene CRH-BP: Association of CRH-BP with alcoholism, anxiety and alpha power SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism/International-Society-for-Biomedical-Rese arch-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Albrecht, A.; Hodgkinson, C. A.; Shen, P-H.; Ducci, F.; Yuan, Q.; White, K. V.; Albaugh, B.; Goldman, D.; Enoch, M-A.] NIAAA, Neurogenet Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 141A EP 141A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497200524 ER PT J AU Bevilacqua, L Hodgkinson, CA Enoch, MA Robin, R Albaugh, B Roy, A Virkunnen, M Ducci, F Goldman, D AF Bevilacqua, L. Hodgkinson, C. A. Enoch, M. A. Robin, R. Albaugh, B. Roy, A. Virkunnen, M. Ducci, F. Goldman, D. TI Influence of opioid genes on vulnerability to alcoholism SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Bevilacqua, L.; Hodgkinson, C. A.; Enoch, M. A.; Robin, R.; Albaugh, B.; Roy, A.; Virkunnen, M.; Ducci, F.; Goldman, D.] NIAAA, Neurogenet Lab, NIH, 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 142A EP 142A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497200526 ER PT J AU Bjork, K Tanda, G Thorsell, A Heilig, M Sommer, WH AF Bjoerk, K. Tanda, G. Thorsell, A. Heilig, M. Sommer, W. H. TI Increased ethanol induced dopamine release and place preference in mice lacking Beta-arrestin 2 SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism/International-Society-for-Biomedical-Rese arch-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Bjoerk, K.; Tanda, G.; Thorsell, A.; Heilig, M.; Sommer, W. H.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD USA. RI Tanda, Gianluigi/B-3318-2009 OI Tanda, Gianluigi/0000-0001-9526-9878 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 145A EP 145A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497200539 ER PT J AU Hodgkinson, C Yuan, QP Xu, K Shen, PH Zhou, ZF Heinz, E Goldman, D AF Hodgkinson, Colin Yuan, Qiaoping Xu, Ke Shen, Pei-hong Zhou, Zhifeng Heinz, Elizabeth Goldman, David TI Addictions biology: A 1536 SNP array for haploype analysis of 130 candidate genes SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism/International-Society-for-Biomedical-Rese arch-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Hodgkinson, Colin; Yuan, Qiaoping; Xu, Ke; Shen, Pei-hong; Zhou, Zhifeng; Heinz, Elizabeth; Goldman, David] NIAAA, Neurogenet Lab, Rockville, MD USA. RI Hodgkinson, Colin/F-9899-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 148A EP 148A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497200549 ER PT J AU Sommer, WH Lidstrom, J Eskay, R Palkovits, M Heilig, M AF Sommer, W. H. Lidstrom, J. Eskay, R. Palkovits, M. Heilig, M. TI Regulation of neuropeptide Y (NPY) gene expression in human anterior cingulate cortex by a common promoter variant SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism/International-Society-for-Biomedical-Rese arch-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 Semmelweis Univ, H-1085 Budapest, Hungary. NIAAA, NIH, Lab Clin & Translat Studies, Bethesda, MD USA. RI Palkovits, Miklos/F-2707-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 149A EP 149A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497200553 ER PT J AU Gawrisch, K AF Gawrisch, K. TI Does ethanol act on proteins like a drug or a solvent? SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Gawrisch, K.] NIAAA, 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 151A EP 151A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497200563 ER PT J AU Niu, SL Greeley, L Mitchell, DC AF Niu, S. L. Greeley, L. Mitchell, D. C. TI Conformational activation and structural stability of a GPCR is modulated by alcohol at the lipid-receptor interface SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Niu, S. L.; Greeley, L.; Mitchell, D. C.] NIAAA, NIH, Lab Membrane Biochem & Biophys, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 151A EP 151A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497200562 ER PT J AU Lovinger, DM Sanghvi, M Hamouda, AK Srivastava, S Davis, MI Morton, R Luo, G Chiara, DC Machu, TK Cohen, JB Blanton, MP AF Lovinger, D. M. Sanghvi, M. Hamouda, A. K. Srivastava, S. Davis, M. I. Morton, R. Luo, G. Chiara, D. C. Machu, T. K. Cohen, J. B. Blanton, M. P. TI Purification and photoaffinity labeling of the 5-HT3A receptor SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 Texas Tech Univ, Hlth Sci Ctr, Lubbock, TX 79430 USA. NIAAA, Bethesda, MD 20852 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ N Texas, Hlth Sci Ctr, Ft Worth, TX 76203 USA. RI Davis, Margaret/F-4165-2010 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 158A EP 158A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497200591 ER PT J AU Schwandt, ML Lindell, SG Suomi, SJ Heilig, M Barr, CS AF Schwandt, M. L. Lindell, S. G. Suomi, S. J. Heilig, M. Barr, C. S. TI Effects of intermittent access to alcohol on voluntary oral consumption in male rhesus macaques (macaca mulatta) SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Schwandt, M. L.; Lindell, S. G.; Suomi, S. J.; Heilig, M.; Barr, C. S.] NIAAA, NIH, LCTS, Poolesville, MD 20837 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 164A EP 164A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497200614 ER PT J AU Hansson, AC Nixon, K Rimondini, R Damadzic, R Sommer, WH Eskay, R Crews, FT Heilig, M AF Hansson, A. C. Nixon, K. Rimondini, R. Damadzic, R. Sommer, W. H. Eskay, R. Crews, F. T. Heilig, M. TI Long-lasting suppression of subventricular zone neurogenesis following a history of ethanol dependence SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism/International-Society-for-Biomedical-Rese arch-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Hansson, A. C.; Damadzic, R.; Sommer, W. H.; Eskay, R.; Heilig, M.] NIAAA, NIH, Bethesda, MD USA. [Nixon, K.] Univ Kentucky, Lexington, KY USA. [Rimondini, R.] Univ Bologna, Bologna, Italy. [Crews, F. T.] Bowles Ctr Alcohol Studies, Chapel Hill, NC USA. RI Rimondini, Roberto/B-2500-2010 OI Rimondini, Roberto/0000-0003-4099-513X NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 168A EP 168A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497200630 ER PT J AU Bloss, G Chen, CM Yi, H AF Bloss, G. Chen, C. M. Yi, H. TI Do uppl laws matter? Effects of changes in maryland's insurance exclusion law on alcohol-induced diagnoses in emergency injury patients, 1999-2004 SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Bloss, G.; Chen, C. M.; Yi, H.] NIAAA, US Dept HHS, NIH, Div Epidemiol & Prevent Res, 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 181A EP 181A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497200684 ER PT J AU Marshall, VJ Ramchandani, VA Kalu, NN Scott, DM Ferguson, CL Taylor, RE AF Marshall, V. J. Ramchandani, V. A. Kalu, N. N. Scott, D. M. Ferguson, C. L. Taylor, R. E. TI Evaluation of the influence of ADH polymorphisms on alcohol elimination rates measured using the alcohol clamp SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 Howard Univ, Alcohol Res Ctr, Washington, DC 20059 USA. NIAAA, 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 210A EP 210A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497200797 ER PT J AU Shen, PH Ducci, F Yuan, Q Enoch, MA Hodgkinson, CA Goldman, D AF Shen, P. -H. Ducci, F. Yuan, Q. Enoch, M. -A. Hodgkinson, C. A. Goldman, D. TI The use of individual ethnic factor scores to evaluate population stratification in association SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Shen, P. -H.; Ducci, F.; Yuan, Q.; Enoch, M. -A.; Hodgkinson, C. A.; Goldman, D.] NIAAA, Neurogenet Lab, 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 210A EP 210A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497200799 ER PT J AU Talani, G Lovinger, DM AF Talani, G. Lovinger, D. M. TI Ethanol and endocannabinoid interactions in the control of GABA release in rat basolateral amygdala SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Talani, G.; Lovinger, D. M.] NIAAA, Sect Synapt Pharmacol, Lab Integrat Neuroscience, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 212A EP 212A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497200808 ER PT J AU Thanos, PK Hwang, YF Michaelides, M Patel, U Rice, O Jayne, M Shea, C Fowler, JS Wang, GJ Volkow, ND AF Thanos, P. K. Hwang, Y. F. Michaelides, M. Patel, U. Rice, O. Jayne, M. Shea, C. Fowler, J. S. Wang, G. J. Volkow, N. D. TI Brain glucose metabolism and dopamine D2 receptor availability following acute ethanol binge drinking in rats SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism/International-Society-for-Biomedical-Rese