FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Shetty, V Morrell, CH Najjar, SS AF Shetty, Veena Morrell, Christopher H. Najjar, Samer S. TI Modeling a cross-sectional response variable with longitudinal predictors: an example of pulse pressure and pulse wave velocity SO JOURNAL OF APPLIED STATISTICS LA English DT Article DE mixed effects; linear regression; area under the curve AB We wish to model pulse wave velocity (PWV) as a function of longitudinal measurements of pulse pressure (PP) at the same and prior visits at which the PWV is measured. A number of approaches are compared. First, we use the PP at the same visit as the PWV in a linear regression model. In addition, we use the average of all available PPs as the explanatory variable in a linear regression model. Next, a two-stage process is applied. The longitudinal PP is modeled using a linear mixed-effects model. This modeled PP is used in the regression model to describe PWV. An approach for using the longitudinal PP data is to obtain a measure of the cumulative burden, the area under the PP curve. This area under the curve is used as an explanatory variable to model PWV. Finally, a joint Bayesian model is constructed similar to the two-stage model. C1 [Morrell, Christopher H.; Najjar, Samer S.] NIA, Baltimore, MD 21224 USA. [Shetty, Veena] Medstat Res Inst, Hyattsville, MD USA. [Morrell, Christopher H.] Loyola Coll, Dept Math Sci, Baltimore, MD 21210 USA. RP Morrell, CH (reprint author), NIA, Baltimore, MD 21224 USA. EM morrellc@mail.nih.gov 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. A portion of that support was through an R& D contract with MedStar Research Institute. We thank an anonymous referee whose comments greatly improved the paper. NR 8 TC 1 Z9 1 U1 0 U2 1 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0266-4763 J9 J APPL STAT JI J. Appl. Stat. PY 2009 VL 36 IS 6 BP 611 EP 619 AR PII 907827955 DI 10.1080/02664760802478208 PG 9 WC Statistics & Probability SC Mathematics GA 445ZA UT WOS:000266088800003 PM 20087408 ER PT J AU Yu, BB AF Yu, Binbing TI Approximating the risk score for disease diagnosis using MARS SO JOURNAL OF APPLIED STATISTICS LA English DT Article DE multivariate adaptive regression spline (MARS); Neyman-Pearson lemma; risk score; ROC ID ADAPTIVE REGRESSION SPLINES; NONPARAMETRIC APPROACH; TESTS; MARKERS; COMBINATIONS AB In disease screening and diagnosis, often multiple markers are measured and combined to improve the accuracy of diagnosis. McIntosh and Pepe [Combining several screening tests: optimality of the risk score, Biometrics 58 (2002), pp. 657-664] showed that the risk score, defined as the probability of disease conditional on multiple markers, is the optimal function for classification based on the Neyman-Pearson lemma. They proposed a two-step procedure to approximate the risk score. However, the resulting receiver operating characteristic (ROC) curve is only defined in a subrange (L, h) of false-positive rates in (0,1) and the determination of the lower limit L needs extra prior information. In practice, most diagnostic tests are not perfect, and it is usually rare that a single marker is uniformly better than the other tests. Using simulation, I show that multivariate adaptive regression spline is a useful tool to approximate the risk score when combining multiple markers, especially when ROC curves from multiple tests cross. The resulting ROC is defined in the whole range of (0,1) and is easy to implement and has intuitive interpretation. The sample code of the application is shown in the appendix. C1 NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Yu, BB (reprint author), NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. EM yubi@mail.nih.gov FU Intramural Research Program of the National Institute on Aging FX This research was supported in part by the Intramural Research Program of the National Institute on Aging. NR 21 TC 1 Z9 2 U1 1 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0266-4763 EI 1360-0532 J9 J APPL STAT JI J. Appl. Stat. PY 2009 VL 36 IS 7 BP 769 EP 778 AR PII 907825576 DI 10.1080/02664760802499352 PG 10 WC Statistics & Probability SC Mathematics GA 451SB UT WOS:000266489300005 PM 20161201 ER PT J AU Novichkov, PS Wolf, YI Dubchak, I Koonin, EV AF Novichkov, Pavel S. Wolf, Yuri I. Dubchak, Inna Koonin, Eugene V. TI Trends in Prokaryotic Evolution Revealed by Comparison of Closely Related Bacterial and Archaeal Genomes SO JOURNAL OF BACTERIOLOGY LA English DT Article ID GENE ORDER; REPLICATION; VARIABILITY; LIKELIHOOD; ALIGNMENT; PROTEINS; DATABASE AB In order to explore microevolutionary trends in bacteria and archaea, we constructed a data set of 41 alignable tight genome clusters (ATGCs). We show that the ratio of the medians of nonsynonymous to synonymous substitution rates (dN/dS) that is used as a measure of the purifying selection pressure on protein sequences is a stable characteristic of the ATGCs. In agreement with previous findings, parasitic bacteria, notwithstanding the sometimes dramatic genome shrinkage caused by gene loss, are typically subjected to relatively weak purifying selection, presumably owing to relatively small effective population sizes and frequent bottlenecks. However, no evidence of genome streamlining caused by strong selective pressure was found in any of the ATGCs. On the contrary, a significant positive correlation between the genome size, as well as gene size, and selective pressure was observed, although a variety of free-living prokaryotes with very close selective pressures span nearly the entire range of genome sizes. In addition, we examined the connections between the sequence evolution rate and other genomic features. Although gene order changes much faster than protein sequences during the evolution of prokaryotes, a strong positive correlation was observed between the "rear-rangement distance" and the amino acid distance, suggesting that at least some of the events leading to genome rearrangement are subjected to the same type of selective constraints as the evolution of amino acid sequences. C1 [Novichkov, Pavel S.; Wolf, Yuri I.; Koonin, Eugene V.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. [Dubchak, Inna] Univ Calif Berkeley, Lawrence Berkeley Lab, Berkeley, CA 94720 USA. [Dubchak, Inna] Joint Genome Inst, Dept Energy, Walnut Creek, CA 94598 USA. RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov FU Department of Health and Human Services; National Library of Medicine, NIH FX The research of P. S. N., Y. I. W., and E. V. K. was supported by the Department of Health and Human Services intramural program (National Library of Medicine, NIH). NR 37 TC 63 Z9 63 U1 3 U2 14 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JAN PY 2009 VL 191 IS 1 BP 65 EP 73 DI 10.1128/JB.01237-08 PG 9 WC Microbiology SC Microbiology GA 382TK UT WOS:000261628100006 PM 18978059 ER PT J AU Booth, BM Shields, JJ Chandler, RK AF Booth, Brenda M. Shields, Joseph J. Chandler, Redonna K. TI Recent Achievements in Alcohol and Drug Abuse Health Services Research SO JOURNAL OF BEHAVIORAL HEALTH SERVICES & RESEARCH LA English DT Editorial Material C1 [Booth, Brenda M.] Univ Arkansas Med Sci, Dept Psychiat, Div Hlth Serv Res, Little Rock, AR 72205 USA. [Booth, Brenda M.] Cent Arkansas Vet Healthcare Syst, Ctr Mental Healthcare Outcomes & Res, Little Rock, AR USA. [Shields, Joseph J.] NIAAA, Bethesda, MD USA. [Shields, Joseph J.] Catholic Univ Amer, Washington, DC 20064 USA. [Chandler, Redonna K.] NIDA, Serv Res Branch, Div Epidemiol Serv & Prevent Res, Bethesda, MD 20892 USA. RP Booth, BM (reprint author), Univ Arkansas Med Sci, Dept Psychiat, Div Hlth Serv Res, Little Rock, AR 72205 USA. EM boothbrendam@uams.edu NR 12 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1094-3412 J9 J BEHAV HEALTH SER R JI J. Behav. Health Serv. Res. PD JAN PY 2009 VL 36 IS 1 BP 5 EP 10 DI 10.1007/s11414-008-9149-8 PG 6 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 407VC UT WOS:000263391400003 PM 18846428 ER PT J AU Kosaka, N Ogawa, M Longmire, MR Choyke, PL Kobayashi, H AF Kosaka, Nobuyuki Ogawa, Mikako Longmire, Michelle R. Choyke, Peter L. Kobayashi, Hisataka TI Multi-targeted multi-color in vivo optical imaging in a model of disseminated peritoneal ovarian cancer SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE molecular imaging; optical probe; cancer; multicolor; multitargeting ID REAL-TIME; FLUORESCENCE; FLUOROPHORE AB Commonly used in flow cytometry, multiplexed optical probes can diagnose multiple types of cell surface marker, potentially leading to improved diagnosis accuracy in vivo. Herein, we demonstrate the targeting of two different tumor markers in models of disseminated ovarian cancer. Two ovarian cancer cell lines (SKOV3 and SHIN3) were employed; both overexpress D-galactose receptor (D-galR), but only SKOV3 overexpresses HER2/neu. Additionally, fusion tumors composed of SKOV3 and SHIN3/RFP were evaluated. Both galactosyl serum albumin-rhodamine green (GSA-RhodG), which binds D-galR, and trastuzumab-Alexa680, which binds HER2/neu, were administered to tumor-bearing mice for in vivo fluorescence imaging and in situ fluorescence microscopy. In vivo fluorescence imaging depicted 64 of 69 SKOV3 tumors (94.2% )based on their dual spectra corresponding to both RhodG and Alexa680, while all 71 SHIN3 tumors (100%) were detected based on their single spectrum corresponding only to RhodG. All 59 SHIN3 and 36 SKOV3 tumors were correctly diagnosed with in situ microscopy. Additionally, in the mixed tumor model, all tumors could be depicted using the RhodG spectrum, but only SKOV3 components also showed the Alexa680 spectrum. In conclusion, multitargeted multicolor optical imaging enabled specific in vivo diagnosis of tumors expressing distinct patterns of receptors, leading to improved diagnostic accuracy. (C) 2009 Society of Photo-Optical Instrumentation Engineers. [DOI: 10.1117/1.3083449] C1 [Kosaka, Nobuyuki; Ogawa, Mikako; Longmire, Michelle R.; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Kosaka, N (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bldg 10,Room 1B40,MSC1088, Bethesda, MD 20892 USA. EM kobayash@mail.nih.gov FU NIH FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 16 TC 20 Z9 21 U1 0 U2 11 PU SPIE-SOC PHOTOPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD JAN-FEB PY 2009 VL 14 IS 1 AR 014023 DI 10.1117/1.3083449 PG 8 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 424FW UT WOS:000264551900028 PM 19256711 ER PT J AU Heath, EI LoRusso, PM Ivy, SP Rubinstein, L Christian, MC Heilbrun, LK AF Heath, Elisabeth I. LoRusso, Patricia M. Ivy, S. Percy Rubinstein, Larry Christian, Michaele C. Heilbrun, Lance K. TI Theoretical and Practical Application of Traditional and Accelerated Titration Phase I Clinical Trial Designs: The Wayne State University Experience SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Accelerated design; Phase I clinical trials; Traditional design ID NONCYTOTOXIC AGENTS; SOLID TUMORS; EPOTHILONE-B; ONCOLOGY; BMS-247550; ESCALATION; TOXICITY; BENEFITS; RISKS AB The traditional and accelerated titration (AT) designs are two frequently utilized Phase I clinical trial designs. Although each design has theoretical advantages and disadvantages, a summary of the practical application of these theories has not been reported. We report our center's experience in evaluating novel agents using both types of Phase I trial designs over a 13-year period. Results from nine Phase I clinical trials of multiple cytotoxic agents conducted at Wayne State University/Karmanos Cancer Institute in Detroit, MI, and published from 1995-2005 were analyzed for this report. Parameters analyzed included the number of patients, the number of dose levels, the total time to completion of the study, and adverse events. The mean number of patients treated on four Phase I trials using the traditional Phase I trial design was 34 compared to a mean of 23.8 patients treated on five Phase I trials using the AT schema. The mean number of dose levels in patients treated using the traditional Phase I trial design was 8.8 (range 7-11) compared to a mean of 10.6 (range 7-15) dose levels using the AT design. The mean length of study time (25-26 months) was similar in both trial designs. The theoretical advantages and disadvantages of both Phase I trial designs did not readily emerge in their actual application in clinical trials conducted at our institution. C1 [Heath, Elisabeth I.; LoRusso, Patricia M.; Heilbrun, Lance K.] Wayne State Univ, Karmanos Canc Inst, Div Hematol & Oncol, Detroit, MI 48201 USA. [Ivy, S. Percy; Rubinstein, Larry; Christian, Michaele C.] NCI, Bethesda, MD 20892 USA. RP Heath, EI (reprint author), Wayne State Univ, Karmanos Canc Inst, Div Hematol & Oncol, 4100 John R,4 HWCRC, Detroit, MI 48201 USA. EM heathe@karmanos.org FU NCI NIH HHS [U01 CA062487, P30 CA022453, CA-22453, U01 CA-062487] NR 27 TC 1 Z9 1 U1 0 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2009 VL 19 IS 3 BP 414 EP 423 AR PII 910600270 DI 10.1080/10543400902800460 PG 10 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 436KX UT WOS:000265414100002 PM 19384685 ER PT J AU Brittain, E Hu, ZH AF Brittain, Erica Hu, Zonghui TI NONINFERIORITY TRIAL DESIGN AND ANALYSIS WITH AN ORDERED THREE-LEVEL CATEGORICAL ENDPOINT SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Clinical trial design; Noninferiority; Ordinal data ID SAMPLE-SIZE FORMULAS; NULL HYPOTHESIS; STATISTICS; DIFFERENCE; ISSUES AB This paper extends standard methodology for noninferiority trial design from a binary endpoint to an ordered three-level endpoint, such as "success," "intermediate," and "failure." A metric that summarizes outcome on this endpoint is proposed, and the corresponding sample size requirements are presented. This ordered endpoint can be collapsed into two different binary endpoints, respectively lumping "intermediate" outcomes with "success" or with "failure." We describe how the ordered three-level endpoint compares with these two binary endpoints with respect to the noninferiority margin and sample size requirements. C1 [Brittain, Erica; Hu, Zonghui] NIAID, Biostat Res Branch, Bethesda, MD 20892 USA. RP Brittain, E (reprint author), NIAID, Biostat Res Branch, Bethesda, MD 20892 USA. EM ebrittain@niaid.nih.gov FU Intramural NIH HHS [Z99 AI999999] NR 12 TC 6 Z9 6 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2009 VL 19 IS 4 BP 685 EP 699 DI 10.1080/10543400902964142 PG 15 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 544DV UT WOS:000273633600009 PM 20183434 ER PT J AU Han, JY Hawkins, RP Shaw, BR Pingree, S McTavish, F Gustafson, DH AF Han, Jeong Yeob Hawkins, Robert P. Shaw, Bret R. Pingree, Suzanne McTavish, Fiona Gustafson, David H. TI Unraveling Uses and Effects of an Interactive Health Communication System SO JOURNAL OF BROADCASTING & ELECTRONIC MEDIA LA English DT Article ID QUALITY-OF-LIFE; BREAST-CANCER; TELEVISION EXPOSURE; WOMEN; SUPPORT; GRATIFICATIONS; EXPERIENCES; THERAPY; SEEKING; IMPACT AB By developing a number of measures distinguishing amount, type of content, and when and how that content is used, the current study revealed effective patterns of use that are associated with quality of life benefits during an eHealth intervention. Results generally suggest that the benefits depend on how a patient uses the system, far more than on sheer amount of exposure or even what type of content is chosen. The next generation of eHealth system should focus on providing new and varying content over time, but even more on encouraging intensity of use and long-term commitment to the system. C1 [Han, Jeong Yeob] Univ Georgia, Dept Telecommun, Athens, GA 30602 USA. [Hawkins, Robert P.] Univ Wisconsin, Sch Journalism & Mass Commun, Madison, WI 53706 USA. [Hawkins, Robert P.] Univ Wisconsin, NCI, Ctr Excellence Canc Commun Res, Madison, WI 53706 USA. [Shaw, Bret R.; Pingree, Suzanne] Univ Wisconsin, Dept Life Sci Commun, Madison, WI 53706 USA. [McTavish, Fiona] Univ Wisconsin, Ctr Hlth Enhancement Syst Studies, Madison, WI 53706 USA. [Gustafson, David H.] Univ Wisconsin, Coll Engn, Madison, WI 53706 USA. RP Han, JY (reprint author), Univ Georgia, Dept Telecommun, Athens, GA 30602 USA. FU NCI NIH HHS [N02CO51108] NR 41 TC 26 Z9 26 U1 0 U2 2 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0883-8151 J9 J BROADCAST ELECTRON JI J. Broadcast. Electron. Media PY 2009 VL 53 IS 1 BP 112 EP 133 AR PII 909493136 DI 10.1080/08838150802643787 PG 22 WC Communication; Film, Radio, Television SC Communication; Film, Radio & Television GA 418FT UT WOS:000264134800008 PM 23172985 ER PT J AU Rutten, LF Hesse, BW Moser, RP Mccaul, KD Rothman, AJ AF Rutten, Lila Finney Hesse, Bradford W. Moser, Richard P. Mccaul, Kevin D. Rothman, Alexander J. TI Public Perceptions of Cancer Prevention, Screening, and Survival: Comparison with State-of-Science Evidence for Colon, Skin, and Lung Cancer SO JOURNAL OF CANCER EDUCATION LA English DT Article AB Background. Lay understanding of cancer prevention, screening, and survival may influence health behavior and health outcomes. Methods. Data were from the 2005 Health Information National Trends Survey (HINTS). In our analyses, we describe population (N = 5586) beliefs about cancer prevention, detection, and survival for colon, lung, and skin cancer and compare beliefs with state-of-science evidence. We examined differences by sociodemographic subgroups. Results. A majority of respondents responded consistently with state-of-science evidence in prevention for colon (78.2%), lung (81.2%), and skin cancer (83.5%). Respondents' perceptions of screening for colon cancer were generally consistent with state-of-science evidence (89.9%); however, fewer respondents' responded consistently with state-of-science in screening for lung (12.6%) and skin cancer (11.9%). Finally, respondents' estimates of survival/cure of colon (66.2%) and skin cancer (63.6%) were consistent with state-of-the-science evidence in survival; however, a minority of respondents' estimates of lung cancer survival (17.3%) were consistent with state-of-science. Sociodemographic associates of state-of-science consistent responses included younger age, greater education, and White race. Conclusions. Public knowledge of cancer prevention, screening, and survival varies by type of cancer, levels of evidence, and sociodemographic factors. These findings provide an evidence base for improving public awareness and understanding of cancer prevention, screening, and survival. C1 [Rutten, Lila Finney; Hesse, Bradford W.; Moser, Richard P.] Natl Canc Inst, Div Canc Control & Populat Sci, Bethesda, MD USA. [Mccaul, Kevin D.] N Dakota State Univ, Dept Psychol, Fargo, ND 58105 USA. [Rothman, Alexander J.] Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA. RP Rutten, LF (reprint author), Hlth Partners Res Fdn, MSC 21111 R,8170 33rd Ave S,POB 1524, Minneapolis, MN 55440 USA. EM lila.j.rutten@healthpartners.com OI Hesse, Bradford/0000-0003-1142-1161 NR 17 TC 18 Z9 18 U1 0 U2 8 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 0885-8195 J9 J CANCER EDUC JI J. Cancer Educ. PY 2009 VL 24 IS 1 BP 40 EP 48 AR PII 909204690 DI 10.1080/08858190802664610 PG 9 WC Oncology; Education, Scientific Disciplines; Public, Environmental & Occupational Health SC Oncology; Education & Educational Research; Public, Environmental & Occupational Health GA 414OJ UT WOS:000263873700009 PM 19259865 ER PT J AU Solomon, FM Thakkar, S Zambon, A Eckstein, DS Michaels, M Johnson, L Squiers, L AF Solomon, Felicia M. Thakkar, Sona Zambon, Allison Eckstein, Daniel S. Michaels, Margo Johnson, Lenora Squiers, Linda TI Evaluating a National Dissemination Approach: The National Cancer Institute's Clinical Trials Education Program SO JOURNAL OF CANCER EDUCATION LA English DT Article ID COMMUNITY-HEALTH; PARTNERSHIPS AB Background. Adult participation in clinical trials is low, and many individuals are unaware of trials as an option. Raising awareness about clinical trials and addressing barriers through education is key to increasing enrollment in trials. Methods. To reach communities, the National Cancer Institute (NCI) worked with partners to disseminate clinical trials education resources. Evaluation was conducted to determine the effectiveness of the dissemination approaches on program goals. Results. Survey results indicated that partners disseminated, used, and were satisfied with the program resources. Focus group results corroborated these findings. Conclusions. NCI's program successfully used partnerships for broad dissemination of resources to improve clinical trials awareness. C1 [Solomon, Felicia M.] NCI, Off Commun & Educ, NIH DHHS, Bethesda, MD 20892 USA. [Zambon, Allison; Eckstein, Daniel S.] NOVA Res Co, Bethesda, MD USA. RP Solomon, FM (reprint author), NCI, Off Commun & Educ, NIH DHHS, 6116 Execut Blvd,Suite 202,Room 2031, Bethesda, MD 20892 USA. EM solomonf@mail.nih.gov NR 10 TC 2 Z9 2 U1 0 U2 1 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 0885-8195 J9 J CANCER EDUC JI J. Cancer Educ. PY 2009 VL 24 IS 1 BP 49 EP 57 AR PII 909204207 DI 10.1080/08858190802664818 PG 9 WC Oncology; Education, Scientific Disciplines; Public, Environmental & Occupational Health SC Oncology; Education & Educational Research; Public, Environmental & Occupational Health GA 414OJ UT WOS:000263873700010 PM 19259866 ER PT J AU Vanderpool, RC Kornfeld, J Rutten, LF Squiers, L AF Vanderpool, Robin C. Kornfeld, Julie Rutten, Lila Finney Squiers, Linda TI Cancer Information-Seeking Experiences: The Implications of Hispanic Ethnicity and Spanish Language SO JOURNAL OF CANCER EDUCATION LA English DT Article CT Data Users Conference 2007 CY MAY 04, 2007 CL Pasadena, CA ID UNITED-STATES; HEALTH COMMUNICATION; DISPARITIES; BREAST; CARE; PREFERENCES; LATINOS; SYSTEM; WOMEN AB Background. Strategies to support cancer information-seeking among Hispanics are needed. Methods. We analyzed data from the 2005 Health Information National Trends Survey (HINTS) to explore cancer information-seeking experiences among respondents according to ethnicity and language of interview. Results. Over 80% of Spanish-speaking Hispanics had never looked for cancer information. Compared to English-speaking respondents, Spanish-speaking Hispanics who sought cancer information indicated their search took a lot of effort (67%), was hard to understand (54%), and frustrating (42%). Spanish-speaking Hispanics noted minimal confidence in obtaining cancer information. Conclusions. Language and cultural differences must be considered in the design, implementation, and dissemination of cancer information. C1 [Vanderpool, Robin C.] Univ Kentucky, Markey Canc Control Program, Mid S Reg Canc Informat Serv, Lexington, KY 40504 USA. [Kornfeld, Julie] Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Coastal Reg Canc Informat Serv, Coral Gables, FL 33124 USA. [Rutten, Lila Finney] NCI, Hlth Commun & Informat Res Branch, NIH, Bethesda, MD 20892 USA. [Squiers, Linda] NCI, Canc Informat Serv, NIH, Bethesda, MD 20892 USA. RP Vanderpool, RC (reprint author), Univ Kentucky, Markey Canc Control Program, Mid S Canc Informat Serv, 2365 Harrodsburg Rd,Suite A230, Lexington, KY 40504 USA. EM robin@cis.uky.edu FU NCI NIH HHS [N02 CO051107, N02 CO051106] NR 33 TC 33 Z9 33 U1 2 U2 8 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 0885-8195 J9 J CANCER EDUC JI J. Cancer Educ. PY 2009 VL 24 IS 2 BP 141 EP 147 AR PII 911056370 DI 10.1080/08858190902854772 PG 7 WC Oncology; Education, Scientific Disciplines; Public, Environmental & Occupational Health SC Oncology; Education & Educational Research; Public, Environmental & Occupational Health GA 444KH UT WOS:000265979400012 PM 19431032 ER PT J AU Davis, SW Diaz-Mendez, M Garcia, MT AF Davis, Sharon Watkins Diaz-Mendez, Marynieves Garcia, Maria Talosig TI Barriers to Seeking Cancer Information Among Spanish-Speaking Cancer Survivors SO JOURNAL OF CANCER EDUCATION LA English DT Article ID NATIONAL TRENDS SURVEY; BREAST-CANCER; KNOWLEDGE; ATTITUDES; WOMEN; BEHAVIORS; LATINOS; MESSAGE; HINTS AB Background. Hispanics face barriers in seeking cancer information from sources such as the National Cancer Institute's Cancer Information Service. Their cancer screening rates are lower than those for whites. Methods. Three focus groups were conducted with 40 Spanish-speaking cancer survivors. Results. Few patients had used a toll-free telephone number to get cancer information. Only five had used the Internet. Fear of feeling worse was a common concern in seeking cancer information, as was trying to discuss their cancer in English. Spanish language media promotions were recommended. Conclusions. Beliefs and attitudes about cancer must be taken into account when developing culturally competent education programs for Spanish speakers. C1 [Davis, Sharon Watkins] NCI, Canc Informat Serv Calif, No Calif Canc Ctr, Fremont, CA 94538 USA. [Diaz-Mendez, Marynieves] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Davis, SW (reprint author), NCI, Canc Informat Serv Calif, No Calif Canc Ctr, 2201 Walnut Ave, Fremont, CA 94538 USA. EM sdavis@nccc.org FU Richard and Rhoda Goldman Fund FX Supported by the Richard and Rhoda Goldman Fund. NR 32 TC 8 Z9 8 U1 0 U2 3 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 0885-8195 J9 J CANCER EDUC JI J. Cancer Educ. PY 2009 VL 24 IS 3 BP 167 EP 171 AR PII 912377074 DI 10.1080/08858190902873053 PG 5 WC Oncology; Education, Scientific Disciplines; Public, Environmental & Occupational Health SC Oncology; Education & Educational Research; Public, Environmental & Occupational Health GA 457ZP UT WOS:000266978800002 PM 19526401 ER PT J AU Costantini, A Baile, WF Lenzi, R Costantini, M Ziparo, V Marchetti, P Grassi, L AF Costantini, Anna Baile, Walter F. Lenzi, Renato Costantini, Massimo Ziparo, Vincenzo Marchetti, Paolo Grassi, Luigi TI Overcoming Cultural Barriers to Giving Bad News: Feasibility of Training to Promote Truth-Telling to Cancer Patients SO JOURNAL OF CANCER EDUCATION LA English DT Article ID TEACHING COMMUNICATION-SKILLS; ONCOLOGY FELLOWS; DISCLOSURE; ATTITUDES; INFORMATION; CARE AB Background. In many countries, physicians are reluctant to disclose unfavorable medical information to patients with advanced cancer and instead give the bad news to the family. Methods. The authors modified standard communication workshops to help Italian senior oncologists overcome cultural, social, and attitudinal barriers to disclosure of diagnosis and prognosis. Results. Fifty-seven physicians participated; 88% believed the workshops would improve their medical practice. Many pursued further training and organized communication skills programs of their own. Conclusions. Communication skills workshops can be modified to meet educational and social norms and help clinicians acquire the interpersonal skills needed for honest communication with patients. C1 [Baile, Walter F.] Univ Texas MD Anderson Canc Ctr, Dept Behav Sci & Fac Dev, Unit 1426, Houston, TX 77230 USA. [Costantini, Anna] St Andrea Hosp, Dept Psychooncol, Rome, Italy. [Ziparo, Vincenzo] St Andrea Hosp, Dept Surg, Rome, Italy. [Marchetti, Paolo] St Andrea Hosp, Dept Med Oncol, Rome, Italy. [Lenzi, Renato] Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77230 USA. [Costantini, Massimo] Natl Canc Inst, Clin Epidemiol Serv, Genoa, Italy. [Grassi, Luigi] Univ Ferrara, Sect Psychiat, I-44100 Ferrara, Italy. [Grassi, Luigi] Dept Mental Hlth, Ferrara, Italy. [Costantini, Anna; Ziparo, Vincenzo] Univ Rome, Fac Med 2, Rome, Italy. RP Baile, WF (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Behav Sci & Fac Dev, Unit 1426, POB 301402, Houston, TX 77230 USA. EM wbaile@mdanderson.org RI costantini, massimo/G-1443-2012; Marchetti, Paolo/K-1469-2016; OI costantini, massimo/0000-0002-5293-7079 FU Novartis Oncology, Janssen-Cilag, Sanofi Aventis; Roche Pharmaceuticals FX Funding for this project was provided by unrestricted educational grants from Novartis Oncology, Janssen-Cilag, Sanofi Aventis, and Roche Pharmaceuticals. NR 29 TC 14 Z9 16 U1 0 U2 1 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 0885-8195 J9 J CANCER EDUC JI J. Cancer Educ. PY 2009 VL 24 IS 3 BP 180 EP 185 AR PII 912376511 DI 10.1080/08858190902876262 PG 6 WC Oncology; Education, Scientific Disciplines; Public, Environmental & Occupational Health SC Oncology; Education & Educational Research; Public, Environmental & Occupational Health GA 457ZP UT WOS:000266978800005 PM 19526404 ER PT J AU Mitschke, DB Kasuya, RT Cassel, K Barcia, AM AF Mitschke, Diane B. Kasuya, Richard T. Cassel, Kevin Barcia, Anthony M. TI Introducing Educational Interventions for First Year Medical Students in the Area of Cancer Clinical Trials: Impact on Attitudes and Confidence SO JOURNAL OF CANCER EDUCATION LA English DT Article ID PARTICIPATION; BARRIERS AB Background. This study tested the feasibility and efficacy of a multi-faceted educational intervention designed to increase medical students' confidence in discussing cancer clinical trials with patients. Method. First year students were provided with written resources, problem-based learning scenarios, and an optional practicum. Results. Pre/Post results indicated significant increases in confidence levels; however, these results were tempered with declines in attitudes related to clinical trials. Conclusions. Integrating clinical trials education into existing medical school curriculum is both feasible and desirable. This intervention was successful in increasing students' confidence levels in discussing clinical trials with patients and deserves continued study. C1 [Mitschke, Diane B.] Univ Texas Arlington, Sch Social Work, Arlington, TX 76019 USA. [Kasuya, Richard T.; Barcia, Anthony M.] Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96822 USA. [Cassel, Kevin] NCI, Canc Informat Serv, Honolulu, HI USA. RP Mitschke, DB (reprint author), Univ Texas Arlington, Sch Social Work, 211 S Cooper St,Box 19129, Arlington, TX 76019 USA. EM dianemitschke@uta.edu NR 10 TC 0 Z9 0 U1 0 U2 1 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 0885-8195 J9 J CANCER EDUC JI J. Cancer Educ. PY 2009 VL 24 IS 3 BP 212 EP 217 AR PII 912376890 DI 10.1080/08858190902910855 PG 6 WC Oncology; Education, Scientific Disciplines; Public, Environmental & Occupational Health SC Oncology; Education & Educational Research; Public, Environmental & Occupational Health GA 457ZP UT WOS:000266978800011 PM 19526410 ER PT J AU Hoffman-Goetz, L Meissner, HI Thomson, MD AF Hoffman-Goetz, L. Meissner, H. I. Thomson, M. D. TI Literacy and Cancer Anxiety as Predictors of Health Status: An Exploratory Study SO JOURNAL OF CANCER EDUCATION LA English DT Article ID SELF-RATED HEALTH; COLORECTAL-CANCER; PERCEIVED HEALTH; PROSTATE-CANCER; EMERGENCY-DEPARTMENT; PSYCHOSOCIAL FACTORS; INFORMATION-SEEKING; LANGUAGE BARRIERS; HISPANIC WOMEN; BREAST-CANCER AB Background. Socioeconomic status is a strong correlate of health status. Low literacy is associated with barriers to health information and anxiety about disease. Methods. Using 2003 Health Information National Trends Survey data, the relationship between self-reported health status and proxy measures of literacy (Hispanic ethnicity, education, and media variables), cancer anxiety, and cancer information seeking were assessed. Results. Low literacy, measured by proxy variables, was associated with a greater likelihood of reporting fair-poor health status. Reporting excellent-good health status was less likely for people reporting frustration finding cancer information (odds ratio [OR] 0.68, 95% confidence interval [CI] 0.52-0.89), worry about cancer (OR 0.56, 95% CI 0.35-0.89), and increased chance of getting cancer (OR 3.5, 95% CI 0.24-0.51). Conclusion. Proxy variables for literacy suggest a possible contribution to health status disparities. C1 [Hoffman-Goetz, L.; Thomson, M. D.] Univ Waterloo, Fac Appl Hlth Sci, Dept Hlth Studies & Gerontol, Waterloo, ON N2L 3G1, Canada. [Meissner, H. I.] NCI, Bethesda, MD 20892 USA. RP Hoffman-Goetz, L (reprint author), Univ Waterloo, Fac Appl Hlth Sci, Dept Hlth Studies & Gerontol, Waterloo, ON N2L 3G1, Canada. EM lhgoetz@uwaterloo.ca OI Thomson, Maria/0000-0002-5729-8720 FU The Social Sciences and Humanities Research Council of Canada FX Supported in part by The Social Sciences and Humanities Research Council of Canada. NR 50 TC 7 Z9 7 U1 3 U2 9 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 0885-8195 J9 J CANCER EDUC JI J. Cancer Educ. PY 2009 VL 24 IS 3 BP 218 EP 224 AR PII 912376571 DI 10.1080/08858190902910871 PG 7 WC Oncology; Education, Scientific Disciplines; Public, Environmental & Occupational Health SC Oncology; Education & Educational Research; Public, Environmental & Occupational Health GA 457ZP UT WOS:000266978800012 PM 19526411 ER PT J AU Kaphingst, KA Lachance, CR Condit, CM AF Kaphingst, Kimberly A. Lachance, Christina R. Condit, Celeste M. TI Beliefs About Heritability of Cancer and Health Information Seeking and Preventive Behaviors SO JOURNAL OF CANCER EDUCATION LA English DT Article ID NATIONAL TRENDS SURVEY; SMOKING-CESSATION TREATMENT; GENETIC SUSCEPTIBILITY; PERCEIVED RISK; SURVEY HINTS; MEDIA; DISSEMINATION; KNOWLEDGE; RESPONSES; SCIENCE AB Background. Individuals' beliefs about cancer heritability could affect their health information seeking and health behaviors. Methods. Data from 5813 English-speaking adult respondents to the 2003 Health Information National Trends Survey were analyzed. Results. Individuals who believed that knowledge of family history or genes can reduce cancer risk were significantly more likely to have ever looked for cancer information. Ever smokers who believed that genes are the main cause of lung cancer were significantly more likely to smoke currently. Conclusions. Patients need to be educated about genetic susceptibility to cancer in ways that support information seeking and engagement in protective behaviors. C1 [Kaphingst, Kimberly A.; Lachance, Christina R.] NHGRI, Bethesda, MD 20892 USA. [Condit, Celeste M.] Univ Georgia, Athens, GA 30602 USA. RP Kaphingst, KA (reprint author), Bldg 31,Room B1B37E,31 Ctr Dr, Bethesda, MD 20892 USA. EM kkaphing@mail.nih.gov FU National Human Genome Research Institute, National Institutes of Health FX Supported by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. NR 25 TC 14 Z9 14 U1 1 U2 12 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 0885-8195 J9 J CANCER EDUC JI J. Cancer Educ. PY 2009 VL 24 IS 4 BP 351 EP 356 AR PII 915933084 DI 10.1080/08858190902876304 PG 6 WC Oncology; Education, Scientific Disciplines; Public, Environmental & Occupational Health SC Oncology; Education & Educational Research; Public, Environmental & Occupational Health GA 515YU UT WOS:000271509600021 PM 19838898 ER PT J AU Berger, AC Roche, PA AF Berger, Adam C. Roche, Paul A. TI MHC class II transport at a glance SO JOURNAL OF CELL SCIENCE LA English DT Article ID DENDRITIC CELL MATURATION; ANTIGEN PRESENTATION; PEPTIDE COMPLEXES; LIPID RAFTS; IMMUNOLOGICAL SYNAPSE; LYSOSOMAL PROTEOLYSIS; PLASMA-MEMBRANE; HLA-DO; MOLECULES; COMPARTMENTS C1 [Berger, Adam C.; Roche, Paul A.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Roche, PA (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM paul.roche@nih.gov FU Intramural Research Program of the National Institutes of Health; National Cancer Institute FX Work in the Roche laboratory is supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. We apologize to the many researchers whose original work could not be cited owing to space limitations. Deposited in PMC for release after 12 months. NR 29 TC 25 Z9 51 U1 0 U2 6 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD JAN 1 PY 2009 VL 122 IS 1 BP 1 EP 4 DI 10.1242/jcs.035089 PG 4 WC Cell Biology SC Cell Biology GA 384YN UT WOS:000261780200001 PM 19092054 ER PT J AU Regenberg, A Mathews, DJH Blass, DM Bok, H Coyle, JT Duggan, P Faden, R Finkel, J Gearhart, JD Hillis, A Hoke, A Johnson, R Johnston, M Kahn, J Kerr, D King, P Kurtzberg, J Liao, SM McDonald, JW McKhann, G Nelson, KB Rao, M Siegel, AW Smith, K Solter, D Song, H Sugarman, J Vescovi, A Young, W Greely, HT Traystman, RJ AF Regenberg, Alan Mathews, Debra J. H. Blass, David M. Bok, Hilary Coyle, Joseph T. Duggan, Patrick Faden, Ruth Finkel, Julia Gearhart, John D. Hillis, Argye Hoke, Ahmet Johnson, Richard Johnston, Michael Kahn, Jeffrey Kerr, Douglas King, Patricia Kurtzberg, Joanne Liao, S. Matthew McDonald, John W. McKhann, Guy Nelson, Karin B. Rao, Mahendra Siegel, Andrew W. Smith, Kirby Solter, Davor Song, Hongjun Sugarman, Jeremy Vescovi, Angelo Young, Wise Greely, Henry T. Traystman, Richard J. TI The role of animal models in evaluating reasonable safety and efficacy for human trials of cell-based interventions for neurologic conditions SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Review DE clinical trials; modeling; neurologic conditions; stem and progenitor cells ID EMBRYONIC STEM-CELLS; ACUTE ISCHEMIC-STROKE; MOUSE MODELS; HUNTINGTONS-DISEASE; PARKINSONS-DISEASE; MULTIPLE-SCLEROSIS; SOCIAL-INTERACTION; CEREBRAL-ISCHEMIA; DRUG DEVELOPMENT; THERAPY AB Progress in regenerative medicine seems likely to produce new treatments for neurologic conditions that use human cells as therapeutic agents; at least one trial for such an intervention is already under way. The development of cell-based interventions for neurologic conditions (CBI-NCs) will likely include preclinical studies using animals as models for humans with conditions of interest. This paper explores predictive validity challenges and the proper role for animal models in developing CBI-NCs. In spite of limitations, animal models are and will remain an essential tool for gathering data in advance of first-in-human clinical trials. The goal of this paper is to provide a realistic lens for viewing the role of animal models in the context of CBI-NCs and to provide recommendations for moving forward through this challenging terrain.Journal of Cerebral Blood Flow & Metabolism (2009) 29, 1-9; doi:10.1038/jcbfm.2008.98; published online 27 August 2008 C1 [Regenberg, Alan; Mathews, Debra J. H.; Bok, Hilary; Duggan, Patrick; Faden, Ruth; Finkel, Julia; Liao, S. Matthew; Siegel, Andrew W.; Sugarman, Jeremy] Johns Hopkins Univ, Johns Hopkins Berman Inst Bioeth, Baltimore, MD 21201 USA. [Blass, David M.] Johns Hopkins Univ, Dept Psychiat & Behav Sci, Baltimore, MD 21201 USA. [Blass, David M.] Abarbanel Mental Hlth Ctr, Bat Yam, Israel. [Blass, David M.] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel. [Coyle, Joseph T.] Harvard Univ, Sch Med, Dept Psychiat, Belmont, MA 02178 USA. [Gearhart, John D.; Song, Hongjun] Johns Hopkins Univ, Inst Cell Engn, Baltimore, MD 21201 USA. [Hillis, Argye; Hoke, Ahmet] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21201 USA. [Johnson, Richard] Johns Hopkins Univ, Dept Mol Microbiol & Immunol, Baltimore, MD 21201 USA. [Johnston, Michael] Kennedy Krieger Inst, Div Neurol & Dev Med, Baltimore, MD USA. [Kahn, Jeffrey] Univ Minnesota, Ctr Bioeth, Minneapolis, MN USA. [Kerr, Douglas] Johns Hopkins Univ, Johns Hopkins Transverse Myelopathy Ctr, Baltimore, MD 21201 USA. [King, Patricia] Georgetown Univ, Sch Law, Washington, DC USA. [Kurtzberg, Joanne] Duke Univ, Med Ctr, Div Pediat Blood & Marrow Transplantat, Durham, NC USA. [Liao, S. Matthew] Univ Oxford, Fac Philosophy, Oxford, England. [McDonald, John W.] Kennedy Krieger Inst, Int Ctr Spinal Cord Injury, Baltimore, MD USA. [McKhann, Guy] Johns Hopkins Univ, Zanvyl Krieger Mind Brain Inst, Baltimore, MD 21201 USA. [Nelson, Karin B.; Rao, Mahendra] NINDS, Natl Inst Hlth, Bethesda, MD 20892 USA. [Smith, Kirby] Invitrogen Corp, Carlsbad, CA USA. [Solter, Davor] Natl Univ Singapore, Inst Med Biol, ASTAR, Singapore 117548, Singapore. [Vescovi, Angelo] Univ Milan, Dept Biol Sci & Biotechnol, Milan, Italy. [Young, Wise] Rutgers State Univ, WM Keck Ctr Collaborat Neurosci, Piscataway, NJ USA. [Greely, Henry T.] Stanford Univ, Stanford Law Sch, Stanford, CA 94305 USA. [Traystman, Richard J.] Univ Colorado, Denver, CO 80202 USA. RP Regenberg, A (reprint author), Johns Hopkins Univ, Johns Hopkins Berman Inst Bioeth, 100 N Charles St,Suite 740, Baltimore, MD 21201 USA. EM aregenbe@jhsph.edu OI Solter, Davor/0000-0002-8438-347X; Hoke, Ahmet/0000-0003-1215-3373 FU NINDS NIH HHS [R01 NS046072, R01 NS046072-08] NR 74 TC 11 Z9 11 U1 2 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JAN PY 2009 VL 29 IS 1 BP 1 EP 9 DI 10.1038/jcbfm.2008.98 PG 9 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 389QS UT WOS:000262110200001 PM 18728679 ER PT J AU Shen, J Rothman, DL Behar, KL Xu, S AF Shen, Jun Rothman, Douglas L. Behar, Kevin L. Xu, Su TI Determination of the glutamate-glutamine cycling flux using two-compartment dynamic metabolic modeling is sensitive to astroglial dilution SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE brain glucose metabolism; glutamate-glutamine neurotransmitter cycling; magnetic resonance spectroscopy; (13)C isotopes ID MAGNETIC-RESONANCE-SPECTROSCOPY; VIVO C-13 NMR; TRICARBOXYLIC-ACID CYCLE; IN-VIVO; RAT-BRAIN; NEUROTRANSMITTER GLUTAMATE; CEREBRAL METABOLISM; GLUCOSE-METABOLISM; TCA CYCLE; ASTROCYTES AB Over the last decade (13)C magnetic resonance spectroscopy ((13)C MRS) combined with the infusion of [1-(13)C] glucose has been used to measure the cerebral rate of the glutamate-glutamine cycle (V(cyc)). However, the effect of the astroglial label dilution pathways on the accuracy and precision of the (13)C MRS measurement of V(cyc) has not been evaluated or realized. In this report, we use the numerical Monte Carlo method to study the effect of astroglial dilution on the reliability of extracting Vcyc using the neuronal-astroglial two-compartment metabolic model and [1-(13)C] glucose infusion. The results show that omission of the astroglial dilution flux leads to a large loss in the sensitivity of the glutamine turnover curve to V(cyc). When the measured isotopic dilution of cerebral glutamine is accounted for in the analysis, the value of V(cyc) can be precisely and accurately determined. C1 [Shen, Jun; Xu, Su] NIMH, Mood & Anxiety Disorders Program, Mol Imaging Branch, Bethesda, MD 20892 USA. [Rothman, Douglas L.] Yale Univ, Sch Med, Dept Diagnost Radiol, Magnet Resonance Res Ctr, New Haven, CT 06510 USA. [Behar, Kevin L.] Yale Univ, Sch Med, Dept Psychiat, Magnet Resonance Res Ctr, New Haven, CT 06510 USA. RP Shen, J (reprint author), NIMH, Mood & Anxiety Disorders Program, Mol Imaging Branch, Bldg 10,Room 2D51A,9000 Rockville Pike, Bethesda, MD 20892 USA. EM shenj@intra.nimh.nih.gov FU NIH; NIMH [NS37527, DK27121] FX This work was supported by the Intramural Program of NIH, NIMH, NS37527 (NINDS), and DK27121 (NIDDK). NR 48 TC 17 Z9 18 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JAN PY 2009 VL 29 IS 1 BP 108 EP 118 DI 10.1038/jcbfm.2008.102 PG 11 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 389QS UT WOS:000262110200013 PM 18766194 ER PT J AU Sharma, HS Kiyatkin, EA AF Sharma, Hari S. Kiyatkin, Eugene A. TI Rapid morphological brain abnormalities during acute methamphetamine intoxication in the rat: An experimental study using light and electron microscopy SO JOURNAL OF CHEMICAL NEUROANATOMY LA English DT Article DE Blood-brain barrier; Brain edema; Brain pathology; Glial cells; Neuronal damage; Myelin vesiculation; Endothelial cells ID CENTRAL-NERVOUS-SYSTEM; SPINAL CORD BARRIER; SUBSTITUTED AMPHETAMINES; DOPAMINERGIC NEUROTOXICITY; ENVIRONMENTAL-TEMPERATURE; INDUCED HYPERTHERMIA; C57BL/6J MOUSE; CHOROID-PLEXUS; HEAT-STRESS; DEATH AB This Study describes morphological abnormalities of brain cells during acute methamphetamine (METH) intoxication in the rat and demonstrates the role of hyperthermia, disruption of the blood-brain barrier (BBB) and edema in their development. Rats with chronically implanted brain, muscle and skin temperature probes and an intravenous (i.v.) catheter were exposed to METH (9 mg/kg) at standard (23 C) and warm (29 C) ambient temperatures, allowing for the observation of hyperthermia ranging from mile to pathological (38-42 C). When brain temperature peaked or reached a level suggestive of possible lethality(>41.5 C), rats were injected wit It Evans blue (EB), rapidly anesthetized, perfused, and their brains were taken for further analyses. Four brain areas (cortex, hippocampus, thalamus and hypothalamus) Were analyzed for EB extravasation, water and electrolyte (Na(+), K(+), Cl) contents, immunostained for albumin and glial fibrillary acidic protein (GFAP), and examined for neuronal, glial and axonal alterations Using standard light and electron microscopy. These examinations revealed Profound abnormalities in neuronal, glial, and endothelial cells, which were Stronger with METH administered at 29 C than 23 C and tightly correlated with brain and body hyperthermia. These changes had some structural Specificity, but in each structure they tightly correlated with increases in EB levels, the numbers of albumin-positive cells, and water and ion contents, suggesting leakage of the BBB, acutely developing brain edema, and Serious shifts in brain ion homeostasis as leading factors Underlying brain abnormalities. While most of these acute structural and functional abnormalities appear to be reversible, they could trigger subsequent cellular alterations in the brain and accelerate neurodegeneration-the most dangerous complication of chronic amphetamine-like drug abuse. Published by Elsevier B.V. C1 [Sharma, Hari S.] Uppsala Univ, Univ Hosp, Dept Surg Sci, Lab Cerebrovasc Res, SE-75185 Uppsala, Sweden. [Sharma, Hari S.; Kiyatkin, Eugene A.] NIDA, Behav Neurosci Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Sharma, HS (reprint author), Frodingsgatan 12-28, SE-75421 Uppsala, Sweden. EM Sharma@surgsci.uu.se RI Sharma, Hari/G-4508-2016 FU NIDA-NIH; Leaderal Foundation; 2006 NIDA Distinguished International Scientist Collaboration Award FX This study was supported by the Intramural Research Program of NIDA-NIH, the Leaderal Foundation, and 2006 NIDA Distinguished International Scientist Collaboration Award (NIH) awarded to Hari S. Sharma. The authors greatly appreciate technical assistance of Mari-Anne Carlsson and Inga Horte (Uppsala University) as well as P. Leon Brown (NIDA-IRP). NR 59 TC 71 Z9 73 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0891-0618 J9 J CHEM NEUROANAT JI J. Chem. Neuroanat. PD JAN PY 2009 VL 37 IS 1 BP 18 EP 32 DI 10.1016/j.jchemneu.2008.08.002 PG 15 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 398QV UT WOS:000262747500002 PM 18773954 ER PT J AU Ihlenfeldt, WD Bolton, EE Bryant, SH AF Ihlenfeldt, Wolf D. Bolton, Evan E. Bryant, Stephen H. TI The PubChem chemical structure sketcher SO JOURNAL OF CHEMINFORMATICS LA English DT Article AB PubChem is an important public, Web-based information source for chemical and bioactivity information. In order to provide convenient structure search methods on compounds stored in this database, one mandatory component is a Web-based drawing tool for interactive sketching of chemical query structures. Web-enabled chemical structure sketchers are not new, being in existence for years; however, solutions available rely on complex technology like Java applets or platform-dependent plug-ins. Due to general policy and support incident rate considerations, Java-based or platform-specific sketchers cannot be deployed as a part of public NCBI Web services. Our solution: a chemical structure sketching tool based exclusively on CGI server processing, client-side JavaScript functions, and image sequence streaming. The PubChem structure editor does not require the presence of any specific runtime support libraries or browser configurations on the client. It is completely platform-independent and verified to work on all major Web browsers, including older ones without support for Web2.0 JavaScript objects. C1 [Bolton, Evan E.; Bryant, Stephen H.