arch-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 Brookhaven Natl Lab, Upton, NY 11973 USA. NIAAA, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. Furman Univ, Dept Psychol, Greenville, SC 29613 USA. RI Michaelides, Michael/K-4736-2013 OI Michaelides, Michael/0000-0003-0398-4917 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 214A EP 214A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497200816 ER PT J AU Thanos, PK Subramani, S Ramalhete, RC Piyis, YK Henn, F Wang, GJ Volkow, ND AF Thanos, P. K. Subramani, S. Ramalhete, R. C. Piyis, Y. K. Henn, F. Wang, G. J. Volkow, N. D. TI The effects of chronic mild stress (CMS) and ethanol intake on D2R binding levels in a rodent model of depression SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism/International-Society-for-Biomedical-Rese arch-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 Brookhaven Natl Lab, Upton, NY 11973 USA. NIAAA, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 214A EP 214A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497200815 ER PT J AU Harford, TC Yi, H AF Harford, T. C. Yi, H. TI The 5-year diagnostic utility of "diagnostic orphans'' in a national sample of young adults SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 NIAAA, Alcohol Epidemiol Data System, NIH, CSR Inc, Arlington, VA 22201 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 263A EP 263A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497201010 ER PT J AU Moss, HB Chen, CM Yi, H AF Moss, H. B. Chen, C. M. Yi, H. TI The structural relationship between compulsive gambling and alcohol and drug use disorders in a general population sample SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Moss, H. B.] NIAAA, Bethesda, MD 20892 USA. [Chen, C. M.; Yi, H.] CSR Inc, Alcohol Epidemiol Data Syst, Arlington, VA 22201 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 264A EP 264A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497201015 ER PT J AU Grant, B AF Grant, B. TI First incidence of DSM-IV alcohol, drug, and psychiatric disorders: Results from NESARC, Wave 2 SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism/International-Society-for-Biomedical-Rese arch-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Grant, B.] NIAAA, Div Intramural Clin & Biol Res, NIH, Lab Epidemiol & Biometry, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 274A EP 274A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497201045 ER PT J AU Horiguchi, N Gao, B AF Horiguchi, N. Gao, B. TI Differential role of cell-specific STAT3 in alcohol-induced liver inflammation SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Horiguchi, N.; Gao, B.] NIAAA, NIH, Sect Liver Biol, 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 275A EP 275A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497201050 ER PT J AU Zhang, XY Tachibana, S Wang, H Gao, B Williams, GM Sun, ZL AF Zhang, Xiuying Tachibana, Shingo Wang, Hua Gao, Bin Williams, George Melville Sun, Zhaoli TI Alcohol induced mitochondria DNA damage and repair: Role of interleukin-6 SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21205 USA. NIAAA, NIH, Sect Liver Biol, Rockville, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 275A EP 275A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497201049 ER PT J AU Barr, CS Schwandt, ML Lindell, SG Higley, JD Goldman, D Heilig, M AF Barr, C. S. Schwandt, M. L. Lindell, S. G. Higley, J. D. Goldman, D. Heilig, M. TI Variations in behavioral responses to binge doses of alcohol as they relate to variants of 5HTT and OPRM1 loci in rhesus macaques SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism/International-Society-for-Biomedical-Rese arch-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 Brigham Young Univ, Dept Psycho, Provo, UT 84602 USA. NIAAA, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 288A EP 288A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497201101 ER PT J AU Rodd, ZA Bell, RL Oster, SM Ding, ZM Engleman, EA Li, TK McBride, WJ AF Rodd, Zachary A. Bell, Richard L. Oster, Scott M. Ding, Zheng-Ming Engleman, Eric A. Li, Ting-Kai McBride, William J. TI The reinforcing properties of ethanol, acetaldehyde and salsolinol in the mesolimbic dopamine system SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 Indiana Univ, Sch Med, Dept Psychiat, Bloomington, IN 47405 USA. NIAAA, Bethesda, MD 20892 USA. RI Rodd, Zachary/L-1580-2015 OI Rodd, Zachary/0000-0002-8105-1920 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 289A EP 289A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497201107 ER PT J AU Goldman, D AF Goldman, D. TI Ethical implications and safeguards for administration of alcohol, alcohol-related cues and drugs that may trigger relapse or drinking in alcoholics SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Goldman, D.] NIAAA, NIH, Neurogenet Lab, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 291A EP 291A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497201114 ER PT J AU Moss, HB AF Moss, Howard B. TI Can parsing the heterogeneity of alcoholism alter risk considerations in research? SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Moss, Howard B.] NIAAA, Off Director, 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 291A EP 291A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497201113 ER PT J AU George, DT AF George, D. T. TI Clinical safeguards for the administration of alcohol to treatment seeking alcoholics SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [George, D. T.] NIAAA, NIH, Lab Clin & Translat Studies, 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 292A EP 292A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497201118 ER PT J AU Johnson, KP AF Johnson, K. P. TI A lay person's perspective on alcoholism research SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Johnson, K. P.] NIH, Neurosci Inst Review Board, 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 292A EP 292A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497201117 ER PT J AU Shippenberg, TS Zapata, A Chefer, VI AF Shippenberg, T. S. Zapata, A. Chefer, V. I. TI Role of dynorphin/kappa opioid receptor systems in the pathophysiology of alcohol and drug addiction SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism/International-Society-for-Biomedical-Rese arch-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Shippenberg, T. S.; Zapata, A.; Chefer, V. I.] NIDA, DHHS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 306A EP 306A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497201175 ER PT J AU Spong, CY Toso, L Roberson, R Vink, J Abebe, DT AF Spong, C. Y. Toso, L. Roberson, R. Vink, J. Abebe, D. T. TI Prevention of alcohol-induced damage in fetal alcohol syndrome with NAP and SAL SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 NICHD, NIH, Bethesda, MD 20892 USA. NIAAA, 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 314A EP 314A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497201208 ER PT J AU Goldstein, RB Dawson, DA Grant, BF AF Goldstein, R. B. Dawson, D. A. Grant, B. F. TI Gender and alcohol use disorders in the US: Findings from the national epidemiologic survey on alcohol and related conditions (NESARC) SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism/International-Society-for-Biomedical-Rese arch-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Goldstein, R. B.; Dawson, D. A.; Grant, B. F.] NIAAA, Lab Epidemiol & Biometr, Div Intramural Clin & Biol Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 316A EP 316A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497201214 ER PT J AU Sommer, WH Bjorck, K Hansson, AC Thorsell, A Rimondini, R Tanda, G Hyytia, P Heilig, M AF Sommer, W. H. Bjoerck, K. Hansson, A. C. Thorsell, A. Rimondini, R. Tanda, G. Hyytiae, P. Heilig, M. TI Modulation of voluntary ethanol consumption by beta-arrestin 2 SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism/International-Society-for-Biomedical-Rese arch-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Sommer, W. H.; Bjoerck, K.; Hansson, A. C.; Thorsell, A.; Rimondini, R.; Tanda, G.; Hyytiae, P.; Heilig, M.] NIAAA, Lab Clin & TRanslat Studies, NIH, Bethesda, MD 20892 USA. RI Tanda, Gianluigi/B-3318-2009; Rimondini, Roberto/B-2500-2010 OI Tanda, Gianluigi/0000-0001-9526-9878; Rimondini, Roberto/0000-0003-4099-513X NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 317A EP 317A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497201219 ER PT J AU Ducci, F Enoch, MA Yuan, Q Shen, PH White, K Hodgkinson, C Albaugh, B Virkkunen, M Goldman, D AF Ducci, F. Enoch, M. A. Yuan, Q. Shen, P. H. White, K. Hodgkinson, C. Albaugh, B. Virkkunen, M. Goldman, D. TI Serotonin genes and alcoholism with antisocial features SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism/International-Society-for-Biomedical-Rese arch-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Ducci, F.; Enoch, M. A.; Yuan, Q.; Shen, P. H.; White, K.; Hodgkinson, C.; Albaugh, B.; Virkkunen, M.; Goldman, D.] NIAAA, Neurogenet Lab, Bethesda, MD USA. RI Hodgkinson, Colin/F-9899-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 318A EP 318A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497201224 ER PT J AU Heilig, M Hansson, A Thorsell, A Cippitelli, A Rimondini, R Sommer, W AF Heilig, M. Hansson, A. Thorsell, A. Cippitelli, A. Rimondini, R. Sommer, W. TI Modelling the dark-side of alcoholism: Implications for medications development SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Heilig, M.; Hansson, A.; Thorsell, A.; Cippitelli, A.; Sommer, W.] NIAAA, LCTS, Bethesda, MD 20892 USA. [Rimondini, R.] Univ Bologna, Bologna, Italy. [Heilig, M.] Karolinska Inst, Stockholm, Sweden. RI Rimondini, Roberto/B-2500-2010 OI Rimondini, Roberto/0000-0003-4099-513X 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 318A EP 318A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497201221 ER PT J AU Enoch, MA Schwartz, LS Yuan, Q Hodgkinson, C Albaugh, B Virkkunen, M Roy, A Goldman, D AF Enoch, M. A. Schwartz, L. S. Yuan, Q. Hodgkinson, C. Albaugh, B. Virkkunen, M. Roy, A. Goldman, D. TI Adjacent GABAA receptor genes, GABRA2 and GABRG1, appear to be independent risk factors for alcoholism SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism/International-Society-for-Biomedical-Rese arch-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Enoch, M. A.; Schwartz, L. S.; Yuan, Q.; Hodgkinson, C.; Albaugh, B.; Virkkunen, M.; Roy, A.; Goldman, D.] NIAAA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RI Hodgkinson, Colin/F-9899-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 319A EP 319A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497201226 ER PT J AU Heilig, M AF Heilig, Markus TI Acute withdrawal, protracted abstinence, and reward allostasis: Are they linked? SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Heilig, Markus] NIAAA, Lab Clin & Translat Studies, Intramural Program, 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 334A EP 334A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497201288 ER PT J AU Marietta, CA Brooks, PJ AF Marietta, C. A. Brooks, P. J. TI DNA repair and DNA damage response pathways for acetaldehyde-derived DNA lesions SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Marietta, C. A.; Brooks, P. J.] NIAAA, Neurogenet Lab, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 340A EP 340A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497201311 ER PT J AU George, DT Gilman, J Hersh, J Thorsell, A Gehlert, DR Tauscher, JT Hunt, SP Hommer, D Heilig, M AF George, D. T. Gilman, J. Hersh, J. Thorsell, A. Gehlert, D. R. Tauscher, J. T. Hunt, S. P. Hommer, D. Heilig, Markus TI Neurokinin 1 (NK1) receptor blockade: A novel anti-stress based mechanisms for treatment of alcoholism SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism/International-Society-for-Biomedical-Rese arch-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [George, D. T.; Gilman, J.; Hersh, J.; Thorsell, A.; Hommer, D.; Heilig, Markus] NIAAA, LCTS, Bethesda, MD USA. [Gehlert, D. R.; Tauscher, J. T.] Lilly Res Labs, Indianapolis, IN USA. [Hunt, S. P.] UCL, London, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 342A EP 342A PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497201317 ER PT J AU France, CP Unzeitig, A Javors, MA Rice, KC Li, JX AF France, Charles P. Unzeitig, Alison Javors, Martin A. Rice, Kenner C. Li, Jun-Xu TI Is there behavioral evidence for constitutive activity at 5-HT2A receptors? SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT Joint Scientific Meeting of the Research-Society-on-Alcoholism and the International-Society-for-Biomedical-Research-on-Alcoholism CY JUN 27-JUL 02, 2008 CL Washington, DC SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [France, Charles P.; Unzeitig, Alison; Li, Jun-Xu] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, Bethesda, MD USA. [Javors, Martin A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, Bethesda, MD USA. [Rice, Kenner C.] Natl Inst Drug Abuse, Chem Biol Res Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 SU 1 BP 367A EP 367A DI 10.1111/j.1530-0277.2008.00689_2.x PG 1 WC Substance Abuse SC Substance Abuse GA 309YX UT WOS:000256497201331 ER PT J AU Perrino, AC Ralevski, E Acampora, G Edgecombe, J Limoncelli, D Petrakis, IL AF Perrino, Albert C., Jr. Ralevski, Elizabeth Acampora, Gregory Edgecombe, Javon Limoncelli, Diana Petrakis, Ismene L. TI Ethanol and pain sensitivity: Effects in healthy subjects using an acute pain paradigm SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE ethanol; analgesia; pain; alcoholism; vulnerability; family history ID ETHYL-ALCOHOL; RISK; RECEPTORS; MECHANISMS; EXPERIENCE; THRESHOLD; BRAC; SONS; MEN AB Background: The primary objective of this study was to determine whether healthy subjects without a history of heavy alcohol use or a family history of alcoholism exhibit a concentration-dependent analgesic effect of ethanol. In a preliminary fashion, we also compared this sample to a group of subjects with a strong positive family history for alcoholism (FHP) to test the secondary hypothesis that FHP individuals will be more sensitive to the analgesic effects of alcohol compared to healthy subjects who are negative for a family history of alcoholism (FHN). Methods: Forty-one healthy FHN subjects and 19 FHP subjects participated. Test days included an ethanol high concentration (breathalyzer = 0.100 g/dl), ethanol low concentration (breathalyzer = 0.040 g/dl) or placebo. The infusion of ethanol was via computerized pump to achieve a steady-state ("clamp") ethanol concentration. Noxious electrical stimulation and pain assessments were performed prior to start of placebo/ethanol infusion and at the 60-min infusion mark. The applied current was progressively increased until the pain was reported as 5 or higher on an 11-point Verbal Numeric Scale (VNS). Outcome variables included measures of pain threshold and tolerance and Visual Analog Scales of mood states. Results: Among FHN subjects there was a significant ethanol concentration effect on pain tolerance (F = 3.0, p = 0.05). The average change in pain stimuli required to reach a VNS of 5 or greater were (-2.4, -1.0, and 2.2 mAmps respectively) for high concentration, low concentration, and placebo. There were no ethanol concentration related differences in pain threshold. The analgesic effect of ethanol was not correlated with changes in mood states, suggesting an independent analgesic effect of the drug. A comparison of FHP to FHN subjects produced no differences on pain responses. Conclusion: The findings support the hypothesis that in healthy subjects intravenous ethanol administration has a concentration effect on pain tolerance but not on pain threshold. Additional studies are planned to further elucidate the mechanisms of ethanol's analgesic effects. C1 [Perrino, Albert C., Jr.] Yale Univ, Sch Med, Dept Anesthesiol, New Haven, CT 06510 USA. [Ralevski, Elizabeth; Acampora, Gregory; Edgecombe, Javon; Limoncelli, Diana; Petrakis, Ismene L.] VA Connecticut Healthcare Syst, Dept Vet Affairs, Alcohol Res Ctr, West Haven, CT USA. [Perrino, Albert C., Jr.; Ralevski, Elizabeth; Acampora, Gregory; Edgecombe, Javon; Limoncelli, Diana; Petrakis, Ismene L.