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Dept Hlth & Human Serv, Bethesda, MD 20894 USA. [Ihlenfeldt, Wolf D.] Xemistry GmbH, D-61462 Konigstein, Germany. RP Bryant, SH (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Dept Hlth & Human Serv, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM wdi@xemistry.com; bolton@ncbi.nlm.nih.gov; bryant@ncbi.nlm.nih.gov FU NIH, National Library of Medicine FX This research was supported [in part] by the Intramural Research Program of the NIH, National Library of Medicine. NR 17 TC 16 Z9 18 U1 1 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1758-2946 J9 J CHEMINFORMATICS JI J. Cheminformatics PY 2009 VL 1 AR 20 DI 10.1186/1758-2946-1-20 PG 9 WC Chemistry, Multidisciplinary; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Chemistry; Computer Science GA V21QM UT WOS:000208222100020 PM 20298522 ER PT J AU Peach, ML Nicklaus, MC AF Peach, Megan L. Nicklaus, Marc C. TI Combining docking with pharmacophore filtering for improved virtual screening SO JOURNAL OF CHEMINFORMATICS LA English DT Article AB Background: Virtual screening is used to distinguish potential leads from inactive compounds in a database of chemical samples. One method for accomplishing this is by docking compounds into the structure of a receptor binding site in order to rank-order compounds by the quality of the interactions they form with the receptor. It is generally established that docking can be reasonably successful at generating good poses of a ligand in an active site. However, the scoring functions that are used with docking are typically not successful at correctly ranking ligands according to binding affinity or even distinguishing correct poses of a given ligand from incorrect ones. Results: We have developed a simple method for reducing the number of false positives in a virtual screen, meaning ligands which are scored highly by the docking program but do not bind well in reality. This method uses a docking program for pose generation without regard to scoring, followed by filtering with receptor-based pharmacophore searches. We applied it to three test-case targets: neuraminidase A, cyclin-dependent kinase 2, and the C1 domain of protein kinase C. Conclusion: The pharmacophore filtering method can perform better than more traditional docking + scoring methods, and allows the advantages of both docking-based and pharmacophore-based approaches to virtual screening to be fully realized. C1 [Nicklaus, Marc C.] NCI, Lab Med Chem, Ctr Canc Res, Frederick, MD 21702 USA. [Peach, Megan L.] NCI, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Nicklaus, MC (reprint author), NCI, Lab Med Chem, Ctr Canc Res, Frederick, MD 21702 USA. EM mpeach@helix.nih.gov; mn1@helix.nih.gov RI Nicklaus, Marc/N-4183-2014; OI Nicklaus, Marc/0000-0002-4775-7030 FU NIH, National Cancer Institute, Center for Cancer Research; National Cancer Institute, National Institutes of Health [N01-CO-12400, HHSN261-2008-00001E] FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. This project has been funded with federal funds from the National Cancer Institute, National Institutes of Health, under contracts N01-CO-12400 and HHSN261-2008-00001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 48 TC 20 Z9 20 U1 0 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1758-2946 J9 J CHEMINFORMATICS JI J. Cheminformatics PY 2009 VL 1 AR 6 DI 10.1186/1758-2946-1-6 PG 15 WC Chemistry, Multidisciplinary; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Chemistry; Computer Science GA V21QM UT WOS:000208222100006 PM 20298524 ER PT J AU Rapoport, JL AF Rapoport, Judith L. TI Personal reflections on observational and experimental research approaches to childhood psychopathology SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE Attention deficit hyperactivity disorder; child psychiatry; childhood onset schizophrenia; epidemiology; experimental research; follow-up studies; observational research; obsessive compulsive disorder; pervasive developmental disorder; stimulants ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; OBSESSIVE-COMPULSIVE DISORDER; ONSET SCHIZOPHRENIA; CLINICAL CHARACTERISTICS; MULTIMODAL TREATMENT; FOLLOW-UP; CHILDREN; PSYCHOSES; CLOMIPRAMINE; DESIPRAMINE AB The past 50 years have seen dramatic changes in childhood psychopathology research. The goal of this overview is to contrast observational and experimental research approaches; both have grown more complex such that the boundary between these approaches may be blurred. Both are essential. Landmark observational studies with long-term follow-up (Robins, 1966; Yarrow, Campbell, & Burton, 1970) have had - and continue to have - unique impact on clinical research and practice. Epidemiological studies showed high rates of psychological disorder and their close tie to neurological impairment (Rutter, Tizard, & Whitemore, 1970). These studies have current impact with respect to brain imaging correlates of clinical outcome. Pharmacological studies, particularly those on stimulants and on treatment of pediatric obsessive compulsive disorder (OCD), have propelled experimental methodology and inspired translational approaches. Predicted future trends are: more informed subgrouping of our heterogeneous phenotypes, reliance on multicenter trials, and documentation of non-conventional methods of care delivery. C1 NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. RP Rapoport, JL (reprint author), NIMH, Child Psychiat Branch, NIH, Bldg 10,Room 3N202, Bethesda, MD 20892 USA. EM rapoporj@mail.nih.gov FU Intramural NIH HHS [ZIA MH002581-19] NR 65 TC 2 Z9 2 U1 3 U2 6 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0021-9630 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry PD JAN-FEB PY 2009 VL 50 IS 1-2 BP 36 EP 43 DI 10.1111/j.1469-7610.2008.01975.x PG 8 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA 400SU UT WOS:000262889700006 PM 19175812 ER PT J AU Domino, ME Burns, BJ Mario, J Reinecke, MA Vitiello, B Weller, EB Kratochvil, CJ AF Domino, Marisa Elena Burns, Barbara J. Mario, Jeremy Reinecke, Mark A. Vitiello, Benedetto Weller, Elizabeth B. Kratochvil, Christopher J. TI Service Use and Costs of Care for Depressed Adolescents: Who Uses and Who Pays? SO JOURNAL OF CLINICAL CHILD AND ADOLESCENT PSYCHOLOGY LA English DT Article ID DISORDERS; BURDEN; CHILD; OUTPATIENT; OUTCOMES; YOUTHS AB Major depressive disorder is common in adolescence and is associated with significant morbidity and family burden. Little is known about service use by depressed adolescents. The purpose of this article is to report the patterns of services use and costs for participants in the Treatment for Adolescents with Depression Study sample during the 3 months before randomization. Costs were assigned across three categories of payors: families, private insurance, and the public sector. We examined whether costs from payors varied by baseline covariates, such as age, gender, insurance status, and family income. The majority (71%) of depressed youth sought services during the 3-month period. Slightly more than one-fifth had contact with a behavioral health specialist. The average participant had just under $300 (SD = $437.67, range = $0 $3,747.71) in treatment-related costs, with most of these costs borne by families and private insurers. C1 [Domino, Marisa Elena; Mario, Jeremy] Univ N Carolina, Dept Hlth Policy & Management, Chapel Hill, NC 27599 USA. [Burns, Barbara J.] Duke Univ, Dept Psychiat & Behav Sci, Durham, NC 27706 USA. [Reinecke, Mark A.] Northwestern Univ, Dept Psychiat & Behav Sci, Evanston, IL 60208 USA. [Vitiello, Benedetto] NIMH, Div Intervent & Res, Bethesda, MD 20892 USA. [Weller, Elizabeth B.] Univ Penn, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Kratochvil, Christopher J.] Nebraska Med Ctr, Psychopharmacol Res Ctr, Omaha, NE 68198 USA. RP Domino, ME (reprint author), Univ N Carolina, Dept Hlth Policy & Adm, 1104G McGavran Greenberg Hall,CB 7411, Chapel Hill, NC 27599 USA. EM domino@unc.edu FU NIMH NIH HHS [N01 MH80008, K01-MH065639] NR 34 TC 4 Z9 4 U1 0 U2 0 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 1537-4416 J9 J CLIN CHILD ADOLESC JI J. Clin. Child Adolesc. Psychol. PY 2009 VL 38 IS 6 BP 826 EP 836 DI 10.1080/15374410903259023 PG 11 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA 528OL UT WOS:000272456000007 PM 20183666 ER PT J AU Nguyen, JH Lodish, MB Patronas, NJ Ugrasbul, F Keil, MF Roberts, MD Popovic, J Stratakis, CA AF Nguyen, Jil Huong Lodish, Maya B. Patronas, Nicholas J. Ugrasbul, Figen Keil, Margaret F. Roberts, Mary D. Popovic, Jadranka Stratakis, Constantine A. TI Extensive and Largely Reversible Ischemic Cerebral Infarctions in a Prepubertal Child with Hypertension and Cushing Disease SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material C1 [Lodish, Maya B.; Keil, Margaret F.; Roberts, Mary D.; Stratakis, Constantine A.] NICHHD, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. [Nguyen, Jil Huong] Univ Calif San Francisco, Childrens Hosp Cent Calif, Div Endocrinol & Diabet, Madera, CA 93636 USA. [Keil, Margaret F.; Roberts, Mary D.; Stratakis, Constantine A.] NICHHD, Pediat Endocrinol Program, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. [Patronas, Nicholas J.] NIH, Dept Diagnost Radiol, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. [Ugrasbul, Figen] Univ Missouri, Childrens Mercy Hosp, Div Endocrinol & Diabet, Sch Med, Kansas City, MO 64108 USA. [Popovic, Jadranka] Univ Pittsburgh, Childrens Hosp Pittsburgh, Med Ctr, Div Endocrinol Diabet & Metab, Pittsburgh, PA 15213 USA. RP Lodish, MB (reprint author), NICHHD, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bldg 10 CRC E,Room 1-3330,10 Ctr Dr MSC 1103, Bethesda, MD 20892 USA. EM lodishma@mail.nih.gov FU Intramural NIH HHS NR 5 TC 5 Z9 6 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2009 VL 94 IS 1 BP 1 EP 2 DI 10.1210/jc.2008-1346 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 391UR UT WOS:000262260200001 PM 19126630 ER PT J AU Savage, DB Semple, RK Clatworthy, MR Lyons, PA Morgan, BP Cochran, EK Gorden, P Raymond-Barker, P Murgatroyd, PR Adams, C Scobie, I Mufti, GJ Alexander, GJM Thiru, S Murano, I Cinti, S Chaudhry, AN Smith, KGC O'Rahilly, S AF Savage, David B. Semple, Robert K. Clatworthy, Menna R. Lyons, Paul A. Morgan, B. Paul Cochran, Elaine K. Gorden, Phillip Raymond-Barker, Philippa Murgatroyd, Peter R. Adams, Claire Scobie, Ian Mufti, Ghulam J. Alexander, Graeme J. M. Thiru, Sathia Murano, Incoronata Cinti, Saverio Chaudhry, Afzal N. Smith, Kenneth G. C. O'Rahilly, Stephen TI Complement Abnormalities in Acquired Lipodystrophy Revisited SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID OF-THE-LITERATURE; INSULIN-RESISTANCE; ADIPOSE-TISSUE; NEPHRITIC FACTOR; GENERALIZED LIPODYSTROPHY; AUTOIMMUNE-DISEASES; CLINICAL-FEATURES; OBESE MICE; ADIPONECTIN; ADIPOCYTE AB Context: Lipodystrophy is a heterogeneous condition characterized by an inherited or acquired deficiency in the number of adipocytes required for the storage of energy as triglycerides. Acquired lipodystrophy is frequently associated with other autoimmune disorders. One well-studied form is characterized by the selective loss of upper body fat in association with activation of the alternative complement pathway by C3 nephritic factor, low complement factor C3, and mesangiocapillary glomerulonephritis. Objective: We now describe an immunologically distinct form of acquired generalized lipodystrophy, with evidence of activation of the classical complement pathway (low C4) and autoimmune hepatitis. Patients and Research Design: Three unrelated patients with acquired lipodystrophy and low complement C4 levels are described. In vitro analysis of the complement pathway was undertaken to determine the reason for the low C4 complement levels. Biopsies were obtained from liver, bone marrow, and adipose tissue for histological analysis. Results: All three patients manifested near-total lipodystrophy, chronic hepatitis with autoimmune features, and low C4 complement levels. Additional autoimmune diseases, including severe hemolytic anemia, autoimmune thyroid disease, and polyneuropathy, were variably present. Detailed studies of complement pathways suggested constitutive classical pathway activation. Conclusions: Although the previously described syndrome, which typically results in a cephalad pattern of partial lipodystrophy, results from activation of the alternative complement pathway, this form, in which lipodystrophy is generalized, is associated with activation of the classical pathway. Future therapeutic approaches to these disorders may benefit from being tailored to their distinct immunopathogenesis. (J Clin Endocrinol Metab 94: 10-16, 2009) C1 [Savage, David B.] Univ Cambridge, Addenbrookes Hosp, Metab Res Labs, Inst Metab Sci, Cambridge CB2 0QQ, England. [Clatworthy, Menna R.; Lyons, Paul A.; Alexander, Graeme J. M.; Chaudhry, Afzal N.; Smith, Kenneth G. C.] Univ Cambridge, Addenbrookes Hosp, Dept Med, Inst Metab Sci, Cambridge CB2 0QQ, England. [Thiru, Sathia] Univ Cambridge, Addenbrookes Hosp, Cambridge Inst Med Res, Cambridge CB2 0QQ, England. [Thiru, Sathia] Univ Cambridge, Addenbrookes Hosp, Dept Pathol, Cambridge CB2 0QQ, England. [Morgan, B. Paul] Cardiff Univ, Sch Med, Dept Med Biochem & Immunol, Cardiff CF10 3AT, S Glam, Wales. [Cochran, Elaine K.; Gorden, Phillip] NIDDK, Clin Endocrinol Branch, Bethesda, MD 20892 USA. [Raymond-Barker, Philippa; Murgatroyd, Peter R.] Addenbrookes Hosp, Wellcome Trust Clin Res Facil, Cambridge CB2 0SP, England. [Scobie, Ian] Medway Maritime Hosp, Gillingham ME7 5NY, Kent, England. [Mufti, Ghulam J.] Kings Coll London, Dept Haematol Med, London WC2R 2LS, England. [Murano, Incoronata; Cinti, Saverio] Univ Ancona, Inst Normal Human Morphol, I-60131 Ancona, Italy. RP Savage, DB (reprint author), Univ Cambridge, Addenbrookes Hosp, Metab Res Labs, Inst Metab Sci, Hills Rd, Cambridge CB2 0QQ, England. EM dbs23@medschl.cam.ac.uk; rks16@cam.ac.uk OI Semple, Robert/0000-0001-6539-3069 FU Wellcome Trust [078986/Z/06/Z]; Intermediate Clinical Fellowship [080952/Z/06/Z, 081020/Z/06/Z]; GlaxoSmithKline; United Kingdom National Institute for Health Research Cambridge Biomedical Research Centre FX This work was supported by Wellcome Trust (Programe Grant 078986/Z/06/Z to S.O., Intermediate Clinical Fellowship 080952/Z/06/Z to R. K. S., and Intermediate Clinical Fellowship 081020/Z/06/Z to M. R. C.), GlaxoSmithKline (GlaxoSmithKline Clinical Fellowship to D. B. S.), Wellcome Trust Clinical Research Facility, and the United Kingdom National Institute for Health Research Cambridge Biomedical Research Centre. NR 33 TC 25 Z9 27 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2009 VL 94 IS 1 BP 10 EP 16 DI 10.1210/jc.2008-1703 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 391UR UT WOS:000262260200004 PM 18854390 ER PT J AU Woyach, JA Kloos, RT Ringel, MD Arbogast, D Collamore, M Zwiebel, JA Grever, M Villalona-Calero, M Shah, MH AF Woyach, Jennifer A. Kloos, Richard T. Ringel, Matthew D. Arbogast, Daria Collamore, Minden Zwiebel, James A. Grever, Michael Villalona-Calero, Miguel Shah, Manisha H. TI Lack of Therapeutic Effect of the Histone Deacetylase Inhibitor Vorinostat in Patients with Metastatic Radioiodine-Refractory Thyroid Carcinoma SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SUBEROYLANILIDE HYDROXAMIC ACID; T-CELL LYMPHOMA; RADIOACTIVE IODINE THERAPY; SODIUM/IODIDE SYMPORTER; DEPSIPEPTIDE FR901228; SODIUM PHENYLBUTYRATE; MYELOID-LEUKEMIA; TRICHOSTATIN-A; VALPROIC ACID; CANCER CELLS AB Context: Aberrant histone deacetylase activity is seen in a variety of malignancies, and histone deacetylase inhibitors such as vorinostat have been shown to induce cell death and sensitize cells to cytotoxic chemotherapy in thyroid cancer cell lines. This phase II study was undertaken to assess objective response to vorinostat in patients with advanced thyroid cancer. Experimental Design: A total of 19 patients with differentiated thyroid cancer (n = 16) and medullary thyroid cancer (n = 3) were enrolled in the study. Patients received oral vorinostat at a starting dose of 200 mg twice daily, with dose adjustments allowed as necessary for toxicity. Patients were treated for 2 wk, followed by 1 wk off therapy (3-wk cycle) until disease progression or study withdrawal. Responses were measured by Response Evaluation Criteria in Solid Tumors criteria and correlated with tumor markers. Results: Nopatient achieved a partial or complete response. Median duration of therapy in patients with differentiated thyroid cancer was 17 wk, whereas in medullary thyroid cancer patients it was 25 wk. Reasons for termination included progression of disease by RECIST criteria (n = 7), clinical progression (n = 3), and adverse events (AEs) (n = 9). AEs were primarily grade 1-3; no clinical grade 4 or grade 5 events were observed. Clinical grade 3 AEs consisted of fatigue, dehydration, ataxia, pneumonia, bruises, and deep vein thrombosis. Severe thrombocytopenia was seen in seven patients (grade 3, n = 5; grade 4, n = 2) and was associated with minor bleeding or bruises. Conclusions: Vorinostat at this dose and schedule is not an effective treatment for advanced thyroid cancer. (J Clin Endocrinol Metab 94: 164-170, 2009) C1 [Woyach, Jennifer A.; Kloos, Richard T.; Ringel, Matthew D.; Arbogast, Daria; Collamore, Minden; Villalona-Calero, Miguel; Shah, Manisha H.] Ohio State Univ, Dept Internal Med, Columbus, OH 43210 USA. [Kloos, Richard T.] Ohio State Univ, Dept Radiol, Columbus, OH 43210 USA. [Zwiebel, James A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Shah, MH (reprint author), A438 Starling Loving Hall,320 West 10th Ave, Columbus, OH 43210 USA. EM manisha.shah@osumc.edu RI Woyach, Jennifer/F-1087-2015 FU National Cancer Institute, Bethesda, Maryland [U01 CA76576, NO1-CM62207] FX This work was supported by grants U01 CA76576 and NO1-CM62207 from the National Cancer Institute, Bethesda, Maryland. (Clinicaltrials.gov identifier no. NCT00134043). NR 34 TC 74 Z9 75 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2009 VL 94 IS 1 BP 164 EP 170 DI 10.1210/jc.2008-1631 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 391UR UT WOS:000262260200027 PM 18854394 ER PT J AU Salama, SA Kamel, MW Diaz-Arrastia, CR Xu, X Veenstra, TD Salih, S Botting, SK Kumar, R AF Salama, Salama A. Kamel, Marwa W. Diaz-Arrastia, Concepcion R. Xu, Xia Veenstra, Timothy D. Salih, Sana Botting, Shaleen K. Kumar, Raj TI Effect of Tumor Necrosis Factor-alpha on Estrogen Metabolism and Endometrial Cells: Potential Physiological and Pathological Relevance SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID 17-BETA-HYDROXYSTEROID-DEHYDROGENASE TYPE-2 EXPRESSION; STEROIDOGENIC-FACTOR-I; BREAST-CANCER CELLS; MESSENGER-RNA; ENDOGENOUS ESTROGENS; MASS-SPECTROMETRY; GENE-EXPRESSION; MECHANISM; AROMATASE; PROTEIN AB Context: Estrogen and its metabolites play a critical role in the pathophysiology of the endometrium. The bioavailability of estrogen and estrogen metabolites in endometrial tissues depends on the expression of enzymes involved in estrogen biosynthesis and metabolism. Substantial evidence indicates that estrogen-dependent endometrial disorders are also associated with proinflammatory milieu. However, the mechanism whereby inflammation contributes to these conditions is not known. Objective: The objective of the study was to investigate the effect of TNF-alpha on estrogen metabolism and the expression of estrogen-metabolizing genes inhuman endometrial glandular epithelial cells (EM1). Design: EM1 were treated with 17 beta-estradiol (E2) with or without TNF-alpha. Capillary liquid chromatography-tandem mass spectrometry analysis was used for quantitative measurement of estrogens and estrogen metabolites. Western blot analysis, reporter gene assay, and real-time RT-PCR were used to assess the expression of estrogen-metabolizing genes. Results: TNF-alpha treatment significantly increased the level of total estrogen and estrogen metabolites and significantly increased the rate of conversion of estrone (E1) into E2. TNF-alpha also enhanced the oxidative metabolism of estrogen into catecholestrogens with concomitant inhibition of their conversion into methoxyestrogens. Gene expression analysis revealed that TNF-alpha induced the expression of genes involved in E2 biosynthesis (steroidogenic factor-1 and aromatase) and activation (17 beta-hydroxysteroid dehydrogenase type 1 and cytochrome P-450, 1B1) with simultaneous repression of genes involved in estrogen inactivation (17 beta-hydroxysteroid dehydrogenase type 2; catechol O-methyltransferase; and nicotinamide adenine dinucleotide phosphate-quinone oxidoreductase 1). Conclusion: TNF-alpha increases the local estrogen biosynthesis in human endometrial glandular cells and directs estrogen metabolism into more hormonally active and carcinogenic metabolites. These effects may impact many physiological and pathological processes that occur within the endometrium. (J Clin Endocrinol Metab 94: 285-293, 2009) C1 [Salama, Salama A.] Univ Texas Med Branch Galveston, Div Gynecol Oncol, Dept Obstet & Gynecol, Galveston, TX 77555 USA. [Salama, Salama A.] Al Azahr Univ, Dept Pharmacol & Toxicol, Fac Pharm, Cairo, Egypt. [Kamel, Marwa W.] Cairo Univ, Dept Tumor Biol, Natl Canc Inst, Cairo, Egypt. [Xu, Xia; Veenstra, Timothy D.] NCI, Lab Prote & Analyt Technol, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21702 USA. [Salih, Sana] Univ Wisconsin, Dept Obstet & Gynecol, Madison, WI 53792 USA. RP Salama, SA (reprint author), Univ Texas Med Branch Galveston, Div Gynecol Oncol, Dept Obstet & Gynecol, 300 Univ Blvd, Galveston, TX 77555 USA. EM sasalama@utmb.edu OI theiler, shaleen/0000-0002-6881-6319 FU University of Texas Medical Branch National Institute of Environmental Health Sciences Center [E506676]; National Cancer Institute; National Institutes of Health [N01-CO-12400] FX This work was supported by University of Texas Medical Branch National Institute of Environmental Health Sciences Center Pilot Project E506676 ( to S. A. S.) and federal funds from the National Cancer Institute, National Institutes of Health, under Contract N01-CO-12400 ( to T. D. V.). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U. S. Government. NR 39 TC 32 Z9 35 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2009 VL 94 IS 1 BP 285 EP 293 DI 10.1210/jc.2008-1389 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 391UR UT WOS:000262260200043 PM 18957495 ER PT J AU Kanda, T Brown, JD Orasanu, G Vogel, S Gonzalez, FJ Sartoretto, J Michel, T Plutzky, J AF Kanda, Takeshi Brown, Jonathan D. Orasanu, Gabriela Vogel, Silke Gonzalez, Frank J. Sartoretto, Juliano Michel, Thomas Plutzky, Jorge TI PPAR gamma in the endothelium regulates metabolic responses to high-fat diet in mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ACTIVATED RECEPTOR-GAMMA; LOW-DENSITY-LIPOPROTEIN; CIRCULATING PROGENITOR CELLS; INDUCED INSULIN-RESISTANCE; ADIPOSE-TISSUE; ACID UPTAKE; ENERGY-EXPENDITURE; CD36 DEFICIENCY; SKELETAL-MUSCLE; LIPID TRANSPORT AB Although endothelial dysfunction, defined as abnormal vasoreactivity, is a common early finding in individuals with type 2 diabetes, the endothelium has not been known to regulate metabolism. As PPAR gamma, a transcriptional regulator of energy balance, is expressed in endothelial cells, we set out to investigate the role of endothelial cell PPAR gamma in metabolism using mice that lack PPAR gamma in the endothelium and BM (gamma EC/BM-KO). When gamma EC/BM-KO mice were fed a high-fat diet, they had decreased adiposity and increased insulin sensitivity compared with control mice, despite increased serum FFA and triglyceride (TG) levels. After fasting or olive oil gavage, gamma EC/BM-KO mice exhibited significant dyslipidemia and failed to respond to the FFA and TG lowering effects of the PPAR gamma agonist rosiglitazone. BM transplantation studies, which reconstituted hematopoietic PPAR gamma, established that these metabolic phenotypes were due to endothelial PPAR gamma deficiency. We further found that the impairment in TG-rich lipoprotein metabolism in gamma EC/BM-KO mice was associated with fatty acid-mediated lipoprotein lipase inhibition and changes in a PPAR gamma-regulated endothelial cell transcriptional program. Despite their metabolic improvements, high-fat diet-fed gamma EC/BM-KO mice had impaired vasoreactivity. Taken together, these data suggest that PPAR gamma in the endothelium integrates metabolic and vascular responses and may contribute to the effects of PPAR gamma agonists, thus expanding what endothelial function and dysfunction may entail. C1 [Kanda, Takeshi; Brown, Jonathan D.; Orasanu, Gabriela; Sartoretto, Juliano; Michel, Thomas; Plutzky, Jorge] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Cardiovasc Med, Boston, MA 02115 USA. [Vogel, Silke] Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY USA. [Gonzalez, Frank J.] NCI, Lab Metab, Nucle Acids Sect, NIH, Bethesda, MD 20892 USA. RP Plutzky, J (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Cardiovasc Med, New Res Bldg,77 Ave Louis Pasteur,NRB 742, Boston, MA 02115 USA. EM jplutzky@rics.bwh.harvard.edu OI sartoretto, juliano/0000-0002-0355-5541 FU Sankyo Foundation of Life Science; Mochida Memorial Foundation for Medical and Pharmaceutical Research; Uehara Memorial Foundation; NIH National Heart Lung and Blood Institute [R01 HL071745, P01 HL48743] FX This work was supported by the Sankyo Foundation of Life Science, the Mochida Memorial Foundation for Medical and Pharmaceutical Research, and the Uehara Memorial Foundation (to T. Kanda) and by the NIH National Heart Lung and Blood Institute grants R01 HL071745 (to J. Plutzky) and P01 HL48743 (to T. Michel and J. Plutzky). NR 72 TC 77 Z9 81 U1 1 U2 5 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JAN PY 2009 VL 119 IS 1 BP 110 EP 124 DI 10.1172/JCI36233 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 390BS UT WOS:000262139900015 PM 19065047 ER PT J AU Nasrallah, HA Keshavan, MS Benes, FM Braff, DL Green, AI Gur, RE Kane, JM Perkins, DO Weiden, PJ Weinberger, DR Correll, CU AF Nasrallah, Henry A. Keshavan, Matcheri S. Benes, Francine M. Braff, David L. Green, Alan I. Gur, Raquel E. Kane, John M. Perkins, Diana O. Weiden, Peter J. Weinberger, Daniel R. Correll, Christoph U. TI Proceedings and Data From The Schizophrenia Summit: A Critical Appraisal to Improve the Management of Schizophrenia SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Review ID ULTRA-HIGH-RISK; RANDOMIZED CONTROLLED-TRIAL; DORSOLATERAL PREFRONTAL CORTEX; CHILDHOOD-ONSET SCHIZOPHRENIA; CATECHOL-O-METHYLTRANSFERASE; 1ST EPISODE SCHIZOPHRENIA; BRAIN VOLUME CHANGES; GRAY-MATTER VOLUME; CORTICAL PYRAMIDAL NEURONS; ANTERIOR CINGULATE CORTEX AB In mid-February 2008, a panel of 10 nationally recognized schizophrenia research experts was assembled in a Schizophrenia Summit to focus on controversies that exist in treating patients with schizophrenia. The current literature related to the diagnosis and etiopathology of schizophrenia was evaluated regarding the identification of a prodromal phase, brain changes, cognitive impairments, genetic factors, and use of neuroimaging in patients with schizophrenia. Further, consideration was given to evidence supporting the neuroprotective benefits of atypical antipsychotic medications, the benefits of treating patients during the prodromal period, the use of combination antipsychotic medications, the need to improve cognitive function, and the management of substance abuse. Summit faculty member opinion is compared with field survey results, and recommendations are made for future research. C1 [Nasrallah, Henry A.] Univ Cincinnati, Coll Med, Dept Psychiat, Cincinnati, OH 45267 USA. [Keshavan, Matcheri S.] Wayne State Univ, Sch Med, Dept Psychiat & Behav Neurosci, Detroit, MI USA. [Benes, Francine M.] Harvard Univ, Sch Med, Program Struct & Mol Neurosci, McLean Hosp, Belmont, MA 02178 USA. [Braff, David L.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Green, Alan I.] Dartmouth Med Sch, Dept Psychiat, Lebanon, NH USA. [Gur, Raquel E.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Kane, John M.; Correll, Christoph U.] Zucker Hillside Hosp, Dept Psychiat, Dept Psychiat & Behav Sci, Albert Einstein Coll Med, Glen Oaks, NY USA. [Perkins, Diana O.] Univ N Carolina, Sch Med, Outreach & Support Intervent Serv, Chapel Hill, NC USA. [Weiden, Peter J.] Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA. [Weinberger, Daniel R.] NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. RP Nasrallah, HA (reprint author), Univ Cincinnati, Coll Med, Dept Psychiat, 260 Stetson St,Suite 3224, Cincinnati, OH 45267 USA. EM NASRALHA@UCMAIL.UC.EDU RI Correll, Christoph/D-3530-2011 FU NIMH NIH HHS [MH-01436, MH-042228, MH-065571, MH-079777] NR 243 TC 6 Z9 7 U1 5 U2 9 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2009 VL 70 SU 1 BP 4 EP 46 PG 43 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 418IK UT WOS:000264141700001 PM 19292973 ER PT J AU Koch, R Sander, C Mensing, C Zeis, M Schmitz, N Jaffe, E AF Koch, R. Sander, C. Mensing, C. Zeis, M. Schmitz, N. Jaffe, E. TI CUTANEOUS GAMMA/DELTA T-CELL LYMPHOMA SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Meeting Abstract C1 [Koch, R.; Sander, C.; Mensing, C.; Zeis, M.; Schmitz, N.] Allgemein Krankenhaus St Georg, Dept Dermatol, Hamburg, Germany. [Jaffe, E.] NCI, Hematopathol Sect, Pathol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD JAN PY 2009 VL 36 IS 1 BP 122 EP 123 PG 2 WC Dermatology; Pathology SC Dermatology; Pathology GA 389XT UT WOS:000262129600094 ER PT J AU Abati, A Thomas, B Marincola, F Filie, A Dicostanzo, D Fetsch, P AF Abati, A. Thomas, B. Marincola, F. Filie, A. Dicostanzo, D. Fetsch, P. TI UTILIZATION OF INFLAMMATORY INFILTRATE AS A DIAGNOSTIC DISCRIMINATOR FOR THE DISTINCTION OF PRIMARY MALIGNANT MELANOMA AND MELANOCYTIC NEVI SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Meeting Abstract C1 [Abati, A.; Thomas, B.; Dicostanzo, D.] Dermpath Diagnost, Port Chester, NY USA. [Marincola, F.; Filie, A.; Fetsch, P.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD JAN PY 2009 VL 36 IS 1 BP 139 EP 140 PG 2 WC Dermatology; Pathology SC Dermatology; Pathology GA 389XT UT WOS:000262129600165 ER PT J AU Bechert, C Hiatt, K AF Bechert, C. Hiatt, K. TI EPIDERMAL ATYPIA IN PATIENTS WITH MYCOSIS FUNGOIDES SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Meeting Abstract C1 [Bechert, C.] NIH, Bethesda, MD 20892 USA. [Hiatt, K.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD JAN PY 2009 VL 36 IS 1 BP 157 EP 158 PG 2 WC Dermatology; Pathology SC Dermatology; Pathology GA 389XT UT WOS:000262129600240 ER PT J AU Yen, CJ Liu, S AF Yen, Cherng-Jyh Liu, Simon TI LEARNER AUTONOMY AS A PREDICTOR OF COURSE SUCCESS AND FINAL GRADES IN COMMUNITY COLLEGE ONLINE COURSES SO JOURNAL OF EDUCATIONAL COMPUTING RESEARCH LA English DT Article ID DROPOUT AB This study employed a quantitative research design to examine the predictive relationships between: (a) learner autonomy and course success; and (b) learner autonomy and final grades in community college online courses. Learner autonomy was defined as the characteristic of an individual who exhibited intentional behavior in learning activities. The results of the binary and ordinal logistic regression analyses suggested that learner autonomy was a valid predictor of course success and final grades in community college online courses. The implications of the results are discussed in the context of early identification and effective intervention. Specifically, two interventions are recommended: (a) blended learning programs, and (b) advisory and counseling services. C1 [Yen, Cherng-Jyh] Old Domin Univ, Dept Educ Fdn & Leadership, Norfolk, VA 23529 USA. [Liu, Simon] Natl Lib Med, Bethesda, MD 20894 USA. RP Yen, CJ (reprint author), Old Domin Univ, Dept Educ Fdn & Leadership, Norfolk, VA 23529 USA. EM cyen@odu.edu NR 53 TC 10 Z9 10 U1 2 U2 6 PU BAYWOOD PUBL CO INC PI AMITYVILLE PA 26 AUSTIN AVE, PO BOX 337, AMITYVILLE, NY 11701 USA SN 0735-6331 J9 J EDUC COMPUT RES JI J. Educ. Comput. Res. PY 2009 VL 41 IS 3 BP 347 EP 367 DI 10.2190/EC.41.3.e PG 21 WC Education & Educational Research SC Education & Educational Research GA 714GT UT WOS:000286796300005 ER PT J AU Rotinen, M Celay, J Alonso, MM Arrazola, A Encio, I Villar, J AF Rotinen, Mirja Celay, Jon Alonso, Marta M. Arrazola, Aranzazu Encio, Ignacio Villar, Joaquin TI Estradiol induces type 8 17 beta-hydroxysteroid dehydrogenase expression: crosstalk between estrogen receptor alpha and C/EBP beta SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID CCAAT/ENHANCER-BINDING PROTEINS; GENE-EXPRESSION; MCF-7 CELLS; RESPONSE ELEMENTS; BREAST-CANCER; TARGET GENES; ER-ALPHA; TRANSCRIPTION; MOUSE; PROLIFERATION AB Hydroxysteroid (17-beta) dehydrogenase (HSD17B) are the enzymes responsible for the reversible interconversion of 17-hydroxy and 17-keto steroids. The human and mouse type 8 17 beta-HSD (HSD 17B8) selectively catalyze the conversion of estradiol (E2) to estrone (E1). We previously described that HSD17B8 is transcriptionally regulated by C/EBP beta, and that C/EBP beta is bound to CCAAT boxes located at -5 and -46 of the transcription start site in basal conditions in HepG2 cells. Furthermore, ectopic expression of C/EBP beta transactivated the HSD17B8 promoter activity. Here, we show that HSD 17135 expression is up-regulated in response to E2 in the estrogen receptor alpha (ER alpha) positive MCF-7 cells. Results showed that this induction is mediated by ER alpha because i) E2 did not induce HSD17B8 expression in ER alpha negative HepG2 cells, ii) ectopic expression of ERa restored E2-induced HSD17B8 expression, and iii) this induction was blocked by the anti-ER ICI 182780. Additional experiments showed that no estrogen response element was necessary for this regulation. However, the CCAAT boxes located at the HSD17B8 proximal promoter were required for E2-induced transcription. Furthermore, co-immunoprecipitation studies revealed tethering of ER alpha to C/EBP beta in response to E2 in cells expressing ER alpha. Additionally, chromatin immunoprecipitation assays demonstrated that, in response to E2, ERa is recruited to the CCAAT boxes in which C/EBP beta is already bound. Taken together, our results reveal that ER alpha is involved in the transcriptional regulation of HSD17B8 gene in response to E2 through its interaction with C/EBP beta. C1 [Rotinen, Mirja; Celay, Jon; Alonso, Marta M.; Arrazola, Aranzazu; Encio, Ignacio; Villar, Joaquin] Univ Publ Navarra, Dept Hlth Sci, Pamplona 31008, Spain. RP Villar, J (reprint author), NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM villarj@mail.nih.gov RI Celay, Jon/A-7296-2017 OI Celay, Jon/0000-0002-2017-4206 FU Departmento de Salud. Gobierno do Navarra, Spain FX This work was supported by a grant from the Departmento de Salud. Gobierno do Navarra, Spain. NR 42 TC 10 Z9 11 U1 3 U2 6 PU BIOSCIENTIFICA LTD PI BRISTOL PA 22 APEX COURT, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD JAN PY 2009 VL 200 IS 1 BP 85 EP 92 DI 10.1677/JOE-08-0134 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 395IB UT WOS:000262516700008 PM 18852215 ER PT J AU White, SS Birnbaum, LS AF White, Sally S. Birnbaum, Linda S. TI An Overview of the Effects of Dioxins and Dioxin-Like Compounds on Vertebrates, as Documented in Human and Ecological Epidemiology SO JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART C-ENVIRONMENTAL CARCINOGENESIS & ECOTOXICOLOGY REVIEWS LA English DT Review DE Dioxin; ecology; environmental toxicology; furan; historical production; historical releases; molecular mechanisms; PCB; PCDD; PCDF; vertebrate health; wildlife ID ARYL-HYDROCARBON RECEPTOR; TOXIC EQUIVALENCY FACTORS; POLYCHLORINATED-BIPHENYLS; RISK-ASSESSMENT; AH RECEPTOR; HARBOR SEALS; 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN; TCDD; EXPOSURE; WILDLIFE AB Dioxins and dioxin-like compounds are primary examples of persistent organic pollutants that induce toxicity in both wildlife and humans. Over the past 200 years these compounds have been almost exclusively generated by human activity and have left a string of disasters in the wake of their accidental release. Most recently, the contamination of the Irish pork supply with dioxins resulted in an international recall of all Irish pork products. Epidemiologic data on human and ecological dioxin exposures have revealed a common pattern of biological response among vertebrate species, which is mediated through activation of the Aryl hydrocarbon Receptor (AhR). These AhR-mediated effects include profound consequences on the vertebrate individual exposed in early life with respect to myriad developmental endpoints including neurologic, immunologic, and reproductive parameters. Humans appear to be susceptible to these effects in a manner similar to that of the laboratory and wildlife species, which have demonstrated such outcomes. Furthermore, epidemiologic data suggest that there is little or no margin of exposure for humans with respect to these developmental effects. Given these concerns, prudent public health policy should include the continued reduction of exposures. C1 [Birnbaum, Linda S.] NIEHS, Off Director, NIH, Res Triangle Pk, NC 27709 USA. [White, Sally S.] US EPA, Natl Ctr Environm Assessment, Res Triangle Pk, NC 27711 USA. RP White, SS (reprint author), NIEHS, Off Director, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM birnbaumls@niehs.nih.gov FU Intramural NIH HHS [Z99 ES999999] NR 52 TC 93 Z9 94 U1 4 U2 41 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1059-0501 J9 J ENVIRON SCI HEAL C JI J. Environ. Sci. Health Pt. C-Environ. Carcinog. Ecotoxicol. Rev. PY 2009 VL 27 IS 4 BP 197 EP 211 AR PII 917258542 DI 10.1080/10590500903310047 PG 15 WC Oncology; Environmental Sciences; Toxicology SC Oncology; Environmental Sciences & Ecology; Toxicology GA 525QO UT WOS:000272231600001 PM 19953395 ER PT J AU Deshpande, N Metter, EJ Lauretani, F Bandinelli, S Ferrucci, L AF Deshpande, Nandini Metter, E. Jeffrey Lauretani, Fulvio Bandinelli, Stefania Ferrucci, Luigi TI Interpreting Fear of Falling in the Elderly: What Do We Need to Consider? SO JOURNAL OF GERIATRIC PHYSICAL THERAPY LA English DT Article DE fear of falling; aging; environment AB Purpose: Fear of falling (FF) is a serious problem in elderly. Available scales quantify FF by generating an aggregate total FF score disregarding the environment in which fear is expressed. This study examined the differences in psychosocial and physical characteristics and global functional capabilities between the elderly who experienced FF exclusively for activities usually performed in community environments and those who reported FF only for home-based activities. Methods: Older participants (age >= 65, n=1155) enrolled in the InCHIANTI study completed the evaluation of FF, personal mastery, depression, cognition, social support, lower limb strength, grip strength, balance, timed