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06510 USA. [Perrino, Albert C., Jr.; Ralevski, Elizabeth; Acampora, Gregory; Edgecombe, Javon; Limoncelli, Diana; Petrakis, Ismene L.] Yale Univ, Sch Med, NIAAA, Ctr Translat Neurosci Alcoholism, New Haven, CT 06510 USA. RP Perrino, AC (reprint author), Yale Univ, Sch Med, Dept Anesthesiol, 333 Cedar St T-3, New Haven, CT 06510 USA. EM albert.perrino@yale.edu FU NIAAA NIH HHS [2P50-AA012870-07] NR 33 TC 24 Z9 24 U1 3 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2008 VL 32 IS 6 BP 952 EP 958 DI 10.1111/j.1530-0277.2008.00653.x PG 7 WC Substance Abuse SC Substance Abuse GA 304NQ UT WOS:000256116600006 PM 18445106 ER PT J AU Shah, S AF Shah, Seema TI How lethal injection reform constitutes impermissible research on prisoners SO AMERICAN CRIMINAL LAW REVIEW LA English DT Article ID QUALITY IMPROVEMENT; MEDICINE AB This Article exposes how recent attempts at lethal injection reform have involved unethical and illegal research on prisoners. States are varying the doses and types of drugs used, developing methods designedfor non-medical professionals to administer medical procedures, and gathering data or making provisions for the gathering of data to learn from executions gone wrong. When individual prisoners are executed under these conditions, states are conducting research on them. Conducting research or experimentation on prisoners in the process of reform is problematic because it violates state laws and ethical principles. The Supreme Court has recently taken up the challenge of elucidating the standard for determining the constitutionality of lethal injection. The Court's fractured decision suggests that states may need to conduct lethal injection reform to develop procedures substantially similar to those used in Kentucky. It follows that the Court's decision may lead states to contravene state laws or ethical precepts regarding research with prisoners. Thus, this Article provides important limitations on the kinds of reform that may be permissible and outlines the open questions that must be addressed before it can be determined whether the risks and uncertainties involved in lethal injection can be remedied C1 [Shah, Seema] NIH, Dept Bioeth, Bethesda, MD 20892 USA. [Shah, Seema] Stanford Univ, Sch Law, Stanford, CA 94305 USA. RP Shah, S (reprint author), NIH, Dept Bioeth, Bethesda, MD 20892 USA. NR 55 TC 6 Z9 6 U1 1 U2 1 PU AMER CRIMINAL LAW REVIEW PI WASHINGTON PA GEORGETOWN UNIV LAW CTR 600 NEW JERSEY AVE NW, WASHINGTON, DC 20001 USA SN 0164-0364 J9 AM CRIM LAW REV JI Am. Crim. Law Rev. PD SUM PY 2008 VL 45 IS 3 BP 1101 EP 1147 PG 47 WC Law SC Government & Law GA 311FD UT WOS:000256585200002 ER PT J AU Pianta, RC Belsky, J Vandergrift, N Houts, R Morrison, FJ AF Pianta, Robert C. Belsky, Jay Vandergrift, Nathan Houts, Renate Morrison, Fred J. TI Classroom effects on children's achievement trajectories in elementary school SO AMERICAN EDUCATIONAL RESEARCH JOURNAL LA English DT Article DE elementary achievement; teacher-child interactions; classroom effects ID TEACHER RELATIONSHIPS; KINDERGARTEN; ADOLESCENTS; QUALITY; RISK; OPPORTUNITIES; CONNECTION; ENGAGEMENT; PREVENTION; DIFFERENCE AB This nonexperimental, longitudinal field study examines the extent to which variation in observed classroom supports (quality of emotional and instructional interactions and amount of exposure to literacy and math activities) predicts trajectories of achievement in reading and math from 54 months to fifth grade. Growth mixture modeling detected two latent classes of readers: fast readers whose skills developed rapidly and leveled off, and a typical group for which reading growth was somewhat less rapid. Only one latent class was identified for math achievement. For reading, there were small positive associations between observed emotional quality of teacher-child interactions and growth. Growth in math achievement showed small positive relations with observed emotional interactions and exposure to math activities. There was a significant interaction between quality and quantity of instruction for reading such that at higher levels of emotional quality there was less of a negative association between amount of literacy exposure and reading growth. C1 [Pianta, Robert C.] Univ Virginia, Ctr Adv Study Teaching & Learning, Charlottesville, VA 22903 USA. [Belsky, Jay] Univ London Birkbeck Coll, Inst Study Children Families & Social Issues, London WC1B 3RA, England. [Vandergrift, Nathan] Univ N Carolina, Frank Porter Graham Child Dev Inst, Chapel Hill, NC 27599 USA. [Houts, Renate] RTI Int, Res Triangle Pk, NC 27709 USA. [Morrison, Fred J.] Univ Michigan, NICHHD, Early Child Care Res Network, Ctr Human Growth & Dev, Ann Arbor, MI 48109 USA. RP Pianta, RC (reprint author), Univ Virginia, Ctr Adv Study Teaching & Learning, 350 Old Ivy Way, Charlottesville, VA 22903 USA. EM pianta@virginia.edu; j.belsky@bbk.ac.uk; vanderg@unc.edu; rhouts@rti.org; fjmorris@umicb.edu RI Marshall, Nancy/C-3428-2012; OI Belsky, Jay/0000-0003-2191-2503; Pianta, Robert/0000-0002-6280-8051 NR 70 TC 129 Z9 132 U1 3 U2 26 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0002-8312 J9 AM EDUC RES J JI Am. Educ. Res. J. PD JUN PY 2008 VL 45 IS 2 BP 365 EP 397 DI 10.3102/0002831207308230 PG 33 WC Education & Educational Research SC Education & Educational Research GA 305CG UT WOS:000256154800005 ER PT J AU Bray, PF Larson, JC LaCroix, AZ Manson, J Limacher, MC Rossouw, JE Lasser, NL Lawson, WE Stefanick, ML Langer, RD Margolis, KL AF Bray, Paul F. Larson, Joseph C. LaCroix, Andrea Z. Manson, JoAnn Limacher, Marian C. Rossouw, Jacques E. Lasser, Norman L. Lawson, William E. Stefanick, Marcia L. Langer, Robert D. Margolis, Karen L. CA Womens Hlth Initiative Investigato TI Usefulness of baseline lipids and C-reactive protein in women receiving menopausal hormone therapy as predictors of treatment-related coronary events SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; ESTROGEN PLUS PROGESTIN; HEART-DISEASE; POSTMENOPAUSAL WOMEN; RISK AB Blood lipids and high-sensitivity C-reactive protein (hs-CRP) are altered by hormone therapy. The goal of the present study was to determine whether lipids and hs-CRP have predictive value for hormone therapy benefit or risk for coronary heart disease events in postmenopausal women without previous cardiovascular disease. A nested case-control study was performed in the Women's Health Initiative hormone trials. Baseline lipids and hs-CRP were obtained from 271 incident patients with coronary heart disease (cases) and 707 controls. In a combined trial analysis, favorable lipid status at baseline tended to predict better coronary heart disease outcomes when using conjugated equine estrogen (CEE) with or without medroxyprogesterone acetate (MPA). Women with a low-density lipoprotein (LDL)/high-density lipoprotein (HDL) cholesterol ratio < 2.5 had no increase in risk of coronary heart disease when using CEE with or without MPA (odds ratio 0.60, 95% confidence interval 0.34 to 1.06), whereas women with an LDL/HDL cholesterol ratio >= 2.5 had increased risk of coronary heart disease (odds ratio 1.73, 95% confidence interval 1.18 to 2.53, p for interaction = 0.02). Low hs-CRP added marginally to the value of LDL/HDL ratio < 2.5 when predicting coronary heart disease benefit on hormone therapy. In conclusion, postmenopausal women with undesirable lipid levels had excess coronary heart disease risk when using CEE with or without MPA. However, women with favorable lipid levels, especially LDL/HDL cholesterol ratio < 2.5, did not have increased risk of coronary heart disease with CEE with or without MPA irrespective of hs-CRP. (c) 2008 Elsevier Inc. All rights reserved. C1 [Bray, Paul F.] Thomas Jefferson Univ, Cardeza Fdn Hematol Res, Philadelphia, PA 19107 USA. [Bray, Paul F.] Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA. [Larson, Joseph C.; LaCroix, Andrea Z.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Manson, JoAnn] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Limacher, Marian C.] Univ Florida, Gainesville, FL USA. [Manson, JoAnn] NHLBI, Program Off, Bethesda, MD 20892 USA. [Lasser, Norman L.] Univ Med & Dent New Jersey, New Jersey Med Sch, Prevent Cardiol Program, Newark, NJ 07103 USA. [Lawson, William E.] SUNY, Div Cardiovasc Med, Stoney Brook, NY USA. [Stefanick, Marcia L.] Stanford Univ, Stanford Ctr Res Dis Prevent, Palo Alto, CA 94304 USA. [Langer, Robert D.] Geisinger Ctr Hlth Res, Danville, PA USA. [Margolis, Karen L.] Univ Minnesota, Minneapolis, MN USA. RP Bray, PF (reprint author), Thomas Jefferson Univ, Cardeza Fdn Hematol Res, Philadelphia, PA 19107 USA. EM paul.bray@jefferson.edu FU WHI NIH HHS [N01 WH022110, N01 WH022110-024] NR 14 TC 33 Z9 34 U1 1 U2 3 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUN 1 PY 2008 VL 101 IS 11 BP 1599 EP 1605 DI 10.1016/j.amjcard.2008.01.043 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 309HG UT WOS:000256450700011 PM 18489937 ER PT J AU Lewis, GD Gona, P Larson, MG Plehn, JF Benjamin, EJ O'Donnell, CJ Levy, D Vasan, RS Wang, TJ AF Lewis, Gregory D. Gona, Philimon Larson, Martin G. Plehn, Jonathan F. Benjamin, Emelia J. O'Donnell, Christopher J. Levy, Daniel Vasan, Ramachandran S. Wang, Thomas J. TI Exercise blood pressure and the risk of incident cardiovascular disease (from the Framingham Heart Study) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CORONARY-ARTERY-DISEASE; MIDDLE-AGED MEN; PROGNOSTIC-SIGNIFICANCE; RATE RECOVERY; HEALTHY-SUBJECTS; GRADED-EXERCISE; MORTALITY; HYPERTENSION AB Exaggerated systolic blood pressure (BP) augmentation with exercise has been associated with impaired endothelial function and cardiovascular risk. However, previous studies were largely restricted to men, did not evaluate diastolic BP, and focused on peak exercise measures, which are influenced by effort and fitness level. The aim of this study was to determine the association of exercise BP responses with risk of incident cardiovascular disease (CVD). BP was assessed during stage 2 of the Bruce protocol and during recovery in 3,045 Framingham Study subjects (mean age 43 years; 53% women). The association between exercise BP and CVD events during 20 years of follow-up was examined using Cox proportional hazards models. In age- and sex-adjusted analyses, exercise systolic and diastolic BP were associated with incident CVD (adjusted hazard ratios [HRs] for top quintile 1.55, 95% confidence interval [CI] 1.18 to 2.04; and 1.77, 95% CI 1.35 to 2.31, respectively, relative to the lower 4 quintiles; p < 0.005). After adjustment for BP at rest and conventional risk factors, exercise diastolic BP (HR 1.41, 95% CI 1.01 to 1.95, p = 0.04), but not exercise systolic BP (HR 0.97, 95% CI 0.68 to 1.38, p = 0.86), remained a significant predictor of CVD. Similarly, in recovery responses after exercise, only diastolic BP (HR 1.53, 95% CI 1.08 to 2.18, p = 0.02) predicted incident CVD in multivariable models. In conclusion, in middle-aged adults, diastolic BP during low-intensity exercise and recovery predicted incident CVD. Our findings support the concept that dynamic BP provides incremental information to BP at rest and suggest that exercise diastolic BP may be a better predictor than exercise systolic BP in this age group. (c) 2008 Elsevier Inc. All rights reserved. C1 [Lewis, Gregory D.; O'Donnell, Christopher J.; Wang, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiol Div, Boston, MA 02115 USA. [Gona, Philimon; Larson, Martin G.; Benjamin, Emelia J.; O'Donnell, Christopher J.; Levy, Daniel; Vasan, Ramachandran S.; Wang, Thomas J.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Gona, Philimon; Larson, Martin G.] Boston Univ, Sch Med, Dept Math & Stat, Boston, MA 02118 USA. [Benjamin, Emelia J.; Levy, Daniel; Vasan, Ramachandran S.] Boston Univ, Sch Med, Epidemiol Sect, Boston, MA 02118 USA. [Benjamin, Emelia J.; Levy, Daniel; Vasan, Ramachandran S.] Boston Univ, Sch Med, Sect Prevent Med, Boston, MA 02118 USA. [Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA. [Plehn, Jonathan F.; O'Donnell, Christopher J.; Levy, Daniel] NHLBI, Bethesda, MD 20892 USA. RP Wang, TJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiol Div, Boston, MA 02115 USA. EM tjwang@partners.org OI Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [K24 HL004334-08, K23 HL074077, K23 HL074077-05, K23-HL074077, K24 HL004334, K24-HL-04334, N01-HC-25195, N01HC25195, R01-HC-25195] NR 30 TC 45 Z9 47 U1 0 U2 2 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUN 1 PY 2008 VL 101 IS 11 BP 1614 EP 1620 DI 10.1016/j.amjcard.2008.01.046 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 309HG UT WOS:000256450700013 PM 18489939 ER PT J AU Mehta, S Manji, KP Young, AM Brown, ER Chasela, C Taha, ET Read, JS Goldenberg, RL Fawzi, WW AF Mehta, Saurabh Manji, Karim P. Young, Alicia M. Brown, Elizabeth R. Chasela, Charles Taha, Taha E. Read, Jennifer S. Goldenberg, Robert L. Fawzi, Wafaie W. TI Nutritional indicators of adverse pregnancy outcomes and mother-to-child transmission of HIV among HIV-infected women SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; BODY-MASS INDEX; LOW-BIRTH-WEIGHT; HIV-1-INFECTED WOMEN; MATERNAL WEIGHT; RANDOMIZED-TRIAL; 3RD TRIMESTER; PRETERM BIRTH; CHINESE WOMEN; ANEMIA AB Background: Poor nutrition may be associated with mother-to-child transmission (MTCT) of HIV and other adverse pregnancy outcomes. Objective: The objective was to examine the relation of nutritional indicators with adverse pregnancy outcomes among HIV-infected women in Tanzania, Zambia, and Malawi. Design: Body mass index (BMI; in kg/m(2)) and hemoglobin concentrations at enrollment and weight change during pregnancy were prospectively related to fetal loss, neonatal death, low birth weight, preterm birth, and MTCT of HIV. Results: In a multivariate analysis, having a BMI < 21.8 was significantly associated with preterm birth [odds ratio (OR): 1.82; 95% Cl: 1.34, 2.46] and low birth weight (OR: 2.09; 95% CI: 1.41, 3.08). A U-shaped relation between weight change during pregnancy and preterm birth was observed. Severe anemia was significantly associated with fetal loss or stillbirth (OR: 3.67; 95% Cl: 1.16, 11.66), preterm birth (OR: 2.08; 95% CI: 1.39, 3. 10), low birth weight (OR: 1.76; 95% Cl: 1.07, 2.90), and MTCT of HIV by the time of birth (OR: 2.26;95%CI: 1.18,4.34) and by 4-6 wk among those negative at birth (OR: 2.33; 95% CI: 1.15, 4.73). Conclusions: Anemia, poor weight gain during pregnancy, and low BMI in HIV-infected pregnant women are associated with increased risks of adverse infant outcomes and MTCT of HIV. Interventions that reduce the risk of wasting or anemia during pregnancy should be evaluated to determine their possible effect on the incidence of adverse pregnancy outcomes and MTCT of HIV. C1 [Mehta, Saurabh; Fawzi, Wafaie W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Manji, Karim P.] Muhimbili Univ, Coll Hlth Sci, Dept Pediat, Dar Es Salaam, Tanzania. [Young, Alicia M.; Brown, Elizabeth R.] Fred Hutchinson Canc Res Ctr, Stat Ctr HIV AIDS Res & Prevent, Seattle, WA 98104 USA. [Chasela, Charles] Univ N Carolina Project, Lilongwe, Malawi. [Taha, Taha E.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Read, Jennifer S.] NICHD, Pediat Adolescent & Maternal AIDS Branch, NIH, DHHS, Bethesda, MD USA. [Goldenberg, Robert L.] Drexel Univ, Coll Med, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. RP Mehta, S (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 655 Huntington Ave, Boston, MA 02115 USA. EM smehta@hsph.harvard.edu RI Brown, Elizabeth/A-8984-2008; Mehta, Saurabh/A-7874-2009 FU NIAID NIH HHS [U01 AI048006, N01-AI-035173-412, N01-AI-035173-117, N01-AI-035173, N01 AI045200, N01 AI035173, N01-AI-045200, U01-AI-048005, U01-AI-047972, U01 AI048005, U01 AI047972, U01-AI-048006, U01 AI048006-01] NR 65 TC 23 Z9 25 U1 0 U2 5 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUN PY 2008 VL 87 IS 6 BP 1639 EP 1649 PG 11 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 313ET UT WOS:000256724600010 PM 18541551 ER PT J AU Walshe, JM Gal, A Murray, DR Premkumar, A Berman, D Hassan, R AF Walshe, Janice M. Gal, Anthony Murray, Douglas R. Premkumar, Ahalya Berman, David Hassan, Raffit TI Malignant mesothelioma of the inguinal canal with an unusually long survival SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article DE mesothelioma; inguinal canal; processus vaginalis C1 [Walshe, Janice M.; Premkumar, Ahalya; Berman, David; Hassan, Raffit] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Gal, Anthony] Emory Univ, Dept Pathol, Atlanta, GA 30322 USA. [Murray, Douglas R.] Emory Univ, Dept Surg, Atlanta, GA 30322 USA. RP Hassan, R (reprint author), NCI, Mol Biol Lab, NIH, 37 Convent Dr,Rm 5116, Bethesda, MD 20892 USA. EM hassanr@mail.nih.gov FU Intramural NIH HHS NR 4 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3732 J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD JUN PY 2008 VL 31 IS 3 BP 306 EP 307 DI 10.1097/01.coc.0000204404.36736.69 PG 2 WC Oncology SC Oncology GA 312CV UT WOS:000256647600017 PM 18525312 ER PT J AU Fang, F Kamel, F Sandler, DP Sparen, P Ye, WM AF Fang, Fang Kamel, Freya Sandler, Dale P. Sparen, Par Ye, Weimin TI Maternal age, exposure to siblings, and risk of amyotrophic lateral sclerosis SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE amyotrophic lateral sclerosis; maternal age; risk; siblings ID MOTOR-NEURON DISEASE; OUTCOMES; SWEDEN AB Between 1987 and 2005, the authors conducted a nested case-control study based on the Swedish Multi-Generation Register to investigate whether early life exposures, namely, maternal age at delivery and exposure to siblings, are associated with an increased risk of amyotrophic lateral sclerosis (ALS). The study comprised 768 ALS cases and five controls per case matched by birth year and gender. Odds ratios and their corresponding 95% confidence intervals for ALS were estimated by conditional logistic regression modeling. Low maternal age (<= 20 years) and high maternal age (>= 41 years) were both associated with higher risk of ALS (odds ratio (OR) = 1.5, 95% confidence interval (CI): 1.1, 2.0 and OR = 1.7, 95% CI: 1.1, 2.4, respectively). The relative risk of ALS increased slightly with increasing number of younger siblings (OR = 1.1, 95% CI: 1.0, 1.1; p = 0.02). Children whose first younger sibling was born after the age of 6 years had the greatest relative risk (OR = 1.8, 95% CI: 1.2, 2.7). Exposure to older siblings was not associated with the risk of ALS. Although the strength of the observed associations was modest, these results provided further support for the theory that early life exposures might contribute to the disease pathogenesis. C1 [Fang, Fang; Sparen, Par; Ye, Weimin] Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden. [Kamel, Freya] Natl Inst Hlth, Natl Inst Environm Hlth Sci, US Dept HHS, Res Triangle Pk, NC USA. RP Fang, F (reprint author), Karolinska Inst, Dept Med Epidemiol & Biostat, Box 281, S-17177 Stockholm, Sweden. EM fang.fang@ki.se RI Ye, Weimin/A-5939-2008; OI Fang, Fang/0000-0002-3310-6456; Kamel, Freya/0000-0001-5052-6615; Sandler, Dale/0000-0002-6776-0018 FU Intramural NIH HHS [Z01 ES049005-16] NR 18 TC 11 Z9 11 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2008 VL 167 IS 11 BP 1281 EP 1286 DI 10.1093/aje/kwn056 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 305HO UT WOS:000256169100003 PM 18367467 ER PT J AU Zhang, Y De Sanjose, S Bracci, PM Morton, LM Wang, R Brennan, P Hartge, P Boffetta, P Becker, N Maynadie, M Foretova, L Cocco, P Staines, A Holford, T Holly, EA Nieters, A Benavente, Y Bernstein, L Zahm, SH Zheng, T AF Zhang, Yawei De Sanjose, Silvia Bracci, Paige M. Morton, Lindsay M. Wang, Rong Brennan, Paul Hartge, Patricia Boffetta, Paolo Becker, Nikolaus Maynadie, Marc Foretova, Lenka Cocco, Pierluigi Staines, Anthony Holford, Theodore Holly, Elizabeth A. Nieters, Alexandra Benavente, Yolanda Bernstein, Leslie Zahm, Shelia Hoar Zheng, Tongzhang TI Personal use of hair dye and the risk of certain subtypes of non-Hodgkin lymphoma SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE case-control studies; hair dyes; lymphoma; non-Hodgkin ID UNITED-STATES; N-ACETYLATION; CANCER; CELLS; POPULATION; NEOPLASMS; N-ACETYLTRANSFERASE-1; PHENYLENEDIAMINE; IDENTIFICATION; EPIDEMIOLOGY AB Personal use of hair dye has been inconsistently linked to risk of non-Hodgkin lymphoma (NHL), perhaps because of small samples or a lack of detailed information on personal hair-dye use in previous studies. This study included 4,461 NHL cases and 5,799 controls from the International Lymphoma Epidemiology Consortium 1988-2003. Increased risk of NHL (odds ratio (OR) = 1.3, 95% confidence interval (CI): 1.1, 1.4) associated with hair-dye use was observed among women who began using hair dye before 1980. Analyses by NHL subtype showed increased risk for follicular lymphoma (FL) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) but not for other NHL subtypes. The increased risks of FL (OR = 1.4, 95% CI: 1.1, 1.9) and CLL/SLL (OR = 1.5, 95% CI: 1.1, 2.0) were mainly observed among women who started using hair dyes before 1980. For women who began using hair dye in 1980 or afterward, increased FL risk was limited to users of dark-colored dyes (OR = 1.5, 95% CI: 1.1, 2.0). These results indicate that personal hair-dye use may play a role in risks of FL and CLL/SLL in women who started use before 1980 and that increased risk of FL among women who started use during or after 1980 cannot be excluded. C1 [Zhang, Yawei; Wang, Rong; Holford, Theodore; Zheng, Tongzhang] Yale Univ, Sch Publ Hlth, Div Environm Sci, New Haven, CT 06520 USA. [De Sanjose, Silvia; Benavente, Yolanda] Catalan Inst Oncol, Epidemiol & Canc Registry, Barcelona, Spain. [Bracci, Paige M.; Holly, Elizabeth A.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Morton, Lindsay M.; Hartge, Patricia; Zahm, Shelia Hoar] Natl Canc Inst, Div Canc Epidemiol & Genet, Rockville, MD USA. [Brennan, Paul; Boffetta, Paolo] Int Agcy Res Canc, F-69372 Lyon, France. [Becker, Nikolaus; Nieters, Alexandra] German Canc Res Ctr, Div Canc Epidemiol, D-6900 Heidelberg, Germany. [Maynadie, Marc] Burgundy Univ, Registry Hematol Malignancies, Dijon, France. [Maynadie, Marc] Univ Hosp, Dijon, France. [Foretova, Lenka] Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno, Czech Republic. [Cocco, Pierluigi] Univ Cagliari, Inst Occupat Med, Cagliari, Italy. [Staines, Anthony] Univ Coll Dublin, Sch Publ Hlth & Populat Sci, Dublin 2, Ireland. [Bernstein, Leslie] City Hope Natl Med Ctr, Dept Canc Epidemiol, Duarte, CA 91010 USA. RP Zhang, Y (reprint author), Yale Univ, Sch Publ Hlth, Div Environm Sci, 60 Coll St,LEPH 440, New Haven, CT 06520 USA. EM yawei.zhang@yale.edu RI Wang, Rong/H-3112-2011; de Sanjose Llongueras, Silvia/H-6339-2014; Zahm, Shelia/B-5025-2015; Morton, Lindsay/B-5234-2015; Benavente, Yolanda/H-9810-2014; OI Wang, Rong/0000-0002-2169-4174; Morton, Lindsay/0000-0001-9767-2310; Staines, Anthony/0000-0001-9161-1357 FU Intramural NIH HHS [ZIA CP010170-13]; NCI NIH HHS [1R03CA110823, N01 PC065064, N01 PC067008, N01 PC067009, N01 PC067010, PC65064, PC67008, PC67009, PC67010, PC71105, R01 CA045614, R01 CA062006, R03 CA110823] NR 35 TC 33 Z9 44 U1 0 U2 11 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2008 VL 167 IS 11 BP 1321 EP 1331 DI 10.1093/aje/kwn058 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 305HO UT WOS:000256169100008 PM 18408225 ER PT J AU Basso, O Pennell, ML Chen, A Longnecker, MP AF Basso, O. Pennell, M. L. Chen, A. Longnecker, M. P. TI Mother's age at menarche and offspring growth SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 24-27, 2008 CL Chicago, IL SP Soc Epidemiol Res C1 [Basso, O.; Pennell, M. L.; Chen, A.; Longnecker, M. P.] NIEHS, NIH, DHHS, Res Triangle Pk, NC 27709 USA. NR 1 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 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2008 VL 167 IS 11 SU S BP S16 EP S16 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 307HO UT WOS:000256310200062 ER PT J AU Bhatti, P Doody, MM Alexander, BH Simon, SL Weinstock, RM Rosenstein, M Stovall, M Abend, M Preston, DL Struewing, JP Sigurdson, AJ AF Bhatti, P. Doody, M. M. Alexander, B. H. Simon, S. L. Weinstock, R. M. Rosenstein, M. Stovall, M. Abend, M. Preston, D. L. Struewing, J. P. Sigurdson, A. J. TI Breast cancer risk polymorphisms and interaction with ionizing radiation among US radiologic technologists SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 24-27, 2008 CL Chicago, IL SP Soc Epidemiol Res C1 [Bhatti, P.; Doody, M. M.; Alexander, B. H.; Simon, S. L.; Weinstock, R. M.; Rosenstein, M.; Stovall, M.; Abend, M.; Preston, D. L.; Struewing, J. P.; Sigurdson, A. J.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2008 VL 167 IS 11 SU S BP S96 EP S96 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 307HO UT WOS:000256310200382 ER PT J AU Brinton, L Richesson, D Gierach, G Lacey, J Park, Y Hollenbeck, A Schatzkin, A AF Brinton, L. Richesson, D. Gierach, G. Lacey, J., Jr. Park, Y. Hollenbeck, A. Schatzkin, A. TI Prospective evaluation of risk factors for male breast cancer SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 24-27, 2008 CL Chicago, IL SP Soc Epidemiol Res C1 [Brinton, L.; Richesson, D.; Gierach, G.; Lacey, J., Jr.; Park, Y.; Hollenbeck, A.; Schatzkin, A.] NCI, Rockville, MD 20852 USA. RI Brinton, Louise/G-7486-2015; Gierach, Gretchen/E-1817-2016 OI Brinton, Louise/0000-0003-3853-8562; Gierach, Gretchen/0000-0002-0165-5522 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 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2008 VL 167 IS 11 SU S BP S90 EP S90 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 307HO UT WOS:000256310200357 ER PT J AU Cao, Y Chen, A Jones, RL Rogan, WJ AF Cao, Y. Chen, A. Jones, R. L. Rogan, W. J. TI Efficacy of succimer chelation for mercury at background levels in 2 year olds SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 24-27, 2008 CL Chicago, IL SP Soc Epidemiol Res C1 [Cao, Y.; Chen, A.; Jones, R. L.; Rogan, W. J.] NIEHS, Res Triangle Pk, NC 27709 USA. RI Jones, Robert/E-1170-2011; Rogan, Walter/I-6034-2012 OI Rogan, Walter/0000-0002-9302-0160 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 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2008 VL 167 IS 11 SU S BP S15 EP S15 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 307HO UT WOS:000256310200061 ER PT J AU D'Aloisio, AA Baird, DD Deroo, LA Sandler, DP AF D'Aloisio, A. A. Baird, D. D. DeRoo, L. A. Sandler, D. P. TI Association of intrauterine and early life exposures with uterine leiomyomata in young women SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 24-27, 2008 CL Chicago, IL SP Soc Epidemiol Res C1 [D'Aloisio, A. A.; Baird, D. D.; DeRoo, L. A.; Sandler, D. P.