repeated sit-to-stand performance, visual acuity, and contrast sensitivity. Functional capacity measures included walking speed, ADL and IADL disability, self-reported difficulty climbing steps without support and difficulty walking at least 400m. Only those who reported FF exclusively for activities usually performed in the community environment (n=232) or in home environment (n=110) were included in the analysis. Results: Multivariate analysis of variance revealed that those who reported FF exclusively for home-based activities were significantly worse in psychosocial and physical characteristics measured (F-(1,F-339)= 4.27; p < 0.01) and were also less able in all global functional capacity measures (p=0.04 to < 0.01). Conclusions: There are significant characteristic and functional differences between the older persons who have FF performing community environment activities and those who express FF in home environment activities. The results strongly indicate the need to classify FF according to the environment or alternatively, to derive an aggregate score by appropriately weighting according to the environment, for valid interpretation of FF. C1 [Deshpande, Nandini] Univ Kansas, Med Ctr, Dept Phys Therapy & Rehabil Sci, Kansas City, KS 66160 USA. [Metter, E. Jeffrey; Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA. Tuscany Reg Hlth Agcy, Florence, Italy. [Bandinelli, Stefania] Azienda Sanit Firenze, Geriatr Rehabil Unit, Florence, Italy. RP Deshpande, N (reprint author), Univ Kansas, Med Ctr, Dept Phys Therapy & Rehabil Sci, MS 2002,3901 Rainbow Blvd, Kansas City, KS 66160 USA. EM ndeshpande@kumc.edu RI Lauretani, Fulvio/K-5115-2016 OI Lauretani, Fulvio/0000-0002-5287-9972 FU Italian Ministry of Health [ICS 110.1\RS97.71]; National Institute on Aging [N01-AG-916413, N01-AG-821336, N01-AG-5-0002]; NIA [R01 AG027012]; National Institute on Aging, NIH FX The InCHIANTI study was supported as a "targeted project" (ICS 110.1\RS97.71) by the Italian Ministry of Health and in part, by National Institute on Aging Contracts N01-AG-916413, N01-AG-821336, N01-AG-5-0002, and NIA Grant R01 AG027012 and the Intramural Research Program, National Institute on Aging, NIH. NR 38 TC 9 Z9 9 U1 3 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1539-8412 J9 J GERIATR PHYS THER JI J. Geriatr. Phys. Ther. PY 2009 VL 32 IS 3 BP 91 EP 96 PG 6 WC Geriatrics & Gerontology; Rehabilitation SC Geriatrics & Gerontology; Rehabilitation GA V23BU UT WOS:000208319100001 PM 20128332 ER PT J AU Jampel, H Vitale, S Ding, Y Knezevich, F Quigley, H Zeimer, R AF Jampel, Henry Vitale, Susan Ding, Yulan Knezevich, Frederick, III Quigley, Harry Zeimer, Ran TI Retinal Thickness in Eyes of Older Normal Individuals and its Implication for the Diagnosis of Glaucoma SO JOURNAL OF GLAUCOMA LA English DT Article DE retina; imaging; normals; aging ID OPTICAL COHERENCE TOMOGRAPHY; DIABETIC MACULAR EDEMA; NERVE-FIBER THICKNESS; HEALTHY-SUBJECTS; POSTERIOR POLE; AXIAL LENGTH; REPRODUCIBILITY; ANALYZER; LAYER; HEAD AB Purpose: Retinal thickness (RT) is a useful measurement for describing, diseases that affect the thickness of the retina. such as glaucoma. Existing normative data are derived from relatively young individuals: however. glaucoma is most prevalent in older individuals. We therefore studied the RT in older normal individuals. Patients and Methods: Participants of the Baltimore Eye Study, persons accompanying patients. and staff were recruited and underwent visual field testing and a comprehensive eve examination by it glaucoma specialist. RT was measured with the retinal thickness analyzer (RTA. Talia Technology) and RT values in specific regions Were derived using it custom-designed Matt-ah program. Results: One hundred and three eyes of sixty-two individuals were studied. Mean age was 61 years. Sixty-six percent were female and 82% were of European descent. The average mean deviation on visual field testing was 0.03 dB and the average pattern SD was 1.51 dB. The mean RT of the entire macula was 159 +/- 16 mu m. and was lowest in the foveal pit and highest in the parafoveal annulus. The average distance from the foveal pit to the thickest point in the parafoveal annulus was 1240 +/- 138 mu m. The mean RT of the entire macula was sliLlitlv less in older individuals (slope =-5.7 mu m/10 y. P = 0.02) but the height of the parafoveal annulus relative to the foveal pit. which is determined by the combined thickness of the parafoveal nerve fibers, ganglion cells. inner plexiform layer. and inner nuclear layer, did not vary with age (P = 0.62). Conclusions: Although the average RT of the entire macula was slightly thinner with increasing age, the height of the parafoveal annulus relative to the foveal pit did not change with age and would therefore seem to be a better marker of neuronal tissue health than the average RT of the entire macula. C1 [Jampel, Henry] Johns Hopkins Med Inst, Wilmer Eye Inst, JHU, Baltimore, MD 21287 USA. [Vitale, Susan] NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA. RP Jampel, H (reprint author), Johns Hopkins Med Inst, Wilmer Eye Inst, JHU, Woods 377,600 N Wolfe St, Baltimore, MD 21287 USA. EM hjampel@jhmi.edu FU National Eye Institute, National Institutes of Health FX The findings and conclusions in this report are those of the authors and do not necessarily represent the view of the funding agency (National Eye Institute, National Institutes of Health). NR 22 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1057-0829 J9 J GLAUCOMA JI J. Glaucoma PD JAN PY 2009 VL 18 IS 1 BP 37 EP 43 PG 7 WC Ophthalmology SC Ophthalmology GA 398VO UT WOS:000262759800007 PM 19142133 ER PT J AU Weichel, EA Colyer, MH Bautista, C Bower, KS French, LM AF Weichel, Eric A. Colyer, Marcus H. Bautista, Charisma Bower, Kraig S. French, Louis M. TI Traumatic Brain Injury Associated With Combat Ocular Trauma SO JOURNAL OF HEAD TRAUMA REHABILITATION LA English DT Article DE closed-globe; ocular trauma; open-globe; Operation Iraqi Freedom; traumatic brain injury ID HETEROTOPIC OSSIFICATION; UNITED-STATES; REHABILITATION; IRAQ; WAR; AFGHANISTAN; IMPAIRMENT; DEPRESSION; MANAGEMENT; OUTCOMES AB Purpose: To determine the impact of traumatic brain injury (TBI) on visual outcomes in combat ocular trauma (COT) and determine the association between TBI severity and types of ocular injuries. Participants: One hundred fifty-two US casualties sustained 207 globe/oculoplastic combat injuries. Methods: Retrospective, hospital-based cross-sectional study of US service members injured during Operations Iraqi Freedom and Enduring Freedom were treated by the Ophthalmology Service at Walter Reed Army Medical Center and screened for TBI by the Defense and Veterans Brain Injury Center from August 2004 to October 2006. Main Outcome Measures: The main outcome measure was best-corrected visual acuity (BCVA). Secondary outcome measures included the severity and frequency of TBI with globe, oculoplastic, and/or neuro-ophthalmic injury. Results: The frequency of COT with positive TBI screening was 101 of 152 cases (66%) in comparison with negative TBI screening, which was 51 of 152 (34%) cases. The Defense and Veterans Brain Injury Center found TBI with concomitant ocular trauma in 101 of 474 (21%) consecutive casualties. Explosive fragmentary munitions accounted for 79% of TBI-associated COT The median follow-up was 185 days. Traumatic brain injury severity did not correlate with worse final BCVA (Spearman coefficient, r = 0.12). The odds that BCVA worse than 20/200 was present with TBI was not statistically significant (OR: 1.5; 95% CI, 0.9-2.6; P =. 10). The presence of TBI in COT was not associated with worse visual outcome (Mann-Whitney U test,P = .10). Globe injuries were more common than oculoplastic or neuro-ophthalmic injury. Closed-globe injuries were more likely to have TBI than open-globe injuries (OR: 2.17; 95% CI, 1.12-4.21; P = .03). Traumatic brain injury severity associated with COT included mild TBI (31%), moderate TBI (30%), severe TBI (25%), and penetrating TBI (14%). Severe TBI is more frequently associated with COT Conclusion: Traumatic brain injury occurs in two thirds of all COT and ocular trauma is a common finding in all TBI cases. Closed-globe injuries are at highest risk for TBI while TBI does not appear to lead to poorer visual outcomes. Every patient with COT needs TBI screening. Those service members who are screened TBI positive need a referral to a TBI rehabilitation specialist. C1 [Weichel, Eric A.] Walter Reed Army Med Ctr, Ophthalmol Serv, Washington, DC 20307 USA. [French, Louis M.] Def & Vet Brain Injury Ctr, Washington, DC USA. [Weichel, Eric A.] NEI, NIH, Bethesda, MD 20892 USA. [Bautista, Charisma; Bower, Kraig S.; French, Louis M.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. RP Weichel, EA (reprint author), Walter Reed Army Med Ctr, Ophthalmol Serv, 6900 Georgia Ave, Washington, DC 20307 USA. EM eweichel@hotmail.com NR 48 TC 20 Z9 20 U1 3 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-9701 J9 J HEAD TRAUMA REHAB JI J. Head Trauma Rehabil. PD JAN-FEB PY 2009 VL 24 IS 1 BP 41 EP 50 PG 10 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 427GT UT WOS:000264768500007 PM 19158595 ER PT J AU Hay, J Harris, JN Waters, EA Clayton, MF Ellington, L Abernethy, AD Prayor-Patterson, H AF Hay, Jennifer Harris, Julie N. Waters, Erika A. Clayton, Margaret F. Ellington, Lee Abernethy, Alexis D. Prayor-Patterson, Heather TI Personal Communication in Primary and Secondary Cancer Prevention: Evolving Discussions, Emerging Challenges SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID LAY HEALTH ADVISERS; UNCERTAINTY MANAGEMENT INTERVENTION; RANDOMIZED CONTROLLED-TRIAL; NATIONAL TRENDS SURVEY; AFRICAN-AMERICAN; COLORECTAL-CANCER; ENTERTAINMENT-EDUCATION; BEHAVIOR-CHANGE; INFORMATION; COMMUNITY AB Over the past several years, the science of cancer communication has been recognized as integral to the dissemination of cancer prevention and control strategies in both the general population as well as higher-risk groups. In this article we draw upon current literature and small group discussion in the 2008 Society for Behavioral Medicine Cancer Special Interest Group Pre-Conference Workshop on Cancer Communication to identify current findings, critical challenges, and future opportunities regarding personal communication of primary and secondary prevention of cancer. We organize our article with six critical questions: (1) What are the most important directions of research in this area? (2) Does personal cancer communication work through rational processes, or are affective and nonrational processes also involved? (3) Are our efforts adequate to reach underserved populations? (4) Are naturalistic communicative contexts given adequate consideration? (5) Has the field been adequately informed by social psychological and communication theories? (6) What are the best outcomes to document communication effectiveness? Our goals are to initiate thought and collaborative efforts among communication, public health, and behavioral science experts, as well as to establish research priorities at the interface of communication and cancer prevention and control sciences. C1 [Hay, Jennifer] Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, New York, NY 10022 USA. [Harris, Julie N.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Waters, Erika A.] NCI, Rockville, MD USA. [Clayton, Margaret F.; Ellington, Lee] Univ Utah, Coll Nursing, Salt Lake City, UT 84112 USA. [Abernethy, Alexis D.] Fuller Theol Seminary, Grad Sch Psychol, Pasadena, CA 91101 USA. [Prayor-Patterson, Heather] Univ Alabama, Birmingham, AL USA. RP Hay, J (reprint author), Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, 641 Lexington Ave,7th Floor, New York, NY 10022 USA. EM hayj@mskcc.org OI Waters, Erika/0000-0001-7402-0133 NR 88 TC 3 Z9 3 U1 14 U2 16 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PY 2009 VL 14 BP 18 EP 29 DI 10.1080/10810730902806828 PG 12 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 473YQ UT WOS:000268248900004 PM 19449265 ER PT J AU Hannon, P Lloyd, GP Viswanath, K Smith, T Basen-Engquist, K Vernon, SW Turner, G Hesse, BW Crammer, C Von Wagner, C Backinger, CL AF Hannon, Peggy Lloyd, Gareth P. Viswanath, K. Smith, Tenbroeck Basen-Engquist, Karen Vernon, Sally W. Turner, Gina Hesse, Bradford W. Crammer, Corinne von Wagner, Christian Backinger, Cathy L. TI Mass Media and Marketing Communication Promoting Primary and Secondary Cancer Prevention SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID DISSEMINATION RESEARCH; HEALTH; CAMPAIGNS; INTERVENTIONS; DISPARITIES; COMMUNITY; EDUCATION; LITERACY; EHEALTH AB People often seek and receive cancer information from mass media (including television, radio, print media, and the Internet), and marketing strategies often inform cancer information needs assessment, message development, and channel selection. In this article, we present the discussion of a 2-hour working group convened for a cancer communications workshop held at the 2008 Society of Behavioral Medicine meeting in San Diego, CA. During the session, aft interdisciplinary group of investigators discussed the current state of the science for mass media and marketing communication promoting primary and secondary cancer prevention. We discussed current research, new research areas, methodologies and theories needed to move the field forward, and critical areas and disciplines for future research. C1 [Hannon, Peggy] Univ Washington, Seattle, WA 98195 USA. [Lloyd, Gareth P.; von Wagner, Christian] UCL, London, England. [Viswanath, K.] Harvard Univ, Cambridge, MA 02138 USA. [Smith, Tenbroeck; Crammer, Corinne] Amer Canc Soc, Atlanta, GA 30329 USA. [Basen-Engquist, Karen] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Vernon, Sally W.] Univ Texas Houston Sch Publ Hlth, Houston, TX USA. [Turner, Gina] Mt Sinai Sch Med, New York, NY USA. [Hesse, Bradford W.; Backinger, Cathy L.] NCI, Bethesda, MD 20892 USA. RP Hannon, P (reprint author), Hlth Serv, 1107 NE 45th St,Ste 200, Seattle, WA 98105 USA. EM peggyh@u.washington.edu OI Hesse, Bradford/0000-0003-1142-1161 NR 27 TC 3 Z9 3 U1 2 U2 7 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PY 2009 VL 14 BP 30 EP 37 DI 10.1080/10810730902806802 PG 8 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 473YQ UT WOS:000268248900005 PM 19449266 ER PT J AU Hesse, BW AF Hesse, Bradford W. TI Cancer Communication: Status and Future Directions SO JOURNAL OF HEALTH COMMUNICATION LA English DT Review ID NATIONAL TRENDS SURVEY; HEALTH INFORMATION; UNITED-STATES; INTERVENTION RESEARCH; DECISION-MAKING; MASS-MEDIA; SCIENCE; PREVENTION; SMOKING; CARE AB On November 7, 2005, the directors of the National Cancer Institute's (NCI's) Comprehensive Cancer Centers met to identify ways of accelerating success against cancer using current knowledge. Not surprisingly, cancer communication was identified as a focal point of research that needed to be conducted to extend the benefits of cancer knowledge throughout the population. There were three foci of communication research identified by the directors: (a) research designed to extend awareness of prevention and early detection, (b) research designed to improve the accuracy and usability of cancer science as portrayed in national news media, and (c) research designed to support behavior through individual and community-level interventions. Each of these foci takes on new meaning when considered in the context of a rapidly changing communication environment. Behavioral science must evolve to keep up with these changes and to offer new evidence-based approaches for extending the reach, effectiveness, and efficiency of cancer communication in order to do its part in accelerating successes against the disease. C1 NCI, Bethesda, MD 20892 USA. RP Hesse, BW (reprint author), NCI, 6130 Execut Blvd,MSC 7365,EPN 4068, Bethesda, MD 20892 USA. EM hesseb@mail.nih.gov OI Hesse, Bradford/0000-0003-1142-1161 NR 125 TC 7 Z9 7 U1 5 U2 6 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 520 CHESTNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1081-0730 EI 1087-0415 J9 J HEALTH COMMUN JI J. Health Commun. PY 2009 VL 14 SU 1 SI SI BP 109 EP 127 DI 10.1080/10810730902806851 PG 19 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 473YQ UT WOS:000268248900013 PM 19449274 ER PT J AU Colon-Ramos, U Atienza, AA Weber, D Taylor, M Uy, C Yaroch, A AF Colon-Ramos, Uriyoan Atienza, Audie A. Weber, Deanne Taylor, Melissa Uy, Christina Yaroch, Amy TI Practicing What They Preach: Health Behaviors of Those Who Provide Health Advice to Extensive Social Networks SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID CORONARY-HEART-DISEASE; CARDIOVASCULAR-DISEASE; SMOKING-CESSATION; RISK-FACTORS; INFORMATION; DIFFUSION; MORTALITY; SUPPORT; MEN AB As a way of identifying a conduit to disseminate health information, this study aims to explore health behaviors and attitudes of a unique group of extensively socially-networked individuals who regularly are asked for their health advice. Respondents from a population-based consumer opinion panel (n=2,639) were categorized as extensively socially-networked (75+ friends and acquaintances, and almost daily giving friends advice on general issues) vs. non-networked. The networked respondents were further divided into health-networked (regularly asked for health advice) versus only-socially-networked groups (asked for general advice, not health). Chi-square analyses, ANOVA tests, and multivariate regressions controlling for sociodemographic variables compared health behaviors and attitudes between groups. Results indicated that health-networked individuals reported more positive health behaviors (e.g., fruit and vegetable consumption) and attitudes than only-socially-networked and non-networked individuals. Future research is warranted to elucidate how providing health advice to a large network contributes to the positive health of health-networked individuals. Exploratory analyses revealed that doctors and health/fitness magazines were main sources of health and nutrition information for health-networked respondents. Through their advice and word-of-mouth, health-networked individuals have the potential to influence the health information of large groups of people and, therefore, may serve as valuable change agents to disseminate health and nutrition information. C1 [Atienza, Audie A.] NCI, Hlth Promot Reasearch Branch, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Weber, Deanne; Taylor, Melissa] Porter Novelli, Washington, DC USA. [Uy, Christina] Discovery Commun, Silver Spring, MD USA. RP Atienza, AA (reprint author), NCI, Hlth Promot Reasearch Branch, Behav Res Program, Div Canc Control & Populat Sci, NIH 6130 Execut Blvd,EPN 4082, Bethesda, MD 20892 USA. EM atienzaa@mail.nih.gov NR 29 TC 6 Z9 6 U1 1 U2 12 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PY 2009 VL 14 IS 2 BP 119 EP 130 AR PII 909489019 DI 10.1080/10810730802659111 PG 12 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 418GY UT WOS:000264137900003 PM 19283537 ER PT J AU Koshiol, J Rutten, LF Moser, RP Hesse, N AF Koshiol, Jill Rutten, Lila Finne Moser, Richard P. Hesse, Nicola TI Knowledge of Human Papillomavirus: Differences by Self-Reported Treatment for Genital Warts and Sociodemographic Characteristics SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID RECURRENT RESPIRATORY PAPILLOMATOSIS; FAMILY PHYSICIANS KNOWLEDGE; CERVICAL-CANCER; UNITED-STATES; COUNSELING PRACTICES; RISK-FACTORS; INFECTION; HEALTH; WOMEN; MANAGEMENT AB The aim of this study was to evaluate knowledge about human papillomavirus (HPV) in individuals with genital warts compared with women from the general population without genital warts. Human papillomavirus (HPV) knowledge among women reporting treatment for genital warts compared with HPV knowledge in women reporting no treatment was assessed using data from the population-based 2005 Health Information National Trends Survey (HINTS). Three percent (N=97) of women answered yes and 97% (N=3,450) no to Have you ever been treated for venereal warts or condyloma? Women who reported treatment for genital warts, were more likely to have heard of HPV (odds ratio (OR): 2.4, 95% confidence interval (CI): 1.4-4.2 vs. no or don't know), to have been told they had HPV (OR: 24.5, 95% CI: 11.4-52.8), and to have accurate information about HPV, such as HPV causes cancer (OR: 2.7, 95% CI: 1.8-4.3). A large proportion (41%) of women who reported treatment for genital warts, however, had not heard of HPV. These women tended to be older, poorer, less educated, non-Hispanic Black, less likely to have had a recent Pap test, and divorced, widowed, or separated. Women with genital warts are learning about HPV, but socioeconomically disadvantaged groups may need to be targeted. C1 [Koshiol, Jill] NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, NIH, Bethesda, MD 20892 USA. [Koshiol, Jill] NCI, Genet Epidemiol Branch, NIH, Bethesda, MD 20892 USA. [Rutten, Lila Finne] NCI, Hlth Commun & Informat Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Hesse, Nicola] Franklin Sq Hosp Ctr, Bethesda, MD USA. RP Koshiol, J (reprint author), NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, NIH, 6120 Execut Blvd,MSC 7248, Bethesda, MD 20892 USA. EM koshiolj@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 42 TC 7 Z9 8 U1 1 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PY 2009 VL 14 IS 4 BP 331 EP 345 AR PII 911664621 DI 10.1080/10810730902873067 PG 15 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 448SM UT WOS:000266282300003 PM 19466646 ER PT J AU Kaphingst, KA Persky, S McCall, C Lachance, C Beall, AC Blascovich, J AF Kaphingst, Kimberly A. Persky, Susan McCall, Cade Lachance, Christina Beall, Andrew C. Blascovich, Jim TI Testing Communication Strategies to Convey Genomic Concepts Using Virtual Reality Technology SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID ENVIRONMENT TECHNOLOGY; INFORMATION-SEEKING; CANCER; MEDIA; MODEL; PSYCHOLOGY; GENETICS; SCIENCE; TOOL AB Health professionals need to be able to communicate information about genomic susceptibility in understandable and usable ways, but substantial challenges are involved. We developed four learning modules that varied along two factors: (1) learning mode (active learning vs. didactic learning) and (2) metaphor (risk elevator vs. bridge) and tested them using a 22 between-subjects, repeated measures design. The study used an innovative virtual reality technology experimental platform; four virtual worlds were designed to convey the concept that genetic and behavioral factors interact to affect common disease risk. The primary outcome was comprehension (recall, transfer). Study participants were 42 undergraduates aged 19-23. The results indicated that the elevator metaphor better supported learning of the concept than the bridge metaphor. Mean transfer score was significantly higher for the elevator metaphor (p0.05). Mean change in recall was significantly higher for didactic learning than active learning (p0.05). Mean ratings for variables posited to be associated with better learning (e.g., motivation), however, were generally higher for the active learning worlds. The results suggested that active learning might not always be more effective than didactic learning in increasing comprehension of health information. The findings also indicated that less complex metaphors might convey abstract concepts more effectively. C1 [Kaphingst, Kimberly A.; Persky, Susan; Lachance, Christina] NHGRI, Bethesda, MD 20892 USA. [McCall, Cade; Beall, Andrew C.; Blascovich, Jim] Univ Calif Santa Barbara, Santa Barbara, CA 93106 USA. RP Kaphingst, KA (reprint author), NHGRI, Bldg 31,Room B1B37E,31 Ctr Dr,MSC 2073, Bethesda, MD 20892 USA. EM kkaphing@mail.nih.gov FU Intramural NIH HHS [Z01 HG200321-03] NR 37 TC 6 Z9 6 U1 4 U2 6 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PY 2009 VL 14 IS 4 BP 384 EP 399 AR PII 911665040 DI 10.1080/10810730902873927 PG 16 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 448SM UT WOS:000266282300006 PM 19466649 ER PT J AU Waters, EA Sullivan, HW Rutten, LJF AF Waters, Erika A. Sullivan, Helen W. Rutten, Lila J. Finney TI Cancer Prevention Information-Seeking Among Hispanic and Non-Hispanic Users of the National Cancer Institute's Cancer Information Service: Trends in Telephone and LiveHelp Use SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID UNITED-STATES; HEALTH; DISPARITIES; COMMUNICATION; LATINOS; CARE; NEED AB Evidence-based strategies to enable, encourage, and support cancer prevention information seeking among Hispanic populations are needed. We examined cancer prevention information requests to the Cancer Information Service (CIS) via telephone (1-800-4-CANCER toll-free telephone information service) and LiveHelp (an instant messaging service provided in English only) from 2003 to 2006. We summarized differences in the communication channel utilized by ethnicity (Hispanic vs. non-Hispanic) and, among Hispanic information seekers, the language used during the contact (English vs. Spanish). Utilization of LiveHelp was higher among non-Hispanic than Hispanic seekers of cancer prevention information. LiveHelp use for seeking cancer prevention information increased between 2003 and 2006 for both groups, but the increase was greater among non-Hispanics than Hispanics. Nearly half of Hispanics who sought cancer prevention information did so in Spanish. Because LiveHelp is not available in Spanish, the number of Spanish-only speakers who preferred to contact CIS via LiveHelp instead of telephone is unknown. When communicating cancer prevention information via multiple channels, it is important to consider differences in access to communication technologies and preferred communication channels among ethnic minority groups. C1 [Waters, Erika A.; Sullivan, Helen W.; Rutten, Lila J. Finney] NCI, Hlth Commun & Informat Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Waters, EA (reprint author), EPN Room 4087B,6130 Execut Blvd,MSC 7365, Bethesda, MD 20892 USA. EM erika.a.waters@gmail.com OI Waters, Erika/0000-0001-7402-0133 FU Intramural NIH HHS [NIH0011143336]; PHS HHS [NIH0011143336] NR 31 TC 8 Z9 8 U1 0 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PY 2009 VL 14 IS 5 BP 476 EP 486 AR PII 913657180 DI 10.1080/10810730903032952 PG 11 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 480GC UT WOS:000268719300007 PM 19657927 ER PT J AU Han, PKJ Reeve, BB Moser, RP Klein, WMP AF Han, Paul K. J. Reeve, Bryce B. Moser, Richard P. Klein, William M. P. TI Aversion to Ambiguity Regarding Medical Tests and Treatments: Measurement, Prevalence, and Relationship to Sociodemographic Factors SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID CANCER PREVENTION RECOMMENDATIONS; PERCEIVED AMBIGUITY; UNCERTAINTY; RISK; DECISIONS; INFORMATION; PERCEPTIONS; VALIDATION; TOLERANCE; CARE AB Aversion to oambiguityouncertainty about the reliability, credibility, or adequacy of risk-related informationis an important problem that may influence judgments and decisions about medical interventions. Ambiguity aversion (AA) varies among individuals, however, and has been understudied in the health domain. To explore this phenomenon further, we developed a new theory-based measure of aversion to ambiguity regarding medical tests and treatments, and examined the prevalence and association of AA with sociodemographic factors. The oAA-Medo scale was developed using a large survey sample of the U.S. public (n=4,398), and scale psychometric properties and the population distribution of AA were evaluated. The scale demonstrated acceptable reliability (=.73) and validity as ascertained by association with respondents' interest in a hypothetical ambiguous cancer screening test. Ambiguity aversion (AA) was associated with older age, non-White race, lower education and income, and female sex. The AA-Med scale is a promising new measure, and AA is associated with several sociodemographic factors. We discuss implications of these findings and potential applications of the scale for future research. C1 [Han, Paul K. J.; Reeve, Bryce B.; Moser, Richard P.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Klein, William M. P.] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. RP Han, PKJ (reprint author), NCI, Outcomes Res Branch, Div Canc Control & Populat Sci, 6130 Execut Blvd,EPN 4091,MSC 7344, Rockville, MD 20892 USA. EM hanp@mail.nih.gov OI Han, Paul/0000-0003-0165-1940 FU Intramural NIH HHS [Z99 HG999999] NR 46 TC 17 Z9 18 U1 2 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PY 2009 VL 14 IS 6 BP 556 EP 572 AR PII 914455193 DI 10.1080/10810730903089630 PG 17 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 490YL UT WOS:000269543900005 PM 19731127 ER PT J AU Ashida, S Koehly, LM Roberts, JS Chen, CA Hiraki, S Green, RC AF Ashida, Sato Koehly, Laura M. Roberts, J. Scott Chen, Clara A. Hiraki, Susan Green, Robert C. TI Disclosing the Disclosure: Factors Associated With Communicating the Results of Genetic Susceptibility Testing for Alzheimer's Disease SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article DE Alzheimer's disease; APOE communication; disclosure; susceptibility genetic testing ID NONPOLYPOSIS COLORECTAL-CANCER; APOLIPOPROTEIN-E GENOTYPE; GENOME-WIDE ASSOCIATION; AT-RISK RELATIVES; 1ST-DEGREE RELATIVES; FAMILY-MEMBERS; HEREDITARY BREAST; DISTANT RELATIVES; COGNITIVE DECLINE; OVARIAN-CANCER AB This study explored the extent to which recipients of genetic susceptibility testing for Alzheimer's disease (AD) communicated their results to others. It also examined demographic characteristics, along with beliefs about AD, associated with such communication. Participants (N=271) in a randomized clinical trial involving genetic testing for Apolipoprotein E (APOE) gene variants among first-degree relatives of AD patients reported their communication behaviors 6 weeks after the results disclosure. Information on beliefs about AD and genetic testing was collected at baseline. Eighty-two percent of participants receiving APOE genotype information shared their results with someone. Specifically, 64% shared with family members, 51% with spouse or significant others, 35% with friends, and 12% with health care professionals. Greater AD treatment optimism was associated with communicating results to family (OR=1.43), spouse (OR=1.62), friends (OR=1.81), and health care professionals (OR=2.20). Lower perceived risk (OR=0.98) and higher perceived importance of genetics in the development of AD (OR=1.93) were associated with results communication in general. Lower perceived drawbacks of AD genetic testing was associated with results communication to friends (OR=0.65). Beliefs about AD risks and causes, genetic testing, and development of treatments partly may determine the interpersonal communication patterns of genetic susceptibility test results. C1 [Ashida, Sato; Koehly, Laura M.] NHGRI, Social & Behav Res Branch, Bethesda, MD 20892 USA. [Roberts, J. Scott] Univ Michigan, Sch Publ Hlth, Dept Hlth Behav & Hlth Educ, Ann Arbor, MI 48109 USA. [Chen, Clara A.] Boston Univ, Sch Publ Hlth, Data Coordinating Ctr, Boston, MA USA. [Hiraki, Susan; Green, Robert C.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Green, Robert C.] Boston Univ, Sch Med, Dept Med Genet, Boston, MA 02118 USA. [Green, Robert C.] Boston Univ, Sch Med, Dept Epidemiol, Boston, MA 02118 USA. [Green, Robert C.] Boston Univ, Sch Publ Hlth, Dept Neurol, Boston, MA USA. [Green, Robert C.] Boston Univ, Sch Publ Hlth, Dept Med Genet, Boston, MA USA. [Green, Robert C.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Ashida, S (reprint author), NHGRI, Social & Behav Res Branch, 31 Ctr Dr,B1B37C, Bethesda, MD 20892 USA. EM ashidas@mail.nih.gov FU Intramural NIH HHS [Z01 HG200335-02]; NCRR NIH HHS [M01 RR000533, M01 RR00533]; NIA NIH HHS [P30 AG013846, P30 AG13846, R01 AG09029, K24 AG027841, R01 AG009029, R01 HG/AG02213, K24 AG027841-04] NR 63 TC 11 Z9 12 U1 1 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 520 CHESTNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1081-0730 EI 1087-0415 J9 J HEALTH COMMUN JI J. Health Commun. PY 2009 VL 14 IS 8 BP 768 EP 784 AR PII 918004594 DI 10.1080/10810730903295518 PG 17 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 535MI UT WOS:000272972000005 PM 20029710 ER PT J AU Sullivan, HW Rutten, LJF AF Sullivan, Helen W. Rutten, Lila J. Finney TI Cancer Prevention Information Seeking: A Signal Detection Analysis of Data From the Cancer Information Service SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID NATIONAL TRENDS SURVEY; DETECTION METHODOLOGY; LOGISTIC-REGRESSION; HEALTH; SUBGROUPS; RISK; STRATEGY; IDENTIFY; NEEDS; HINTS AB Communication and health information seeking play a significant role in the promotion of cancer prevention behaviors, including screening. Data from a sample of information seekers who contacted the National Cancer Institute's (NCI's) Cancer Information Service (CIS; N=20,412) were split randomly into an exploratory and validation sample to conduct signal detection analysis predicting cancer prevention information seeking. Important predictors of seeking prevention information in the exploratory sample were type of information seeker, communication channel, age, and gender; these findings generally were confirmed in the validation sample. Our findings also reveal important information about the demographic characteristics and communication channel preferences of cancer prevention information seekers. C1 [Sullivan, Helen W.] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Sullivan, Helen W.] NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, NIH, Bethesda, MD 20892 USA. [Rutten, Lila J. Finney] HealthPartners Res Fdn, Minneapolis, MN USA. RP Sullivan, HW (reprint author), NCI, Div Canc Control & Populat Sci, NIH, 6130 Execut Blvd, Bethesda, MD 20892 USA. EM helen@aya.yale.edu NR 28 TC 6 Z9 6 U1 0 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PY 2009 VL 14 IS 8 BP 785 EP 796 AR PII 917994635 DI 10.1080/10810730903295534 PG 12 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 535MI UT WOS:000272972000006 PM 20029711 ER PT J AU Holman, WL Kormos, RL Naftel, DC Miller, MA Pagani, FD Blume, E Cleeton, T Koenig, SC Edwards, L Kirklin, JK AF Holman, William L. Kormos, Robert L. Naftel, David C. Miller, Marissa A. Pagani, Frank D. Blume, Elizabeth Cleeton, Timothy Koenig, Steven C. Edwards, Leah Kirklin, James K. TI Predictors of Death and Transplant in Patients With a Mechanical Circulatory Support Device: A Multi-institutional Study SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article ID VENTRICULAR ASSIST DEVICE; AWAITING HEART-TRANSPLANTATION; CLINICAL-TRIAL DESIGN; RISK-FACTORS; FAILURE; SURVIVAL; INFECTION; INSERTION; SELECTION; SYSTEM AB Background: INTERMACS is a registry of FDA-approved durable mechanical circulatory support (MCS) devices used for the strategies of destination therapy (DT) and bridge to transplantation (BTT) or recovery. This study identifies predictors for death and transplantation based on initial results from INTERMACS. Methods: From June 23, 2006 to December 31, 2007, 420 patients from 75 institutions were prospectively entered into the INTERMACS database in which pre-implant data, indication for MCS device use, adverse events, demographics, hemodynamics, laboratory values and outcomes were recorded. Using competing outcomes methodology, risk factors were identified for the events of death and transplantation. Results: The devices included 314 left ventricular assist devices (LVADs), 5 right VADs (RVADs), 77 biventricular VADs (biVADs) and 24 total artificial hearts (TAHs) for a total of 497 pumps in 420 patients. Among the BTT patients at 6 months, 33% were alive with a device in place, 42% were transplanted, 22% had died, and 3% were explanted for recovery. Among the DT patients at 6 months, 68% were alive with a device in place, 5% were transplanted, 25% had died, and 2% were explanted for recovery. The risk factors identified for death across all patient groups include older age (relative risk [RR] = 1.41, p < 0.001), ascites (RR = 2.04, p = 0.003), increased bilirubin (RR = 1.49,p < 0.05) and INTERMACS Level I (cardiogenic shock) (RR = 1.59,p = 0.02). The most common causes of death were central nervous system (CNS) event (18.3% of deaths), multiple-organ failure (16.4%) and cardiac cause (right ventricular failure and arrhythmias, 15.4%). Conclusions: Cardiogenic shock, advanced age and severe right heart failure manifested as ascites or increased bilirubin are risk factors for death after MCS therapy. BTT patients who require biVAD support have a transplant rate similar to that of LVAD-only patients, but their mortality at 6 and 12 months exceeds that of LVAD-only patients. Consideration should be given to MCS referral before the sequelae of right ventricular failure dominate the advanced heart failure syndrome. J Heart Lung Transplant 2009; 28:44-50. Copyright (C) 2009 by the International Society for Heart and Lung Transplantation. C1 [Holman, William L.; Naftel, David C.; Kirklin, James K.] Univ Alabama, Dept Surg, Birmingham, AL 35294 USA. [Kormos, Robert L.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA. [Miller, Marissa A.] NHLBI, Dept Pediat, Rockville, MD USA. [Pagani, Frank D.] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. [Blume, Elizabeth] Childrens Hosp, Boston, MA 02115 USA. [Cleeton, Timothy] Univ Florida, Shands Hosp, Gainesville, FL USA. [Koenig, Steven C.] Univ Louisville, Jewish Hosp, Louisville, KY 40292 USA. [Edwards, Leah] United Network Organ Sharing, Richmond, VA USA. RP Holman, WL (reprint author), Univ Alabama, Dept Surg, Room 719 ZRB,703 19th St S, Birmingham, AL 35294 USA. EM wholman@uab.edu NR 20 TC 105 Z9 107 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD JAN PY 2009 VL 28 IS 1 BP 44 EP 50 DI 10.1016/j.healun.2008.10.011 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 395WO UT WOS:000262554400008 PM 19134530 ER PT J AU Koh, C Liang, TJ AF Koh, Christopher Liang, T. Jake TI Settling the "score" with liver cancer SO JOURNAL OF HEPATOLOGY LA English DT Editorial Material ID HEPATITIS-B-VIRUS; HEPATOCELLULAR-CARCINOMA; E-ANTIGEN; RISK; EPIDEMIOLOGY; CIRRHOSIS C1 [Koh, Christopher; Liang, T. Jake] NIDDKD, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. RP Liang, TJ (reprint author), NIDDKD, Liver Dis Branch, NIH, 10 Ctr Dr,Bldg 10,Room 9B16, Bethesda, MD 20892 USA. EM JakeL@bdg10.niddk.nih.gov FU Intramural NIH HHS [Z01 DK054500-11] NR 16 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD JAN PY 2009 VL 50 IS 1 BP 7 EP 9 DI 10.1016/j.jhep.2008.10.008 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 386SM UT WOS:000261902900003 PM 19014877 ER PT J AU Seefl, LB AF Seefl, Leonard B. TI Are herbals as safe as their advocates believe? SO JOURNAL OF HEPATOLOGY LA English DT Editorial Material ID ADVERSE DRUG-REACTIONS; HERBALIFE(R) NUTRITIONAL SUPPLEMENTS; ALTERNATIVE MEDICINE; DIETARY-SUPPLEMENTS; NATIONAL-SURVEY; LIVER-DISEASE; UNITED-STATES; HEPATITIS-C; HEPATOTOXICITY; PRODUCTS C1 NIDDKD, NIH, Bethesda, MD 20892 USA. RP Seefl, LB (reprint author), NIDDKD, NIH, 31 Ctr Dr,Room 9A27, Bethesda, MD 20892 USA. EM seeffl@extra.niddk.nih.gov NR 35 TC 14 Z9 14 U1 2 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD JAN PY 2009 VL 50 IS 1 BP 13 EP 16 DI 10.1016/j.jhep.2008.10.015 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 386SM UT WOS:000261902900005 PM 19017552 ER PT J AU Andersen, JB Raggi, C Marquardt, JU Conner, EA Lee, YH Factor, VM Thorgeirsson, SS AF Andersen, J. B. Raggi, C. Marquardt, J. U. Conner, E. A. Lee, Y. H. Factor, V. M. Thorgeirsson, S. S. TI MODULATION OF DEMETHYLATION AND ANTITUMOR POTENTIAL OF ZEBULARINE IN LIVER CANCER SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the European-Association-for-the-Study-of-the-Liver CY APR 22-26, 2009 CL Copenhagen, DENMARK SP European Assoc Study Liver C1 [Andersen, J. B.; Raggi, C.; Marquardt, J. U.; Conner, E. A.; Lee, Y. H.; Factor, V. M.; Thorgeirsson, S. S.] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM andersej@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PY 2009 VL 50 MA 113 BP S46 EP S46 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 450EV UT WOS:000266384700114 ER PT J AU Blair, BM Broering, TJ Babcock, GJ Szabo, G Finberg, RW Cheslock, PS Knauber, M Leav, BA Lanford, R Purcell, RH Ambrosino, DM Molrine, DC AF Blair, B. M. Broering, T. J. Babcock, G. J. Szabo, G. Finberg, R. W. Cheslock, P. S. Knauber, M. Leav, B. A. Lanford, R. Purcell, R. H. Ambrosino, D. M. Molrine, D. C. TI A NOVEL HUMAN MONOCLONAL ANTIBODY DIRECTED AGAINST THE E2 GLYCOPROTEIN OF HEPATITIS C VIRUS (HCV) PREVENTS INFECTION IN CHIMPANZEES SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the European-Association-for-the-Study-of-the-Liver CY APR 22-26, 2009 CL Copenhagen, DENMARK SP European Assoc Study Liver C1 [Blair, B. M.; Broering, T. J.; Babcock, G. J.; Cheslock, P. S.; Knauber, M.; Leav, B. A.; Ambrosino, D. M.; Molrine, D. C.] Univ Massachusetts, Sch Med, Boston, MA 02125 USA. [Szabo, G.; Finberg, R. W.] Univ Massachusetts, Sch Med, Worcester, MA USA. [Lanford, R.] SW Fdn Biomed Res, San Antonio, TX 78284 USA. [Purcell, R. H.] NIH, Bethesda, MD 20892 USA. EM donna.ambrosino@umassmed.edu NR 0 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PY 2009 VL 50 MA 1048 BP S381 EP S381 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 450EV UT WOS:000266384701531 ER PT J AU Gottwein, JM Lademann, JB Scheel, TKH Jensen, TB Prentoe, JC Bukh, J AF Gottwein, J. M. Lademann, J. B. Scheel, T. K. H. Jensen, T. B. Prentoe, J. C. Bukh, J. TI MONOCISTRONIC HEPATITIS C REPORTER VIRUS RECOMBINANTS OF ALL MAJOR GENOTYPES EXPRESSING ENHANCED GREEN FLUORESCENT PROTEIN TAGGED NS5A PROTEIN SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the European-Association-for-the-Study-of-the-Liver CY APR 22-26, 2009 CL Copenhagen, DENMARK SP European Assoc Study Liver C1 [Gottwein, J. M.; Lademann, J. B.; Scheel, T. K. H.; Jensen, T. B.; Prentoe, J. C.; Bukh, J.] Univ Copenhagen, Hvidovre Hosp, Copenhagen Hepatitis Program CO HEP C, Dept Infect Dis, DK-2650 Hvidovre, Denmark. [Gottwein, J. M.; Lademann, J. B.; Scheel, T. K. H.; Jensen, T. B.; Prentoe, J. C.; Bukh, J.] Univ Copenhagen, Hvidovre Hosp, Clin Res Ctr, DK-2650 Hvidovre, Denmark. [Gottwein, J. M.; Lademann, J. B.; Scheel, T. K. H.; Jensen, T. B.; Prentoe, J. C.; Bukh, J.] Univ Copenhagen, Fac Hlth Sci, Dept Int Hlth Immunol & Microbiol, CO HEP, Copenhagen, Denmark. [Bukh, J.] NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. EM judith@gottwein.eu NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PY 2009 VL 50 MA 79 BP S33 EP S33 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 450EV UT WOS:000266384700080 ER PT J AU Lambotin, M Thumann, C Robinet, E Stoll-Keller, F Liang, JT Barth, H Baumert, TF AF Lambotin, M. Thumann, C. Robinet, E. Stoll-Keller, F. Liang, J. T. Barth, H. Baumert, T. F. TI UPTAKE AND TRAFFICKING OF CELL CULTURE-DERIVED HEPATITIS C VIRUS (HCVCC) IN HUMAN PLASMACYTOID DENDRITIC CELLS SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the European-Association-for-the-Study-of-the-Liver CY APR 22-26, 2009 CL Copenhagen, DENMARK SP European Assoc Study Liver C1 [Lambotin, M.; Thumann, C.; Robinet, E.; Stoll-Keller, F.; Baumert, T. F.] INSERM, Inst Virol, U748, Strasbourg, France. [Lambotin, M.; Thumann, C.; Robinet, E.; Stoll-Keller, F.; Baumert, T. F.] Univ Strasbourg, Strasbourg, France. [Liang, J. T.; Barth, H.] NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA. [Baumert, T. F.] Hop Univ Strasbourg, Serv Hepatogastroenterol, Strasbourg, France. EM melanie.lambotin@viro-ulp.u-strasbg.fr NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 EI 1600-0641 J9 J HEPATOL JI J. Hepatol. PY 2009 VL 50 SU 1 MA 81 BP S33 EP S34 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 450EV UT WOS:000266384700082 ER PT J AU Maass, T Thieringer, F Becker, K Kanzler, S Galle, PR Teufel, A AF Maass, T. Thieringer, F. Becker, K. Kanzler, S. Galle, P. R. Teufel, A. TI ANALYSIS OF SIGNALING NETWORKS IN PDGF-B MEDIATED LIVER FIBROSIS SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the European-Association-for-the-Study-of-the-Liver CY APR 22-26, 2009 CL Copenhagen, DENMARK SP European Assoc Study Liver C1 [Maass, T.; Thieringer, F.; Galle, P. R.; Teufel, A.] Johannes Gutenberg Univ Mainz, Dept Med 1, D-6500 Mainz, Germany. [Becker, K.] NIA, Gene Express Unit, NIH, Baltimore, MD 21224 USA. [Kanzler, S.] Leopoldina Hosp, Dept Med 2, Schweinfurt, Germany. EM teufel@uni-mainz.de 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 0168-8278 J9 J HEPATOL JI J. Hepatol. PY 2009 VL 50 MA 299 BP S116 EP S117 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 450EV UT WOS:000266384700300 ER PT J AU Wang, M Lakatta, EG AF Wang, Mingyi Lakatta, Edward G. TI The salted artery and angiotensin II signaling: a deadly duo in arterial disease SO JOURNAL OF HYPERTENSION LA English DT Editorial Material DE aging; angiotensin II; arterial diseases; dietary sodium ID SPONTANEOUSLY HYPERTENSIVE RATS; BLOOD-PRESSURE; OXIDATIVE STRESS; NITRIC-OXIDE; SODIUM; INHIBITION; RECEPTOR; SYSTEM; WALL; INCREASE C1 [Lakatta, Edward G.] NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, Natl Inst Hlth,Intramural Res Program, Baltimore, MD 21224 USA. RP Lakatta, EG (reprint author), NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, Natl Inst Hlth,Intramural Res Program, 5600 Nathan Shock Dr,3-B-03, Baltimore, MD 21224 USA. EM lakattae@grc.nia.nih.gov FU Intramural NIH HHS [Z01 AG000240-01] NR 37 TC 9 Z9 9 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD JAN PY 2009 VL 27 IS 1 BP 19 EP 21 DI 10.1097/HJH.0b013e32831d1fed PG 3 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 379TO UT WOS:000261419300004 PM 19050444 ER PT J AU He, J Gu, DF Chen, J Jaquish, CE Rao, DC Hixson, JE Chen, JC Duan, XF Huang, JF Chen, CS Kelly, TN Bazzano, LA Whelton, PK AF He, Jiang Gu, Dongfeng Chen, Jing Jaquish, Cashell E. Rao, Dabeeru C. Hixson, James E. Chen, Ji-chun Duan, Xiufang Huang, Jian-feng Chen, Chung-Shiuan Kelly, Tanika N. Bazzano, Lydia A. Whelton, Paul K. CA GenSalt Collaborat Res Grp TI Gender difference in blood pressure responses to dietary sodium intervention in the GenSalt study SO JOURNAL OF HYPERTENSION LA English DT Article DE blood pressure; gender; potassium sensitivity; salt sensitivity ID SALT-SENSITIVITY; HYPERTENSION; ESTROGEN; SYSTEM; TRIAL; WOMEN AB Objective To examine factors related to blood pressure (BP) responses to dietary sodium and potassium interventions. Methods We conducted a dietary feeding study that included a 7-day low-salt intervention (51.3mmol sodium/day), a 7-day high-salt intervention (307.8 mmol sodium/day), and a 7-day high-salt and potassium-supplementation (60mmol potassium/ day) intervention among 1906 study participants in rural China. The BP was measured nine times during the 3-day baseline observation and during the last 3 days of each intervention phase using a random-zero sphygmomanometer. Results The BP responses to low-sodium intervention were significantly greater in women than in men: S8.1 [95% confidence interval (-8.6 to -7.6)] versus -7.0 (-7.5 to -6.6) mmHg for systolic and -4.5 (-4.9 to -4.1) versus -3.4 (-3.8 to -3.0) mmHg for diastolic. Likewise, BP responses to high-sodium interventions were significantly greater in women than in men: 6.4 (5.9-6.8) versus 5.2 (4.8-5.7) mmHg for systolic and 3.1 (2.7-3.5) versus 1.7 (1.4-2.1) mmHg for diastolic (all P<0.001). In addition, systolic BP responses to sodium interventions increased with age, and both systolic and diastolic BP responses to sodium interventions increased with baseline BP levels. BP responses to potassium supplementation also increased with baseline BP levels. Conclusion These results suggest that female gender, older age, and hypertension increase the sensitivity to dietary sodium intervention. Furthermore, low dietary sodium intake may be more effective in reducing BP among these subgroups. J Hypertens 27: 48 - 54 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [He, Jiang; Chen, Jing; Chen, Chung-Shiuan; Kelly, Tanika N.; Bazzano, Lydia A.] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA 70112 USA. [He, Jiang; Chen, Jing; Bazzano, Lydia A.] Tulane Univ, Sch Med, Dept Med, New Orleans, LA 70112 USA. [Gu, Dongfeng; Chen, Ji-chun; Duan, Xiufang; Huang, Jian-feng] Chinese Acad Med Sci, Cardiovasc Inst, Beijing 100037, Peoples R China. [Gu, Dongfeng; Chen, Ji-chun; Duan, Xiufang; Huang, Jian-feng] Chinese Acad Med Sci, Fu Wai Hosp, Beijing 100037, Peoples R China. [Jaquish, Cashell E.] NHLBI, Natl Inst Hlth, Bethesda, MD 20892 USA. [Rao, Dabeeru C.] Washington Univ, St Louis Sch Med, St Louis, MO USA. [Hixson, James E.] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA. [Whelton, Paul K.] Loyola Univ, Ctr Med, Maywood, IL 60153 USA. RP He, J (reprint author), Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, 1440 Canal St,Suite 2000, New Orleans, LA 70112 USA. EM jhe@tulane.edu FU National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA [U01HL072507]; Upsher-Smith Laboratories, Inc [Klor-ConM20] FX The GenSalt Study Steering Committee consists of Dongfeng Gu, Jiang He ( Chair), James E. Hixson, Cashell E. Jaquish, Depei Liu, Dabeeru C. Rao, Paul K. Whelton, and Zhijian Yao.; The GenSalt Collaborative Research Group consists of: Tulane University Health Sciences Center, New Orleans, Louisiana, USA: Jiang He (Principal Investigator), Lydia A. Bazzano, Chung-Shiuan Chen, Jing Chen, Mei Hao, Lee Hamm, Tanika Kelly, Paul Muntner, Kristi Reynolds, Paul K. Whelton, Wenjie Yang, and Qi Zhao; Washington University School of Medicine, St. Louis, Missouri, USA: Dabeeru C. Rao (PI), Matthew Brown, Charles Gu, Hongyan Huang, Treva Rice, Karen Schwander, and Shiping Wang; University of Texas Health Sciences Center at Houston: James E. Hixson (PI) and Lawrence C. Shimmin; National Heart, Lung, and Blood Institute: Cashell E. Jaquish; Chinese Academy of Medical Sciences, Beijing, China: Dongfeng Gu (PI), Jie Cao, Jichun Chen, Jingping Chen, Zhenhan Du, Jianfeng Huang, Hongwen Jiang, Jianxin Li, Xiaohua Liang, Depei Liu, Xiangfeng Lu, Donghua Liu, Qunxia Mao, Dongling Sun, Hongwei Wang, Qianqian Wang, Xigui Wu, Ying Yang, and Dahai Yu; Shandong Academy of Medical Sciences, Shandong, China: Fanghong Lu (PI), Zhendong Liu, Shikuan Jin, Yingxin Zhao, Shangwen Sun, Shujian Wang, Qengjie Meng, Baojin Liu, Zhaodong Yang, and Chuanrui Wei; Shandong Center for Diseases Control and Prevention, Shandong, China: Jixiang Ma (PI), Jiyu Zhang, and Junli Tang; Zhengzhou University: Dongsheng Hu, Hongwei Wen, Chongjian Wang, Minghui Shen, Jingjing Pan, and Liming Yang; Xinle Traditional Chinese Medicine Hospital, Hebei, China: Xu Ji (PI), Rongyan Li, Haijun Zu, and Junwei Song; Ganyu Center for Disease Control and Prevention: Delin Wu (PI), Xushan Wang, and Xiaofeng Zhang; Xi'an Jiaotong University, Shanxi, China: Jianjun Mu (PI), Enrang Chen, Fuqiang Liu, and Guanji Wu; Chinese National Human Genome Center at Beijing: Zhi-Jian Yao (PI), Shufeng Chen, Dongfeng Gu, Hongfan Li, Laiyuan Wang, and Penghua Zhang.; The Genetic Epidemiology Network of Salt Sensitivity (GenSalt) is supported by a cooperative agreement project grant (U01HL072507) from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA. The GenSalt investigators acknowledge Upsher-Smith Laboratories, Inc. for providing potassium chloride tablets (Klor-ConM20). NR 18 TC 62 Z9 71 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD JAN PY 2009 VL 27 IS 1 BP 48 EP 54 DI 10.1097/HJH.0b013e328316bb87 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 379TO UT WOS:000261419300011 PM 19145767 ER PT J AU Kelley-Hedgepeth, A Peter, I Montefusco, MC Levy, D Benjamin, EJ Vasan, RS Mendelsohn, ME Housman, D Huggins, GS Mitchell, GF AF Kelley-Hedgepeth, Alyson Peter, Inga Montefusco, Maria Claudia Levy, Daniel Benjamin, Emelia J. Vasan, Ramachandran S. Mendelsohn, Michael E. Housman, David Huggins, Gordon S. Mitchell, Gary F. TI The KCNMB1 E65K variant is associated with reduced central pulse pressure in the community-based Framingham Offspring Cohort SO JOURNAL OF HYPERTENSION LA English DT Article DE genetics; KCNMB1; single nucleotide polymorphism; vascular tonometry ID CORONARY-HEART-DISEASE; BETA-1 SUBUNIT; CARDIOVASCULAR MORTALITY; DIASTOLIC HYPERTENSION; INDEPENDENT PREDICTOR; ARTERIAL STIFFNESS; POTASSIUM CHANNEL; WAVE REFLECTION; ACTIVATION; MUTATION AB Objectives Genetic variants that influence large conductance calcium-activated potassium channel's function may alter arterial function and contribute to the known heritability of arterial stiffness and blood pressure. The beta(1)-subunit (KCNMB1) of the large conductance calcium-activated potassium channel includes two coding region polymorphisms. E65K, a gain-of-function polymorphism, is predicted to enhance large conductance calcium-activated potassium channel opening and vasorelaxation, whereas V110L has no known effect. We and others have reported that E65K carriers have reduced blood pressure. Methods To test our hypothesis that E65K has a favorable effect on arterial function, we related arterial tonometry and brachial artery phenotypes to genotypes in 1100 Framingham Offspring Study participants with available genotypes and phenotypes (53% women; mean age 61.5 +/- 9.4 years). Results The minor allele frequency was 0.10 for E65K and 0.09 for V110L; both were in Hardy-Weinberg equilibrium (chi(2), P>0.05), and haplotype analysis found R(2) = 0.01. E65K was associated with lower augmented pressure (7.4 +/- 3.3 versus 9.0 +/- 3.8 mmHg, P = 0.01) and central pulse pressure (47.1 +/- 7.3 versus 50.7 +/- 7.8 mmHg, P = 0.01) in multivariable analyses. No association was noted between E65K and mean arterial pressure, carotid-femoral pulse wave velocity or brachial artery diameter, flow velocity or volume flow. V110L was not associated with tonometry or brachial measures. Conclusion A diminished augmented pressure in K-carriers suggests a reduced or delayed wave reflection and supports the hypothesis that E65K reduces arterial impedance mismatch in the arterial tree. Our findings in a middle-aged community-based cohort, if replicated, would support that E65K has a favorable effect on arterial function and pulsatile hemodynamic load. J Hypertens 27: 55-60 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Huggins, Gordon S.] Tufts Univ, Sch Med, MCRI Ctr Translat Genom, Mol Cardiol Res Inst, Boston, MA 02111 USA. [Peter, Inga] Tufts Med Ctr, Ctr Genet Epidemiol & Modeling, Inst Clin Res & Hlth Policy Studies, Boston, MA USA. [Levy, Daniel; Benjamin, Emelia J.; Vasan, Ramachandran S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. [Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med & Prevent Med, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA. [Housman, David] MIT, Cambridge, MA 02139 USA. [Mitchell, Gary F.] Cardiovasc Engn Inc, Waltham, MA USA. RP Huggins, GS (reprint author), Tufts Univ, Sch Med, MCRI Ctr Translat Genom, Mol Cardiol Res Inst, 750 Washington St,Box 8486, Boston, MA 02111 USA. EM ghuggins@tuftsmedicalcenter.org OI Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [HL069770, 2K24HL04334, HL077378, HL080124, HL60040, HL70100, K24 HL004334, N01-HC-25195, N01HC25195, P01 HL077378, P01 HL077378-05, R01 HL060040, R01 HL070100, R01 HL080124, T32 HL069770, T32 HL069770-05] NR 25 TC 14 Z9 13 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD JAN PY 2009 VL 27 IS 1 BP 55 EP 60 DI 10.1097/HJH.0b013e328317c8ae PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 379TO UT WOS:000261419300012 PM 19050450 ER PT J AU Lissina, A Ladell, K Skowera, A Clement, M Edwards, E Seggewiss, R van den Berg, HA Gostick, E Gallagher, K Jones, E Melenhorst, JJ Godkin, AJ Peakman, M Price, DA Sewell, AK Wooldridge, L AF Lissina, Anna Ladell, Kristin Skowera, Ania Clement, Matthew Edwards, Emily Seggewiss, Ruth van den Berg, Hugo A. Gostick, Emma Gallagher, Kathleen Jones, Emma Melenhorst, J. Joseph Godkin, Andrew J. Peakman, Mark Price, David A. Sewell, Andrew K. Wooldridge, Linda TI Protein kinase inhibitors substantially improve the physical detection of T-cells with peptide-MHC tetramers SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE T cell; Tetramer; Low avidity CTL; Cancer immunology; Autoimmunity ID CD8 CORECEPTOR; ANTIGEN RECEPTOR; DOWN-REGULATION; ACTIVATION; COMPLEX; SPECIFICITY; SURFACE; KIT; PHOSPHORYLATION; INTERNALIZATION AB Flow cytometry with fluorochrome-conjugated peptide-major histocompatibility complex (pMHC) tetramers has transformed the study of antigen-specific T-cells by enabling their visualization, enumeration, phenotypic characterization and isolation from ex vivo samples. Here, we demonstrate that the reversible protein kinase inhibitor (PKI) dasatinib improves the staining intensity of human (CD8+ and CD4+) and murine T-cells without concomitant increases in background staining. Dasatinib enhances the capture of cognate pMHC tetramers from solution and produces higher intensity staining at lower pMHC concentrations. Furthermore. dasatinib reduces pMHC tetramer-induced cell death and substantially lowers the T-cell receptor (TCR)/pMHC interaction affinity threshold required for cell staining. Accordingly, dasatinib permits the identification of T-cells with very low affinity TCR/pMHC interactions, such as those that typically predominate in tumour-specific responses and autoimmune conditions that are not amenable to detection by current technology. (c) 2008 Elsevier B.V. All rights reserved. C1 [Lissina, Anna; Ladell, Kristin; Clement, Matthew; Edwards, Emily; Gostick, Emma; Gallagher, Kathleen; Jones, Emma; Godkin, Andrew J.; Price, David A.; Sewell, Andrew K.; Wooldridge, Linda] Cardiff Univ, Sch Med, Cardiff CF14 4XN, S Glam, Wales. [Skowera, Ania; Peakman, Mark] Kings Coll London, Dept Immunobiol, London, England. [Skowera, Ania; Peakman, Mark] Guys & St Thomas NHS Fdn Trust, NIHR Biomed Res Ctr, London, England. [Seggewiss, Ruth] Univ Wurzburg, Med Klin & Poliklin 2, Immune Recovery Sect, D-97070 Wurzburg, Germany. [van den Berg, Hugo A.] Univ Warwick, Warwick Syst Biol Ctr, Coventry CV4 7AL, W Midlands, England. [Melenhorst, J. Joseph] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Wooldridge, L (reprint author), Henry Wellcome Bldg,Heath Pk, Cardiff CF14 4XN, S Glam, Wales. EM wooldridgel@cardiff.ac.uk RI Edwards, Emily/C-3219-2013; Ladell, Kristin/K-2475-2013; Price, David/C-7876-2013; Ladell, Kristin/C-8301-2013; OI Price, David/0000-0001-9416-2737; Ladell, Kristin/0000-0002-9856-2938; Sewell, Andrew/0000-0003-3194-3135; Edwards, Emily/0000-0002-0240-4370 FU Intramural NIH HHS; Medical Research Council [G0501963]; Wellcome Trust NR 34 TC 48 Z9 48 U1 2 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD JAN 1 PY 2009 VL 340 IS 1 BP 11 EP 24 DI 10.1016/j.jim.2008.09.014 PG 14 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 400LP UT WOS:000262869800002 PM 18929568 ER PT J AU Tarantino-Hutchison, LM Sorrentino, C Nadas, A Zhu, YW Rubin, EM Tinkle, SS Weston, A Gordon, T AF Tarantino-Hutchison, Lauren M. Sorrentino, Claudio Nadas, Arthur Zhu, Yiwen Rubin, Edward M. Tinkle, Sally S. Weston, Ainsley Gordon, Terry TI Genetic determinants of sensitivity to beryllium in mice SO JOURNAL OF IMMUNOTOXICOLOGY LA English DT Article DE Beryllium; chronic beryllium disease; mouse model ID MURINE STRAIN DIFFERENCES; DIESEL EXHAUST PARTICLES; MHC-CLASS-II; AIRWAY INFLAMMATION; DISEASE; SENSITIZATION; SUSCEPTIBILITY; ANTIGEN; EXPOSURE; EPITOPES AB Chronic beryllium disease (CBD), an irreversible, debilitating granulomatous lung disease is caused by exposure to beryllium. This occupational hazard occurs in primary production and machining of Be-metal, BeO, beryllium containing alloys, and other beryllium products. CBD begins as an MHC Class II-restricted, T(H)1 hypersensitivity, and the Human Leukocyte Antigen, HLA-DPB1E(69), is associated with risk of developing CBD. Because inbred strains of mice have not provided good models of CBD to date, three strains of HLA-DPB1 transgenic mice in an FVB/N background were developed; each contains a single allele of HLA-DPB1 that confers a different magnitude of risk for chronic beryllium disease: HLA-DPB1*0401 (OR approximate to 0.2), HLA-DPB1*0201 (OR approximate to 3), and HLA-DPB1*1701 (OR approximate to 46). The mouse ear swelling test ( MEST) was employed to determine if these different alleles would support a hypersensitivity response to beryllium. Mice were first sensitized on the back and subsequently challenged on the ear. In separate experiments, mice were placed into one of three groups (sensitization/challenge): C/C, C/Be, and Be/Be. In the HLA-DPB1*1701 mice, the strain with the highest risk transgene, the Be/Be group was the only group that displayed significant maximum increased ear thickness of 19.6% +/- 3.0% over the baseline measurement (p < 0.05). No significant changes were observed in the other transgenic strains for any treatment condition. In addition, inter-strain differences in response to beryllium in seven inbred strains were investigated through use of the MEST, these included: FVB/N, AKR, Balb/c, C3H/HeJ, C57/BL6, DBA/2, and SJL/J. The FVB/N strain was least responsive, while the SJL/J and C57/BL6 strains were the highest responders. Our results suggest that the HLA-DPB1*1701 transgene product is an important risk factor for induction of the beryllium-sensitive phenotype. This model should be a useful tool for investigating beryllium sensitization. C1 [Tarantino-Hutchison, Lauren M.; Sorrentino, Claudio; Nadas, Arthur; Gordon, Terry] NYU, Sch Med, Dept Environm Med, Tuxedo Pk, NY 10987 USA. [Zhu, Yiwen; Rubin, Edward M.] Univ Calif Berkeley, Lawrence Berkeley Lab, Dept Genome Sci, Berkeley, CA 94720 USA. [Tinkle, Sally S.] Natl Inst Environm Hlth Sci, Off Director, Res Triangle Pk, NC USA. [Weston, Ainsley] NIOSH, Div Resp Dis Studies, Morgantown, WV 26505 USA. RP Gordon, T (reprint author), NYU, Sch Med, Dept Environm Med, 57 Old Forge Rd, Tuxedo Pk, NY 10987 USA. EM terry.gordon@nyumc.org FU Department of Energy [DE-FG02-04ER63919]; National Institute of Environmental Health Sciences [ES011473] FX Department of Energy (DE-FG02-04ER63919); National Institute of Environmental Health Sciences (ES011473). NR 26 TC 10 Z9 11 U1 0 U2 2 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 1547-691X J9 J IMMUNOTOXICOL JI J. Immunotoxicol. PY 2009 VL 6 IS 2 BP 130 EP 135 DI 10.1080/15476910902977399 PG 6 WC Toxicology SC Toxicology GA 481HG UT WOS:000268797800006 PM 19589099 ER PT J AU Malyguine, A Umansky, V Shurin, MR AF Malyguine, Anatoli Umansky, Victor Shurin, Michael R. TI Cancer Immunotherapy and Immunomonitoring (CITIM): Redefining Cancer Therapy SO JOURNAL OF IMMUNOTOXICOLOGY LA English DT Article DE Cancer; immunotherapy; immunomonitoring AB The immune system is a critical element involved in the control of tumor development and progression. While we have learned how to manipulate the immune system to generate tumor-specific immune responses, cancer immunotherapy has not yet delivered substantial clinical benefits. It has become increasingly clear that tumor-induced abnormalities in the immune system not only hamper natural tumor immune surveillance, but also limit the effect of cancer immunotherapy. If the results of recent studies are of any indication, then we are on the verge of a real breakthrough in our understanding of the immunobiology of tumor-host interactions and of ways to manipulate it. This 1(st) International Conference on "Cancer Immunotherapy and Immunomonitoring (CITIM)" was the first meeting in Eastern Europe to specifically focus on the issue of immune regulation in the tumor environment, cancer immunotherapy, and immunomonitoring of immunotherapeutic clinical trials. This CITIM Conference held in Kiev, Ukraine, was comprised from eight plenary sessions and two special selected poster presentation sessions. Selected contributions from the participants of the Conference are presented in this issue of the Journal of Immunotoxicology. C1 [Malyguine, Anatoli] NCI, Lab Cell Mediated Immun, SAIC Frederick Inc, Frederick, MD 21702 USA. [Umansky, Victor] German Canc Res Ctr, D-6900 Heidelberg, Germany. [Shurin, Michael R.] Univ Pittsburgh, Med Ctr, Dept Pathol, Pittsburgh, PA USA. [Shurin, Michael R.] Univ Pittsburgh, Med Ctr, Dept Immunol, Pittsburgh, PA USA. RP Malyguine, A (reprint author), NCI, Lab Cell Mediated Immun, SAIC Frederick Inc, Frederick, MD 21702 USA. EM malyguinea@mail.nih.gov FU National Cancer Institute; National Institutes of Health [HHSN261200800001E]; NIH [CA84270] FX This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E (to A. M.) and NIH grant CA84270 (to M. R. S.). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 0 TC 0 Z9 1 U1 0 U2 1 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 1547-691X J9 J IMMUNOTOXICOL JI J. Immunotoxicol. PY 2009 VL 6 IS 4 BP 205 EP 208 DI 10.3109/15476910903120932 PG 4 WC Toxicology SC Toxicology GA 561TJ UT WOS:000275001500001 PM 19908938 ER PT J AU Wang, SS Bratti, MC Rodriguez, AC Herrero, R Burk, RD Porras, C Gonzalez, P Sherman, ME Wacholder, S Lan, ZE Schiffman, M Chanock, SJ Hildesheim, A AF Wang, Sophia S. Concepcion Bratti, M. Rodriguez, Ana Cecilia Herrero, Rolando Burk, Robert D. Porras, Carolina Gonzalez, Paula Sherman, Mark E. Wacholder, Sholom Lan, Z. Elizabeth Schiffman, Mark Chanock, Stephen J. Hildesheim, Allan TI Common Variants in Immune and DNA Repair Genes and Risk for Human Papillomavirus Persistence and Progression to Cervical Cancer SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 24th International Papillomavirus Conference and Clinical Workshop CY NOV 03-09, 2007 CL Beijing, PEOPLES R CHINA ID P53 CODON-72 POLYMORPHISM; UTERINE CERVIX; COSTA-RICA; INFECTION; SUSCEPTIBILITY; METAANALYSIS; NEOPLASIA; INTERLEUKIN-10; CARCINOMA; PATHWAYS AB Background. We examined host genetic factors to identify those more common in individuals whose human papillomavirus (HPV) infections were most likely to persist and progress to cervical intraepithelial neoplasia grade 3 (CIN3) and cancer. Methods. We genotyped 92 single-nucleotide polymorphisms (SNPs) from 49 candidate immune response and DNA repair genes obtained from 469 women with CIN3 or cancer, 390 women with persistent HPV infections (median duration, 25 months), and 452 random control subjects from the 10,049-woman Guanacaste Costa Rica Natural History Study. We calculated odds ratios and 95% confidence intervals (CIs) for the association of SNP and haplotypes in women with CIN3 or cancer and HPV persistence, compared with random control subjects. Results. A SNP in the Fanconi anemia complementation group A gene (FANCA) (G501S) was associated with increased risk of CIN3 or cancer. The AG and GG genotypes had a 1.3-fold (95% CI, 0.95-1.8-fold) and 1.7-fold ( 95% CI, 1.1-2.6-fold) increased risk for CIN3 or cancer, respectively (P(trend) =.008; referent, AA). The FANCA haplotype that included G501S also conferred increased risk of CIN3 or cancer, as did a different haplotype that included 2 other FANCA SNPs (G809A and T266A). A SNP in the innate immune gene IRF3 (S427T) was associated with increased risk for HPV persistence (P(trend) =.009). Conclusions. Our results require replication but support the role of FANCA variants in cervical cancer susceptibility and of IRF3 in HPV persistence. C1 [Wang, Sophia S.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. [Chanock, Stephen J.] NCI, Core Genotyping Facil, Gaithersburg, MD USA. [Burk, Robert D.] Albert Einstein Coll Med, New York, NY USA. [Concepcion Bratti, M.; Herrero, Rolando; Porras, Carolina; Gonzalez, Paula] Fdn Inst Costarricense Invest & Ensenanza Nutr &, San Jose, Costa Rica. RP Wang, SS (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Rm 5104, Rockville, MD 20852 USA. EM wangso@mail.nih.gov RI Hildesheim, Allan/B-9760-2015 OI Hildesheim, Allan/0000-0003-0257-2363 FU Intramural NIH HHS; NCI NIH HHS [CA-78527, CO-12400, CP-21081, CP-31061, N01CO12400, R01 CA078527, U01 CA078527] NR 39 TC 62 Z9 67 U1 0 U2 4 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 JAN 1 PY 2009 VL 199 IS 1 BP 20 EP 30 DI 10.1086/595563 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 384OP UT WOS:000261754400005 PM 19012493 ER PT J AU Broliden, K Haase, AT Ahuja, SK Shearer, GM Andersson, J AF Broliden, K. Haase, A. T. Ahuja, S. K. Shearer, G. M. Andersson, J. TI Introduction: Back to basics: mucosal immunity and novel HIV vaccine concepts SO JOURNAL OF INTERNAL MEDICINE LA English DT Article ID T-CELLS; TRANSMISSION; SUSCEPTIBILITY; VIRUS C1 [Broliden, K.] Karolinska Univ Hosp, Karolinska Inst, Ctr Mol Med, Dept Med,Unit Infect Dis, S-17176 Stockholm, Sweden. [Haase, A. T.] Univ Minnesota, Dept Microbiol, Minneapolis, MN 55455 USA. [Haase, A. T.] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. [Ahuja, S. K.] Vet Adm Res Ctr AIDS & HIV 1 Infect, San Antonio, TX USA. [Ahuja, S. K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med Microbiol & Immunol & Biochem, San Antonio, TX 78229 USA. [Shearer, G. M.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. [Andersson, J.] Karolinska Univ Hosp, Karolinska Inst, Ctr Infect Med, Dept Med, S-17176 Stockholm, Sweden. RP Broliden, K (reprint author), Karolinska Univ Hosp, Karolinska Inst, Ctr Mol Med, Dept Med,Unit Infect Dis, B2-03, S-17176 Stockholm, Sweden. EM kristina.broliden@karolinska.se NR 26 TC 18 Z9 19 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0954-6820 J9 J INTERN MED JI J. Intern. Med. PD JAN PY 2009 VL 265 IS 1 BP 5 EP 17 DI 10.1111/j.1365-2796.2008.02053.x PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 381IM UT WOS:000261529400003 PM 19093956 ER PT J AU Boasso, A Shearer, GM Chougnet, C AF Boasso, A. Shearer, G. M. Chougnet, C. TI Immune dysregulation in human immunodeficiency virus infection: know it, fix it, prevent it? SO JOURNAL OF INTERNAL MEDICINE LA English DT Review DE acquired immunodeficiency syndrome; human immunodeficiency virus; pathogenesis ID CD4(+) T-CELLS; PLASMACYTOID DENDRITIC CELLS; HEPATITIS-C VIRUS; NATURAL-KILLER-CELLS; CHRONIC HELMINTH INFECTIONS; INTERFERON-PRODUCING CELLS; PRIMARY HUMAN MACROPHAGES; BLOOD MONONUCLEAR-CELLS; HIV-INFECTION; INDOLEAMINE 2,3-DIOXYGENASE AB Infection of humans by the human immunodeficiency virus (HIV) causes a progressive, multifactorial impairment of the immune system eventually leading to the acquired immunodeficiency syndrome (AIDS). No cure or vaccine exists yet against HIV infection. More worrisome is the fact that despite having identified HIV as the cause of the AIDS, we still do not understand what pathogenic mechanisms lead to the debacle of the immune system. In this review we consider the extent and the limits of our knowledge of HIV pathogenesis, and how this knowledge may be used to design preventive and therapeutic approaches. C1 [Chougnet, C.] Univ Cincinnati, Coll Med, Ctr Med, Cincinnati Childrens Hosp,Div Mol Immunol, Cincinnati, OH USA. [Chougnet, C.] Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH USA. [Boasso, A.] Univ London Imperial Coll Sci Technol & Med, Chelsea & Westminster Hosp, Fac Med, Dept Immunol, London, England. [Shearer, G. M.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Chougnet, C (reprint author), Cincinnati Childrens Hosp, Med Ctr, Div Mol Immunol ML 7021, 3333 Burnet Ave, Cincinnati, OH 45229 USA. EM claire.chougnet@cchmc.org OI Boasso, Adriano/0000-0001-9673-6319 FU Wellcome Trust [DQAD-P04191]; Westminster Medical School Research Trust [PMS/MMS-07/0810124]; Intramural research Program of the CCR; NCI; Intramural AIDS Targeted Antiviral Program; National Institutes of Health [AI 056927, AI068524] FX A. B. was supported by the Wellcome Trust (value in people award DQAD-P04191) and by the Westminster Medical School Research Trust (PMS/MMS-07/0810124); G. M. S. was supported by the Intramural research Program of the CCR, NCI and by the Intramural AIDS Targeted Antiviral Program (IATAP); C. C. was supported by grants from the National Institutes of Health (AI 056927 and AI068524). NR 161 TC 17 Z9 19 U1 0 U2 7 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0954-6820 J9 J INTERN MED JI J. Intern. Med. PD JAN PY 2009 VL 265 IS 1 BP 78 EP 96 DI 10.1111/j.1365-2796.2008.02043.x PG 19 WC Medicine, General & Internal SC General & Internal Medicine GA 381IM UT WOS:000261529400009 PM 19093962 ER PT J AU Buck, CB Lowy, DR AF Buck, Christopher B. Lowy, Douglas R. TI Getting Stronger: The Relationship Between a Newly Identified Virus and Merkel Cell Carcinoma SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Editorial Material ID POLYOMAVIRUS AB Merkel cell carcinoma (MCC) is an aggressive skin cancer that develops in individuals who are over the age of 50 or immunosuppressed. DNA from a new polyomavirus, MCPyV, was recently shown to be clonally integrated in several MCC cases. In this issue, Becker et al. demonstrate that MCPyV DNA can be isolated from 85% of primary European MCC specimens and their metastases, and Garneski et al. present data indicating that the percentage of Australian MCC cases containing MCPyV may be lower than that of north American cases. These reports support the possibility that MCPyV is etiologically involved in at least some cases of MCC. C1 [Buck, Christopher B.; Lowy, Douglas R.] NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. RP Lowy, DR (reprint author), NCI, Cellular Oncol Lab, Bldg 37,Room 4106,9000 Rockville Pike, Bethesda, MD 20892 USA. EM drl@helix.nih.gov OI Buck, Christopher/0000-0003-3165-8094 FU Intramural NIH HHS [ZIA BC011090-03] NR 16 TC 14 Z9 14 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JAN PY 2009 VL 129 IS 1 BP 9 EP 11 DI 10.1038/jid.2008.302 PG 4 WC Dermatology SC Dermatology GA 385QQ UT WOS:000261829100003 PM 19078983 ER PT J AU Passeron, T Namiki, T Passeron, HJ Le Pape, E Hearing, VJ AF Passeron, Thierry Namiki, Takeshi Passeron, Helene J. Le Pape, Elodie Hearing, Vincent J. TI Forskolin Protects Keratinocytes from UVB-Induced Apoptosis and Increases DNA Repair Independent of its Effects on Melanogenesis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID RADIATION-INDUCED APOPTOSIS; CYCLIC-AMP; SKIN PIGMENTATION; HUMAN MELANOCYTES; MELANIN CONTENT; DAMAGE; RESPONSES; CAPACITY; CELLS; MC1R AB Melanin pigments provide efficient protection against ultraviolet B (UVB) radiation but DNA repair also plays a key role in eliminating UV-induced damage and preventing the development of skin cancers. In this study, we demonstrate that forskolin (FSK), an agent that increases intracellular levels of cAMP, protects keratinocytes from UVB-induced apoptosis independently from the amount of melanin in the skin. FSK enhances the removal of the two major types of UVB-induced DNA damage, cyclobutane pyrimidine dimers and 6,4-photoproducts, by facilitating DNA repair. These findings suggest new preventive approaches with topical formulations of FSK or other bioactive agents that could be applied to the skin before sun exposure to increase its ability to repair DNA damage. C1 [Passeron, Thierry; Namiki, Takeshi; Passeron, Helene J.; Le Pape, Elodie; Hearing, Vincent J.] NCI, Pigment Cell Biol Sect, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Hearing, VJ (reprint author), NCI, Pigment Cell Biol Sect, Cell Biol Lab, NIH, Bldg 37,Room 2132,MSC 4256, Bethesda, MD 20892 USA. EM hearingv@nih.gov OI Passeron, Thierry/0000-0002-0797-6570 FU Intramural Research Program of the NIH; National Cancer Institute FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute. We thank Dr Ettore Appella, National Cancer Institute, for his useful comments and suggestions. NR 21 TC 26 Z9 26 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JAN PY 2009 VL 129 IS 1 BP 162 EP 166 DI 10.1038/jid.2008.182 PG 5 WC Dermatology SC Dermatology GA 385QQ UT WOS:000261829100020 PM 18580960 ER PT J AU Jeong, M Walker, J Colucci, W Moore, R Vinson, C Long, C AF Jeong, M. Walker, J. Colucci, W. Moore, R. Vinson, C. Long, C. TI AFos INHIBITS PHENYLEPHRINE MEDIATED CONTRACTILE DYSFUNCTION BY ALTERING PHOSPHOLAMBAN AND TROPONIN T PHOSPHORYLATION SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 28-31, 2009 CL Carmel, CA SP Amer Federat Med Res, Western Reg, Western Soc Clin Invest, Western Assoc Phys, Western Soc Pediat Res, Western Student Med Res Forum C1 [Jeong, M.; Walker, J.; Long, C.] Univ Colorado Denver, Aurora, CO USA. [Colucci, W.] Boston Univ, Boston, MA 02215 USA. [Moore, R.] Univ Colorado Boulder, Boulder, CO USA. [Vinson, C.] Natl Canc Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2009 VL 57 IS 1 BP 108 EP 109 PG 2 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 497VU UT WOS:000270092400048 ER PT J AU Blevins, EM Yang, J McDonnell, NB Willis, MJ AF Blevins, E. M. Yang, J. McDonnell, N. B. Willis, M. J. TI INTRAVENTRICULAR HEMORRHAGE IN KYPHOSCOLIOTIC EHLERS-DANLOS SYNDROME SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 28-31, 2009 CL Carmel, CA SP Amer Federat Med Res, Western Reg, Western Soc Clin Invest, Western Assoc Phys, Western Soc Pediat Res, Western Student Med Res Forum C1 [Blevins, E. M.; Willis, M. J.] USN, San Diego Med Ctr, San Diego, CA 92152 USA. [Yang, J.; McDonnell, N. B.] NIA, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2009 VL 57 IS 1 BP 174 EP 174 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 497VU UT WOS:000270092400282 ER PT J AU Behshad, S Nelson, RG AF Behshad, S. Nelson, R. G. TI DEVELOPMENT OF PROTOCOLS AND STUDY DESIGN FOR AN INTENSIVE LIFESTYLE INTERVENTION PROVIDED TO HIGH RISK PREGNANT AMERICAN INDIAN WOMEN SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 28-31, 2009 CL Carmel, CA SP Amer Federat Med Res, Western Reg, Western Soc Clin Invest, Western Assoc Phys, Western Soc Pediat Res, Western Student Med Res Forum C1 [Behshad, S.] Univ Arizona, Coll Med, Tucson, AZ USA. [Nelson, R. G.] NIDDKD, Phoenix, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2009 VL 57 IS 1 BP 198 EP 198 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 497VU UT WOS:000270092400368 ER PT J AU Dunn, JH Hadley-Miller, N Cook, S Swindle, K Marosy, B Justice, C Wilson, AF AF Dunn, J. H. Hadley-Miller, N. Cook, S. Swindle, K. Marosy, B. Justice, C. Wilson, A. F. TI FAMILIAL IDIOPATHIC SCOLIOSIS IN MALES: LOCALIZATION TO CHROMOSOME 22Q SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 28-31, 2009 CL Carmel, CA SP Amer Federat Med Res, Western Reg, Western Soc Clin Invest, Western Assoc Phys, Western Soc Pediat Res, Western Student Med Res Forum C1 [Dunn, J. H.; Hadley-Miller, N.; Cook, S.; Swindle, K.] Univ Colorado, Denver Sch Med, Aurora, CO USA. [Marosy, B.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. [Justice, C.; Wilson, A. F.] NHGRI, Baltimore, MD USA. [Hadley-Miller, N.] Childrens Hosp, Aurora, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2009 VL 57 IS 1 BP 227 EP 227 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 497VU UT WOS:000270092400471 ER PT J AU Bao, X Morse, CL Lu, S Simeon, FG Pike, VW AF Bao, X. Morse, C. L. Lu, S. Simeon, F. G. Pike, V. W. TI SYNTHESIS OF [C-11]RHODAMINE-123 AS A POTENTIAL TRACER FOR IMAGING P-GLYCOPROTEIN FUNCTION SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract C1 [Bao, X.; Morse, C. L.; Lu, S.; Simeon, F. G.; Pike, V. W.] NIMH, NIH, Mol Imaging Branch, Bethesda, MD 20892 USA. RI Bao, Xiaofeng/K-5278-2013 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 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PY 2009 VL 52 SU 1 BP S427 EP S427 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 480HQ UT WOS:000268724900428 ER PT J AU Bao, X Lu, S Simeon, FG Morse, CL Pike, VW AF Bao, X. Lu, S. Simeon, F. G. Morse, C. L. Pike, V. W. TI SYNTHESIS OF A PROSPECTIVE F-18-LABELED TRACER FOR IMAGING P-GLYCOPROTEIN FUNCTION SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract C1 [Bao, X.; Lu, S.; Simeon, F. G.; Morse, C. L.; Pike, V. W.] NIMH, NIH, Mol Imaging Branch, Bethesda, MD 20892 USA. RI Bao, Xiaofeng/K-5278-2013 NR 0 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PY 2009 VL 52 SU 1 BP S350 EP S350 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 480HQ UT WOS:000268724900351 ER PT J AU Cai, L Ozaki, H Fujita, M Hong, JS Bukhari, M Innis, RB Pike, VW AF Cai, L. Ozaki, H. Fujita, M. Hong, J. S. Bukhari, M. Innis, R. B. Pike, V. W. TI [C-11]GO6976 AS A POTENTIAL RADIOLIGAND FOR IMAGING PROTEIN KINASE C WITH PET SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract C1 [Cai, L.; Ozaki, H.; Fujita, M.; Hong, J. S.; Bukhari, M.; Innis, R. B.; Pike, V. W.] NIMH, NIH, Mol Imaging Branch, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PY 2009 VL 52 SU 1 BP S337 EP S337 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 480HQ UT WOS:000268724900338 ER PT J AU Cai, L Liow, JS Houlihan, B Morse, CL Gladding, RL Innis, RB Pike, VW AF Cai, L. Liow, J. S. Houlihan, B. Morse, C. L. Gladding, R. L. Innis, R. B. Pike, V. W. TI [F-18]FBTA2 AS A POTENTIAL RADIOLIGAND FOR IMAGING BRAIN BETA-AMYLOID SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract C1 [Cai, L.; Liow, J. S.; Houlihan, B.; Morse, C. L.; Gladding, R. L.; Innis, R. B.; Pike, V. W.] NIMH, NIH, Mol Imaging Branch, 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 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PY 2009 VL 52 SU 1 BP S89 EP S89 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 480HQ UT WOS:000268724900090 ER PT J AU Chun, J Lu, S Lee, YS Pike, VW AF Chun, J. Lu, S. Lee, Y. S. Pike, V. W. TI RADIOFLUORINATION OF UNSYMMETRICAL DIARYLIODONIUM SALT COMPLIES WITH THE CURTIN-HAMMETT PRINCIPLE SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract C1 [Chun, J.; Lu, S.; Pike, V. W.] NIMH, NIH, Mol Imaging Branch, Bethesda, MD 20892 USA. [Lee, Y. S.] NIH, Ctr Informat Technol, Div Computat Biosci, Ctr Mol Modeling, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PY 2009 VL 52 BP S159 EP S159 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 480HQ UT WOS:000268724900160 ER PT J AU Chun, J Lu, S Pike, VW AF Chun, J. Lu, S. Pike, V. W. TI PROBING THE ORTHO-EFFECT IN THE RADIOFLUORINATION OF DIARYLIODONIUM SALTS SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract C1 [Chun, J.; Lu, S.; Pike, V. W.] NIMH, NIH, Mol Imaging Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PY 2009 VL 52 BP S158 EP S158 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 480HQ UT WOS:000268724900159 ER PT J AU Chun, J Lu, S Pike, VW AF Chun, J. Lu, S. Pike, V. W. TI KINETICS AND ENERGETICS OF THE RADIOFLUORINATION OF DIARYLIODONIUM CHLORIDES STUDIED WITH A MICROFLUIDIC REACTOR SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract C1 [Chun, J.; Lu, S.; Pike, V. W.] NIMH, NIH, Mol Imaging Branch, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PY 2009 VL 52 BP S14 EP S14 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 480HQ UT WOS:000268724900015 ER PT J AU Chun, J Lu, S Pike, VW AF Chun, J. Lu, S. Pike, V. W. TI RADIOFLUORINATION OF UNSYMMETRICAL META-SUBSTITUTED DIARYLIODONIUM SALTS WITHIN A MICRO-REACTOR SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract C1 [Chun, J.; Lu, S.; Pike, V. W.] NIMH, NIH, Mol Imaging Branch, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PY 2009 VL 52 BP S2 EP S2 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 480HQ UT WOS:000268724900003 ER PT J AU Donohue, SR Jia, Z Eriksson, S Gulyas, B Pike, VW Halldin, C AF Donohue, S. R. Jia, Z. Eriksson, S. Gulyas, B. Pike, V. W. Halldin, C. TI SYNTHESIS, RADIOIODINATION AND IN VITRO AUTORADIOGRAPHIC EVALUATION OF A NOVEL HIGH-AFFINITY LIGAND FOR IMAGING BRAIN CANNABINOID SUBTYPE-1 (CB1) RECEPTORS SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract C1 [Donohue, S. R.] Johns Hopkins Univ, Dept Radiol, Div Nucl Med, Baltimore, MD USA. [Pike, V. W.] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. [Jia, Z.; Eriksson, S.; Gulyas, B.; Halldin, C.] Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, Stockholm, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PY 2009 VL 52 BP S397 EP S397 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 480HQ UT WOS:000268724900398 ER PT J AU Griffiths, GL Wilson, CM Shenoy, N Wu, H Teng, B Cheal, SM Shi, Z AF Griffiths, G. L. Wilson, C. M. Shenoy, N. Wu, H. Teng, B. Cheal, S. M. Shi, Z. TI THE IMAGING PROBE DEVELOPMENT CENTER: FACILITATING INTERDISCIPLINARY IMAGING RESEARCH THROUGH THE PRODUCTION AND SUPPLY OF MOLECULAR PROBES SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract C1 [Griffiths, G. L.; Wilson, C. M.; Shenoy, N.; Wu, H.; Teng, B.; Cheal, S. M.; Shi, Z.] NHLBI, NIH, Imaging Probe Dev Ctr, Rockville, MD USA. RI Shenoy, Nalini/O-2132-2013 NR 0 TC 0 Z9 0 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PY 2009 VL 52 BP S114 EP S114 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 480HQ UT WOS:000268724900115 ER PT J AU Helin, S Nagren, K Airaksinen, AJ Steiger, C Bergstrom, JP Takano, A Pike, VW Halldin, C AF Helin, S. Nagren, K. Airaksinen, A. J. Steiger, C. Bergstrom, J. P. Takano, A. Pike, V. W. Halldin, C. TI LABELLING OF RTI-32 WITH C-11 IN THREE DIFFERENT POSITIONS: A STUDY OF THE INFLUENCE OF LABELLING POSITION ON BRAIN DISTRIBUTION AND METABOLITE PATTERN MEASURED IN MONKEY BY PET SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract C1 [Helin, S.] Univ Turku, Turku PET Ctr, Turku, Finland. [Nagren, K.] Univ Copenhagen, Rigshosp, Dept Clin Physiol & Nucl Med, DK-2100 Copenhagen, Denmark. [Airaksinen, A. J.] Univ Helsinki, Dept Chem, Radiochem Lab, SF-00100 Helsinki, Finland. [Steiger, C.; Bergstrom, J. P.; Takano, A.; Halldin, C.] Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, Stockholm, Sweden. [Pike, V. W.] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. RI Airaksinen, Anu/N-9070-2014 OI Airaksinen, Anu/0000-0002-5943-3105 NR 1 TC 0 Z9 0 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PY 2009 VL 52 BP S423 EP S423 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 480HQ UT WOS:000268724900424 ER PT J AU Jacobson, O Weiss, ID Szajek, L Ma, Y Farber, JM Kiesewetter, DO AF Jacobson, O. Weiss, I. D. Szajek, L. Ma, Y. Farber, J. M. Kiesewetter, D. O. TI 64Cu-AMD3100-A NOVEL IMAGING AGENT FOR TARGETING CHEMOKINE RECEPTOR CXCR4 POSITIVE TUMORS SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract C1 [Jacobson, O.; Ma, Y.; Kiesewetter, D. O.] NIBIB, Positron Emiss Tomog Radiochem Grp, NIH, Bethesda, MD USA. [Weiss, I. D.; Farber, J. M.] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. [Szajek, L.] NIH, Positron Emiss Tomog Dept, CC, Bethesda, MD 20892 USA. NR 0 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 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PY 2009 VL 52 BP S44 EP S44 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 480HQ UT WOS:000268724900045 ER PT J AU Kiesewetter, DO Jacobson, O Lang, L AF Kiesewetter, D. O. Jacobson, O. Lang, L. TI STUDIES ON THE AUTOMATED PRODUCTION OF [18F]FLUOROBENZOATE SYNTHONS SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract C1 [Kiesewetter, D. O.; Jacobson, O.; Lang, L.] NIBIB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PY 2009 VL 52 BP S283 EP S283 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 480HQ UT WOS:000268724900284 ER PT J AU Lang, L Shinkre, B Bhattacharjee, A Ma, Y Shi, Y Jacobson, O Gao, Z Trenkle, WC Jacobson, KA Kiesewetter, DO AF Lang, L. Shinkre, B. Bhattacharjee, A. Ma, Y. Shi, Y. Jacobson, O. Gao, Z. Trenkle, W. C. Jacobson, K. A. Kiesewetter, D. O. TI FLUORINE-18 LABELED SCH 442416 DERIVATIVE FOR IMAGING ADENOSINE A2A RECEPTORS SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract C1 [Lang, L.; Bhattacharjee, A.; Ma, Y.; Shi, Y.; Jacobson, O.; Kiesewetter, D. O.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA. [Shinkre, B.; Gao, Z.; Trenkle, W. C.; Jacobson, K. A.] NIDDK, NIH, Bethesda, MD USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 0 TC 0 Z9 0 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PY 2009 VL 52 BP S330 EP S330 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 480HQ UT WOS:000268724900331 ER PT J AU Lee, YS Chun, J Pike, VW AF Lee, Y. S. Chun, J. Pike, V. W. TI STRUCTURE OF 2-METHYLPHENYL(2-METHOXYPHENYL)IODONIUM CHLORIDE DIMER SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract C1 [Lee, Y. S.] NIH, Ctr Informat Technol, Div Computat Biosci, Ctr Mol Modeling, Bethesda, MD 20892 USA. [Chun, J.; Pike, V. W.] NIMH, NIH, Mol Imaging Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PY 2009 VL 52 BP S156 EP S156 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 480HQ UT WOS:000268724900157 ER PT J AU Link, JM Anderson, L Collins, J AF Link, J. M. Anderson, L. Collins, J. TI SYNTHESIS OF [C-11]-DOXORUBICIN SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract C1 [Link, J. M.] Univ Washington, Dept Radiol, Div Nucl Med, Seattle, WA 98195 USA. [Anderson, L.] US FDA, Lab Clin Pharmacol, Silver Spring, MD USA. [Collins, J.] NCI, NIH, Dev Therapeut Program, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PY 2009 VL 52 BP S430 EP S430 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 480HQ UT WOS:000268724900431 ER PT J AU Lu, S Lee, YS Pike, VW AF Lu, S. Lee, Y. S. Pike, V. W. TI SYNTHESIS OF [F-18]XENON DIFLUORIDE FROM [F-18]FLUORIDE ION IN A COILED SILICA GLASS MICRO-REACTOR SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract C1 [Lu, S.; Pike, V. W.] NIMH, NIH, Mol Imaging Branch, Bethesda, MD 20892 USA. [Lee, Y. S.] NIH, CIT, Ctr Mol Modeling, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PY 2009 VL 52 SU 1 BP S496 EP S496 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 480HQ UT WOS:000268724900497 ER PT J AU Lu, S Hong, J Itoh, T Fujita, M Innis, RB Pike, VW AF Lu, S. Hong, J. Itoh, T. Fujita, M. Innis, R. B. Pike, V. W. TI [CARBONYL-C-11]BENZYL ACETATE: SYNTHESIS FROM [C-11]CARBON MONOXIDE AND PET EVALUATION OF BRAIN UPTAKE IN MONKEY SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract C1 [Lu, S.; Hong, J.; Itoh, T.; Fujita, M.; Innis, R. B.; Pike, V. W.] NIMH, NIH, Mol Imaging Branch, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PY 2009 VL 52 SU 1 BP S419 EP S419 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 480HQ UT WOS:000268724900420 ER PT J AU Ma, Y Lang, L Bhattachatjee, A Shi, Y Kiesewetter, D AF Ma, Y. Lang, L. Bhattachatjee, A. Shi, Y. Kiesewetter, D. TI LC-MS EVALUATED THE PET TRACERS OF 5-HT1A LIGANDS [BR]-WAY SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract C1 [Ma, Y.; Lang, L.; Bhattachatjee, A.; Shi, Y.; Kiesewetter, D.] Natl Inst Biomed Imaging & Bioengn NIBIB, PET Radiochem Grp, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PY 2009 VL 52 BP S261 EP S261 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 480HQ UT WOS:000268724900262 ER PT J AU Nayak, T Garmestani, K Baidoo, K Milenic, D Brechbiel, M AF Nayak, T. Garmestani, K. Baidoo, K. Milenic, D. Brechbiel, M. TI PET IMAGING OF VEGF-A TUMOR ANGIOGENESIS WITH 86Y-CHX-A ''-DTPA-BEVACIZUMAB SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract C1 [Nayak, T.; Garmestani, K.; Baidoo, K.; Milenic, D.; Brechbiel, M.] NCI, ROB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PY 2009 VL 52 BP S335 EP S335 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 480HQ UT WOS:000268724900336 ER PT J AU Nayak, T Garmestani, K Baidoo, K Milenic, D Brechbiel, M AF Nayak, T. Garmestani, K. Baidoo, K. Milenic, D. Brechbiel, M. TI PREPARATION, BIOLOGICAL EVALUATION AND PHARMACOKINETICS OF 86Y-CHX-A ''-DTPA-PANITUMUMAB FOR QUANTITATIVE PET IMAGING OF HER1-EXPRESSING CANCER SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract C1 [Nayak, T.; Garmestani, K.; Baidoo, K.; Milenic, D.; Brechbiel, M.] NCI, Radioimmune & Inorgan Chem Sect, ROB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PY 2009 VL 52 BP S325 EP S325 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 480HQ UT WOS:000268724900326 ER PT J AU Panico, M Lang, L Larobina, M Greco, A Gargiulo, S Iaccino, E Palmieri, C Scala, G Alfano, B Salvatore, M AF Panico, M. Lang, L. Larobina, M. Greco, A. Gargiulo, S. Iaccino, E. Palmieri, C. Scala, G. Alfano, B. Salvatore, M. TI ONE-STEP SYNTHESIS OF 18F LABELED [18F]-N-SUCCINIMIDYL 4-FLUOROBENZOATE FOR A20 AND A20-36 PEPTIDES LABELING SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract C1 [Panico, M.; Larobina, M.; Alfano, B.] CNR, Biostruct & Bioimaging Inst, I-80125 Naples, Italy. [Lang, L.] NIH, PET Dept, Ctr Clin, Bethesda, MD 20892 USA. [Greco, A.; Gargiulo, S.; Salvatore, M.] Univ Med Federico 2, Naples, Italy. [Iaccino, E.; Palmieri, C.; Scala, G.] Univ Catanzaro, Dept Clin & Expt Med, Catanzaro, Italy. NR 1 TC 2 Z9 2 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PY 2009 VL 52 BP S200 EP S200 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 480HQ UT WOS:000268724900201 ER PT J AU Shetty, HU Morse, CL Zhang, Y Pike, VW AF Shetty, H. U. Morse, C. L. Zhang, Y. Pike, V. W. TI MEASUREMENT OF THE SPECIFIC RADIOACTIVITY OF C-11-LABELED PET TRACERS WITH LC-MS/MS ALONE SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract C1 [Shetty, H. U.; Morse, C. L.; Zhang, Y.; Pike, V. W.] NIMH, NIH, Mol Imaging Branch, 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 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PY 2009 VL 52 SU 1 BP S61 EP S61 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 480HQ UT WOS:000268724900062 ER PT J AU Simeon, FG Hong, J Liow, J Gladding, R Innis, RB Pike, VW AF Simeon, F. G. Hong, J. Liow, J. Gladding, R. Innis, R. B. Pike, V. W. TI LABELING OF SP203 WITH CARBON-11 FOR EVALUATION AS AN MGLUR5 RADIOLIGAND IN MONKEY WITH PET SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract C1 [Simeon, F. G.; Hong, J.; Liow, J.; Gladding, R.; Innis, R. B.; Pike, V. W.] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PY 2009 VL 52 BP S387 EP S387 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 480HQ UT WOS:000268724900388 ER PT J AU Szajek, L Plascjak, P Herscovitch, R AF Szajek, L. Plascjak, P. Herscovitch, R. TI CYCLOTRON PRODUCTION OF Cu-64 FROM TANGENTIAL AND CUP TARGETS OF Zn-64 METAL SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract C1 [Szajek, L.; Plascjak, P.; Herscovitch, R.] NIH, Ctr Clin, PET Dept, Bethesda, MD 20892 USA. NR 4 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PY 2009 VL 52 BP S246 EP S246 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 480HQ UT WOS:000268724900247 ER PT J AU Telu, S Chun, J Simeon, FG Lu, S Pike, VW AF Telu, S. Chun, J. Simeon, F. G. Lu, S. Pike, V. W. TI SYNTHESIS OF AN MGLUR5 RADIOLIGAND, [F-18]SP203B, THROUGH RADIOFLUORINATION OF A DIARYLIODONIUM SALT PRECURSOR SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract C1 [Telu, S.; Chun, J.; Simeon, F. G.; Lu, S.; Pike, V. W.] NIMH, NIH, Mol Imaging Branch, Bethesda, MD 20892 USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PY 2009 VL 52 SU 1 BP S4 EP S4 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 480HQ UT WOS:000268724900005 ER PT J AU Vuong, B Kusmierze, J Channing, M AF Vuong, B. Kusmierze, J. Channing, M. TI [18F]FALLYPRIDE SYNTHESIS WITH PROTIC SOLVENT MIXTURE SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract C1 [Vuong, B.; Kusmierze, J.; Channing, M.] NIH, Ctr Clin, PET Dept, Bethesda, MD 20892 USA. NR 2 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PY 2009 VL 52 BP S298 EP S298 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 480HQ UT WOS:000268724900299 ER PT J AU Wendahl, MT Simeon, FG Pike, VW AF Wendahl, M. T. Simeon, F. G. Pike, V. W. TI SYNTHESIS AND FLUORINE-18 LABELING OF CANDIDATE METABOLICALLY-RESISTANT MGLUR5 LIGANDS SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract C1 [Wendahl, M. T.; Simeon, F. G.; Pike, V. W.] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PY 2009 VL 52 BP S16 EP S16 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 480HQ UT WOS:000268724900017 ER PT J AU Xu, R Hong, JS Pike, VW AF Xu, R. Hong, J. S. Pike, V. W. TI SYNTHESIS OF HIGH-AFFINITY SB 207710 ANALOGS AS POTENTIAL BRAIN 5-HT4 RECEPTOR RADIOLIGANDS FOR PET IMAGING SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract C1 [Xu, R.; Hong, J. S.; Pike, V. W.] NIMH, NIH, Mol Imaging Branch, 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 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PY 2009 VL 52 SU 1 BP S425 EP S425 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 480HQ UT WOS:000268724900426 ER PT J AU Chattopadhyay, PK Betts, MR Price, DA Gostick, E Horton, H Roederer, M De Rosa, SC AF Chattopadhyay, Pratip K. Betts, Michael R. Price, David A. Gostick, Emma Horton, Helen Roederer, Mario De Rosa, Stephen C. TI The cytolytic enzymes granyzme A, granzyme B, and perforin: expression patterns, cell distribution, and their relationship to cell maturity and bright CD57 expression SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE cytotoxicity; differentiation; CTL; NK cells ID HUMAN-IMMUNODEFICIENCY-VIRUS; CD8(+) T-CELLS; GRANULE-MEDIATED CYTOTOXICITY; NATURAL-KILLER-CELLS; EPSTEIN-BARR-VIRUS; EFFECTOR MOLECULES; CYTOSOLIC DELIVERY; LYMPHOID-TISSUE; DEFICIENT MICE; TARGET-CELLS AB Cytolytic enzymes (CEs) are critical mediators of anti-viral and -tumor immunity; however, as a number of molecules belong to this enzyme family, our understanding of CEs remains limited. Specifically, it remains unclear what combinations of granzymes and perforin (Perf) are expressed by various immune cells and how CE content relates to cellular differentiation. Using polychromatic flow cytometry, we simultaneously measured expression of the most common human CEs [granzyme A (gA), granzyme B (gB), and Perf] alongside markers of alpha beta and gamma delta T cell maturation (CD45RO, CCR7, CD27, CD57). Additionally, we measured CE content in NK cell subsets ( defined by their expression of CD16 and CD56). We found that among a wide variety of immune cells, CE content was linked to cellular maturity. Moreover, common expression patterns were shared across cell types, such that gB+ cells always contained gA, and Perf+ cells were primarily gA+ gB+. Most importantly, CD57 expression correlated strongly with simultaneous expression of gA, gB, and Perf. Thus, the use of CD57 provides a means to easily isolate viable cells with high cytolytic potential, without the need for lethal fixation/permeabilization techniques. J. Leukoc. Biol. 85: 88-97; 2009. C1 [Chattopadhyay, Pratip K.; Roederer, Mario] NIH, Immuno Technol Sect, Immunol Lab, Vaccine Res Ctr, Bethesda, MD 20892 USA. [Betts, Michael R.] Univ Penn, Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA. [Price, David A.; Gostick, Emma] Cardiff Univ, Sch Med, Cardiff, S Glam, Wales. [Horton, Helen] Seattle Biomed Res Inst, Seattle, WA 98109 USA. [De Rosa, Stephen C.] Fred Hutchinson Canc Res Ctr, HIV Vaccine Trials Network Lab Program, Seattle, WA 98109 USA. [De Rosa, Stephen C.] Univ Washington, Sch Med, Dept Lab Med, Seattle, WA 98195 USA. [De Rosa, Stephen C.] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Inst, Seattle, WA 98109 USA. RP De Rosa, SC (reprint author), Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Inst, 1100 Fairview Ave N,LE 200, Seattle, WA 98109 USA. EM sderosa@fhcrc.org RI Chattopadhyay, Pratip/B-9227-2008; Price, David/C-7876-2013; OI Price, David/0000-0001-9416-2737; Chattopadhyay, Pratip/0000-0002-5457-9666 FU Intramural NIH HHS [Z99 AI999999]; Medical Research Council [G0501963]; NIAID NIH HHS [P30 AI027757] NR 57 TC 118 Z9 122 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD JAN 1 PY 2009 VL 85 IS 1 BP 88 EP 97 DI 10.1189/jlb.0208107 PG 10 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 385YG UT WOS:000261848900011 PM 18820174 ER PT J AU Li, ZW Garantziotis, S Jia, W Potts, EN Lalani, S Liu, Z He, YW Foster, WM Hollingsworth, JW AF Li, Zhuowei Garantziotis, Stavros Jia, Wei Potts, Erin N. Lalani, Sikander Liu, Zhi He, You-Wen Foster, W. Michael Hollingsworth, John W. TI The extracellular matrix protein mindin regulates trafficking of murine eosinophils into the airspace SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE integrin; environmental airways disease; asthma; IL-13; spondin2 ID RESPIRATORY HEALTH SURVEY; CELL-ADHESION MOLECULE-1; SMOOTH-MUSCLE-CELLS; TRANSENDOTHELIAL MIGRATION; ENDOTHELIAL-CELLS; DIAGNOSED ASTHMA; EXPRESSION; IL-13; LUNG; PATHOGENESIS AB Asthma remains a major cause of morbidity and hospitalizations in developed nations. Despite the widespread prevalence of this disease, the genetic and environmental factors that mediate development and progression of allergic airways disease remain poorly understood. Pulmonary recruitment of eosinophils is believed to contribute to many cardinal features of allergic airways disease. Therefore, it is paramount to understand host factors that contribute to pulmonary eosinophil recruitment into the lungs. Mindin is a component of pulmonary extracellular matrix, which can regulate inflammatory cell recruitment. We characterized the role of mindin in the severity of allergic airways disease using established murine models. There were no baseline differences in wild-type and mindin-deficient animals in cell counts or airway physiology. Using the OVA murine model of allergic airways disease, we observed that mindin-deficient animals have less-severe allergic airways disease with fewer airspace eosinophils and lower lung-lavage levels of inflammatory Th(2) cytokines such as IL-13 and IL-4. Furthermore, mindin-deficient animals have reduced airway hyper-responsiveness after methacholine challenge. To determine the role of mindin in eosinophil trafficking, independent of antigen immunization or T lymphocyte activation, we instilled IL-13 directly into the lungs of mice. In this model, mindin regulates eosinophil recruitment into the airspace. In vitro experiments demonstrate that mindin can enhance eotaxin-mediated eosinophil adhesion and migration, which are dependent on the expression of integrins alpha(M)beta(2) and alpha(4)beta(1). In conclusion, these data suggest that mindin participates in integrin-dependent trafficking of eosinophils and can contribute to the severity of allergic airways disease. J. Leukoc. Biol. 85: 124-131; 2009. C1 [Li, Zhuowei; Garantziotis, Stavros; Potts, Erin N.; Lalani, Sikander; Foster, W. Michael; Hollingsworth, John W.] Duke Univ, Med Ctr, Div Pulm Allergy & Crit Care Med, Durham, NC 27710 USA. [He, You-Wen] Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27710 USA. [Liu, Zhi] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. [Liu, Zhi] Univ N Carolina, Dept Dermatol, Chapel Hill, NC 27514 USA. RP Hollingsworth, JW (reprint author), Duke Univ, Med Ctr, Div Pulm Allergy & Crit Care Med, Durham, NC 27710 USA. EM holli017@mc.duke.edu RI Garantziotis, Stavros/A-6903-2009 OI Garantziotis, Stavros/0000-0003-4007-375X FU National Institute of Environmental Health Services [ES11961, ES12496, ES16126]; National Heart, Lung, and Blood Institute [HL91335] FX The authors gratefully receive support from the National Institute of Environmental Health Services ( Research Triangle Park, NC, USA; ES11961, ES12496, ES16126) and the National Heart, Lung, and Blood Institute ( Bethesda, MD, USA; HL91335). Dr. James Lee at the Mayo Clinic Scottsdale generously provided IL-5 transgenic mice. NR 38 TC 7 Z9 8 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD JAN 1 PY 2009 VL 85 IS 1 BP 124 EP 131 DI 10.1189/jlb.0208135 PG 8 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 385YG UT WOS:000261848900015 PM 18818374 ER PT J AU Pawlosky, RJ Hibbeln, JR Herion, D Kleiner, DE Salem, N AF Pawlosky, Robert J. Hibbeln, Joseph R. Herion, David Kleiner, David E. Salem, Norman, Jr. TI Compartmental analysis of plasma and liver n-3 essential fatty acids in alcohol-dependent men during withdrawal SO JOURNAL OF LIPID RESEARCH LA English DT Article DE ethanol; alpha-linolenic acid; docosahexaenoic acid; isotope tracer; compartmental modeling; d(5)-fatty acids; eicosapentaenoic acid; cigarette smoking ID DELTA-5 DESATURASE ACTIVITIES; LIPID-PEROXIDATION; DOCOSAHEXAENOIC ACID; RHESUS-MONKEYS; ETHANOL; CONSUMPTION; METABOLISM; PRODUCTS; SMOKING; RATS AB The mechanism by which chronic ethanol consumption reduces concentrations of long chain polyunsaturated (LCP) fatty acids (FA) in tissues of humans was investigated in alcohol-dependent (AD) men during early withdrawal and to a well-matched control group by fitting the concentration-time curves of d(5)-labeled n-3 FA from plasma and liver, which originated from an oral dose of d(5)-linolenic acid (d(5)-18:3n-3) ethyl ester to a compartmental model. Blood sampled over 168 h and a liver specimen obtained 96 h after isotope administration were analyzed for d(5)-18:3n-3, d(5)-20:5n-3, d(5)-22:5n-3, and d(5)-22:6n-3. Plasma 20:5n-3 and 22:5n-3 were lower in AD subjects, compared with controls (20:5n-3: -50%, 22:5n-3: -34%). Increased amounts of d(5)-18:3n-3 were directed toward synthesis of d(5)-20:5n-3 in AD subjects (P < .05). However, this effect was offset by larger amounts of 20:5n-3 lost from plasma (control:2.0 vs. AD:4.2 mg d(-1)). In livers of AD subjects, more d(5)-18:3n-3 and d(5)-22:5n-3 were utilized for synthesis of d(5)-20:5n-3 (+200%) and d(5)-22:6n-3 (+210%), respectively, than was predicted from plasma kinetics. Although, the potential to utilize linolenic acid for synthesis of LCP FA was greater in AD subjects compared with controls, heightened disappearance rates of 20:5n-3 reduced overall plasma concentrations of several endogenous n-3 LCP FA.-Pawlosky, R. J., J. R. Hibbeln, D. Herion, D. E. Kleiner, and N. Salem, Jr. Compartmental analysis of plasma and liver n-3 essential fatty acids in alcohol-dependent men during withdrawal. J. Lipid Res. 2009. 50:154-161. C1 [Pawlosky, Robert J.] NCI, Lab Metab Control, NIH, Bethesda, MD 20892 USA. [Hibbeln, Joseph R.; Salem, Norman, Jr.] NCI, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA. [Herion, David] NCI, Lab Clin & Translat Studies, NIAAA, NIH, Bethesda, MD 20892 USA. [Kleiner, David E.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Pawlosky, RJ (reprint author), NCI, Lab Metab Control, NIH, Bethesda, MD 20892 USA. EM bpawl@niaaa.nih.gov OI Kleiner, David/0000-0003-3442-4453 NR 44 TC 7 Z9 8 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD JAN PY 2009 VL 50 IS 1 BP 154 EP 161 DI 10.1194/jlr.M800322-JLR200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 383RR UT WOS:000261691600017 PM 18723835 ER PT J AU Chi, CY Shi, B Liang, P Li, JM Ito, Y AF Chi Chunyan Shi Bo Liang Ping Li Jingmei Ito, Yoichiro TI Isolation and Purification of Psoralen and Bergapten from Ficus carica L. Leaves by High-Speed Countercurrent Chromatography SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE Bergapten; Ficus carica L leaves; High-speed countercurrent chromatography; Psoralen AB High-speed countercurrent chromatography (HSCCC) was successfully applied for the first time for the isolation and purification of psoralen and bergapten from the plant Ficus carica L leaves. The crude extract was obtained by extraction with light petroleum (b.p.: 60C-90C) from the dried leaves of Ficus carica L. n-Hexane-ethyl acetate-methanol-water (1:1:1:1, v/v) was used as the two-phase solvent system. Each peak fraction was analyzed by high performance liquid chromatography (HPLC). The method yielded 4.4mg of psoralen at 99.1% purity and 2.1mg of bergapten at 98.2% purity from 400mg of the crude extract in a single run. The structures of the two compounds were identified by 1H-NMR, 13C-NMR, and MS. C1 [Ito, Yoichiro] NHLBI, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA. [Chi Chunyan; Shi Bo; Liang Ping] Chinese Acad Agr Sci, Feed Res Inst, Beijing, Peoples R China. [Li Jingmei] Minist Agr, Cereal Qual Supervis & Testing Ctr, Beijing, Peoples R China. RP Ito, Y (reprint author), NHLBI, Biochem & Biophys Ctr, NIH, Bldg 10,Room 8N230, Bethesda, MD 20892 USA. EM itoy2@mail.nih.gov RI wang, zhihong/D-9357-2012 FU Eleventh Five Years Science and Technology Plan Project of P. R. China [2006BAD12B05-02] FX We gratefully acknowledge the financial support received by The Eleventh Five Years Science and Technology Plan Project of P. R. China 2006BAD12B05-02. NR 7 TC 5 Z9 6 U1 1 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2009 VL 32 IS 1 BP 136 EP 143 AR PII 905626263 DI 10.1080/10826070802548747 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 374BE UT WOS:000261016400010 ER PT J AU Phillips, LR Hill, KD Majerova, E AF Phillips, Lawrence R. Hill, Kimberly D. Majerova, Eva TI Liquid Chromatographic Determination of NSC 737664 (ABT-888: An Inhibitor of Poly(ADP-ribose) Polymerase (PARP)) in Plasma and Urine in a Phase 0 Clinical Trial SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE ABT-888; PARP inhibitor; Phase 0 study ID ADP-RIBOSE POLYMERASE; CANCER; MODELS AB A gradient reversed-phase high performance liquid chromatographic method was developed for determining NSC 737664 (2-[(2R)-2-methylpyrrolidin2- yl]-1H-benzimidazole-4-carboxamide; ABT-888) in human plasma and urine. The chromatographic separation used a mobile phase composed of 0.1% formic acid in water and 0.1% formic acid in acetonitrile, and a C(18) column (150 mm X 4.6 mm, 5 mu). Quantitation was performed using UV detection at 300 nm. Chromatographic peak identity was confirmed using positive-ion electrospray ionization mass spectrometry. The method was shown to be specific, accurate, and reproducible, and thereby appropriate for monitoring plasma and urine levels of the agent in support of a phase 0 clinical study. C1 [Phillips, Lawrence R.] NCI, Biol Testing Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21702 USA. [Hill, Kimberly D.; Majerova, Eva] SAIC Frederick Inc, BTB Support, NCI Frederick, Frederick, MD USA. RP Phillips, LR (reprint author), NCI, Biol Testing Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21702 USA. EM phillipl@mail.nih.gov FU National Cancer Institute, National Institutes of Health [NO1-CO-12400]; Developmental Therapeutics Program in the Division of Cancer Treatment and Diagnosis of the Natural Cancer Institute FX This work was facilitated by consultations and technical assistance by Raymond Klecker and Lawrence W. Anderson of the FDA clinical pharmacology laboratory, as part of the NCI-FDA Interagency Oncology Task Force. This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. NO1-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organization imply endorsement by the U. S. Government. This research was supported ( in part) by the Developmental Therapeutics Program in the Division of Cancer Treatment and Diagnosis of the Natural Cancer Institute. NR 12 TC 5 Z9 6 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2009 VL 32 IS 2 BP 261 EP 272 DI 10.1080/10826070802603351 PG 12 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 386ID UT WOS:000261875000007 PM 20046211 ER PT J AU Cao, XY Wei, Y Ito, YC AF Cao, Xiaoying Wei, Yun Ito, Yoichiro TI Preparative Isolation of Isorhamnetin from Stigma Maydis using High Speed Countercurrent Chromatography SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE High speed countercurrent chromatography; Isorhamnetin; Preparative isolation; Stigma maydis ID PURIFICATION AB Preparative high speed countercurrent chromatography (HSCCC) has been successfully used for the isolation and purification of isorhamnetin from Stigma maydis. This was achieved in two stages: the first separation was performed with a two phase solvent system composed of n-hexane-ethyl acetate-methanol-water (HEMW) at a volume ratio of 5: 5: 5: 5, yielding isorhamnetin at 65.6%, which is followed by the second run using a two phase solvent system composed of HEMW 5: 5: 6: 4, v/v. From 700mg of the crude extract, 11.8 mg of isorhamnetin was obtained at a high purity of 98%. The final identification was performed by MS, 1 H-NMR and 13 C-NMR spectra. C1 [Cao, Xiaoying; Wei, Yun] Beijing Univ Chem Technol, Fac Sci, Dept Appl Chem, Beijing 100029, Peoples R China. [Ito, Yoichiro] NHLBI, Bioseparat Technol Lab, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA. RP Wei, Y (reprint author), Beijing Univ Chem Technol, Fac Sci, Dept Appl Chem, 15 Beisanhuan E Rd, Beijing 100029, Peoples R China. EM weiyun@mail.buct.edu.cn FU Beijing Natural Science Foundation [2073028]; Ministry of Agriculture of the People's Republic of China [200803022] FX Financial support from Beijing Natural Science Foundation ( Project 2073028) and Ministry of Agriculture of the People's Republic of China ( Project 200803022) are gratefully acknowledged. NR 8 TC 12 Z9 13 U1 0 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2009 VL 32 IS 2 BP 273 EP 280 DI 10.1080/10826070802603369 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 386ID UT WOS:000261875000008 PM 20046959 ER PT J AU Ito, Y Yu, H AF Ito, Yoichiro Yu, Henry TI Triangular Helical Column for Centrifugal Countercurrent Chromatography SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE Dipeptides; Effective column space; Laser sintering for rapid prototyping; Retention of the stationary phase; Toroidal coil countercurrent chromatography; Triangular helical column ID ROTATING SEALS; ENTEROTOXIN; SEPARATION AB Effective column space and stationary phase retention have been improved by changing the configuration of the helical column originally used for toroidal coil countercurrent chromatography. The use of an equilateral triangular core for the helix column doubles effective column space and retains the stationary phase over 40% of the total column capacity without increasing the column pressure. The present results suggest that the stationary phase retention and the peak resolution will be further improved using new column designs fabricated by a new technology called laser sintering for rapid prototyping. C1 [Ito, Yoichiro; Yu, Henry] NHLBI, Bioseparat Technol Lab, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA. RP Ito, Y (reprint author), NHLBI, Bioseparat Technol Lab, Biochem & Biophys Ctr, NIH, Bldg 10,Rm 8N230,10 Ctr Dr, Bethesda, MD 20892 USA. EM itoy@nhlbi.nih.gov FU Intramural NIH HHS [Z01 HL001054-05] NR 8 TC 13 Z9 13 U1 1 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2009 VL 32 IS 4 BP 560 EP 566 AR PII 908112874 DI 10.1080/10826070802671580 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 398EX UT WOS:000262716500007 PM 20046940 ER PT J AU Wei, Y Xie, QQ Ito, Y AF Wei, Yun Xie, Qianqian Ito, Yoichiro TI Preparative Separation of Axifolin-3-Glucoside, Hyperoside and Amygdalin from Plant Extracts by High Speed Countercurrent Chromatography SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE Agrimonia pilosa Ledeb; Amygdalin; High speed countercurrent chromatography (HSCCC); Hyperoside; Taxifolin-3-glucoside AB High speed countercurrent chromatography (HSCCC) was successfully used to isolate three bioactive compounds, i.e., amygdalin from bitter almond and taxifolin-3-glucoside and quercetin-3-galactoside (hyperoside) from water extract of A. pilosa Ledeb, respectively. From 1g of the crude extract 65mg of amygdalin was isolated at 97% purity using a two phase solvent system composed of ethyl acetate-n-butanol-water (5:2:5, v/v) by preparative HSCCC. From a 400mg amount of crude extract of A. pilosa Ledeb, 11mg of taxifolin-3-glucoside and 8mg of hyperoside were isolated at 96% purity, using a two phase solvent system composed of ethyl acetate-methanol-water (25:1:25, v/v) similarly by preparative HSCCC. The final structural identification was performed by MS, 1H-NMR, and 13C-NMR spectra. C1 [Wei, Yun; Xie, Qianqian] Beijing Univ Chem Technol, Fac Sci, Dept Analyt Chem, Beijing 100029, Peoples R China. [Ito, Yoichiro] NHLBI, Bioseparat Technol Lab, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA. RP Wei, Y (reprint author), Beijing Univ Chem Technol, Fac Sci, Dept Analyt Chem, 15 Beisanhuan E Rd, Beijing 100029, Peoples R China. EM weiyun@mail.buct.edu.cn FU Ministry of Agriculture of the People's Republic of China [200803022] FX Financial support (Project No. 200803022) from Ministry of Agriculture of the People's Republic of China is gratefully acknowledged. NR 16 TC 5 Z9 6 U1 0 U2 7 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2009 VL 32 IS 7 BP 1010 EP 1022 AR PII 909317616 DI 10.1080/10826070902790983 PG 13 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 416GF UT WOS:000263993000009 PM 20046896 ER PT J AU Shinomiya, K Ito, Y AF Shinomiya, Kazufusa Ito, Yoichiro TI Partition Efficiency of Newly Designed Locular Multilayer Coil for Countercurrent Chromatographic Separation of Proteins Using Small-Scale Cross-Axis Coil Planet Centrifuge with Aqueous-Aqueous Polymer Phase Systems SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE Aqueous-aqueous polymer phase system; Countercurrent chromatography; Cross-axis coil planet centrifuge; Locular multilayer coil; Protein; Separation ID ROTARY SEALS; APPARATUS; ASSEMBLIES; COLUMNS AB Countercurrent chromatographic performance of the locular multilayer coil separation column newly designed in our laboratory, was evaluated in terms of theoretical plate number, peak resolution, and retention of the stationary phase in protein separation with an aqueous polymer phase system, using the small-scale cross-axis coil planet centrifuge (X-axis CPC) fabricated in our laboratory. The locular column was made from 1.0mm I.D., 2.0mm O.D., or 1.5mm I.D., 2.5mm O.D. PTFE tubing, compressed with a pair of hemostat at 2 or 4cm intervals. The protein separation was performed using a set of stable proteins including cytochrome C, myoglobin, and lysozyme with the 12.5% (w/w) polyethylene glycol 1000 and 12.5% (w/w) dibasic potassium phosphate system under 1000rpm of column revolution. The 1.5mm I.D., 2.5mm O.D. locular tubing compressed at 2cm intervals yielded better partition efficiencies than the non-clamped tubing, using both lower and upper mobile phases with satisfactory retention of the stationary phase. The overall results suggest that the newly designed locular multilayer coil is useful to the preparative separation of proteins with aqueous-aqueous polymer phase system using our small scale X-axis CPC. C1 [Shinomiya, Kazufusa] Nihon Univ, Coll Pharm, Funabashi, Chiba 2748555, Japan. [Ito, Yoichiro] NHLBI, Bioseparat Technol Lab, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA. RP Shinomiya, K (reprint author), Nihon Univ, Coll Pharm, 7-7-1 Narashinodai, Funabashi, Chiba 2748555, Japan. EM shinomiya.kazufusa@nihom-u-ac.jp FU Intramural NIH HHS [Z99 HL999999] NR 13 TC 4 Z9 4 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2009 VL 32 IS 8 BP 1096 EP 1106 AR PII 910021483 DI 10.1080/10826070902841547 PG 11 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 426ZW UT WOS:000264748500004 PM 20046931 ER PT J AU Ito, Y Clary, R Powell, J Knight, M Finn, TM AF Ito, Y. Clary, R. Powell, J. Knight, M. Finn, T. M. TI Spiral Tube Assembly for High-Speed Countercurrent Chromatography: Choice of Elution Modes for Four Typical Two-Phase Solvent Systems SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE Elution modes; High-speed countercurrent chromatography; Spiral tube assembly; Two-phase solvent systems AB Optimal elution modes were determined for four typical two-phase solvent systems, each with different physical parameters, to achieve the best peak resolution and retention of the stationary phase by spiral tube high-speed countercurrent chromatography using a suitable set of test samples. Both retention of the stationary phase and partition efficiency are governed by an interplay between two forces, i.e., Archimedean Screw force and radial centrifugal force gradient of the spiral channel. In the polar solvent system represented by 1-butanol/acetic acid/water (4:1:5, v/v/v) with settling time of over 30s, the effect by the radial centrifugal gradient force dominates, giving the best separation of dipeptides either by pumping the lower phase from the inner terminal or the upper phase from the outer terminal of the spiral channel. In the moderately hydrophobic two-phase solvent system represented by hexane/ethyl acetate/methanol/0.1M HCl (1:1:1:1) with settling time of 19s, and two hydrophobic solvent systems of hexane/ethanol/water (5:4:1, v/v/v) and non-aqueous binary system of hexane/acetonitrile both having settling time of 9, the effect of the Archimedean screw force plays a major role in hydrodynamic equilibrium, giving the best separations by pumping the lower phase from the head or the upper phase from the tail of the spiral channel. C1 [Ito, Y.] NHLBI, Bioseparat Technol Lab, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA. [Knight, M.; Finn, T. M.] CC Biotech LLC, Rockville, MD USA. RP Ito, Y (reprint author), NHLBI, Bioseparat Technol Lab, Biochem & Biophys Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. EM itoy@nhibi.nih.gov OI Knight, Martha/0000-0003-4863-8858 NR 11 TC 6 Z9 6 U1 1 U2 8 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2009 VL 32 IS 14 BP 2013 EP 2029 AR PII 913816271 DI 10.1080/10826070903126823 PG 17 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 481ST UT WOS:000268832800003 ER PT J AU Yang, Y Aisa, HA Ito, Y AF Yang, Yi Aisa, Haji Akber Ito, Yoichiro TI Novel Design for Centrifugal Countercurrent Chromatography: I. Zigzag Toroidal Column SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE Countercurrent chromatography; Dipeptide; DNP-amino acid; Resolution; Retention of the stationary phase; Zigzag pattern column AB The toroidal coil using an equilateral triangular core has improved both retention of the stationary phase and peak resolution of the conventional toroidal coil in centrifugal countercurrent chromatography. To further improve the retention of stationary phase and peak resolution, a novel zigzag toroidal coil was designed and the performance of the system was evaluated at various flow rates. The results indicated that both retention of stationary phase and peak resolution were improved as the flow rate was decreased. Modification of the tubing by pressing at given intervals with a pair of pliers improved the peak resolution without increasing the column pressure. All these separations were performed under low column pressure indicating the separation can be further improved by increasing the column length and/or revolution speed without damaging the separation column. C1 [Yang, Yi; Ito, Yoichiro] NHLBI, Bioseparat Technol Lab, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA. [Yang, Yi; Aisa, Haji Akber] Chinese Acad Sci, Xinjiang Tech Inst Phys & Chem, Xinjiang Key Lab Plant Resources & Nat Prod Chem, Urumqi, Peoples R China. [Yang, Yi] Chinese Acad Sci, Grad Univ, Beijing, Peoples R China. RP Ito, Y (reprint author), NHLBI, Bioseparat Technol Lab, Biochem & Biophys Ctr, NIH, 10 Ctr Dr,Bldg 10,Room 8N230, Bethesda, MD 20892 USA. EM itoy@nhlbi.nih.gov FU Intramural NIH HHS [Z99 HL999999, ZIA HL006022-01] NR 8 TC 16 Z9 16 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2009 VL 32 IS 14 BP 2030 EP 2042 AR PII 913816348 DI 10.1080/10826070903126856 PG 13 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 481ST UT WOS:000268832800004 PM 20046954 ER PT J AU Shinomiya, K Li, HR Kitanaka, S Ito, Y AF Shinomiya, Kazufusa Li, Heran Kitanaka, Susumu Ito, Yoichiro TI Countercurrent Chromatographic Separation of Lipophilic Ascorbic Acid Derivatives and Extract from Kadsura coccinea Using Hydrophobic Organic-Aqueous Two-Phase Solvent Systems SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE Countercurrent chromatography; Lignan; Lipophilic ascorbic acid derivative; Natural product; Triterpenoid; Two-phase solvent system ID COIL PLANET CENTRIFUGE; OXIDE INHIBITORY-ACTIVITIES; ASSEMBLIES; VITAMINS; LIGNANS AB Countercurrent chromatographic (CCC) separation of lipophilic ascorbic acid derivatives and the crude extract from Kadsura coccinea was performed using the type-J multilayer coil planet centrifuge with a hydrophobic organic-aqueous two-phase solvent system composed of n-hexane/ethyl acetate/ethanol/aqueous 0.1% trifluoroacetic acid at the volume ratio of 5:5:6:2. The lipophilic ascorbic acid derivatives were separated in the order of L-ascorbyl 2,6-dibutyrate, L-ascorbyl 6-palmitate and L-ascorbyl 6-stearate by eluting the lower phase as the mobile phase, and L-ascorbyl 2,6-dipalmitate was separated by eluting the upper phase at the opposite direction. The above solvent system was then applied to the CCC separation of the extract prepared from K. coccinea. With lower phase mobile, the extract was mainly separated into two peaks corresponding to lignans and triterpenoids accordingly. The HPLC analysis of the fractions showed that the former peak contained Kadsulignan N, Schizandrin H and Neokadsuranin as lignans, and the latter peak, Micranoic acid A, Neokadsuranic acid B and beta-Sitosterol as triterpenoids. The overall results indicate that the hydrophobic organic-aqueous two-phase solvent system used in the present studies was useful for the CCC separation of lignans and triterpenoids present in the natural products. C1 [Shinomiya, Kazufusa; Li, Heran; Kitanaka, Susumu] Nihon Univ, Coll Pharm, Funabashi, Chiba 2748555, Japan. [Ito, Yoichiro] NHLBI, Bioseparat Technol Lab, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA. RP Shinomiya, K (reprint author), Nihon Univ, Coll Pharm, 7-7-1 Narashinodai, Funabashi, Chiba 2748555, Japan. EM shinomiya.kazufusa@nihon-u.ac.jp FU Ministry of Education, Culture, Sports, Science and Technology of Japan; College of Pharmacy, Nihon University, Chiba, Japan FX This work was supported in part by grants from both of the Ministry of Education, Culture, Sports, Science and Technology of Japan and College of Pharmacy, Nihon University, Chiba, Japan. NR 14 TC 3 Z9 3 U1 0 U2 6 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2009 VL 32 IS 16 BP 2361 EP 2371 AR PII 914514084 DI 10.1080/10826070903187981 PG 11 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 491NY UT WOS:000269587100006 PM 20046934 ER PT J AU Ju, XY Sun, Y Cao, XY Jiang, JH Zhang, TY Ito, Y AF Ju, Xiuyun Sun, Yong Cao, Xiaoying Jiang, Jihong Zhang, Tianyou Ito, Yoichiro TI Two-Step Purification of Cordycepin from Cordyceps millitaris by High-Speed Countercurrent Chromatography SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE Cordycepin; Cordyceps millitaris; High-speed countercurrent chromatography; HPLC ID PREPARATIVE ISOLATION; L. AB Cordycepin is successfully isolated and purified from Cordyceps millitaris in a two-step purification by high-speed countercurrent chromatography. Two solvent systems, ethyl acetate-1-butanol-water (3:2:5, v/v/v) and trichloromethane-methanol-1-butanol-water (2:1:0.25:1, v/v/v/v), were used for the two-step purification. The purity of the prepared cordycepin was 98.1% according to the high-performance liquid chromatographic analysis. C1 [Ito, Yoichiro] NHLBI, Bioseparat Technol Lab, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA. [Ju, Xiuyun; Sun, Yong; Cao, Xiaoying; Jiang, Jihong; Zhang, Tianyou] Xuzhou Normal Univ, Key Lab Biotechnol Med Plant Jiangsu Prov, Xuzhou 221116, Peoples R China. RP Ito, Y (reprint author), NHLBI, Bioseparat Technol Lab, Biochem & Biophys Ctr, NIH, Bldg 10,Room 8N230, Bethesda, MD 20892 USA. EM jhjiang@xznu.edu.cn; itoy2@mail.nih.gov FU China National 863 Hi-Tech Program [2007 AA021506] FX This research is partially supported by the China National 863 Hi-Tech Program under Grant 2007 AA021506. NR 11 TC 5 Z9 5 U1 0 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 520 CHESTNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1082-6076 EI 1520-572X J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2009 VL 32 IS 16 BP 2417 EP 2423 AR PII 914494754 DI 10.1080/10826070903188153 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 491NY UT WOS:000269587100011 PM 20046921 ER PT J AU Peng, CL Liang, Y Wang, XH Xie, HC Zhang, TY Ito, Y AF Peng, Cuilin Liang, Yong Wang, Xiaohong Xie, Huichun Zhang, Tianyou Ito, Yoichiro TI Preparative Isolation and Purification of Flavonoids from the Chinese Medicinal Herb Belamcanda by High-Speed Countercurrent Chromatography SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE Belamcanda; Flavonoids; HPLC; HSCCC ID CHINENSIS; ISOFLAVONOIDS; RHIZOMES AB High-speed countercurrent chromatography (HSCCC) was applied for separation and purification of flavanoids from the extract of belamcanda. High efficiency of HSCCC separation was achieved on a two-phase solvent system of n-hexane-ethyl acetate-methanol-water (4:5:5:5, v/v) by eluting the lower mobile phase at a flow-rate of 1.2mL/min and a revolution speed of 800rpm. Three well-separated peaks were obtained in the HSCCC chromatogram and their purities were determined by HPLC-UV absorption spectrometry. These peaks were characterized by ESI-MSn and NMR, and the data compared with the reference standards where three peaks were identified as isorhamnetin, irigenin and hispidulin. The purities of each peak were 94, 95 and 90% respectively. In HSCCC experiment, 100mg of the crude extract were separated yielding 10mg of isorhamnetin, 8mg of irigenin and 7mg of hispidulin. HSCCC thus provides a cost-effective alternative to preparative scale HPLC for the semi-preparative scale separation and purification of flavonoids from Belamcanda. C1 [Peng, Cuilin; Liang, Yong; Wang, Xiaohong; Xie, Huichun] S China Normal Univ, Sch Chem & Environm, Inst Analyt Chem, Guangzhou 510006, Guangdong, Peoples R China. [Zhang, Tianyou] Beijing Inst New Technol Applicat, Beijing, Peoples R China. [Ito, Yoichiro] NHLBI, Bioseparat Technol Lab, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA. RP Liang, Y (reprint author), S China Normal Univ, Sch Chem & Environm, Inst Analyt Chem, Guangzhou 510006, Guangdong, Peoples R China. EM liangy@scnu.edu.cn FU Intramural NIH HHS [Z99 HL999999] NR 8 TC 8 Z9 8 U1 1 U2 8 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2009 VL 32 IS 16 BP 2451 EP 2461 AR PII 914506511 DI 10.1080/10826070903188245 PG 11 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 491NY UT WOS:000269587100014 PM 20046920 ER PT J AU Lv, QY Yang, Y Zhao, YX Gu, DY He, DJ Yili, A Ma, QL Cheng, Z Gao, YH Aisa, HA Ito, Y AF Lv, Qiaoying Yang, Yi Zhao, Yongxin Gu, Dongyu He, Dajun Yili, Abulimiti Ma, Qingling