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. 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 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2008 VL 167 IS 11 SU S BP S143 EP S143 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 307HO UT WOS:000256310200569 ER PT J AU Danforth, K Brinton, L Hartge, P Leitzmann, M Schatzkin, A Lacey, J AF Danforth, K. Brinton, L. Hartge, P. Leitzmann, M. Schatzkin, A. Lacey, J., Jr. TI Postmenopausal hormone use and ovarian cancer risk in the NIH-AARP diet and health study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 24-27, 2008 CL Chicago, IL SP Soc Epidemiol Res C1 [Danforth, K.; Brinton, L.; Hartge, P.; Leitzmann, M.; Schatzkin, A.; Lacey, J., Jr.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20852 USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 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 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2008 VL 167 IS 11 SU S BP S141 EP S141 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 307HO UT WOS:000256310200559 ER PT J AU Deroo, LA Johnson, J Sandler, DP AF Deroo, L. A. Johnson, J. Sandler, D. P. TI Obesity and depression: What comes first? SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 24-27, 2008 CL Chicago, IL SP Soc Epidemiol Res C1 [Deroo, L. A.; Johnson, J.; Sandler, D. P.] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. 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 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2008 VL 167 IS 11 SU S BP S31 EP S31 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 307HO UT WOS:000256310200123 ER PT J AU Doria-Rose, VP Miller, AB Prorok, PC Marcus, PM AF Doria-Rose, V. P. Miller, A. B. Prorok, P. C. Marcus, P. M. TI Do death certificates provide an adequate source of cause of death information in randomized controlled trials of cancer screening? SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 24-27, 2008 CL Chicago, IL SP Soc Epidemiol Res C1 [Doria-Rose, V. P.; Miller, A. B.; Prorok, P. C.; Marcus, P. M.] NCI, Bethesda, MD 20892 USA. 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 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2008 VL 167 IS 11 SU S BP S108 EP S108 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 307HO UT WOS:000256310200429 ER PT J AU Doria-Rose, VP Marcus, PM AF Doria-Rose, V. P. Marcus, P. M. TI Lung cancer screening by sputum cytology and chest x-ray: Mortality results from the Johns Hopkins lung project (JHLP) and the memorial sloan-kettering lung study (MSKLS) SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 24-27, 2008 CL Chicago, IL SP Soc Epidemiol Res C1 [Doria-Rose, V. P.; Marcus, P. M.] NCI, Bethesda, MD 20892 USA. 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 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2008 VL 167 IS 11 SU S BP S108 EP S108 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 307HO UT WOS:000256310200430 ER PT J AU Ferrucci, L Flood, A Schatzkin, A Schoenfeld, PS Cash, BD Sinha, R Cross, AJ AF Ferrucci, L. Flood, A. Schatzkin, A. Schoenfeld, P. S. Cash, B. D. Sinha, R. Cross, A. J. TI Meat, total iron, and heme iron intake in relation to colorectal adenoma in asymptomatic women SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 24-27, 2008 CL Chicago, IL SP Soc Epidemiol Res C1 [Ferrucci, L.; Flood, A.; Schatzkin, A.; Schoenfeld, P. S.; Cash, B. D.; Sinha, R.; Cross, A. J.] NCI, Rockville, MD 20852 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 OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2008 VL 167 IS 11 SU S BP S13 EP S13 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 307HO UT WOS:000256310200051 ER PT J AU Gierach, G Chang, S Brinton, L Lacey, J Hollenbeck, A Schatzkin, A Leitzmann, M AF Gierach, G. Chang, S. Brinton, L. Lacey, J., Jr. Hollenbeck, A. Schatzkin, A. Leitzmann, M. TI Physical activity and endometrial cancer risk in the NIH-AARP diet and health study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 24-27, 2008 CL Chicago, IL SP Soc Epidemiol Res C1 [Gierach, G.; Chang, S.; Brinton, L.; Lacey, J., Jr.; Hollenbeck, A.; Schatzkin, A.; Leitzmann, M.] NCI, Bethesda, MD 20892 USA. RI Brinton, Louise/G-7486-2015; Gierach, Gretchen/E-1817-2016 OI Brinton, Louise/0000-0003-3853-8562; Gierach, Gretchen/0000-0002-0165-5522 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 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2008 VL 167 IS 11 SU S BP S8 EP S8 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 307HO UT WOS:000256310200031 ER PT J AU Hoppin, JA Karnel, F Korell, M Umbach, DM Ross, GW Goldman, S Bhudhikanok, GS Blair, A Sandler, DP Tanner, CM AF Hoppin, J. A. Karnel, F. Korell, M. Umbach, D. M. Ross, G. W. Goldman, S. Bhudhikanok, G. S. Blair, A. Sandler, D. P. Tanner, C. M. TI Blood metal levels in Parkinson's disease SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 24-27, 2008 CL Chicago, IL SP Soc Epidemiol Res C1 [Hoppin, J. A.; Karnel, F.; Korell, M.; Umbach, D. M.; Ross, G. W.; Goldman, S.; Bhudhikanok, G. S.; Blair, A.; Sandler, D. P.; Tanner, C. M.] NIEHS, Res Triangle Pk, NC 27709 USA. 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 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2008 VL 167 IS 11 SU S BP S116 EP S116 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 307HO UT WOS:000256310200463 ER PT J AU Jukic, AM Weinberg, CR Wilcox, AJ Baird, DD AF Jukic, A. M. Weinberg, C. R. Wilcox, A. J. Baird, D. D. TI How might early pregnancy loss increase fecundability in the next cycle? Effects of early loss on hormone levels and sexual intercourse SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 24-27, 2008 CL Chicago, IL SP Soc Epidemiol Res C1 [Jukic, A. M.; Weinberg, C. R.; Wilcox, A. J.; Baird, D. D.] NIEHS, Durham, NC 27709 USA. 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 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2008 VL 167 IS 11 SU S BP S23 EP S23 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 307HO UT WOS:000256310200091 ER PT J AU Kalaydjian, A Cui, L Angst, J Rossler, W Merikangas, K AF Kalaydjian, A. Cui, L. Angst, J. Roessler, W. Merikangas, K. TI Association between migraine and mood and anxiety disorders in the Zurich Cohort Study of young adults SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 24-27, 2008 CL Chicago, IL SP Soc Epidemiol Res C1 [Kalaydjian, A.; Cui, L.; Angst, J.; Roessler, W.; Merikangas, K.] NIMH, Bethesda, MD 20892 USA. 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 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2008 VL 167 IS 11 SU S BP S99 EP S99 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 307HO UT WOS:000256310200395 ER PT J AU Keim, SA AF Keim, S. A. TI Association between maternal body mass index and daughter's age at menarche SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 24-27, 2008 CL Chicago, IL SP Soc Epidemiol Res C1 [Keim, S. A.] NICHHD, NIH, Bethesda, MD 20852 USA. RI Keim, Sarah/F-8929-2013 OI Keim, Sarah/0000-0003-3490-3649 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 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2008 VL 167 IS 11 SU S BP S101 EP S101 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 307HO UT WOS:000256310200403 ER PT J AU Klebanoff, M Cole, S AF Klebanoff, M. Cole, S. TI Use of imputation in the epidemiologic literature SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 24-27, 2008 CL Chicago, IL SP Soc Epidemiol Res C1 [Klebanoff, M.; Cole, S.] NIH, NCHHD, Bethesda, MD 20892 USA. 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 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2008 VL 167 IS 11 SU S BP S109 EP S109 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 307HO UT WOS:000256310200433 ER PT J AU Laughlin, S Hartmann, K Baird, D AF Laughlin, S. Hartmann, K. Baird, D. TI Fibroids disappear after pregnancy SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 24-27, 2008 CL Chicago, IL SP Soc Epidemiol Res C1 [Laughlin, S.; Hartmann, K.; Baird, D.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. 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 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2008 VL 167 IS 11 SU S BP S33 EP S33 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 307HO UT WOS:000256310200133 ER PT J AU MacLehose, R Dunson, D Richardson, D AF MacLehose, R. Dunson, D. Richardson, D. TI Flexible non-parametric estimation of dose-response curves SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 24-27, 2008 CL Chicago, IL SP Soc Epidemiol Res C1 [MacLehose, R.; Dunson, D.; Richardson, D.] NIEHS, Res Triangle Pk, NC 27709 USA. 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 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2008 VL 167 IS 11 SU S BP S115 EP S115 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 307HO UT WOS:000256310200458 ER PT J AU Meinhold, CL de Gonzalz, AB Albanes, D Weinstein, SJ Taylor, PR Virtamo, J Stolzenberg-Solomon, RZ AF Meinhold, C. L. de Gonzalez, A. B. Albanes, D. Weinstein, S. J. Taylor, P. R. Virtamo, J. Stolzenberg-Solomon, R. Z. TI Independent predictors of baseline fasting serum insulin and glucose and the risk of pancreatic cancer in male smokers SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 24-27, 2008 CL Chicago, IL SP Soc Epidemiol Res C1 [Meinhold, C. L.; de Gonzalez, A. B.; Albanes, D.; Weinstein, S. J.; Taylor, P. R.; Virtamo, J.; Stolzenberg-Solomon, R. Z.] NCI, Div Canc Epidemiol & Genet, Nutr Branch, Rockville, MD 20892 USA. RI Albanes, Demetrius/B-9749-2015; Kitahara, Cari/R-8267-2016 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 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2008 VL 167 IS 11 SU S BP S39 EP S39 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 307HO UT WOS:000256310200157 ER PT J AU Mikolajczyk, RT Grewal, J Ford, J Zhang, J AF Mikolajczyk, R. T. Grewal, J. Ford, J. Zhang, J. TI Effects of inter-pregnancy interval on vascular adaptation in consecutive pregnancies SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 24-27, 2008 CL Chicago, IL SP Soc Epidemiol Res C1 [Mikolajczyk, R. T.; Grewal, J.; Ford, J.; Zhang, J.] NICHD, NIH, Bethesda, MD 20892 USA. 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 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2008 VL 167 IS 11 SU S BP S26 EP S26 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 307HO UT WOS:000256310200102 ER PT J AU Murphy, G Shu, XO Gao, YT Ji, BT Cook, M Yang, G Li, HL Rothman, N Zheng, W Chow, WH AF Murphy, G. Shu, X. O. Gao, Y-T Ji, B-T Cook, M. Yang, G. Li, H-L Rothman, N. Zheng, W. Chow, W-H TI Family cancer history, adolescent exposures, and risk of colorectal cancer in a prospective cohort of Chinese women SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 24-27, 2008 CL Chicago, IL SP Soc Epidemiol Res C1 [Murphy, G.; Shu, X. O.; Gao, Y-T; Ji, B-T; Cook, M.; Yang, G.; Li, H-L; Rothman, N.; Zheng, W.; Chow, W-H] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. 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 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2008 VL 167 IS 11 SU S BP S61 EP S61 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 307HO UT WOS:000256310200243 ER PT J AU Perkins, NJ Schisterman, EF Vexler, A AF Perkins, N. J. Schisterman, E. F. Vexler, A. TI Generalized roc curve inference for a biomarker subject to a limit of detection and measurement error SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 24-27, 2008 CL Chicago, IL SP Soc Epidemiol Res C1 [Perkins, N. J.; Schisterman, E. F.; Vexler, A.] NICHD, DESPR, NIH, Bethesda, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2008 VL 167 IS 11 SU S BP S112 EP S112 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 307HO UT WOS:000256310200445 ER PT J AU Purdue, MP Engel, LS Anderson, A Langseth, H Needham, LL Barr, DB Blair, A Rothman, N McGlynn, KA AF Purdue, M. P. Engel, L. S. Anderson, A. Langseth, H. Needham, L. L. Barr, D. B. Blair, A. Rothman, N. McGlynn, K. A. TI Serum levels of organochlorine compounds and risk of testicular germ cell tumors. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 24-27, 2008 CL Chicago, IL SP Soc Epidemiol Res C1 [Purdue, M. P.; Engel, L. S.; Anderson, A.; Langseth, H.; Needham, L. L.; Barr, D. B.; Blair, A.; Rothman, N.; McGlynn, K. A.] NCI, Bethesda, MD 20892 USA. RI Barr, Dana/E-6369-2011; Barr, Dana/E-2276-2013; Purdue, Mark/C-9228-2016 OI Purdue, Mark/0000-0003-1177-3108 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 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2008 VL 167 IS 11 SU S BP S140 EP S140 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 307HO UT WOS:000256310200557 ER PT J AU Rosenthal, LA Perkins, NJ Whitcomb, BW Schisterman, EF AF Rosenthal, L. A. Perkins, N. J. Whitcomb, B. W. Schisterman, E. F. TI Analyzing data subject to a limit of detection: Common practices in current research SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 24-27, 2008 CL Chicago, IL SP Soc Epidemiol Res C1 [Rosenthal, L. A.; Perkins, N. J.; Whitcomb, B. W.; Schisterman, E. F.] NICHD, DESPR, NIH, Bethesda, MD 20852 USA. 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 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2008 VL 167 IS 11 SU S BP S112 EP S112 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 307HO UT WOS:000256310200446 ER PT J AU Schisterman, EF Browne, RW Little, RJ Harel, O AF Schisterman, E. F. Browne, R. W. Little, R. J. Harel, O. TI Methodological issues in the analysis of new biomarkers SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 24-27, 2008 CL Chicago, IL SP Soc Epidemiol Res C1 [Schisterman, E. F.; Browne, R. W.; Little, R. J.; Harel, O.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Rockville, MD 20852 USA. 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 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2008 VL 167 IS 11 SU S BP S92 EP S92 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 307HO UT WOS:000256310200368 ER PT J AU Stolzenberg-Solomon, RZ Horst, R Hayes, RB Silverman, DT AF Stolzenberg-Solomon, R. Z. Horst, R. Hayes, R. B. Silverman, D. T. TI Serum vitamin D and risk of pancreatic cancer SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 24-27, 2008 CL Chicago, IL SP Soc Epidemiol Res C1 [Stolzenberg-Solomon, R. Z.; Horst, R.; Hayes, R. B.; Silverman, D. T.] NCI, NEB, DCEG, Rockville, MD 20854 USA. 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 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2008 VL 167 IS 11 SU S BP S39 EP S39 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 307HO UT WOS:000256310200154 ER PT J AU von Ehrenstein, OS Mikolajczyk, RT Zhang, J Grewal, U Troendle, J AF von Ehrenstein, O. S. Mikolajczyk, R. T. Zhang, J. Grewal, U. Troendle, J. TI Time window dependant fetal growth and IQ at age five SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 24-27, 2008 CL Chicago, IL SP Soc Epidemiol Res C1 [von Ehrenstein, O. S.; Mikolajczyk, R. T.; Zhang, J.; Grewal, U.; Troendle, J.] NICHHD, NIH, Bethesda, MD 20892 USA. 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 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2008 VL 167 IS 11 SU S BP S50 EP S50 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 307HO UT WOS:000256310200199 ER PT J AU Ye, X Skjaerven, R Basso, O Baird, D Eggesbo, M Uicab, LAC Haug, K Longnecker, MP AF Ye, X. Skjaerven, R. Basso, O. Baird, D. Eggesbo, M. Uicab, L. A. C. Haug, K. Longnecker, M. P. TI Early life exposure to tobacco smoking and subsequent reduced fertility among females SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 24-27, 2008 CL Chicago, IL SP Soc Epidemiol Res C1 [Ye, X.; Skjaerven, R.; Basso, O.; Baird, D.; Eggesbo, M.; Uicab, L. A. C.; Haug, K.; Longnecker, M. P.] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. 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 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2008 VL 167 IS 11 SU S BP S36 EP S36 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 307HO UT WOS:000256310200144 ER PT J AU Yoon, J AF Yoon, J. TI The role of perpetrator alcohol use in adolescent crime victimization SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 24-27, 2008 CL Chicago, IL SP Soc Epidemiol Res C1 [Yoon, J.] NIAAA, NIH, Bethesda, MD 20892 USA. 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 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2008 VL 167 IS 11 SU S BP S135 EP S135 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 307HO UT WOS:000256310200534 ER PT J AU Zhang, C Li, TY Rexrode, KM AF Zhang, C. Li, T. Y. Rexrode, K. M. TI Abdominal obesity and the risk of stroke in women: 18 years of follow-up SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 24-27, 2008 CL Chicago, IL SP Soc Epidemiol Res C1 [Zhang, C.; Li, T. Y.; Rexrode, K. M.] NICHD, NIH, Bethesda, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2008 VL 167 IS 11 SU S BP S71 EP S71 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 307HO UT WOS:000256310200283 ER EF