Cheng, Zhen Gao, Yanhua Aisa, Haji Akber Ito, Yoichiro TI Comparative Study on Separation and Purification of Isoflavones from the Seeds and Sprouts of Chickpea by High-Speed Countercurrent Chromatography SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE Biosynthesis; Chickpea; High speed countercurrent chromatography; Isoflavone; Seed; Sprout ID GERMINATION; BEANS; ACID AB Chickpea is known as a plant that is rich in protein, carbohydrates, and nutrition, and its seeds and sprouts have been processed into various health foods. In the present study, four isoflavones were purified from the seeds and sprouts of chickpea by high-speed countercurrent chromatography (HSCCC) using two biphasic solvent systems composed of n-hexane-ethyl acetate-methanol-water (5:5:5:5, v/v) and ethyl acetate-water (1:1, v/v). The results indicated that 14.2mg of formononetin, 15.7mg of biochanin A, 9.1mg of ononin, 11.3mg of biochanin A-7-O--D-glucoside were obtained from 150mg of sprout extracts with the purity of 92.26%, 95.86%, 95.32%, and 96.56%, respectively. Compared with the sprouts, separation of seed extracts yielded less amounts of biochanin A-7-O--D-glucoside and biochanin A with lower purity. The results indicate that four main isoflavones in chickpea, i.e., isoflavones, formononetin, biochanin A, ononin, and biochanin A-7-O--D-glucoside, are substantially increased by biosynthesis during the seed germination. C1 [Yang, Yi; Ito, Yoichiro] NHLBI, Bioseparat Technol Lab, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA. [Lv, Qiaoying; Yang, Yi; Zhao, Yongxin; Gu, Dongyu; He, Dajun; Yili, Abulimiti; Ma, Qingling; Cheng, Zhen; Gao, Yanhua; Aisa, Haji Akber] Chinese Acad Sci, Xinjiang Tech Inst Phys & Chem, Xinjiang Key Lab Plant Resources & Nat Prod Chem, Urumqi, Peoples R China. [Lv, Qiaoying; He, Dajun] Chinese Acad Sci, Grad Univ, Beijing, Peoples R China. [Lv, Qiaoying; Yili, Abulimiti; Aisa, Haji Akber] Union Labs Bioact Ingredients Edible Plants Cent, Urumqi, Peoples R China. RP Ito, Y (reprint author), NHLBI, Bioseparat Technol Lab, Biochem & Biophys Ctr, NIH, 10 Ctr Dr,Bldg 10,Room 8N230, Bethesda, MD 20892 USA. EM haji@ms.xjb.ac.cn; itoy2@mail.nih.gov FU Chinese Academy of Sciences [KGCX2-YW-503] FX This work was financially supported by the Chinese Academy of Sciences Innovative Research International Partnership Project, grant (code: KGCX2-YW-503) from Key Project of Knowledge Innovation Program of Chinese Academy of Sciences and a grant from "Western Light'' (XIBUZHIGUANG) program of Talent Cultivation of Chinese Academy of Sciences at 2007. NR 20 TC 9 Z9 11 U1 1 U2 12 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2009 VL 32 IS 19 BP 2879 EP 2892 AR PII 915828402 DI 10.1080/10826070903297277 PG 14 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 506XY UT WOS:000270812700009 PM 20046900 ER PT J AU He, DJ Gu, DY Huang, Y Ayupbek, A Yang, Y Aisa, HA Ito, Y AF He, Dajun Gu, Dongyu Huang, Yun Ayupbek, Amatjan Yang, Yi Aisa, Haji Akber Ito, Yoichiro TI Separation and Purification of Phenolic Acids and Myricetin from Black Currant by High-Speed Countercurrent Chromatography SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE Black currant; Caffeic acid; High-speed countercurrent chromatography (HSCCC); 4-Hydroxybenzoic acid; Myricetin; Protocatechuic acid ID FLAVONOIDS AB Black currant is an important material in the food industry, but little research has been reported on the isolation of phenolic acids because of their low content. In the present study, high-speed countercurrent chromatography (HSCCC) has been successfully used for the preparative isolation of the minor phenolic compounds from the ethyl acetate extracts of black currant fruit. The HSCCC separation was performed with a two phase solvent system composed of n-hexane/EtOAc/MeOH/H2O (5:15:4:7v/v) at a flow rate of 1.5mL/min. From a 500mg crude sample 0.8mg of protocatechuic acid, 1.0mg of caffeic acid, 0.5mg of 4-hydroxybenzoic acid, and 2.5mg of myricetin were purified by a one step HSCCC operation,. Their chemical structures were confirmed by MS and NMR. C1 [Ito, Yoichiro] NHLBI, Bioseparat Technol Lab, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA. [He, Dajun; Gu, Dongyu; Huang, Yun; Ayupbek, Amatjan; Yang, Yi; Aisa, Haji Akber] Chinese Acad Sci, Xinjiang Tech Inst Phys & Chem, Xinjiang Key Lab Plant Resources & Nat Prod Chem, Urumqi 830011, Peoples R China. [Aisa, Haji Akber] Union Labs Bioact Ingredients Edible Plants Cent, Urumqi, Peoples R China. [He, Dajun] Shihezi Univ, Sch Life Sci, Shihezi, Peoples R China. [He, Dajun; Gu, Dongyu; Huang, Yun; Ayupbek, Amatjan] Chinese Acad Sci, Grad Univ, Beijing, Peoples R China. RP Ito, Y (reprint author), NHLBI, Bioseparat Technol Lab, Biochem & Biophys Ctr, NIH, 10 Ctr Dr,Bldg 10,Room 8N230, Bethesda, MD 20892 USA. EM haji@ms.xjb.ac.cn; itoy2@mail.nih.gov FU Chinese Academy of Sciences [KSCX2YWR- 132]; State Administration of Foreign Experts Affairs FX This work was financially supported by a grant ( code: KSCX2YWR- 132) from Key Project of Knowledge Innovation Program of Chinese Academy of Sciences and another grant from the International Partnership Program for Creative Teams "Study on Bioactive Ingredients and Application of Arid Region Edible Plant'' of Chinese Academy of Sciences and the State Administration of Foreign Experts Affairs. NR 22 TC 8 Z9 8 U1 0 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2009 VL 32 IS 20 BP 3077 EP 3088 AR PII 916846556 DI 10.1080/10826070903320756 PG 12 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 520EM UT WOS:000271822900013 PM 20161415 ER PT J AU Bharatiya, B Patel, K Song, H Ma, JH Aswal, VK Bahadur, P AF Bharatiya, B. Patel, K. Song, H. Ma, J. H. Aswal, V. K. Bahadur, P. TI Lipophilic Diol Induced Micellization of Pluronic F88 in Water SO JOURNAL OF MACROMOLECULAR SCIENCE PART A-PURE AND APPLIED CHEMISTRY LA English DT Article DE Micelle; aggregation number; CMT ID BLOCK-COPOLYMER MICELLES; ANGLE NEUTRON-SCATTERING; AQUEOUS-SOLUTIONS; TRIBLOCK COPOLYMERS; LIGHT-SCATTERING; SOLUBILIZATION; AGGREGATION; VISCOSITY; TEMPERATURE; MIXTURES AB The presence of a lipophilic S104 (also known as C14diol) induces micellization in a highly hydrophilic ethylene oxide-propylene oxide-ethylene oxide triblock copolymer Pluronic F88 [(EO)103(PO)39-(EO)103] in water. The dynamic light scattering (DLS) and small angle neutron scattering (SANS) reveal that F88 remains as molecularly dissolved at ambient temperature even at fairly high concentrations (5 wt% or more). However, the micellization is induced at lower concentration/temperature in the presence of S104. The scattering measurements indicated micellar growth, though no phase transition was observed. The addition of hydrophobic S104 increases the aggregation numbers of the micellar system, but does not show a considerable increase in hydrodynamic size. The micellar parameters for the copolymer in the presence of S104 are reported at 30 and 40C. Hydrophobic S104 interacts with PPO blocks of F88, makes the decreasing CMT of F88, which may be the synergistic effect. Using intermolecular rotating-frame nuclear overhauser effect (ROE) profiles, the interactions between PPO methyl and S104 terminal methyl groups can be obviously observed. C1 [Bharatiya, B.; Patel, K.; Bahadur, P.] Veer Narmad S Gujarat Univ, Dept Chem, Surat 395007, India. [Song, H.] Chinese Acad Sci, Inst Proc Engn, State Key Lab Biochem Engn, Lab Separat Sci & Engn, Beijing, Peoples R China. [Aswal, V. K.] Bhabha Atom Res Ctr, Div Solid State Phys, Bombay 400085, Maharashtra, India. [Ma, J. H.] NIH, Bethesda, MD 20892 USA. RP Bharatiya, B (reprint author), Veer Narmad S Gujarat Univ, Dept Chem, Surat 395007, India. EM bhaveshbharatiya@gmail.com FU CSIR, New Delhi [01(2068)/06/EMR-II] FX P. B. thanks CSIR, New Delhi; Project No. 01(2068)/06/EMR-II for financial support. The authors gratefully acknowledge Dr. P. A. Hassan, BARC, Mumbai for providing the DLS facilities. NR 40 TC 3 Z9 3 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1060-1325 J9 J MACROMOL SCI A JI J. Macromol. Sci. Part A-Pure Appl. Chem. PY 2009 VL 46 IS 3 BP 304 EP 311 AR PII 908115547 DI 10.1080/10601320802637417 PG 8 WC Polymer Science SC Polymer Science GA 397FD UT WOS:000262647200010 ER PT J AU Thurber, KR Tycko, R AF Thurber, Kent R. Tycko, Robert TI Measurement of sample temperatures under magic-angle spinning from the chemical shift and spin-lattice relaxation rate of Br-79 in KBr powder SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE Solid state NMR; Magnetic resonance; Magic-angle spinning; Temperature calibration ID SOLID-STATE NMR; NUCLEAR-MAGNETIC-RESONANCE; MAS NMR; PHASE-TRANSITIONS; THERMOMETER; CALIBRATION; DEPENDENCE; CRYSTALS; STANDARD; SPECTRA AB Accurate determination of sample temperatures in solid state nuclear magnetic resonance (NMR) with magic-angle spinning (MAS) can be problematic, particularly because frictional heating and heating by radio-frequency irradiation can make the internal sample temperature significantly different from the temperature outside the MAS rotor. This paper demonstrates the use of Br-79 chemical shifts and spin-lattice relaxation rates in KBr powder as temperature-dependent parameters for the determination of internal sample temperatures. Advantages of this method include high signal-to-noise, proximity of the Br-79 NMR frequency to that of C-13, applicability from 20 K to 320 K or higher, and simultaneity with adjustment of the MAS axis direction. We show that spin-lattice relaxation in KBr is driven by a quadrupolar mechanism. We demonstrate a simple approach to including KBr powder in hydrated samples. such as biological membrane samples, hydrated amyloid fibrils, and hydrated microcrystalline proteins, that allows direct assessment of the effects of frictional and radio-frequency heating under experimentally relevant conditions. Published by Elsevier Inc. C1 [Thurber, Kent R.; Tycko, Robert] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Tycko, R (reprint author), NIDDK, Chem Phys Lab, NIH, Bldg 5,Room 112, Bethesda, MD 20892 USA. EM robertty@mail.nih.gov FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); NIH FX This work was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), a component of the National Institutes of Health (NIH), and by a grant from the NIH Intramural AIDS Targeted Antiviral Program. We thank Dr. Junxia Lu for assistance with the measurements in Fig. 3. NR 36 TC 89 Z9 90 U1 6 U2 53 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD JAN PY 2009 VL 196 IS 1 BP 84 EP 87 DI 10.1016/j.jmr.2008.09.019 PG 4 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 397RZ UT WOS:000262681100012 PM 18930418 ER PT J AU Kobayashi, H Kosaka, N Ogawa, M Morgan, NY Smith, PD Murray, CB Ye, XC Collins, J Kumar, GA Bell, H Choyke, PL AF Kobayashi, Hisataka Kosaka, Nobuyuki Ogawa, Mikako Morgan, Nicole Y. Smith, Paul D. Murray, Christopher B. Ye, Xingchen Collins, Josh Kumar, G. Ajith Bell, Howard Choyke, Peter L. TI In vivo multiple color lymphatic imaging using upconverting nanocrystals SO JOURNAL OF MATERIALS CHEMISTRY LA English DT Article ID UP-CONVERSION; QUANTUM DOTS AB Upconverting nanocrystals are unique nano-sized particles that emit light at shorter wavelengths (visible and near infrared) after excitation in the near infrared that dramatically reduces background autofluorescence in in vivo two color lymphatic imaging for depicting the lymphatic channels and nodes. C1 [Kobayashi, Hisataka; Kosaka, Nobuyuki; Ogawa, Mikako; Choyke, Peter L.] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Morgan, Nicole Y.; Smith, Paul D.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA. [Murray, Christopher B.; Ye, Xingchen; Collins, Josh] Univ Penn, Philadelphia, PA 19104 USA. [Kumar, G. Ajith; Bell, Howard] Sunstone BioSci Inc, Philadelphia, PA 19104 USA. RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bldg 10,Room 1B40,MSC 1088, Bethesda, MD 20892 USA. EM Kobayash@mail.nih.gov RI Ye, Xingchen/D-3202-2017 OI Ye, Xingchen/0000-0001-6851-2721 FU NIH, National Cancer Institute, Center for Cancer Research; Ben Franklin Technology Partners of Southeastern Pennsylvania; Nanotechnology Institute FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, and supported by the Ben Franklin Technology Development Authority through the Ben Franklin Technology Partners of Southeastern Pennsylvania and The Nanotechnology Institute. NR 16 TC 81 Z9 86 U1 1 U2 41 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 0959-9428 J9 J MATER CHEM JI J. Mater. Chem. PY 2009 VL 19 IS 36 BP 6481 EP 6484 DI 10.1039/b910512c PG 4 WC Chemistry, Physical; Materials Science, Multidisciplinary SC Chemistry; Materials Science GA 490IH UT WOS:000269493600004 ER PT J AU Gotsch, F Romero, R Erez, O Vaisbuch, E Kusanovic, JP Mazaki-Tovi, S Kim, SK Hassan, S Yeo, L AF Gotsch, Francesca Romero, Roberto Erez, Offer Vaisbuch, Edi Kusanovic, Juan Pedro Mazaki-Tovi, Shali Kim, Sun Kwon Hassan, Sonia Yeo, Lami TI The preterm parturition syndrome and its implications for understanding the biology, risk assessment, diagnosis, treatment and prevention of preterm birth SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article ID TUMOR-NECROSIS-FACTOR; AMNIOTIC-FLUID INTERLEUKIN-6; FETAL INFLAMMATORY RESPONSE; CHRONIC LUNG-DISEASE; EXPERIMENTAL INTRAUTERINE INFECTION; MESSENGER-RIBONUCLEIC-ACID; PLACEBO-CONTROLLED TRIAL; SMOOTH-MUSCLE-CELLS; ULTRASONOGRAPHIC CERVICAL LENGTH; MYOMETRIAL OXYTOCIN RECEPTOR C1 [Gotsch, Francesca; Romero, Roberto; Erez, Offer; Vaisbuch, Edi; Kusanovic, Juan Pedro; Mazaki-Tovi, Shali; Kim, Sun Kwon; Hassan, Sonia; Yeo, Lami] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Gotsch, Francesca; Romero, Roberto; Erez, Offer; Vaisbuch, Edi; Kusanovic, Juan Pedro; Mazaki-Tovi, Shali; Kim, Sun Kwon; Hassan, Sonia; Yeo, Lami] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA. [Romero, Roberto] Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp,Dept Obstet & Gynecol, Detroit, MI 48201 USA. RP Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp,Dept Obstet & Gynecol, 3990 John R Box 4, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu OI Vaisbuch, Edi/0000-0002-8400-9031 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, DHHS FX This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, DHHS. NR 445 TC 50 Z9 52 U1 0 U2 8 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 EI 1476-4954 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2009 VL 22 SU 2 BP 5 EP 23 DI 10.1080/14767050902860690 PG 19 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA V15ST UT WOS:000207822400003 PM 19951079 ER PT J AU Lee, SE Romero, R Kim, EC Yoon, BH AF Lee, Si Eun Romero, Roberto Kim, Eui-Chong Yoon, Bo Hyun TI A high Nugent score but not a positive culture for genital mycoplasmas is a risk factor for spontaneous preterm birth SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med DE Nugent score; bacterial vaginosis; genital mycoplasmas; Ureaplasma urealyticum; Mycoplasma hominis; preterm birth; prematurity ID UREAPLASMA-UREALYTICUM COLONIZATION; BACTERIAL VAGINOSIS; MICROBIAL INVASION; AMNIOTIC-FLUID; INFLAMMATORY RESPONSE; PREGNANT-WOMEN; DELIVERY; INTERLEUKIN-6; FLORA; LABOR AB Objective. This study was performed to evaluate the relationship among the Nugent score for the diagnosis of bacterial vaginosis (BV), the results of vaginal fluid culture for genital mycoplasmas, and the subsequent occurrence of preterm birth. Methods. The Nugent score and culture for genital mycoplasmas were performed in vaginal fluid obtained from 977 pregnant women (gestational age 13-30 weeks). Vaginal samples were obtained with sterile cotton swabs. The relationship among the Nugent score, vaginal fluid culture results and the occurrence of spontaneous preterm birth was examined. Results. (1) Of the 977 women, 14% (137) had a Nugent score of 8; (2) The prevalence of a positive vaginal culture for genital mycoplasmas was 30% (288); Ureaplasma urealyticum was isolated in 252 (88%), Mycoplasma hominis in 9 (3%), and both in 27 (9%) women; (3) Cases with a Nugent score of 8 had a higher rate of a positive vaginal culture for genital mycoplasmas than those with the lower Nugent score (55%vs. 25%; p0.001); (4) Women with a Nugent score of 8 had a significantly higher rate of spontaneous preterm birth 37 (10%vs. 4%), 34 (5%vs. 2%), and 32 (4%vs. 1%) weeks of gestation than those with the lower Nugent score (at each gestational age, p0.05); (5) In contrast, a positive vaginal culture for genital mycoplasmas was not associated with an increased risk for spontaneous preterm birth; (6) Among patients with a positive culture and a Nugent score of 8, the frequency of spontaneous preterm delivery (37 weeks) was 10% (7/72); (7) There was no difference in the incidence of spontaneous preterm delivery according to the results of vaginal culture in patients with a Nugent score of 8, as well as in those with a lower Nugent score. Conclusion. A high Nugent score (8) for the detection of BV but not a positive vaginal culture for genital mycoplasmas is a risk factor for spontaneous preterm birth. C1 [Lee, Si Eun; Yoon, Bo Hyun] Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul 110744, South Korea. [Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. [Kim, Eui-Chong] Seoul Natl Univ, Coll Med, Dept Lab Med, Seoul 110744, South Korea. RP Yoon, BH (reprint author), Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul 110744, South Korea. EM yoonbh@snu.ac.kr RI Yoon, Bo Hyun/H-6344-2011; Kim, Eu Chong/J-5424-2012 FU Intramural NIH HHS [Z01 HD002400-17, ZIA HD002401-17] NR 22 TC 23 Z9 23 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2009 VL 22 IS 3 BP 212 EP 217 AR PII 909979730 DI 10.1080/14767050802616994 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 425TM UT WOS:000264660000005 PM 19330704 ER PT J AU Lee, SM Lee, J Seong, HS Lee, SE Park, JS Romero, R Yoon, BH AF Lee, Seung Mi Lee, Joonho Seong, Hyo Suk Lee, Si Eun Park, Joong Shin Romero, Roberto Yoon, Bo Hyun TI The clinical significance of a positive Amnisure test in women with term labor with intact membranes SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE Amnisure ROM test; placental microglobulin-1; rupture of membranes; labor; term birth ID RUPTURED FETAL MEMBRANES; FACTOR BINDING PROTEIN-1; PREMATURE RUPTURE; NITRAZINE TEST; VAGINAL FLUID; FERN TEST; DIAGNOSIS; SECRETIONS AB Objective. The Amnisure ROM test is approved for the diagnosis of rupture of membranes (ROM). Yet, a fraction of patients with a positive test have intact membranes by sterile speculum examination. The objective of this study was to determine the clinical significance of this finding. Methods. The study population consisted of four groups of nulliparous women at term: (1) not in labor without clinical evidence of ROM (n=125); (2) in labor without clinical ROM with a negative Amnisure test (n=56); (3) in labor without clinical ROM with a positive Amnisure test (n=25); and (4) in labor with clinical ROM (n=30). The Amnisure test was performed in cases without clinical ROM (Groups 1, 2 and 3). Results. (1) The Amnisure test was positive more frequently in women in labor with intact membranes than in patients not in labor at term without ROM (30.9% (25/81 women) vs. 4.8% (6/125 women); p0.001); (2) patients in labor without clinical ROM with a positive Amnisure test had a significantly shorter admission-to-delivery interval than those in labor without clinical ROM with a negative Amnisure test (p0.05). Conclusion. (1) A positive Amnisure test is present in about one-third nulliparous women at term presenting in labor with intact membranes; (2) patients with a positive Amnisure test had a shorter admission-to-delivery interval than those with a negative test. C1 [Lee, Seung Mi; Lee, Joonho; Seong, Hyo Suk; Lee, Si Eun; Park, Joong Shin; Yoon, Bo Hyun] Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul 110744, South Korea. [Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. RP Yoon, BH (reprint author), Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul 110744, South Korea. EM yoonbh@snu.ac.kr RI Yoon, Bo Hyun/H-6344-2011; OI Park, Joong Shin/0000-0002-5246-0477 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; NIH; DHHS FX This research was supported in part by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. The Amnisure ROM test (TM) (the placental alpha-microglobulin-1 immunoassay) kits were provided free of charge by the Korean supplier of N-Dia Inc. (New York, NY). N-Dia Inc. did not contribute funds towards this study. None of the authors own any stock in this company and are either current or former employees of this company or are members of a speaker's bureau for this company. NR 20 TC 22 Z9 27 U1 0 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2009 VL 22 IS 4 BP 305 EP 310 AR PII 910259603 DI 10.1080/14767050902801694 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 438VG UT WOS:000265583100004 PM 19350444 ER PT J AU Erez, O Romero, R Vaisbuch, E Mazaki-Tovi, S Kusanovic, JP Chaiworapongsa, T Than, NG Gotsch, F Kim, CJ Mittal, P Edwin, S Pacora, P Kim, SK Yeo, L Mazor, M Hassan, SS AF Erez, Offer Romero, Roberto Vaisbuch, Edi Mazaki-Tovi, Shali Kusanovic, Juan Pedro Chaiworapongsa, Tinnakorn Than, Nandor Gabor Gotsch, Francesca Kim, Chong Jai Mittal, Pooja Edwin, Samuel Pacora, Percy Kim, Sun Kwon Yeo, Lami Mazor, Moshe Hassan, Sonia S. TI Maternal anti-protein Z antibodies in pregnancies complicated by pre-eclampsia, SGA and fetal death SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE Autoantibodies; antiphospholipid; pregnancy; hypertension; placenta; vasculitis protein Z ID INTRAUTERINE GROWTH-RETARDATION; SYSTEMIC-LUPUS-ERYTHEMATOSUS; GESTATIONAL-AGE INFANTS; ANTIPHOSPHOLIPID ANTIBODIES; FACTOR-VIII; NATURAL AUTOANTIBODIES; PROTHROMBIN ANTIBODIES; Z-DEFICIENCY; EPIDEMIOLOGIC ASSOCIATIONS; CLINICAL-SIGNIFICANCE AB Objective. Low maternal plasma protein Z (PZ) concentrations were reported in patients with pre-eclampsia (PE), a small for gestational age (SGA) neonate, and a fetal demise (FD). Anti-protein Z antibodies (APZ-AB) have been proposed as a possible underlying mechanism leading to low plasma PZ concentrations. The objective of this study was to determine the maternal plasma concentration of APZ-AB in women with a normal pregnancy, and patients with PE, an SGA neonate or a FD. Study design. A cross-sectional study included women in the following groups: (1) non-pregnant women (n = 45); and pregnant women with: (2) normal pregnancies (n = 70); (3) PE (n = 123); (4) SGA neonates (n = 51); and (5) a FD (n = 51). Plasma concentrations of anti-protein Z IgM and IgG antibodies were measured by ELISA. Elevated APZ-AB was defined as >75th, 90th and 95th percentile of the normal pregnancy group. Non-parametric statistics were used for analyses. Results. (1) Patients with an SGA neonate had a higher median maternal plasma IgG APZ-AB concentration than women with normal pregnancies (p < 0.001), and patients with PE (p < 0.001) or with a FD (p = 0.001). (2) The proportion of patients with a maternal plasma IgM APZ-AB concentration >90th percentile was higher in the SGA group than in the PE group (p = 0.01). (3) Patients with PE maternal plasma IgM APZ-AB concentration >90th percentile had a higher rate of villous thrombosis (p = 0.03) and persistent muscularisation of basal plate arteries (p = 0.01) than those with IgM APZ-AB concentration <90th percentile; and (5) Patients with FD and maternal plasma IgM APZ-AB concentration >90th percentile had a higher rate of umbilical phlebitis and arteritis than those with IgM APZ-AB concentration <90th percentile (p = 0.003). Conclusions. (1) Patients with SGA neonates have a higher median plasma concentration of IgG APZ-AB than normal pregnant women, or patients with PE or FD; and (2) maternal plasma IgM APZ-AB concentration >90th percentile was associated with vascular placental lesions in patients with PE, but not in those with an SGA neonate, suggesting that in a subset of patients, these antibodies can be associated with abnormal placentation and pregnancy complications. C1 [Erez, Offer; Romero, Roberto; Vaisbuch, Edi; Mazaki-Tovi, Shali; Kusanovic, Juan Pedro; Chaiworapongsa, Tinnakorn; Than, Nandor Gabor; Gotsch, Francesca; Kim, Chong Jai; Mittal, Pooja; Edwin, Samuel; Pacora, Percy; Kim, Sun Kwon; Yeo, Lami; Hassan, Sonia S.] NICHD, Perinatol Res Branch, NIH, US Dept HHS, Bethesda, MD USA. [Erez, Offer; Romero, Roberto; Vaisbuch, Edi; Mazaki-Tovi, Shali; Kusanovic, Juan Pedro; Chaiworapongsa, Tinnakorn; Mittal, Pooja; Yeo, Lami; Hassan, Sonia S.] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. [Kim, Chong Jai] Wayne State Univ, Dept Pathol, Detroit, MI 48202 USA. [Mazor, Moshe] Ben Gurion Univ Negev, Dept Obstet & Gynecol, Soroka Univ Med Ctr, IL-84105 Beer Sheva, Israel. RP Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, NICHD, Perinatol Res Branch,NIH,DHHS, 3990 John R,Box 4, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu OI Vaisbuch, Edi/0000-0002-8400-9031 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS FX This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. NR 76 TC 12 Z9 13 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2009 VL 22 IS 8 BP 662 EP 671 DI 10.1080/14767050902801751 PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 508NG UT WOS:000270938100006 PM 19591071 ER PT J AU Erez, O Gotsch, F Mazaki-Tovi, S Vaisbuch, E Kusanovic, JP Kim, CJ Chaiworapongsa, T Hoppensteadt, D Fareed, J Than, NG Nhan-Chang, CL Yeo, L Pacora, P Mazor, M Hassan, SS Mittal, P Romero, R AF Erez, Offer Gotsch, Francesca Mazaki-Tovi, Shali Vaisbuch, Edi Kusanovic, Juan Pedro Kim, Chong Jai Chaiworapongsa, Tinnakorn Hoppensteadt, Deborah Fareed, Jawed Than, Nandor G. Nhan-Chang, Chia-Ling Yeo, Lami Pacora, Percy Mazor, Moshe Hassan, Sonia S. Mittal, Pooja Romero, Roberto TI Evidence of maternal platelet activation, excessive thrombin generation, and high amniotic fluid tissue factor immunoreactivity and functional activity in patients with fetal death SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Review DE Soluble CD40L; thrombin-antithrombin complexes; prothrombin fragments 1+2; pregnancy; abruption; preeclampsia ID FACTOR PATHWAY INHIBITOR; SOLUBLE CD40 LIGAND; DISSEMINATED INTRAVASCULAR COAGULATION; FLOW-CYTOMETRIC DETECTION; ANTITHROMBIN-III COMPLEX; FACTOR-X ACTIVATION; INTRAUTERINE GROWTH-RETARDATION; COLONY-STIMULATING FACTOR; C-REACTIVE PROTEIN; EX-VIVO THROMBI AB Objective. Fetal death can lead to disseminated intravascular coagulation or fetal death syndrome. However, currently it is not clear what are the changes in the coagulation system in patients with a fetal death without the fetal death syndrome. This study was undertaken to determine: (1) whether fetal death in the absence of fetal death syndrome is associated with changes in hemostatic markers in maternal plasma and amniotic fluid; and (2) whether maternal hypertension or placental abruption are associated with further changes in the hemostatic profile of these patients. Methods. A cross-sectional study included the following: (1) determination of changes in markers of coagulation and platelet activation in patients with a normal pregnancy (n = 71) and patients with fetal demise (FD) without disseminated intravascular coagulation (n = 65); (2) determination of the amniotic fluid (AF)-tissue factor concentration and activity, as well as the concentrations of thrombin-antithrombin III (TAT) complexes in patients with a normal pregnancy (n = 25) and those with a FD (n = 36) who underwent amniocentesis. Plasma and AF concentrations of TAT complexes and TF (an index of thrombin generation), as well as maternal plasma concentrations of sCD40L (a marker of platelet activation), tissue factor pathway inhibitor (TFPI) and prothrombin fragments (PF) 1 + 2 (also an indicator of in vivo thrombin generation) were measured by ELISA. TF and TFPI activity were measured using chromogenic assays. Results. (1) patients with FD without hypertension had a higher median maternal plasma sCD40L concentration than normal pregnant women (P < 0.001); (2) patients with FD had a higher median maternal plasma TAT III complexes than women with a normal pregnancy (P < 0.001); (3) the median AF-TF concentration and activity were higher in the FD group than in the normal pregnancy group (P < 0.001 for both); (4) patients with preeclampsia and FD had a higher median maternal plasma immunoreactive TF concentration than both normotensive patients with FD and women with normal pregnancies (P < 0.001 and P = 0.001, respectively); (5) the median plasma TF activity was higher in patients with preeclampsia and FD than that of women with normal pregnancies (P = 0.003); (6) among patients with a FD, those with placental abruption had a higher median AF-TAT complexes concentration than those without abruption (P = 0.0004). Conclusions. Our findings indicate that: (1) mothers with a FD have evidence of increased in vivo thrombin generation and platelet activation than women with normal pregnancies; (2) patients with a FD and hypertension had a higher degree of TF activation than those with fetal death but without hypertension; (3) the AF of women with a FD had a higher median TF concentration and activity than that of normal pregnant women. AF can be a potential source for tissue factor and it participates in the development of fetal death syndrome in patients with a retained dead fetus. C1 [Erez, Offer; Gotsch, Francesca; Mazaki-Tovi, Shali; Vaisbuch, Edi; Kusanovic, Juan Pedro; Kim, Chong Jai; Chaiworapongsa, Tinnakorn; Than, Nandor G.; Nhan-Chang, Chia-Ling; Yeo, Lami; Pacora, Percy; Hassan, Sonia S.; Mittal, Pooja; Romero, Roberto] NICHD, Perinatol Res Branch, NIH, US Dept HHS, Bethesda, MD USA. [Erez, Offer; Mazaki-Tovi, Shali; Vaisbuch, Edi; Kusanovic, Juan Pedro; Chaiworapongsa, Tinnakorn; Nhan-Chang, Chia-Ling; Yeo, Lami; Hassan, Sonia S.; Mittal, Pooja; Romero, Roberto] Wayne State Univ, Dept OB GYN, Detroit, MI USA. [Kim, Chong Jai] Wayne State Univ, Dept Pathol, Detroit, MI 48202 USA. [Hoppensteadt, Deborah; Fareed, Jawed] Loyola Univ Hlth Syst, Dept Pathol, Maywood, IL USA. [Mazor, Moshe] Beer Sheva Univ Negev, Soroka Med Ctr, Dept OB GYN, Beer Sheva, Israel. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. RP Erez, O (reprint author), Wayne State Univ, Hutzel Womens Hosp, NICHD, Perinatol Res Branch,NIH,DHHS, 3990 John R,Box 4, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu OI Vaisbuch, Edi/0000-0002-8400-9031 FU Perinatology Research Branch; Division of Intramural Research; Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS FX This research was supported (in part) by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. NR 165 TC 26 Z9 26 U1 0 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2009 VL 22 IS 8 BP 672 EP 687 DI 10.1080/14767050902853117 PG 16 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 508NG UT WOS:000270938100007 PM 19736615 ER PT J AU Mazaki-Tovi, S Romero, R Vaisbuch, E Erez, O Chaiworapongsa, T Mittal, P Kim, SK Pacora, P Gotsch, F Dong, Z Hassan, SS Kusanovic, JP AF Mazaki-Tovi, Shali Romero, Roberto Vaisbuch, Edi Erez, Offer Chaiworapongsa, Tinnakorn Mittal, Pooja Kim, Sun Kwon Pacora, Percy Gotsch, Francesca Dong, Zhong Hassan, Sonia S. Kusanovic, Juan Pedro TI Maternal plasma visfatin in preterm labor SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Review DE Visfatin; adipokines; pregnancy; preterm labor; intra-amniotic infection; inflammation; chorioamnionitis; preterm delivery; energy requirements; energy expenditure; preterm birth; metabolism ID COLONY-ENHANCING FACTOR; TUMOR-NECROSIS-FACTOR; INFLAMMATORY RESPONSE SYNDROME; AMNIOTIC-FLUID INTERLEUKIN-6; HUMAN FETAL MEMBRANES; POLYMERASE-CHAIN-REACTION; TYPE-2 DIABETES-MELLITUS; NORMAL HUMAN-PREGNANCY; BLOOD-CELL COUNT; FREE FATTY-ACIDS AB Objective. Visfatin, a novel adipokine with diabetogenic and immunoregulatory properties, has been implicated in the pathophysiology of insulin resistance, as well as in various acute and chronic inflammatory disorders. We have previously reported that amniotic fluid concentrations of visfatin are higher in patients with preterm labor (PTL) and intra- amniotic infection than in patients with PTL without infection. The aim of this study was to determine whether spontaneous PTL with intact membranes and intra-amniotic infection/inflammation (IAI) is associated with changes in maternal plasma circulating visfatin concentrations. Study design. This cross-sectional study included patients in the following groups: (1) normal pregnant women (n = 123); (2) patients with an episode of PTL and intact membranes without IAI who delivered at term (n = 57); (3) PTL without IAI who delivered preterm (n = 47); and (4) PTL with IAI who delivered preterm (n = 57). Plasma visfatin concentrations were determined by ELISA. Non-parametric statistics were used for analysis. Results. (1) PTL with IAI leading to preterm delivery was associated with a higher median maternal plasma concentration of visfatin than normal pregnancy; (2) among patients with PTL, those with IAI had the highest median maternal concentration of visfatin; (3) the changes in maternal plasma visfatin remained significant after adjusting for maternal age, body mass index, gestational age at sampling, and birth weight. Conclusion. (1) PTL with IAI is characterized by high maternal circulating visfatin concentrations; (2) these findings suggest that visfatin plays a role in the regulation of the metabolic adaptations to insults resulting in PTL in the context of IAI. C1 [Mazaki-Tovi, Shali; Romero, Roberto; Vaisbuch, Edi; Erez, Offer; Chaiworapongsa, Tinnakorn; Mittal, Pooja; Kim, Sun Kwon; Pacora, Percy; Gotsch, Francesca; Dong, Zhong; Hassan, Sonia S.; Kusanovic, Juan Pedro] Hutzel Womens Hosp, NICHD, Perinatol Res Branch, Intramural Div,NIH,DHHS, Detroit, MI 48201 USA. [Mazaki-Tovi, Shali; Romero, Roberto; Vaisbuch, Edi; Erez, Offer; Chaiworapongsa, Tinnakorn; Mittal, Pooja; Kim, Sun Kwon; Pacora, Percy; Gotsch, Francesca; Dong, Zhong; Hassan, Sonia S.; Kusanovic, Juan Pedro] Hutzel Womens Hosp, NICHD, Perinatol Res Branch, Intramural Div,NIH,DHHS, Bethesda, MD USA. [Mazaki-Tovi, Shali; Romero, Roberto; Vaisbuch, Edi; Erez, Offer; Chaiworapongsa, Tinnakorn; Mittal, Pooja; Hassan, Sonia S.; Kusanovic, Juan Pedro] Wayne State Univ, Hutzel Womens Hosp, Dept Obstet & Gynecol, Detroit, MI USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. RP Romero, R (reprint author), Hutzel Womens Hosp, NICHD, Perinatol Res Branch, Intramural Div,NIH,DHHS, Box 4,3990 John R, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu OI Vaisbuch, Edi/0000-0002-8400-9031 FU Perinatology Research Branch; Division of Intramural Research; Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS FX This research was supported (in part) by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. NR 195 TC 25 Z9 25 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1476-7058 EI 1476-4954 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2009 VL 22 IS 8 BP 693 EP 704 DI 10.1080/14767050902994788 PG 12 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 508NG UT WOS:000270938100009 PM 19572235 ER PT J AU Lee, SE Park, IS Romero, R Yoon, BH AF Lee, Si Eun Park, In-Sook Romero, Roberto Yoon, Bo Hyun TI Amniotic fluid prostaglandin F2 increases even in sterile amniotic fluid and is an independent predictor of impending delivery in preterm premature rupture of membranes SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Mat Fetal Med DE Amniotic fluid infection; intra-amniotic inflammation; prostaglandin; preterm PROM; parturition ID CORTICOTROPIN-RELEASING HORMONE; POLYMERASE-CHAIN-REACTION; INTRAAMNIOTIC INFECTION; MATRIX METALLOPROTEINASE-8; UREAPLASMA-UREALYTICUM; SPONTANEOUS LABOR; GESTATIONAL-AGE; FETAL MEMBRANES; HUMAN PLACENTA; PARTURITION AB Objective. To determine whether amniotic fluid (AF) concentration of prostaglandins (PGs) increases in patients with intra-amniotic inflammation and/or proven AF infection in preterm PROM, and can predict impending delivery. Methods. AF PGF2a concentrations were determined by ELISA in 140 singleton pregnancies with preterm premature rupture of membranes (PROM) (<= 35 weeks). AF was cultured for aerobic and anaerobic bacteria, and genital mycoplasmas. Intra-amniotic inflammation was defined as an elevated AF matrix metalloproteinase-8 concentration (>23 ng/ml). Results. (1) Patients with intra-amniotic inflammation and a negative AF culture had a significantly higher median AF PGF2a than those without intra-amniotic inflammation and with a negative culture (p<0.001); (2) However, there was no difference in the median AF PGF2a between patients with intra-amniotic inflammation with a negative culture and those with culture-proven AF infection (p > 0.1); (3) Patients with an elevated AF PGF2a had a significantly shorter interval-to-delivery than those with a low AF PGF2a (<= 170 pg/mL) (p<0.001); (4) An elevated AF PGF2a (<= 170 pg/mL) concentration was a significant predictor of the duration of pregnancy after adjusting for gestational age and AF inflammation/infection (p<0.005). Conclusions. AF PGF2a (>= 170 pg/mL) concentration increased in patients with intra-amniotic inflammation regardless of AF culture results. Moreover, an elevated AF PGF2a concentration was an independent predictor of impending delivery in preterm PROM. C1 [Lee, Si Eun; Park, In-Sook; Yoon, Bo Hyun] Seoul Natl Univ, Dept Obstet & Gynecol, Coll Med, Seoul 110744, South Korea. [Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Heath & Hu, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. RP Yoon, BH (reprint author), Seoul Natl Univ, Dept Obstet & Gynecol, Coll Med, Seoul 110744, South Korea. EM yoonbh@snu.ac.kr RI Yoon, Bo Hyun/H-6344-2011 FU Intramural NIH HHS [Z01 HD002400-16] NR 39 TC 22 Z9 22 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2009 VL 22 IS 10 BP 880 EP 886 DI 10.1080/14767050902994648 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 508NK UT WOS:000270938600011 PM 19544157 ER PT J AU Mazaki-Tovi, S Romero, R Vaisbuch, E Erez, O Mittal, P Chaiworapongsa, T Kim, SK Pacora, P Yeo, L Gotsch, F Dong, Z Nhan-Chang, CL Jodicke, C Yoon, BH Hassan, SS Kusanovic, JP AF Mazaki-Tovi, Shali Romero, Roberto Vaisbuch, Edi Erez, Offer Mittal, Pooja Chaiworapongsa, Tinnakorn Kim, Sun Kwon Pacora, Percy Yeo, Lami Gotsch, Francesca Dong, Zhong Nhan-Chang, Chia-Ling Jodicke, Cristiano Yoon, Bo Hyun Hassan, Sonia S. Kusanovic, Juan Pedro TI Dysregulation of maternal serum adiponectin in preterm labor SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Review DE Adiponectin; adipokines; pregnancy; high molecular weight; medium molecular weight; low molecular weight; preterm labor; intra-amniotic infection; inflammation; chorioamnionitis; preterm delivery; energy requirements; energy expenditure; preterm birth; metabolism; metaflammation ID TUMOR-NECROSIS-FACTOR; GESTATIONAL DIABETES-MELLITUS; C-REACTIVE PROTEIN; INFLAMMATORY RESPONSE SYNDROME; SYSTEMIC-LUPUS-ERYTHEMATOSUS; COLONY-ENHANCING FACTOR; COMPLEMENT-RELATED PROTEIN; INDUCED INSULIN-RESISTANCE; POLYMERASE-CHAIN-REACTION; ADIPOSE-SPECIFIC PROTEIN AB Objective. Intra-amniotic and systemic infection/inflammation have been causally linked to preterm parturition and fetal injury. An emerging theme is that adipose tissue can orchestrate a metabolic response to insults, but also an inflammatory response via the production of adipocytokines, and that these two phenomenons are interrelated. Adiponectin, an insulin-sensitising, anti-inflammatory adipocytokine, circulates in multimeric complexes including low-molecular weight (LMW) trimers, medium-molecular weight (MMW) hexamers and high-molecular weight (HMW) isoforms. Each of these complexes can exert differential biological effects. The aim of this study was to determine whether spontaneous preterm labor (PTL) with intact membranes and intra-amniotic infection/inflammation (IAI) is associated with changes in maternal serum circulating adiponectin multimers. Study design. This cross-sectional study included patients in the following groups: (1) normal pregnant women (n = 158); (2) patients with an episode of preterm labor and intact membranes without IAI who delivered at term (n = 41); (3) preterm labor without IAI who delivered preterm (n = 27); and (4) preterm labor with IAI who delivered preterm (n = 36). Serum adiponectin multimers (total, HMW, MMW and LMW) concentrations were determined by ELISA. Non-parametric statistics were used for analyses. Results. (1) Preterm labor leading to preterm delivery or an episode of preterm labor that does not lead to preterm delivery was associated with a lower median maternal serum concentration of total and HMW adiponectin, a lower median HMW/total adiponectin ratio and a higher median LMW/total adiponectin ratio than normal pregnancy; (2) among patients with preterm labor, those with IAI had the lowest median concentration of total and HMW adiponectin, as well as the lowest median HMW/total adiponectin ratio; (3) the changes in maternal adiponectin and adiponectin multimers remained significant after adjusting for confounding factors such as maternal age, BMI, gestational age at sampling and parity. Conclusion. (1) Preterm labor is characterised by a change in the profile of adiponectin multimers concentrations and their relative isoforms. These changes were observed in patients with an episode of preterm labor not leading to preterm delivery, in patients with intra-amniotic inflammation, or in those without evidence of intra-amniotic inflammation. (2) The changes in adiponectin multimer concentrations reported in preterm labor are different from those previously reported in spontaneous labor at term, suggesting that there is a fundamental difference between preterm labor and labor at term. (3) The findings reported herein provide the first evidence for the participation of adiponectin multimer in preterm parturition. We propose that adiponectins and adipokines in general provide a mechanism to organise the metabolic demands generated by the process of preterm parturition regardless of the nature of the insult (intra-amniotic inflammation or not). C1 [Mazaki-Tovi, Shali; Romero, Roberto; Vaisbuch, Edi; Erez, Offer; Mittal, Pooja; Chaiworapongsa, Tinnakorn; Kim, Sun Kwon; Pacora, Percy; Yeo, Lami; Gotsch, Francesca; Dong, Zhong; Nhan-Chang, Chia-Ling; Jodicke, Cristiano; Hassan, Sonia S.; Kusanovic, Juan Pedro] NICHD, Perinatol Res Branch, Intramural Div, NIH,DHHS,Hutzel Womens Hosp, Bethesda, MD USA. [Mazaki-Tovi, Shali; Vaisbuch, Edi; Erez, Offer; Mittal, Pooja; Chaiworapongsa, Tinnakorn; Yeo, Lami; Nhan-Chang, Chia-Ling; Jodicke, Cristiano; Hassan, Sonia S.; Kusanovic, Juan Pedro] Wayne State Univ, Dept Obstet & Gynecol, Hutzel Womens Hosp, Detroit, MI USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. [Yoon, Bo Hyun] Seoul Natl Univ, Dept Obstet & Gynecol, Seoul, South Korea. RP Romero, R (reprint author), NICHD, Perinatol Res Branch, Intramural Div, NIH,DHHS,Hutzel Womens Hosp, Box 4,3990 John R, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu RI Yoon, Bo Hyun/H-6344-2011; OI Vaisbuch, Edi/0000-0002-8400-9031 FU Perinatology Research Branch, Division of Intramural Research; Eunice Kennedy Shriver National Institute of Child Health and Human Development; NIH; DHHS FX This research was supported (in part) by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. NR 212 TC 20 Z9 20 U1 1 U2 6 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2009 VL 22 IS 10 BP 887 EP 904 DI 10.1080/14767050902994655 PG 18 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 508NK UT WOS:000270938600012 PM 19579094 ER PT J AU Vaisbuch, E Romero, R Erez, O Mazaki-Tovi, S Pedro, KJ Soto, E Gotsch, F Dong, Z Chaiworapongsa, T Kim, SK Mittal, P Pacora, P Yeo, L Hassan, SS AF Vaisbuch, Edi Romero, Roberto Erez, Offer Mazaki-Tovi, Shali Pedro, Kusanovic Juan Soto, Eleazar Gotsch, Francesca Dong, Zhong Chaiworapongsa, Tinnakorn Kim, Sun Kwon Mittal, Pooja Pacora, Percy Yeo, Lami Hassan, Sonia S. TI Fragment Bb in amniotic fluid: evidence for complement activation by the alternative pathway in women with intra-amniotic infection/inflammation SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Review DE Alternative pathway; chorioamnionitis; complement; pregnancy; preterm labor; prelabor rupture of membranes; PPROM; microbial invasion of the amniotic cavity ID TUMOR-NECROSIS-FACTOR; INFLAMMATORY RESPONSE SYNDROME; PRETERM LABOR; INTRAUTERINE INFECTION; PREMATURE LABOR; CEREBRAL-PALSY; TERM LABOR; CYTOKINES INTERLEUKIN-6; CLINICAL-SIGNIFICANCE; PSYCHOLOGICAL STRESS AB Objective. Fragment Bb is an activator of the alternative pathway of the complement system. Recently, increased first trimester maternal plasma concentrations of this fragment were reported in patients destined to have a spontaneous preterm delivery before 34 weeks of gestation. The aim of this study was to determine whether the amniotic fluid (AF) concentrations of fragment Bb change with gestational age, spontaneous labor (term and preterm) and in the presence of intra-amniotic infection/inflammation (IAI). Study design. This cross-sectional study included patients in the following groups: (1) mid-trimester (n = 64); (2) term in spontaneous labor (n = 70); (3) term not in labor (n = 43); (4) spontaneous preterm labor (PTL) who delivered at term (n = 76); (5) PTL without IAI who delivered preterm (n = 73); (6) PTL with IAI (n = 76); (7) preterm prelabor rupture of membranes (PROM) without IAI (n = 71); and (8) preterm PROM with IAI (n = 71). Fragment Bb concentration in AF was determined by an enzyme-linked immunoassay. Non-parametric statistics were used for analyses. Results. (1) Fragment Bb was detected in all AF samples (n = 544); (2) The median AF concentration of fragment Bb in patients at term not in labor was significantly higher than that of those in the mid-trimester [2.42 mu g/ml, interquartile range (IQR) 1.78-3.22 vs. 1.64 mu g/ml, IQR 1.06-3.49; p<0.001]; (3) Among patients with PTL, those with IAI had a higher median AF fragment Bb concentration than that of woman without IAI, who delivered preterm (4.82 mu g/ml, IQR 3.32-6.08 vs. 3.67 mu g/ml, IQR 2.35-4.57; p<0.001) and than that of women with an episode of PTL, who delivered at term (3.21 mu g/ml, IQR 2.39-4.16; p<0.001); (4) Similarly, among patients with preterm PROM, the median AF fragment Bb concentration was higher in individuals with IAI than in those without IAI (4.24 mu g/ml, IQR 2.58-5.79 vs. 2.79 mu g/ml, IQR 2.09-3.89; p<0.001). (5) Among patients at term, the median AF fragment Bb concentration did not differ between women with spontaneous labor and those without labor (term in labor: 2.47 mu g/ml, IQR 1.86-3.22; p=0.97). Conclusions. (1) Fragment Bb, an activator of the alternative complement pathway, is a physiologic constituent of the AF, and its concentration increases with advancing gestational age; (2) AF concentrations of fragment Bb are higher in pregnancies complicated with IAI; and (3) labor at term is not associated with changes in the AF concentrations of fragment Bb. These findings suggest a role for fragment Bb in the host immune response against IAI. C1 [Vaisbuch, Edi; Romero, Roberto; Erez, Offer; Mazaki-Tovi, Shali; Pedro, Kusanovic Juan; Soto, Eleazar; Gotsch, Francesca; Dong, Zhong; Chaiworapongsa, Tinnakorn; Kim, Sun Kwon; Mittal, Pooja; Pacora, Percy; Yeo, Lami; Hassan, Sonia S.] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Vaisbuch, Edi; Romero, Roberto; Erez, Offer; Mazaki-Tovi, Shali; Pedro, Kusanovic Juan; Chaiworapongsa, Tinnakorn; Mittal, Pooja; Yeo, Lami; Hassan, Sonia S.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA. [Vaisbuch, Edi; Romero, Roberto; Erez, Offer; Mazaki-Tovi, Shali; Pedro, Kusanovic Juan; Soto, Eleazar; Gotsch, Francesca; Dong, Zhong; Chaiworapongsa, Tinnakorn; Kim, Sun Kwon; Mittal, Pooja; Pacora, Percy; Yeo, Lami; Hassan, Sonia S.] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. RP Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, 3990 John R,Box 4, Detroit, MI 48201 USA. EM evaisbuch@med.wayne.edu; prbchiefstaff@med.wayne.edu OI Vaisbuch, Edi/0000-0002-8400-9031 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; NIH; DHHS FX This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. NR 103 TC 22 Z9 22 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2009 VL 22 IS 10 BP 905 EP 916 DI 10.1080/14767050902994663 PG 12 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 508NK UT WOS:000270938600013 PM 19603351 ER PT J AU Lee, J Oh, KJ Yang, HJ Park, JS Romero, R Yoon, BH AF Lee, Joonho Oh, Kyung Joon Yang, Hye Jin Park, Joong Shin Romero, Roberto Yoon, Bo Hyun TI The importance of intra-amniotic inflammation in the subsequent development of atypical chronic lung disease SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE Amniotic fluid matrix metalloproteinase-8; atypical chronic lung disease; intra-amniotic inflammation ID FLUID MATRIX METALLOPROTEINASE-8; RESPIRATORY-DISTRESS-SYNDROME; BRONCHOALVEOLAR LAVAGE FLUID; PRETERM PREMATURE RUPTURE; AMNIOTIC-FLUID; BRONCHOPULMONARY DYSPLASIA; INTRAUTERINE INFECTION; SURFACTANT PROTEINS; SPONTANEOUS LABOR; HISTOLOGIC CHORIOAMNIONITIS AB Objective. To examine whether the intra-amniotic inflammation is a risk factor for the development of atypical chronic lung disease (CLD). Study design. A retrospective cohort study was undertaken in 72 patients who delivered preterm neonates (gestational age: 24-32 weeks) within 5 days of amniocentesis and whose neonates subsequently developed CLD. Atypical CLD was defined as CLD without respiratory distress syndrome (RDS). Intra-amniotic inflammation was defined as an elevated amniotic fluid (AF) concentration of matrix metalloproteinase-8 (MMP-8) (>23 ng/ml). Results. (1) Atypical CLD was identified in 54.2% (39/72) of cases with CLD; (2) there were no significant differences in the median gestational age at birth and the rate of antenatal corticosteroid use between infants with atypical CLD and CLD with RDS; (3) preterm newborns with atypical CLD had a significantly higher median AF MMP-8 concentration (median 373.1 ng/ml vs. 8.6 ng/ml, p=0.003) and median AF white blood cell count (median 450.0/mm(3) vs. 5.5/mm(3), p=0.009), and a higher rate of intra-amniotic inflammation (74.4% vs. 45.5%, p=0.012) than those with CLD with RDS. Conclusion. Intra-amniotic inflammation confers a greater risk for atypical CLD than for typical CLD with initial RDS. This novel observation strengthens the importance of prenatal inflammation as a mechanism of lung injury. C1 [Lee, Joonho; Oh, Kyung Joon; Yang, Hye Jin; Park, Joong Shin; Yoon, Bo Hyun] Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul 110744, South Korea. [Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Detroit, MI USA. RP Yoon, BH (reprint author), Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul 110744, South Korea. EM yoonbh@snu.ac.kr RI Yoon, Bo Hyun/H-6344-2011; OI Park, Joong Shin/0000-0002-5246-0477 FU Korea government (MOST) [R01-2006000-10607-0]; Eunice Kennedy Shriver National Institute of Child Heath and Human Development; NIH; DHHS FX This work was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MOST) (No. R01-2006000-10607-0), and in part by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Heath and Human Development, NIH and DHHS. NR 53 TC 28 Z9 29 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2009 VL 22 IS 10 BP 917 EP 923 DI 10.1080/14767050902994705 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 508NK UT WOS:000270938600014 PM 19718578 ER PT J AU Erez, O Romero, R Vaisbuch, E Chaiworapongsa, T Kusanovic, JP Mazaki-Tovi, S Gotsch, F Gomez, R Maymon, E Pacora, P Edwin, SS Kim, CJ Than, NG Mittal, P Yeo, L Dong, Z Yoon, BH Hassan, SS Mazor, M AF Erez, Offer Romero, Roberto Vaisbuch, Edi Chaiworapongsa, Tinnakorn Kusanovic, Juan Pedro Mazaki-Tovi, Shali Gotsch, Francesca Gomez, Ricardo Maymon, Eli Pacora, Percy Edwin, Samuel S. Kim, Chong Jai Than, Nandor Gabor Mittal, Pooja Yeo, Lami Dong, Zhong Yoon, Bo Hyun Hassan, Sonia S. Mazor, Moshe TI Changes in amniotic fluid concentration of thrombin-antithrombin III complexes in patients with preterm labor: Evidence of an increased thrombin generation SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Review DE Preterm parturition; delivery; inflammation; protease-activated receptors; survival curvel ID TUMOR-NECROSIS-FACTOR; PROTEASE-ACTIVATED RECEPTORS; COLONY-STIMULATING FACTOR; TISSUE FACTOR EXPRESSION; HUMAN MYOMETRIAL CELLS; PREMATURE RUPTURE; NORMAL-PREGNANCY; INTRAAMNIOTIC INFECTION; ENDOTHELIAL-CELLS; BLOOD-COAGULATION AB Objective. Preterm labor is associated with excessive maternal thrombin generation, as evidenced by increased circulating thrombin-antithrombin (TAT) III complexes concentration. In addition to its hemostatic functions, thrombin has uterotonic properties that may participate in the mechanism leading to preterm birth in cases of intrauterine bleeding. Thrombin also has a proinflammatory role, and inflammation is associated with increased thrombin generation. The aim of this study was to determine whether intra-amniotic infection/inflammation (IAI) is associated with increased amniotic fluid (AF) thrombin generation in women with preterm and term deliveries. Study design. This cross-sectional study included the following groups: (1) mid-trimester (n = 74); (2) term not in labor (n = 39); (3) term in labor (n = 25); (4) term in labor with IAI (n = 22); (5) spontaneous preterm labor (PTL) who delivered at term (n = 62); (6) PTL without IAI who delivered preterm (n = 59); (7) PTL with IAI (n = 71). The AF TAT III complexes concentration was measured by enzyme linked immunosorbent assay (ELISA). Non-parametric statistics were used for analysis. Results. (1) TAT III complexes were identified in all AF samples; (2) patients with PTL who delivered preterm, with and without IAI, had a higher median AF TAT III complexes concentration than those with an episode of PTL who delivered at term (p < 0.001, p = 0.03, respectively); (3) among patients with PTL without IAI, elevated AF TAT III complexes concentration were independently associated with a shorter amniocentesis-to-delivery interval (hazard ratio, 1.5; 95% CI, 1.07-2.1); (4) among patients at term, those with IAI had a higher median AF TAT III complexes concentration than those without IAI, whether in labor or not in labor (p = 0.02); (5) there was no significant difference between the median AF TAT III complexes concentration of patients at term with and without labor; (6) patients who had a mid-trimester amniocentesis had a lower median AF TAT III complexes concentration than that of patients at term not in labor (p < 0.001). Conclusions. We present herein a distinct difference in the pattern of intra-amniotic thrombin generation between term and preterm parturition. PTL leading to preterm delivery is associated with an increased intra-amniotic thrombin generation regardless of the presence of IAI. In contrast, term delivery is associated with an increased intra-amniotic thrombin generation only in patients with IAI. C1 [Erez, Offer; Romero, Roberto; Vaisbuch, Edi; Chaiworapongsa, Tinnakorn; Kusanovic, Juan Pedro; Mazaki-Tovi, Shali; Gotsch, Francesca; Pacora, Percy; Edwin, Samuel S.; Kim, Chong Jai; Than, Nandor Gabor; Mittal, Pooja; Yeo, Lami; Dong, Zhong; Hassan, Sonia S.] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Erez, Offer] Wayne State Univ, NICHD, Perinatol Res Branch, NIH,DHHS,Hutzel Womens Hosp, Detroit, MI 48201 USA. [Erez, Offer; Romero, Roberto; Vaisbuch, Edi; Chaiworapongsa, Tinnakorn; Kusanovic, Juan Pedro; Mazaki-Tovi, Shali; Mittal, Pooja; Yeo, Lami; Hassan, Sonia S.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Romero, Roberto] Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI 48201 USA. [Gomez, Ricardo] Pontificia Univ Catolica Chile, Hosp Dr Sotero del Rio, Ctr Perinatal Diag & Res CEDIP, Puente Alto, Chile. [Maymon, Eli; Mazor, Moshe] Ben Gurion Univ Negev, Soroka Univ Med Ctr, Dept Obstet & Gynecol, Fac Hlth Sci, IL-84105 Beer Sheva, Israel. [Kim, Chong Jai] Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. [Yoon, Bo Hyun] Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul, South Korea. RP Erez, O (reprint author), Wayne State Univ, NICHD, Perinatol Res Branch, NIH,DHHS,Hutzel Womens Hosp, 3990 John R,Box 4, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu RI Yoon, Bo Hyun/H-6344-2011; OI Vaisbuch, Edi/0000-0002-8400-9031 FU Perinatology Research Branch, Division of Intramural Research; Eunice Kennedy Shriver National Institute of Child Health and Human Development; NIH; DHHS FX This research was supported (in part) by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. NR 162 TC 21 Z9 22 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2009 VL 22 IS 11 BP 971 EP 982 DI 10.3109/14767050902994762 PG 12 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 508NR UT WOS:000270939400002 PM 19900035 ER PT J AU Soto, E Romero, R Richani, K Yoon, BH Chaiworapongsa, T Vaisbuch, E Mittal, P Erez, O Gotsch, F Mazor, M Kusanovic, JP AF Soto, Eleazar Romero, Roberto Richani, Karina Yoon, Bo H. Chaiworapongsa, Tinnakorn Vaisbuch, Edi Mittal, Pooja Erez, Offer Gotsch, Francesca Mazor, Moshe Kusanovic, Juan P. TI Evidence for complement activation in the amniotic fluid of women with spontaneous preterm labor and intra-amniotic infection SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE C5a; C4a; C3a; anaphylatoxins; pregnancy; MIAC; chorioamnionitis; intra-amniotic inflammation; prematurity; complement ID ISCHEMIA-REPERFUSION INJURY; TUMOR-NECROSIS-FACTOR; RESPIRATORY BURST; HUMAN-NEUTROPHILS; HUMAN EOSINOPHILS; NEONATAL INFECTION; ANAPHYLATOXINS C3A; MONONUCLEAR-CELLS; GENE-EXPRESSION; C5A FORMATION AB Objective. The complement system plays an important role in host defense against infection. Concentrations of complement split products or anaphylatoxins (C3a, C4a, and C5a) in biological fluids are considered to reflect complement activation. The purpose of this study was to determine if term and preterm parturition are associated with evidence of complement activation in the amniotic fluid. Study design. Amniotic fluid (AF) samples were collected from 270 women in the following groups: (1) normal pregnant women in midtrimester (n - 70), (2) term not in labor (n - 23), (3) term in labor (n - 48), and (4) preterm labor (PTL) (n = 129). PTL was categorized into: (a) PTL without microbial invasion of the amniotic cavity (MIAC) who delivered at term (n = 42), (b) PTL who delivered preterm without MIAC (n = 57), and (c) PTL with MIAC (n = 30). C5a, C4a, and C3a concentrations in amniotic fluid were determined by ELISA. Nonparametric tests were used for statistical analysis. Results. (1) The median AF C5a concentration was higher in women at term than that of those in the midtrimester (p = 0.02); (2) Spontaneous labor at term was not associated with changes in AF concentrations of anaphylatoxins C3a, C4a, and C5a (all p > 0.05); (3) Among patients with PTL who delivered preterm, those with MIAC had higher AF C4a and C5a concentrations than those without infection (p < 0.01); and (4) AF C3a, C4a, and C5a concentrations were higher in patients with PTL with MIAC than in those with PTL without MIAC who delivered at term. Conclusion. Patients with spontaneous preterm labor and intact membranes with microbial invasion of the amniotic cavity had higher median amniotic fluid concentration of complement split products C3a, C4a, and C5a than patients without intra-amniotic infection. These findings suggest that preterm labor in the context of infection is associated with activation of the complement system. C1 [Romero, Roberto] Wayne State Univ, NICHD, Perinatol Res Branch, NIH,DHHS,Hutzel Womens Hosp, Detroit, MI 48201 USA. [Soto, Eleazar; Romero, Roberto; Richani, Karina; Chaiworapongsa, Tinnakorn; Vaisbuch, Edi; Mittal, Pooja; Erez, Offer; Gotsch, Francesca; Kusanovic, Juan P.] Hutzel Womens Hosp, NICHD, Perinatol Res Branch, NIH,DHHS, Bethesda, MD USA. [Soto, Eleazar; Romero, Roberto; Chaiworapongsa, Tinnakorn; Vaisbuch, Edi; Mittal, Pooja; Erez, Offer; Kusanovic, Juan P.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA. [Yoon, Bo H.] Seoul Natl Univ, Dept Obstet & Gynecol, Seoul, South Korea. [Mazor, Moshe] Ben Gurion Univ Negev, Dept Obstet & Gynecol, IL-84105 Beer Sheva, Israel. RP Romero, R (reprint author), Wayne State Univ, NICHD, Perinatol Res Branch, NIH,DHHS,Hutzel Womens Hosp, 3990 John R,Box 4, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu RI Yoon, Bo Hyun/H-6344-2011; OI Vaisbuch, Edi/0000-0002-8400-9031 FU Perinatology Research Branch; Division of Intramural Research; Eunice Kennedy Shriver National Institute of Child Health and Human Development; NIH; DHHS FX This research was supported (in part) by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. NR 90 TC 27 Z9 28 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2009 VL 22 IS 11 BP 983 EP 992 DI 10.3109/14767050902994747 PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 508NR UT WOS:000270939400003 PM 19900036 ER PT J AU Than, NG Romero, R Tarca, AL Draghici, S Erez, O Chaiworapongsa, T Kim, YM Kim, SK Vaisbuch, E Tromp, G AF Than, Nandor Gabor Romero, Roberto Tarca, Adi L. Draghici, Sorin Erez, Offer Chaiworapongsa, Tinnakorn Kim, Yeon Mee Kim, Sun Kwon Vaisbuch, Edi Tromp, Gerard TI Mitochondrial manganese superoxide dismutase mRNA expression in human chorioamniotic membranes and its association with labor, inflammation, and infection SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Review DE Fetal gender; gene expression; preterm delivery; preterm labor; preterm prelabor rupture of the membranes; reactive oxygen species; scavenger ID TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; PRETERM PREMATURE RUPTURE; HUMAN FETAL MEMBRANES; ANTIOXIDANT ENZYME EXPRESSION; AMNIOTIC-FLUID INTERLEUKIN-6; HYDROGEN-PEROXIDE PRODUCTION; PLACENTAL OXIDATIVE STRESS; ENDOMETRIAL STROMAL CELLS; REACTIVE OXYGEN AB Objective. Human parturition is characterized by the activation of genes involved in acute inflammatory responses in the fetal membranes. Manganese superoxide dismutase (Mn SOD) is a mitochondrial enzyme that scavenges reactive oxygen species (ROS). Mn SOD is up-regulated in sites of inflammation and has an important role in the down-regulation of acute inflammatory processes. Therefore, the aim of this study was to determine the differences in Mn SOD mRNA expression in the fetal membranes in patients with term and preterm labor (PTL) as well as in acute chorioamnionitis. Study design. Fetal membranes were obtained from patients in the following groups: (1) term not in labor (n = 29); (2) term in labor (n = 29); (3) spontaneous PTL with intact mebranes (n = 16); (4) PTL with histological chorioamnionitis (n = 12); (5) preterm prelabor rupture of the membranes (PPROM; n = 17); and (6) PPROM with histological chorioamnionitis (n = 21). Mn SOD mRNA expression in the membranes was determined by quantitative real-time reverse transcription-polymerase chain reaction. Results. (1) Mn SOD mRNA expression was higher in the fetal membranes of patients at term in labor than those not in labor (2.4-fold; p = 0.02); (2) the amount of Mn SOD mRNA in the fetal membranes was higher in PTL than in term labor or in PPROM (7.2-fold, p = 0.03; 3.2-fold, p = 0.03, respectively); (3) Mn SOD mRNA expression was higher when histological chorioamnionitis was present both among patients with PPROM (3.8-fold, p = 0.02) and with PTL (5.4-fold, p = 0.02) than in patients with these conditions without histological chorioamnionitis; (4) expression of Mn SOD mRNA was higher in PTL with chorioamnionitis than in PPROM with chorioamnionitis (4.3-fold, p = 0.03). Conclusion. The increase in Mn SOD mRNA expression by fetal membranes in term labor and in histological chorioamnionitis in PTL and PPROM suggests that the fetus deploys anti-oxidant mechanisms to constrain the inflammatory processes in the chorioamniotic membranes. C1 [Romero, Roberto] Wayne State Univ, NICHD, Perinatol Res Branch, NIH,DHHS,Hutzel Womens Hosp, Detroit, MI 48201 USA. [Romero, Roberto; Erez, Offer; Chaiworapongsa, Tinnakorn; Vaisbuch, Edi] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Romero, Roberto; Tarca, Adi L.; Tromp, Gerard] Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI 48201 USA. [Tarca, Adi L.; Draghici, Sorin] Wayne State Univ, Sch Med, Dept Comp Sci, Detroit, MI 48201 USA. RP Romero, R (reprint author), Wayne State Univ, NICHD, Perinatol Res Branch, NIH,DHHS,Hutzel Womens Hosp, 3990 John R,Box 4, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu RI Draghici, Sorin/B-3074-2013; Tromp, Gerard/B-2677-2017; OI Draghici, Sorin/0000-0002-0786-8377; Tromp, Gerard/0000-0002-7761-0806; Vaisbuch, Edi/0000-0002-8400-9031 FU Perinatology Research Branch; Division of Intramural Research; Eunice Kennedy Shriver National Institute of Child Health and Human Development; NIH; DHHS FX This research was supported (in part) by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. The authors acknowledge the Lark Technologies, Inc. (Houston, TX) for performing the qRT-PCR experiments. They appreciate the invaluable contributions of Sandy Field, Gerardo Rodriguez and the nursing staff of the Perinatology Research Branch and the Detroit Medical Center for this manuscript. They thank Sara Tipton for her critical reading of the manuscript. NR 145 TC 24 Z9 24 U1 0 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2009 VL 22 IS 11 BP 1000 EP 1013 DI 10.3109/14767050903019676 PG 14 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 508NR UT WOS:000270939400005 PM 19900038 ER PT J AU Kusanovic, JP Romero, R Chaiworapongsa, T Erez, O Mittal, P Vaisbuch, E Mazaki-Tovi, S Gotsch, F Edwin, SS Gomez, R Yeo, L Conde-Agudelo, A Hassan, SS AF Kusanovic, Juan Pedro Romero, Roberto Chaiworapongsa, Tinnakorn Erez, Offer Mittal, Pooja Vaisbuch, Edi Mazaki-Tovi, Shali Gotsch, Francesca Edwin, Samuel S. Gomez, Ricardo Yeo, Lami Conde-Agudelo, Agustin Hassan, Sonia S. TI A prospective cohort study of the value of maternal plasma concentrations of angiogenic and anti-angiogenic factors in early pregnancy and midtrimester in the identification of patients destined to develop preeclampsia SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Review DE Angiogenic factors; anti-angiogenic state; sFlt-1; sVEGFR-1; PlGF; placental growth factor; sEng; soluble Endoglin; vascular endothelial growth factor; prediction; cohort study; uterine artery Doppler velocimetry; early-onset preeclampsia ID UTERINE ARTERY DOPPLER; ENDOTHELIAL GROWTH-FACTOR; FOR-GESTATIONAL-AGE; BED SPIRAL ARTERIES; CIRCULATING ANTIANGIOGENIC FACTORS; FACTOR RECEPTOR-1 CONCENTRATION; UTEROPLACENTAL BLOOD-FLOW; FETAL-GROWTH; PLACENTAL BED; TYROSINE KINASE-1 AB Objective. Changes in the maternal plasma concentrations of angiogenic (placental growth factor (PlGF) and vascular endothelial growth factor (VEGF)) and anti-angiogenic factors (sEng and vascular endothelial growth factor receptor-1 (sVEGFR-1)) precede the clinical presentation of preeclampsia. This study was conducted to examine the role of maternal plasma PlGF, sEng, and sVEGFR-1 concentrations in early pregnancy and midtrimester in the identification of patients destined to develop preeclampsia. Methods. This longitudinal cohort study included 1622 consecutive singleton pregnant women. Plasma samples were obtained in early pregnancy (6-15 weeks) and midtrimester (20-25 weeks). Maternal plasma PlGF, sEng, and sVEGFR-1 concentrations were determined using sensitive and specific immunoassays. The primary outcome was the development of preeclampsia. Secondary outcomes included term, preterm, and early-onset preeclampsia. Receiving operating characteristic curves, sensitivity, specificity, positive and negative likelihood ratios, and multivariable logistic regression were applied. A p-value of 50.05 was considered significant. Results. (1) The prevalence of preeclampsia, term, preterm, (537 weeks) and early-onset preeclampsia (534 weeks) was 3.8 (62/1622), 2.5 (40/1622), 1.4 (22/1622) and 0.6% (9/1622), respectively; (2) Higher likelihood ratios were provided by ratios of midtrimester plasma concentrations of PlGF, sEng, and sVEGFR-1 than single analytes; (3) Individual angiogenic and anti-angiogenic factors did not perform well in the identification of preeclampsia as a whole; in particular, they perform poorly in the prediction of term preeclampsia; (4) In contrast, a combination of these analytes such as the PlGF/sEng ratio, its delta and slope had the best predictive performance with a sensitivity of 100%, a specificity of 98-99%, and likelihood ratios for a positive test of 57.6, 55.6 and 89.6, respectively, for predicting early-onset preeclampsia. Conclusions. (1) The PlGF/sEng ratio and its delta and slope had an excellent predictive performance for the prediction of early-onset preeclampsia, with very high likelihood ratios for a positive test result and very low likelihood ratios for a negative test result; and (2) Although the positive likelihood ratios are high and the positive predictive values low, the number of patients needed to be closely followed is 4:1 for the PlGF/sEng ratio and 3:1 for the slope of PlGF/sEng. C1 [Romero, Roberto] Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, Detroit, MI 48201 USA. [Kusanovic, Juan Pedro; Romero, Roberto; Chaiworapongsa, Tinnakorn; Erez, Offer; Mittal, Pooja; Vaisbuch, Edi; Mazaki-Tovi, Shali; Gotsch, Francesca; Edwin, Samuel S.; Yeo, Lami; Conde-Agudelo, Agustin; Hassan, Sonia S.] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Kusanovic, Juan Pedro; Romero, Roberto; Chaiworapongsa, Tinnakorn; Erez, Offer; Mittal, Pooja; Vaisbuch, Edi; Mazaki-Tovi, Shali; Yeo, Lami; Hassan, Sonia S.] Wayne State Univ, Hutzel Hosp, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA. [Gomez, Ricardo] Pontificia Univ Catolica Chile, Sotero del Rio Hosp, CEDIP Ctr Perinatal Diag & Res, Dept Obstet & Gynecol, Santiago, Chile. RP Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, 3990 John R,Box 4, Detroit, MI 48201 USA. EM jkusanov@med.wayne.edu; prbchiefstaff@med.wayne.edu FU Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development; NIH; DHHS FX This research was supported (in part) by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. NR 154 TC 143 Z9 154 U1 0 U2 12 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2009 VL 22 IS 11 BP 1021 EP 1038 DI 10.3109/14767050902994754 PG 18 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 508NR UT WOS:000270939400007 PM 19900040 ER PT J AU Erez, O Romero, R Tarca, AL Chaiworapongsa, T Kim, YM Than, NG Vaisbuch, E Draghici, S Tromp, G AF Erez, Offer Romero, Roberto Tarca, Adi L. Chaiworapongsa, Tinnakorn Kim, Yeon Mee Than, Nandor Gabor Vaisbuch, Edi Draghici, Sorin Tromp, Gerard TI Differential expression pattern of genes encoding for anti-microbial peptides in the fetal membranes of patients with spontaneous preterm labor and intact membranes and those with preterm prelabor rupture of the membranes SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Review DE Human neutrophil peptide; alpha-defensin; beta-defensin; calgranulin; calprotectin; granulysin; preterm prelabour rupture of membranes; spontaneous preterm delivery ID HUMAN BETA-DEFENSINS; HIGH-DIMENSIONAL BIOLOGY; INNATE IMMUNE-SYSTEM; CERVICAL-MUCUS PLUG; AMNIOTIC-FLUID; IN-VITRO; ADAPTIVE IMMUNITY; EPITHELIAL-CELLS; HOST-DEFENSE; ANTIBACTERIAL PROPERTIES AB Objective. Increased amniotic fluid concentrations of anti-microbial peptides, components of the innate immune system, have been reported in patients with preterm labor (PTL) with intact membranes and intra-amniotic infection and/or inflammation (IAI), as well as in patients with preterm prelabor rupture of the membranes (PPROM). This study was designed to confirm these results using a targeted approach, detecting DEFA1, DEFB1, GNLY, and S100A9 gene expression in the choriamniotic membranes in pregnancies complicated with PTL and intact membranes or PPROM, with and without histologic chorioamnionitis. Study design. Human fetal membranes were obtained from patients in the following groups: (1) PTL with intact membranes (n = 15); (2) PTL with intact membranes with histologic chorioamnionitis (n = 12); (3) PPROM (n = 17); and (4) PPROM with histologic chorioamnionitis (n = 21). The mRNA expression of alpha-defensin-1, beta-defensin-1, calgranulin B and granulysin in the fetal membranes was determined by qRT-PCR. Results. (1) The expression of alpha-defensin-1 mRNA in the fetal membranes was higher in patients with PTL and intact membranes with histologic chorioamnionitis, than those without chorioamnionitis (19.4-fold, p<0.001); (2) Among patients with histologic chorioamnionitis, patients with PTL and intact membranes had a higher alpha-defensin-1 mRNA expression than those with PPROM (5.5-fold, p = 0.003); (3) Histologic chorioamnionitis was associated with a higher calgranulin B mRNA expression in the chorioamniotic membranes of patients with both PTL and intact membranes (7.9-fold, p = 0.03) and PPROM (7.6-fold, p<0.0001); (4) The expression of calgranulin B mRNA in the fetal membranes was higher in patients with PTL and intact membranes without histologic chorioamnionitis than in those with PPROM without histologic chorioamnionitis (2.7-fold, p = 0.03); (5) There were no differences in the expression of beta-defensin-1 and granulysin in the chorioamniotic membranes between the study groups even in the presence of histologic chorioamnioniotis. Conclusions. (1) Among patients with histologic chorioamnionitis, the mRNA expression of alpha-defensin-1 and calgranulin B in the fetal membranes of patients with PTL and intact membranes as well as that of calgranulin B in the fetal membranes of patients with PPROM is higher than in the membranes of those without histologic chorioamnionitis; (2) histologic chorioamnionitis is associated with differences in the pattern of alpha-defensin-1 mRNA expression in the fetal membranes in patients with PTL and intact membranes and those with PPROM. C1 [Erez, Offer; Romero, Roberto; Chaiworapongsa, Tinnakorn; Vaisbuch, Edi] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Romero, Roberto; Tromp, Gerard] Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI 48201 USA. [Tarca, Adi L.; Draghici, Sorin] Wayne State Univ, Dept Comp Sci, Detroit, MI 48201 USA. [Romero, Roberto] Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch, NICHD,NIH,DHHS, Detroit, MI 48201 USA. RP Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch, NICHD,NIH,DHHS, 3990 John R,Box 4, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu RI Draghici, Sorin/B-3074-2013; Tromp, Gerard/B-2677-2017; OI Draghici, Sorin/0000-0002-0786-8377; Tromp, Gerard/0000-0002-7761-0806; Vaisbuch, Edi/0000-0002-8400-9031 FU Intramural NIH HHS [ZIA HD002401-17] NR 134 TC 20 Z9 20 U1 0 U2 5 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2009 VL 22 IS 12 BP 1103 EP 1115 DI 10.3109/14767050902994796 PG 13 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 529EC UT WOS:000272497700001 PM 19916708 ER PT J AU Chaiworapongsa, T Romero, R Tarca, A Kusanovic, JP Mittal, P Kim, SK Gotsch, F Erez, O Vaisbuch, E Mazaki-Tovi, S Pacora, P Ogge, G Dong, Z Kim, CJ Yeo, L Hassan, SS AF Chaiworapongsa, Tinnakorn Romero, Roberto Tarca, Adi Kusanovic, Juan Pedro Mittal, Pooja Kim, Sun Kwon Gotsch, Francesca Erez, Offer Vaisbuch, Edi Mazaki-Tovi, Shali Pacora, Percy Ogge, Giovanna Dong, Zhong Kim, Chong Jai Yeo, Lami Hassan, Sonia S. TI A subset of patients destined to develop spontaneous preterm labor has an abnormal angiogenic/anti-angiogenic profile in maternal plasma: Evidence in support of pathophysiologic heterogeneity of preterm labor derived from a longitudinal study SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Review DE Preterm labor; preterm parturition; endoglin; VEGFR-1; VEGFR-2; PlGF; angiogenesis; longitudinal study; prematurity; placenta ID ENDOTHELIAL-GROWTH-FACTOR; CORTICOTROPIN-RELEASING HORMONE; FOR-GESTATIONAL-AGE; INTERLEUKIN-1 RECEPTOR ANTAGONIST; ULTRASONOGRAPHIC CERVICAL LENGTH; PREGNANT HUMAN MYOMETRIUM; AMNIOTIC-FLUID INFECTION; LATE-ONSET PREECLAMPSIA; UTERINE ARTERY DOPPLER; SOLUBLE ENDOGLIN AB Objective. An imbalance between angiogenic and anti-angiogenic factors in maternal blood has been observed in several obstetrical syndromes including preeclampsia, pregnancies with fetal growth restriction and fetal death. Vascular lesions have been identified in a subset of patients with spontaneous preterm labor (PTL). It is possible that PTL may be one of the manifestations of an anti-angiogenic state. The aim of this study was to determine if patients prior to the clinical diagnosis of PTL leading to preterm delivery had plasma concentrations of angiogenic and anti-angiogenic factors different from normal pregnant women. Study Design. This longitudinal nested case-control study included normal pregnant women (n = 208) and patients with PTL leading to preterm delivery (n = 52). Maternal blood samples were collected at 6 gestational age intervals from 6 to 36.9 weeks of gestation. The end point (time of diagnosis) of the study, 'True PTL', was defined as patients presenting with PTL and delivered within 1 day. Plasma concentrations of sVEGFR-1, sVEGFR-2, sEng and PlGF were determined by ELISA. Analysis was performed with both cross-sectional and longitudinal (mixed effects model) approaches. Results. (1) Plasma sEng concentration in patients destined to develop PTL was higher than that in normal pregnant women from 15-20 weeks of gestation. The difference became statistical significant at 28 weeks of gestation, or approximately 5-10 weeks prior to the diagnosis of 'true PTL'. (2) Backward analysis suggests that plasma concentrations of PlGF and sVEGFR-2 were lower, and those of sVEGFR-1 were higher in patients with PTL than in normal pregnant women less than 5 weeks prior to the diagnosis of 'true PTL'; and (3) Plasma concentrations of sEng and sVEGFR-1 were higher and those of PlGF and sVEGFR-2 were lower in patients diagnosed with PTL and delivery within 1 day than in normal pregnant women who delivered at term. Conclusion. The changes in sEng are demonstrable several weeks prior to the onset of preterm parturition. In contrast, the changes in the other angiogenic proteins are present close to the onset of PTL and delivery. This observation supports the view that an imbalance of angiogenic factors participates in the pathophysiology of spontaneous preterm parturition. C1 [Romero, Roberto] Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch, NICHD,NIH,DHHS, Detroit, MI 48201 USA. [Chaiworapongsa, Tinnakorn; Romero, Roberto; Kusanovic, Juan Pedro; Mittal, Pooja; Erez, Offer; Vaisbuch, Edi; Mazaki-Tovi, Shali; Yeo, Lami; Hassan, Sonia S.] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA. [Tarca, Adi] Wayne State Univ, Dept Comp Sci, Detroit, MI 48201 USA. [Kim, Chong Jai] Wayne State Univ, Dept Pathol, Detroit, MI 48201 USA. RP Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch, NICHD,NIH,DHHS, 3990 John R,Box 4, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu RI Ogge, Giovanna/G-6109-2011; OI Vaisbuch, Edi/0000-0002-8400-9031 FU Perinatology Research Branch; Division of Intramural Research; Eunice Kennedy Shriver National Institute of Child Health and Human Development; NIH; DHHS FX This research was supported (in part) by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. NR 129 TC 41 Z9 41 U1 1 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2009 VL 22 IS 12 BP 1122 EP 1139 DI 10.3109/14767050902994838 PG 18 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 529EC UT WOS:000272497700003 PM 19916710 ER PT J AU Kusanovic, JP Romero, R Jodicke, C Mazaki-Tovi, S Vaisbuch, E Erez, O Mittal, P Gotsch, F Chaiworapongsa, T Edwin, SS Pacora, P Hassan, SS AF Kusanovic, Juan Pedro Romero, Roberto Jodicke, Cristiano Mazaki-Tovi, Shali Vaisbuch, Edi Erez, Offer Mittal, Pooja Gotsch, Francesca Chaiworapongsa, Tinnakorn Edwin, Sam S. Pacora, Percy Hassan, Sonia S. TI Amniotic fluid soluble human leukocyte antigen-G in term and preterm parturition, and intra-amniotic infection/inflammation SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Review DE sHLA-G; preterm labor; preterm delivery; preterm prelabor rupture of membranes; pregnancy; amniocentesis; microbial invasion of the amniotic cavity; chorioamnionitis ID HLA-G EXPRESSION; NATURAL-KILLER-CELLS; FETAL INFLAMMATORY RESPONSE; CLASS-I GENE; RECURRENT SPONTANEOUS-ABORTIONS; INTRAUTERINE GROWTH-RETARDATION; VITRO FERTILIZED EMBRYOS; G PROTEIN CONCENTRATIONS; NECROSIS-FACTOR-ALPHA; CD4(+) T-CELLS AB Objective. Circulating soluble human leukocyte antigen-G (sHLA-G) has been associated with pregnancy complications, and determination of sHLA-G concentrations in amniotic fluid (AF) has been reported in normal pregnancies. Our aim was to determine if the AF concentrations of sHLA-G change with advancing gestation, spontaneous labor at term, and in patients with spontaneous preterm labor (PTL) with intact membranes, as well as in those with preterm prelabor rupture of membranes (PROM), in the presence or absence of intra-amniotic infection/inflammation (IAI). Study design. This cross-sectional study included the following groups: (1) mid-trimester (n = 55); (2) normal pregnancy at term with (n = 50) and without (n = 50) labor; (3) spontaneous PTL with intact membranes divided into: (a) PTL who delivered at term (n = 153); (b) PTL who delivered preterm without IAI (n = 108); and (c) PTL with IAI (n = 84); and (4) preterm PROM with (n = 46) and without (n = 44) IAI. sHLA-G concentrations were determined by ELISA. Nonparametric statistics were used for analysis. Results. (1) Among patients with PTL, the median AF sHLA-G concentration was higher in patients with IAI than in those without IAI or women that delivered at term (p<0.001 for both comparisons); (2) Similarly, patients with preterm PROM and IAI had higher median AF sHLA-G concentrations than those without IAI (p < 0.004); (3) Among patients with PTL and delivery, those with histologic chorioamnionitis and/or funisitis had a higher median AF sHLA-G concentration than those without histologic inflammation (p<0.001); and (4) The median AF sHLA-G concentration did not change with advancing gestational age. Conclusions. AF sHLA-G concentrations are elevated in preterm parturition associated to IAI as well as in histologic chorioamnionitis. We propose that sHLA-G may participate in the regulation of the host immune response against intra-amniotic infection. C1 [Romero, Roberto] Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch, NICHD,NIH,DHHS, Detroit, MI 48201 USA. [Kusanovic, Juan Pedro; Romero, Roberto; Jodicke, Cristiano; Mazaki-Tovi, Shali; Vaisbuch, Edi; Erez, Offer; Mittal, Pooja; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA. [Kusanovic, Juan Pedro; Romero, Roberto; Jodicke, Cristiano; Mazaki-Tovi, Shali; Vaisbuch, Edi; Erez, Offer; Mittal, Pooja; Gotsch, Francesca; Chaiworapongsa, Tinnakorn; Edwin, Sam S.; Pacora, Percy; Hassan, Sonia S.] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. RP Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch, NICHD,NIH,DHHS, 3990 John R,Box 4, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu OI Vaisbuch, Edi/0000-0002-8400-9031 FU Perinatology Research Branch; Division of Intramural Research; Eunice Kennedy Shriver National Institute of Child Health and Human Development; NIH; DHHS FX This research was supported by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. The authors acknowledge the contribution of Dr. Carole Ober in the conduction of this work. NR 203 TC 19 Z9 19 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2009 VL 22 IS 12 BP 1151 EP 1166 DI 10.3109/14767050903019684 PG 16 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 529EC UT WOS:000272497700006 PM 19916713 ER PT J AU Mittal, P Romero, R Mazaki-Tovi, S Tromp, G Tarca, AL Kim, YM Chaiworapongsa, T Kusanovic, JP Erez, O Than, NG Hassan, SS AF Mittal, Pooja Romero, Roberto Mazaki-Tovi, Shali Tromp, Gerard Tarca, Adi L. Kim, Yeon Mee Chaiworapongsa, Tinnakorn Kusanovic, Juan Pedro Erez, Offer Than, Nandor Gabor Hassan, Sonia S. TI Fetal membranes as an interface between inflammation and metabolism: Increased Aquaporin 9 expression in the presence of spontaneous labor at term and chorioamnionitis SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE Aquaporin 9; water channels; pregnancy; parturition; preterm prelabor rupture of membranes; premature birth; intra-amniotic infection/inflammation; metabolism; chorioamniotic membranes; PCR; microarray ID AMNIOTIC-FLUID VOLUME; FREE FATTY-ACIDS; PRETERM PARTURITION; WATER CHANNELS; INTRAMEMBRANOUS ABSORPTION; CATECHOLAMINERGIC NEURONS; INTRAUTERINE INFECTION; NORMAL-PREGNANCY; GENE-EXPRESSION; AQP9 AB Objective. Aquaporin 9 (AQP9) is a water channel protein characterized by its high permeability to nutrients such as lactate and glycerol, as well as urea and other small solutes. These unique properties of AQP9 suggest that this molecule may play a role in the modulation of nutrient flux through the fetal membranes in conditions associated with increased metabolic demand, such as spontaneous labor and inflammation. The objective of this study was to determine the expression of AQP9 in the chorioamniotic membranes from women with and without term labor, as well as those with preterm prelabor rupture of membranes (PPROM) with and without histologic chorioamnionitis. Study design. A cross-sectional study was performed which included patients in the following groups: (1) term not in labor (TNL; n = 14); (2) term, spontaneous labor (n = 14); and (3) PPROM with (n = 20) and without (n = 17) histologic chorioamnionitis. AQP9 mRNA expression in fetal membranes was quantified using quantitative real-time reverse transcription-polymerase chain reaction and analyzed with a linear model including gestational age as a covariate. Results. (1) AQP9 mRNA expression was identified in all chorioamniotic membrane specimens; (2) AQP9 expression in fetal membranes was significantly higher in spontaneous term labor when compared with TNL (fold change 3.6; p = 0.01); and (3) Among patients with PPROM, the presence of histologic chorioamnionitis was associated with a higher expression of AQP9 in the chorioamniotic membranes compared with those from women without histologic chorioamnionitis (fold change 8.7; p<0.001). Conclusion. Aquaporin 9 mRNA expression is higher in the fetal membranes from patients with spontaneous term labor and those with PPROM and histologic chorioamnionitis. These findings are novel, and suggest a role for aquaporin 9 in membrane-mediated transfer of nutrients to support the increased metabolic demands associated with the host immune response of the terminal pathway of parturition and histologic chorioamnionitis. C1 [Mittal, Pooja] Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch, NICHD,NIH,DHHS, Detroit, MI 48201 USA. [Mittal, Pooja; Romero, Roberto; Mazaki-Tovi, Shali; Chaiworapongsa, Tinnakorn; Kusanovic, Juan Pedro; Erez, Offer; Hassan, Sonia S.] Wayne State Univ, Dept Obstet & Gynecol, Sch Med, Detroit, MI 48201 USA. [Romero, Roberto; Tromp, Gerard; Tarca, Adi L.] Wayne State Univ, Ctr Mol Med & Genet, Sch Med, Detroit, MI 48201 USA. [Tarca, Adi L.] Wayne State Univ, Dept Comp Sci, Sch Med, Detroit, MI 48201 USA. RP Mittal, P (reprint author), Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch, NICHD,NIH,DHHS, 3990 John R,Box 4, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu RI Tromp, Gerard/B-2677-2017 OI Tromp, Gerard/0000-0002-7761-0806 FU Perinatology Research Branch; Division of Intramural Research; Eunice Kennedy Shriver National Institute of Child Health and Human Development; NIH; DHHS FX This research was supported (in part) by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. The authors would like to acknowledge the invaluable contributions of the nursing staff of the Perinatology Research Branch and Hutzel Women's Hospital to this manuscript. NR 61 TC 13 Z9 13 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1476-7058 EI 1476-4954 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2009 VL 22 IS 12 BP 1167 EP 1175 DI 10.3109/14767050903019692 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 529EC UT WOS:000272497700007 PM 19916714 ER PT J AU Rid, A Biller-Andorno, N AF Rid, Annette Biller-Andorno, Nikola TI Justice in action? Introduction to the minisymposium on Norman Daniels' Just health: meeting health needs fairly SO JOURNAL OF MEDICAL ETHICS LA English DT Editorial Material C1 [Rid, Annette] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA. [Biller-Andorno, Nikola] Univ Zurich, Inst Biomed Eth, Zurich, Switzerland. RP Rid, A (reprint author), NIH, Dept Bioeth, Ctr Clin, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM shulzbaldesa@cc.nih.gov NR 7 TC 1 Z9 1 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0306-6800 J9 J MED ETHICS JI J. Med. Ethics PD JAN PY 2009 VL 35 IS 1 BP 1 EP 2 DI 10.1136/jme.2008.025783 PG 2 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 387CM UT WOS:000261929300001 PM 19103933 ER PT J AU Rid, A AF Rid, A. TI Justice and procedure: how does "accountability for reasonableness'' result in fair limit-setting decisions? SO JOURNAL OF MEDICAL ETHICS LA English DT Article ID MANAGED CARE; LEGITIMACY AB Norman Daniels' theory of justice and health faces a serious practical problem: his theory can ground the special moral importance of health and allows distinguishing just from unjust health inequalities, but it provides little practical guidance for allocating resources when they are especially scarce. Daniels' solution to this problem is a fair process that he specifies as "accountability for reasonableness''. Daniels claims that accountability for reasonableness makes limit-setting decisions in healthcare not only legitimate, but also fair. This paper assesses the latter claim. Does accountability for reasonableness result in fair limit-setting decisions? It is argued that the answer to this question is not a clear yes. Daniels is remarkably unclear about the criterion of fairness that accountability for reasonableness satisfies. The paper discusses different options for resolving this lack of clarity and examines how they apply to Daniels' accountability for reasonableness framework. It is concluded, first, that accountability for reasonableness is not a paradigm case of any of the classic notions of procedural justice; second, that what might be called "constrained pure procedural justice'' best reflects how accountability for reasonableness results in fair limit-setting decisions; and third, that the procedural conditions of accountability for reasonableness must be further specified and amended to better achieve a fair process, and hence fair limit-setting decisions. C1 NIH, Dept Bioeth, Ctr Clin, Inst Biomed Eth, Bethesda, MD 20892 USA. RP Rid, A (reprint author), NIH, Dept Bioeth, Ctr Clin, Inst Biomed Eth, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM schulzbaldesa@cc.nih.gov FU Swiss National Science Foundation FX This work was completed with financial support from the Swiss National Science Foundation. NR 12 TC 22 Z9 22 U1 1 U2 4 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0306-6800 J9 J MED ETHICS JI J. Med. Ethics PD JAN PY 2009 VL 35 IS 1 BP 12 EP 16 DI 10.1136/jme.2008.024430 PG 5 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 387CM UT WOS:000261929300004 PM 19103936 ER PT J AU Xu, JL Prorok, PC AF Xu, Jian-Lun Prorok, Philip C. TI On testing independence of repeated screening tests SO JOURNAL OF MEDICAL SCREENING LA English DT Letter ID FALSE-POSITIVE TEST; CUMULATIVE RISK; PROGRAM C1 [Xu, Jian-Lun; Prorok, Philip C.] NCI, Bethesda, MD 20892 USA. RP Xu, JL (reprint author), NCI, EPN-3131,6130 Execut Blvd,MSC 7354, Bethesda, MD 20892 USA. EM jianxu@helix.nih.gov NR 8 TC 1 Z9 1 U1 0 U2 0 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 0969-1413 J9 J MED SCREEN JI J. Med. Screen. PY 2009 VL 16 IS 1 BP 50 EP 50 DI 10.1258/jms.2009.008099 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 446ID UT WOS:000266114400011 PM 19349533 ER PT J AU Hofvind, S Yankaskas, BC Bulliard, JL Klabunde, CN Fracheboud, J AF Hofvind, Solveig Yankaskas, Bonnie C. Bulliard, Jean-Luc Klabunde, Carrie N. Fracheboud, Jacques TI Comparing interval breast cancer rates in Norway and North Carolina: results and challenges SO JOURNAL OF MEDICAL SCREENING LA English DT Article ID INDEPENDENT DOUBLE INTERPRETATION; MAMMOGRAPHY SCREENING-PROGRAMS; QUALITY ASSURANCE; PERFORMANCE; SURVIVAL; COUNTRIES; SWEDEN; WOMEN AB Objective To compare interval breast cancer rates (ICR) between a biennial organized screening programme in Norway and annual opportunistic screening in North Carolina (NC) for different conceptualizations of interval cancer. Setting Two regions with different screening practices and performance. Methods 620,145 subsequent screens (1996-2002) performed in women aged 50-69 and 1280 interval cancers were analysed. Various definitions and quantification methods for interval cancers were compared. Results ICR for one year follow-up were lower in Norway compared with NC both when the rate was based on all screens (0.54 versus 1.29 per 1000 screens), negative final assessments (0.54 versus 1.29 per 1000 screens), and negative screening assessments (0.53 versus 1.28 per 1000 screens). The rate of ductal carcinoma in situ was significantly lower in Norway than in NC for cases diagnosed in both the first and second year after screening. The distributions of histopathological tumour size and lymph node involvement in invasive cases did not differ between the two regions for interval cancers diagnosed during the first year after screening. In contrast, in the second year after screening, tumour characteristics remained stable in Norway but became prognostically more favorable in NC. Conclusion Even when applying a common set of definitions of interval cancer, the ICR was lower in Norway than in NC. Different definitions of interval cancer did not influence the ICR within Norway or NC. Organization of screening and screening performance might be major contributors to the differences in ICR between Norway and NC. C1 [Hofvind, Solveig] Canc Registry Norway, Dept Screening Based Res, N-0304 Oslo, Norway. [Yankaskas, Bonnie C.] Univ N Carolina, Dept Radiol, Chapel Hill, NC 27599 USA. [Bulliard, Jean-Luc] Univ Inst Social & Prevent Med, Canc Epidemiol Unit, Lausanne, Switzerland. [Klabunde, Carrie N.] NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Fracheboud, Jacques] Univ Med Ctr Rotterdam, Erasmus MC, Dept Publ Hlth, NETB, Rotterdam, Netherlands. RP Hofvind, S (reprint author), Canc Registry Norway, Dept Screening Based Res, NO-0310 Oslo, Norway. EM solveig.hofvind@kreftregisteret.no FU National Cancer Institute [U01-CA70040]; North Carolina Central Cancer Registry [NC U58 DP000123-02] FX The CMR is supported by a grant from the National Cancer Institute, U01-CA70040. The collection of cancer incidence data was in part, supported by the North Carolina Central Cancer Registry which is partially supported by the Centers for Disease Control and Prevention under cooperative agreement NC U58 DP000123-02. The content of this publication is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the Centers for Disease Control and Prevention. NR 29 TC 10 Z9 10 U1 0 U2 0 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 0969-1413 J9 J MED SCREEN JI J. Med. Screen. PY 2009 VL 16 IS 3 BP 131 EP 139 DI 10.1258/jms.2009.009012 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 518FS UT WOS:000271676700005 PM 19805754 ER PT J AU Taylor, K Notkins, AL AF Taylor, Keith Notkins, Abner Louis TI Virus Triggers in Type 1 Diabetes in Children: Reports of an International Meeting, Held in London, October 5, 2007 SO JOURNAL OF MEDICAL VIROLOGY LA English DT Editorial Material C1 [Taylor, Keith] Royal London Hosp, London E1 1BB, England. [Notkins, Abner Louis] NIH, Bethesda, MD 20892 USA. RP Taylor, K (reprint author), Ctr Diabet & Metab Med, Barts & London Sch Med & Dent, Inst Cell & Mol Sci, Blizard Bldg,4 Newark St, London E1 2AT, England. EM kwt@ryebay.fsnet.co.uk NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD JAN PY 2009 VL 81 IS 1 BP 193 EP 193 DI 10.1002/jmv.21358 PG 1 WC Virology SC Virology GA 377QU UT WOS:000261266500025 ER PT J AU Newman, JD Harris, JC AF Newman, John D. Harris, James C. TI The Scientific Contributions of Paul D. MacLean (1913-2007) SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Biographical-Item DE Limbic system; triune brain AB Paul D. MacLean, a leading brain scientist of the 20th century, died on December 26, 2007. We review his life as a scientist and highlight some of his most important research contributions. C1 [Newman, John D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Comparat Ethol Lab, NIH, Poolesville, MD 20837 USA. [Harris, James C.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Harris, James C.] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA. RP Newman, JD (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Comparat Ethol Lab, NIH, Poolesville, MD 20837 USA. EM newmanj@lce.nichd.nih.gov FU Intramural NIH HHS NR 1 TC 4 Z9 4 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD JAN PY 2009 VL 197 IS 1 BP 3 EP 5 DI 10.1097/NMD.0b013e31818ec5d9 PG 3 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 394KS UT WOS:000262446200001 PM 19155803 ER PT J AU Rath, MF Bailey, MJ Kim, JS Coon, SL Klein, DC Moller, M AF Rath, Martin F. Bailey, Michael J. Kim, Jong-So Coon, Steven L. Klein, David C. Moller, Morten TI Developmental and daily expression of the Pax4 and Pax6 homeobox genes in the rat retina: localization of Pax4 in photoreceptor cells SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE Pax4; Pax6; retina; development; diurnal rhythm ID PINEAL-GLAND; N-ACETYLTRANSFERASE; MESSENGER-RNA; TRANSCRIPTIONAL REPRESSOR; FATE DETERMINATION; OPSIN EXPRESSION; MAMMALIAN RETINA; DIFFERENTIATION; BETA; OTX2 AB Pax4 is a homeobox gene encoding Pax4, a transcription factor that is essential for embryonic development of the endocrine pancreas. In the pancreas, Pax4 counters the effects of the related transcription factor, Pax6, which is known to be essential for eye morphogenesis. In this study, we have discovered that Pax4 is strongly expressed in retinal photoreceptors of the rat. Pax4 expression is not detectable in the foetal eye; however, postnatal Pax4 transcript levels rapidly increase. In contrast, Pax6 exhibits an inverse developmental pattern of expression being more strongly expressed in the foetal eye. Histological analysis revealed that Pax4 mRNA is exclusively expressed in the retinal photoreceptors, whereas Pax6 mRNA and protein are present in the inner nuclear layer and in the ganglion cell layer of the mature retina. In the adult retina, Pax4 transcripts exhibit a diurnal rhythm with maximal levels occurring during the light period, whereas retinal Pax6 transcript levels do not change throughout the day. The daily changes in Pax4 expression may contribute to daily changes in function in the differentiated retinal photoreceptor. C1 [Rath, Martin F.; Moller, Morten] Univ Copenhagen, Panum Inst, Dept Neurosci & Pharmacol, DK-2200 Copenhagen, Denmark. [Rath, Martin F.; Bailey, Michael J.; Kim, Jong-So; Coon, Steven L.; Klein, David C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, Sect Neuroendocrinol, NIH, Bethesda, MD USA. RP Rath, MF (reprint author), Univ Copenhagen, Panum Inst, Dept Neurosci & Pharmacol, 24-3-37,Blegdamsvej 3, DK-2200 Copenhagen, Denmark. EM mrath@sund.ku.dk OI Rath, Martin/0000-0002-4047-6324 FU Lundbeck Foundation; Danish Medical Research Council [271-07-0412, 271-060754]; Novo Nordisk Foundation; Carlsberg Foundation; Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH FX This study was supported by the Lundbeck Foundation, the Danish Medical Research Council (grant numbers 271-07-0412 and 271-060754), the Novo Nordisk Foundation, the Carlsberg Foundation, Fonden til Laegevidenskabens Fremme, Simon Fougner Hartmanns Familiefond and the Division of Intramural Research of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH. We wish to thank Mrs Ursula Rentzmann for expert histological assistance. NR 55 TC 22 Z9 28 U1 2 U2 5 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JAN PY 2009 VL 108 IS 1 BP 285 EP 294 DI 10.1111/j.1471-4159.2008.05765.x PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 380BV UT WOS:000261441500025 PM 19012751 ER PT J AU Meinertzhagen, IA Takemura, SY Lu, ZY Huang, SL Gao, SY Ting, CY Lee, CH AF Meinertzhagen, Ian A. Takemura, Shin-ya Lu, Zhiyuan Huang, Songling Gao, Shuying Ting, Chun-Yuan Lee, Chi-Hon TI From Form to Function: the Ways to Know a Neuron SO JOURNAL OF NEUROGENETICS LA English DT Article DE Golgi impregnation; GFP; photoreceptor; optic lobe; serial-section EM ID DROSOPHILA MUSHROOM BODY; GENETIC DISSECTION; VISUAL-SYSTEM; LOBULA PLATE; OPTIC LOBE; CELL-TYPES; SENSORY PROJECTIONS; NERVOUS-SYSTEM; FRUIT-FLY; WILD-TYPE AB The shape of a neuron, its morphological signature, dictates the neuron's function by establishing its synaptic partnerships. Here, we review various anatomical methods used to reveal neuron shape and the contributions these have made to our current understanding of neural function in the Drosophila brain, especially the optic lobe. These methods, including Golgi impregnation, genetic reporters, and electron microscopy (EM), necessarily incorporate biases of various sorts that are easy to overlook, but that filter the morphological signatures we see. Nonetheless, the application of these methods to the optic lobe has led to reassuringly congruent findings on the number and shapes of neurons and their connection patterns, indicating that morphological classes are actually genetic classes. Genetic methods using, especially, GAL4 drivers and associated reporters have largely superceded classical Golgi methods for cellular analyses and, moreover, allow the manipulation of neuronal activity, thus enabling us to establish a bridge between morphological studies and functional ones. While serial-EM reconstruction remains the only reliable, albeit labor-intensive, method to determine actual synaptic connections, genetic approaches in combination with EM or high-resolution light microscopic techniques are promising methods for the rapid determination of synaptic circuit function. C1 [Meinertzhagen, Ian A.; Takemura, Shin-ya; Lu, Zhiyuan] Dalhousie Univ, Life Sci Ctr, Dept Psychol, Halifax, NS B3H 4J1, Canada. [Huang, Songling; Gao, Shuying; Ting, Chun-Yuan; Lee, Chi-Hon] NICHHD, Unit Neuronal Connect, NIH, Bethesda, MD USA. RP Meinertzhagen, IA (reprint author), Dalhousie Univ, Life Sci Ctr, Dept Psychol, Halifax, NS B3H 4J1, Canada. EM iam@dal.ca RI Gao, Shuying/D-8183-2011; Lee, Chi-Hon/G-9190-2012; Ting, chun-yuan/F-6448-2013; Marion-Poll, Frederic/D-8882-2011; OI Marion-Poll, Frederic/0000-0001-6824-0180; Takemura, Shin-ya/0000-0003-2400-6426; Meinertzhagen, Ian/0000-0002-6578-4526 NR 89 TC 18 Z9 18 U1 1 U2 6 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0167-7063 EI 1563-5260 J9 J NEUROGENET JI J. Neurogenet. PY 2009 VL 23 IS 1-2 BP 68 EP 77 AR PII 907468344 DI 10.1080/01677060802610604 PG 10 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA 421RQ UT WOS:000264376400010 PM 19132600 ER PT J AU Pollock, JD Ramaswami, M AF Pollock, Jonathan D. Ramaswami, Mani TI Preface: The Genetics and Epigenetics of Addiction SO JOURNAL OF NEUROGENETICS LA English DT Editorial Material C1 [Pollock, Jonathan D.] NIDA, Genet & Mol Neurobiol Res Branch, Div Basic Neurosci & Behav Res, NIH, Bethesda, MD 20892 USA. [Ramaswami, Mani] Trinity Coll Dublin, Dublin, Ireland. RP Pollock, JD (reprint author), NIDA, Genet & Mol Neurobiol Res Branch, Div Basic Neurosci & Behav Res, NIH, 6001 Execut Blvd, Bethesda, MD 20892 USA. RI Pollock, Jonathan/B-1554-2009 NR 0 TC 0 Z9 0 U1 0 U2 6 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0167-7063 J9 J NEUROGENET JI J. Neurogenet. PY 2009 VL 23 IS 3 BP 251 EP 251 AR PII 908488800 DI 10.1080/01677060802669774 PG 1 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA 480AX UT WOS:000268705100001 PM 19194816 ER PT J AU Uhl, GR Drgon, T Johnson, C Liu, QR AF Uhl, George R. Drgon, Tomas Johnson, Catherine Liu, Qing-Rong TI Addiction Genetics and Pleiotropic Effects of Common Haplotypes that Make Polygenic Contributions to Vulnerability to Substance Dependence SO JOURNAL OF NEUROGENETICS LA English DT Article; Proceedings Paper CT Short Course on the Genetics and Epigenetics of Addiction CY MAR 31-APR 04, 2008 CL Bethesda, MD SP NIDA DE addiction; psychiatric genetics; complex genetics; genomewide association ID GENOME-WIDE ASSOCIATION; ALDEHYDE DEHYDROGENASE GENOTYPES; ALCOHOL-METABOLIZING GENES; CELL-ADHESION MOLECULES; POPULATION-BASED SAMPLE; T-CADHERIN; NICOTINE DEPENDENCE; LINKAGE ANALYSIS; ENVIRONMENTAL-INFLUENCES; MEMORY CONSOLIDATION AB Abundant evidence from family, adoption, and twin studies point to large genetic contributions to individual differences in vulnerability to develop dependence on one or more addictive substances. Twin data suggest that most of this genetic vulnerability is shared by individuals who are dependent on a variety of addictive substances. Molecular genetic studies, especially genomewide and candidate gene association studies, have elucidated common haplotypes in dozens of genes that appear to make polygenic contributions to vulnerability to developing dependence. Most genes that harbor currently identified addiction-associated haplotypes are expressed in the brain. Haplotypes in many of the same genes are identified in genomewide association studies that compare allele frequencies in substance dependent vs. control individuals from European, African, and Asian racial/ethnic backgrounds. Many of these addiction-associated haplotypes display pleiotropic influences on a variety of related brain-based phenotypes that display 1) substantial heritability and 2) clinical cooccurence with substance dependence. C1 [Uhl, George R.; Drgon, Tomas; Johnson, Catherine; Liu, Qing-Rong] NIDA, Mol Neurobiol Branch, NIH IRP, Baltimore, MD 21224 USA. RP Uhl, GR (reprint author), NIDA, Mol Neurobiol Branch, NIH IRP, Box 5180, Baltimore, MD 21224 USA. EM guhl@intra.nida.nih.gov RI Liu, Qing-Rong/A-3059-2012 OI Liu, Qing-Rong/0000-0001-8477-6452 FU Intramural NIH HHS [Z99 DA999999] NR 109 TC 14 Z9 14 U1 2 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0167-7063 J9 J NEUROGENET JI J. Neurogenet. PY 2009 VL 23 IS 3 BP 272 EP 282 AR PII 907903371 DI 10.1080/01677060802572929 PG 11 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA 480AX UT WOS:000268705100004 PM 19152208 ER PT J AU Campbell, JL Gu, Q Guo, DY Nash, HA AF Campbell, Joseph L. Gu, Qun Guo, Dongyu Nash, Howard A. TI Genetic Effects in Drosophila on the Potency of Diverse General Anesthetics: A Distinctive Pattern of Altered Sensitivity SO JOURNAL OF NEUROGENETICS LA English DT Article DE arousal; locomotion; volatile anesthetics; cocaine; ethanol ID BLOOD-BRAIN-BARRIER; COUNTERCURRENT DISTRIBUTION; VOLATILE ANESTHETICS; MUTATIONS; MELANOGASTER; MUTANTS; REVEAL; CONSERVATION; EXPRESSION; BEHAVIORS AB Mutations that influence the sensitivity of an organism to a volatile general anesthetic can be divided into two classes. In one, sensitivity to all other volatile agents is affected to a similar degree. Although this class may contain mutations of interest for understanding anesthesia, it is also likely to contain mutations that merely alter general health. In the second class, mutations confer non-uniform effects on potency (NEP), i.e., larger effects for some volatile anesthetics than for others. Members of this class are of special interest for studies of arousal and its pharmacological suppression because they not only avoid the pitfall of effects on global health, but also imply the existence of drug targets that are preferentially affected by particular agents. In this work, we provide the first systematic investigation of the relative frequency and diversity of NEP mutations in Drosophila. As a first step, we isolated and characterized a set of P element insertion mutations that confer altered sensitivity of the fruit fly to the clinical anesthetic halothane. Then we tested the members of this collection for their effect on the sensitivity of flies to five other volatile agents. Not only do we find that most of the mutations show non-uniform effects, they also share a characteristic arrangement of altered potencies (halothane >>desflurane >= enflurane similar to isoflurane similar to methoxyflurane >sevoflurane). From this result, although we do not know how direct or indirect are the effects of the mutations, we infer the existence of a biologically relevant target for anesthetic action that has a distinct preference for halothane over other agents. Intriguingly, P element insertions that co-map with several NEP loci have been shown to alter the fly's response to cocaine and ethanol, suggesting that common genetic elements are involved in the response to all three drugs. C1 [Campbell, Joseph L.; Gu, Qun; Guo, Dongyu; Nash, Howard A.] NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. RP Nash, HA (reprint author), NIMH, Mol Biol Lab, Bldg 35,Rm 1B-1002, Bethesda, MD 20892 USA. EM howardnash@mail.nih.gov FU National Institute of Mental Health FX We are most grateful to Barry Chestnut and Jessica Keys for their invaluable assistance with the initial genetic screen and mutant characterization. Thanks are also due to Robert Scott, Bruno van Swinderen, and Benjamin White for their comments on the manuscript. Ulrike Heberlein is acknowledged for provision of fly stocks and for permission to cite unpublished data. This work was supported by the Intramural Program of the National Institute of Mental Health. NR 46 TC 5 Z9 6 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0167-7063 EI 1563-5260 J9 J NEUROGENET JI J. Neurogenet. PY 2009 VL 23 IS 4 BP 412 EP 421 DI 10.3109/01677060903177800 PG 10 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA 515LC UT WOS:000271470500006 PM 19863272 ER PT J AU Root, C Masuyama, K Green, D Enell, L Nassel, D Lee, CH Wang, J AF Root, Cory Masuyama, Kaoru Green, David Enell, Lina Nassel, Dick Lee, Chi-Hong Wang, Jing TI A Presynaptic Gain Control Mechanism Fine-Tunes Olfactory Behavior SO JOURNAL OF NEUROGENETICS LA English DT Meeting Abstract C1 [Root, Cory; Masuyama, Kaoru; Green, David; Wang, Jing] Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA. [Enell, Lina; Nassel, Dick] Stockholm Univ, Dept Zool, Stockholm, Sweden. [Lee, Chi-Hong] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 5 U2 5 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0167-7063 J9 J NEUROGENET JI J. Neurogenet. PY 2009 VL 23 SU 1 MA V7 BP S34 EP S34 PG 1 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA 410DC UT WOS:000263555500100 ER PT J AU Takemura, S Gao, SY Ting, CY Lulee, CH Meinertzhagen, I AF Takemura, Shinya Gao, Shuying Ting, Chun-Yuan Lulee, Chi-Hon Meinertzhagen, Ian TI Synaptic circuits in the medulla of the Drosophila visual system SO JOURNAL OF NEUROGENETICS LA English DT Meeting Abstract C1 [Takemura, Shinya; Meinertzhagen, Ian] Dalhousie Univ, Halifax, NS, Canada. [Gao, Shuying; Ting, Chun-Yuan; Lulee, Chi-Hon] NIMH, Unit Neuronal Connect, NIH, Bethesda, MD 20892 USA. RI Ting, chun-yuan/F-6448-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0167-7063 J9 J NEUROGENET JI J. Neurogenet. PY 2009 VL 23 MA VI.50 BP S59 EP S60 PG 2 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA 410DC UT WOS:000263555500174 ER PT J AU Cronin, S Berger, S Ding, J Schymick, JC Washecka, N Hernandez, DG Greenway, MJ Bradley, DG Traynor, BJ Hardiman, O AF Cronin, S. Berger, S. Ding, J. Schymick, J. C. Washecka, N. Hernandez, D. G. Greenway, M. J. Bradley, D. G. Traynor, B. J. Hardiman, O. TI A GENOME-WIDE ASSOCIATION STUDY OF AMYOTROPHIC LATERAL SCLEROSIS IN A HOMOGENEOUS IRISH POPULATION: DPP6 AS A CANDIDATE LOCUS SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Meeting Abstract CT Spring Scientific Meeting of the Association-of-British-Neurologists CY MAR 26-JUN 28, 2008 CL Dublin, IRELAND SP Assoc British Neurologists C1 Beaumont Hosp, Dublin 9, Ireland. Royal Coll Surgeons Ireland, Dublin 2, Ireland. NIH, Bethesda, MD 20892 USA. Univ Oxford, Oxford, England. Trinity Coll Dublin, Dublin, Ireland. EM scronin@rcsi.ie RI Bradley, Daniel/A-3240-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD JAN PY 2009 VL 80 IS 1 BP 105 EP 105 PG 1 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 384RM UT WOS:000261761900068 ER PT J AU Julien, C Tremblay, C Emond, V Lebbadi, M Norman, S Bennett, DA Calon, F AF Julien, Carl Tremblay, Cyntia Emond, Vincent Lebbadi, Meryem Salem, Norman, Jr. Bennett, David A. Calon, Frederic TI Sirtuin 1 Reduction Parallels the Accumulation of Tau in Alzheimer Disease SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE Sirtuins; Amyloid-beta peptide; Cognitive function; Fatty acids; Mild cognitive impairment; Postmortem analysis; Silent information regulator 2 (Sir-2) ID MILD COGNITIVE IMPAIRMENT; CALORIE RESTRICTION; MOUSE MODEL; A-BETA; NEUROFIBRILLARY TANGLES; AMYLOID NEUROPATHOLOGY; TRANSGENIC MODEL; OLDER PERSONS; FATTY-ACIDS; RISK AB Aging and metabolism-related disorders are risk factors for Alzheimer disease (AD). Because sirtuins may increase the life span through regulation of cellular metabolism, we compared the concentration of sirtuin 1 (SIRTI) in the brains of AD patients (n = 19) and controls (n = 22) using Western immunoblots and in situ hybridization. We report a significant reduction of SIRTI (messenger RNA [mRNA], -29%; protein, -45%) in the parietal cortex of AD patients, but not in the cerebellum. Further analyses in a second cohort of 36 subjects confirmed that cortical SIRT1 was decreased in AD but not in individuals with mild cognitive impairment. SIRT1 mRNA and its translated protein correlated negatively with the duration of symptoms (mRNA, r(2) = -0.367; protein, r(2) = -0.326) and the accumulation of paired helical filament tau (mRNA, r(2) = -0.230; protein, r(2) = -0.119), but weakly with insoluble amyloid-beta 42 (mRNA, r(2) = -0.090; protein, r(2) = -0.072). A significant relationship between SIRTI levels and global cognition scores proximate to death was also found (r(2) = +0.009, p = 0.049). In contrast, cortical SIRTI levels remained unchanged in a tiple-transgenic animal model of AD. Collectively, our results indicate that loss of SIRTI is closely associated with the accumulation of amyloid-beta and tau in the cerebral cortex of persons with AD. C1 [Julien, Carl; Tremblay, Cyntia; Emond, Vincent; Lebbadi, Meryem; Calon, Frederic] CHU Laval, Res Ctr, Mol Endocrinol & Oncol Res Ctr, Quebec City, PQ G1V 4G2, Canada. [Julien, Carl; Tremblay, Cyntia; Emond, Vincent; Lebbadi, Meryem; Calon, Frederic] Univ Laval, Fac Pharm, Quebec City, PQ G1K 7P4, Canada. [Salem, Norman, Jr.] NIAAA, Sect Nutr Neurosci, Lab Membrane Biochem & Biophys, Div Intramural Clin & Biol Res,NIH, Rockville, MD 20852 USA. [Bennett, David A.] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA. RP Calon, F (reprint author), CHU Laval, Res Ctr, Mol Endocrinol & Oncol Res Ctr, 2705 Laurier Blvd, Quebec City, PQ G1V 4G2, Canada. EM frederic.calon@crchul.ulaval.ca FU Canadian Institutes of Health Research [MOP74443]; Alzheimer Society Canada [ASC 0516]; Canada Foundation [10307]; National Institute on Aging grants [P30AG10161, R01AG15819]; Clinical Research Initiative; CIHR Institute of Aging [CAN-76833] FX This work was supported by Grant MOP74443 from the Canadian Institutes of Health Research, by Grant ASC 0516 from the Alzheimer Society Canada. by Grant No. 10307 from the Canada Foundation to:,Innovation (to Frederic Calon), and by Grant No. P30AG10161 and R01AG15819 from the National Institute on Aging grants (to David Bennett). Carl Julien is supported by studentships from the Alzheimer Society Canada. Fonds de la Recherche en Sante du Quebee, and Laval University "Fonds d'Enseignement et de Recherche," The work of Frederic salon was supported by a New Investigator Award from the Clinical Research Initiative and the CIHR Institute of Aging (CAN-76833). NR 66 TC 130 Z9 139 U1 3 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JAN PY 2009 VL 68 IS 1 BP 48 EP 58 PG 11 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 390YY UT WOS:000262200800005 PM 19104446 ER PT J AU Minamimoto, T La Camera, G Richmond, BJ AF Minamimoto, Takafumi La Camera, Giancarlo Richmond, Barry J. TI Measuring and Modeling the Interaction Among Reward Size, Delay to Reward, and Satiation Level on Motivation in Monkeys SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID NEURONAL-ACTIVITY; SUBJECTIVE VALUE; RHESUS-MONKEYS; INTERTEMPORAL CHOICE; HIPPOCAMPAL-LESIONS; PREFRONTAL CORTEX; PRIMATE STRIATUM; ADJUSTING-AMOUNT; FRONTAL-CORTEX; RESPONSES AB Minamimoto T, La Camera G, Richmond BJ. Measuring and modeling the interaction among reward size, delay to reward and satiation level on motivation in monkeys. J Neurophysiol 101: 437-447, 2009. First published November 5, 2008; doi:10.1152/jn.90959.2008. Motivation is usually inferred from the likelihood or the intensity with which behavior is carried out. It is sensitive to external factors (e. g., the identity, amount, and timing of a rewarding outcome) and internal factors (e. g., hunger or thirst). We trained macaque monkeys to perform a nonchoice instrumental task (a sequential red-green color discrimination) while manipulating two external factors: reward size and delay-to-reward. We also inferred the state of one internal factor, level of satiation, by monitoring the accumulated reward. A visual cue indicated the forthcoming reward size and delay-to-reward in each trial. The fraction of trials completed correctly by the monkeys increased linearly with reward size and was hyperbolically discounted by delay-to-reward duration, relations that are similar to those found in free operant and choice tasks. The fraction of correct trials also decreased progressively as a function of the satiation level. Similar (albeit noiser) relations were obtained for reaction times. The combined effect of reward size, delay-to-reward, and satiation level on the proportion of correct trials is well described as a multiplication of the effects of the single factors when each factor is examined alone. These results provide a quantitative account of the interaction of external and internal factors on instrumental behavior, and allow us to extend the concept of subjective value of a rewarding outcome, usually confined to external factors, to account also for slow changes in the internal drive of the subject. C1 [Minamimoto, Takafumi; La Camera, Giancarlo; Richmond, Barry J.] NIMH, NIH, Neuropsychol Lab, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Richmond, BJ (reprint author), NIMH, NIH, Neuropsychol Lab, Dept Hlth & Human Serv, Rm 1B-80,49 Convent Dr, Bethesda, MD 20892 USA. EM bjr@ln.nimh.nih.gov RI Minamimoto, Takafumi/D-6610-2012 OI Minamimoto, Takafumi/0000-0003-4305-0174 FU National Institute of Mental Health; Japan Society for the Promotion of Science Research Fellowship FX This study was supported by the Intramural Research Program of the National Institute of Mental Health. T. Minamimoto was partly supported by a Japan Society for the Promotion of Science Research Fellowship for Japanese Biomedical and Behavioral Researchers at the NIH. NR 40 TC 27 Z9 27 U1 4 U2 7 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JAN PY 2009 VL 101 IS 1 BP 437 EP 447 DI 10.1152/jn.90959.2008 PG 11 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 393XW UT WOS:000262410800037 PM 18987119 ER PT J AU Peterson, MM Craciun, L Heiss, JD AF Peterson, Matthew M. Craciun, Liviu Heiss, John D. TI Long-term result of the Echols procedure for treating syringomyelia SO JOURNAL OF NEUROSURGERY-SPINE LA English DT Article DE Chiari malformation; Echols procedure; scoliosis; syringomyelia; thoracic myelopathy ID TETHERED CORD SYNDROME; CHIARI-I MALFORMATION; SURGICAL-TREATMENT; PATHOPHYSIOLOGY; MODALITIES AB In 1974, a 9-year-old girl with syringomyelia and scoliosis was treated using the Echols procedure, a surgical technique that makes use of a metal stent to maintain drainage of fluid from the syrinx into the subarachnoid space. The patient presented to the authors' institution 34 years later with a history of progressive myelopathy and surgically treated deformities of the thoracic spine, lumbar spine, and right foot. Computer-assisted myelography indicated that the metal wire remained in place and that the syrinx had collapsed. Neurological examination and neurophysiological testing confirmed the presence of thoracic myelopathy, which may have been due to the wire tethering the thoracic spinal cord to the dorsal dura. This case is believed to be the only long-term report of the effects of the Echols procedure. The history of direct treatment of syringomyelia is reviewed and is contrasted with indirect treatment of syringomyelia, which relieves the condition by opening obstructed CSF pathways within the foramen magnum or spine. (DOI: 10.3171/2008.10.SPI08291) C1 [Peterson, Matthew M.; Heiss, John D.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. [Craciun, Liviu] NINDS, Electromyog Sect, NIH, Bethesda, MD 20892 USA. RP Heiss, JD (reprint author), NINDS, Surg Neurol Branch, NIH, 10 Ctr Dr,Bldg 10,Room 5D37, Bethesda, MD 20892 USA. EM heissj@ninds.nih.gov OI Heiss, John/0000-0002-3890-0165 FU National Institute of Neurological Disorders and Stroke; National Institutes of Health, Bethesda, Maryland FX This research was supported (in part) by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland. NR 39 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 1547-5654 J9 J NEUROSURG-SPINE JI J. Neurosurg.-Spine PD JAN PY 2009 VL 10 IS 1 BP 73 EP 78 DI 10.3171/2008.10.SPI08291 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 388JM UT WOS:000262016100015 PM 19119937 ER PT J AU Jaeger, LB Sparks, RR Delannoy, MJ Monaco, MC Stins, MF Major, EO Nath, A AF Jaeger, Laura B. Sparks, Rashidah R. Delannoy, Michael J. Monaco, Maria C. Stins, Monique F. Major, Eugene O. Nath, Avindra TI Migration of JC virus across the human blood-brain barrier occurs via clathrin-mediated endocytosis SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract CT 9th International Symposium on NeuroVirology CY JUN 02-06, 2009 CL Miami Beach, FL C1 [Jaeger, Laura B.; Sparks, Rashidah R.; Stins, Monique F.; Nath, Avindra] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Delannoy, Michael J.] Johns Hopkins Univ, Sch Med, Dept Cell Biol, Baltimore, MD USA. [Monaco, Maria C.; Major, Eugene O.] Natl Inst Neurol Disorders & Stroke, Lab Mol Med & Neurosci, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PY 2009 VL 15 MA P80 BP 37 EP 37 PG 1 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 500DT UT WOS:000270278700081 ER PT J AU Manuel, SL Makedonas, G Acheampong, E Gardner, J Wigdahl, B Goedert, JJ Betts, MR Jain, P AF Manuel, Sharron L. Makedonas, George Acheampong, Edward Gardner, Jaya Wigdahl, Brian Goedert, James J. Betts, Michael R. Jain, Pooja TI Polychromatic FACS analyses of the phenotypic and functional characteristics of dendritic cells and T cells in a cohort of HTLV-1-infected samples from the Jamaican region SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract CT 9th International Symposium on NeuroVirology CY JUN 02-06, 2009 CL Miami Beach, FL C1 [Manuel, Sharron L.; Acheampong, Edward; Wigdahl, Brian; Jain, Pooja] Drexel Univ, Coll Med, Dept Microbiol & Immunol, Philadelphia, PA USA. [Makedonas, George; Gardner, Jaya; Betts, Michael R.] Univ Penn, Sch Med, Dept Microbiol & Immunol, Philadelphia, PA 19104 USA. [Goedert, James J.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PY 2009 VL 15 MA P113 BP 54 EP 54 PG 1 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 500DT UT WOS:000270278700114 ER PT J AU Marshall, LJ Major, EO AF Marshall, Leslie J. Major, Eugene O. TI Spi-B Binding to Target Sequences within the JC Virus Regulatory Region SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract CT 9th International Symposium on NeuroVirology CY JUN 02-06, 2009 CL Miami Beach, FL C1 [Marshall, Leslie J.; Major, Eugene O.] NINDS, Lab Mol Med & Neurosci, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PY 2009 VL 15 MA P116 BP 55 EP 56 PG 2 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 500DT UT WOS:000270278700117 ER PT J AU Meoli, EM Burbelo, P Graham, J Leahy, HP Yao, K Oh, U Mahieux, R Kashanchi, F Iadarola, MJ Jacobson, S AF Meoli, Elise M. Burbelo, Peter Graham, Jhanelle Leahy, Hannah P. Yao, Karen Oh, Unsong Mahieux, Renaud Kashanchi, Fatah Iadarola, Michael J. Jacobson, Steven TI A subset of seroindeterminate patients have detectable antibodies to HTLV-I GAG and Tax as defined by a novel luciferase immunoprecipitation system (LIPS) SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract CT 9th International Symposium on NeuroVirology CY JUN 02-06, 2009 CL Miami Beach, FL C1 [Meoli, Elise M.; Graham, Jhanelle; Yao, Karen; Oh, Unsong; Jacobson, Steven] NINDS, Viral Immunol Sect, Neuroimmunol Branch, Bethesda, MD 20892 USA. [Meoli, Elise M.] Howard Hughes Med Inst, Bethesda, MD 20814 USA. [Burbelo, Peter; Leahy, Hannah P.; Iadarola, Michael J.] Natl Inst Dent & Craniofacial Res, Neurobiol & Pain Therapeut Sect, Lab Sensory Biol, Bethesda, MD 20892 USA. [Mahieux, Renaud] Inst Pasteur, Unite Epidemiol & Physiopathol Virus Oncogenes, CNRS, Dept Virol,URA 3015, F-75015 Paris, France. [Mahieux, Renaud; Kashanchi, Fatah] George Washington Univ, Med Ctr, Dept Microbiol Immunol & Trop Med, Washington, DC 20037 USA. RI Burbelo, Peter/B-1027-2009 NR 0 TC 0 Z9 0 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PY 2009 VL 15 MA P124 BP 60 EP 60 PG 1 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 500DT UT WOS:000270278700125 ER PT J AU Monaco, MCG Maric, D Nelson, DB Major, EO AF Monaco, Maria Chiara G. Maric, Dragan Nelson, David B. Major, Eugene O. TI Establishment of a human fetal brain progenitor-derived oligodendrocyte culture system and its use for study of JC virus infection SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract CT 9th International Symposium on NeuroVirology CY JUN 02-06, 2009 CL Miami Beach, FL C1 [Monaco, Maria Chiara G.; Nelson, David B.; Major, Eugene O.] Natl Inst Neurol Disorders & Stroke, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. [Maric, Dragan] Natl Inst Neurol Disorders & Stroke, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PY 2009 VL 15 MA P128 BP 62 EP 63 PG 2 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 500DT UT WOS:000270278700129 ER PT J AU Oh, U Turner, R Graham, J Enose-Akahata, Y Jacobson, S AF Oh, Unsong Turner, Richard Graham, Jhanelle Enose-Akahata, Yoshimi Jacobson, Steven TI STAT1 dependent activation of STAT5 in peripheral blood of HTLV-I-associated myelopathy/tropical spastic paraparesis SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract CT 9th International Symposium on NeuroVirology CY JUN 02-06, 2009 CL Miami Beach, FL C1 [Oh, Unsong; Turner, Richard; Graham, Jhanelle; Enose-Akahata, Yoshimi; Jacobson, Steven] NINDS, Viral Immunol Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PY 2009 VL 15 MA P141 BP 68 EP 69 PG 2 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 500DT UT WOS:000270278700142 ER PT J AU Soulas, C Donahue, RE Alvarez, X Williams, KC AF Soulas, Caroline Donahue, Robert E. Alvarez, Xavier Williams, Kenneth C. TI Genetically Modified CD34+Hematopoietic Stem Cells Contribute to Turnover of Brain Perivascular Macrophages in Long-term Repopulated Primates SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract CT 9th International Symposium on NeuroVirology CY JUN 02-06, 2009 CL Miami Beach, FL C1 [Soulas, Caroline; Williams, Kenneth C.] Boston Coll, Dept Biol, Chestnut Hill, MA 02467 USA. [Donahue, Robert E.] NHLBI, Hematol Branch, Rockville, MD 20850 USA. [Alvarez, Xavier] Tulane Natl Primate Res Ctr, Div Comparat Pathol, Covington, LA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PY 2009 VL 15 MA P190 BP 92 EP 92 PG 1 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 500DT UT WOS:000270278700191 ER PT J AU Steinberg, SM Major, EO Jensen, PN AF Steinberg, Shannon M. Major, Eugene O. Jensen, Peter N. TI Establishment of a Homogeneous Clonal Cell Line That Supports Persistent Infection with the Human Polyomavirus JC SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract CT 9th International Symposium on NeuroVirology CY JUN 02-06, 2009 CL Miami Beach, FL C1 [Steinberg, Shannon M.; Major, Eugene O.; Jensen, Peter N.] NINDS, Lab Mol Med & Neurosci, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PY 2009 VL 15 MA P191 BP 92 EP 93 PG 2 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 500DT UT WOS:000270278700192 ER PT J AU Tabatadze, N Mattson, M Yang, F Pomerantz, D Haughey, NJ AF Tabatadze, Nino Mattson, Mark Yang, Fang Pomerantz, Daniel Haughey, Norman J. TI HIV-1 gp120 enhances beta- and gamma-secretase activity in human neuroblastoma cells SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract CT 9th International Symposium on NeuroVirology CY JUN 02-06, 2009 CL Miami Beach, FL C1 [Tabatadze, Nino; Yang, Fang; Pomerantz, Daniel; Haughey, Norman J.] Johns Hopkins Univ, Sch Med, Richard T Johnson Div Neuroimmunol & Neurol Infec, Dept Neurol, Baltimore, MD 21287 USA. [Mattson, Mark] NIA, Intramural Res Program, Neurosci Lab, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PY 2009 VL 15 MA P201 BP 97 EP 97 PG 1 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 500DT UT WOS:000270278700202 ER PT J AU Yao, K OKeefe, E Maric, D Ohayon, J Henkin, R Jacobson, S AF Yao, Karen OKeefe, Erin Maric, Dragin Ohayon, Joan Henkin, Robert Jacobson, Steven TI Human herpesvirus associated with smell loss may reflect infection of resident olfactory glial cells (olfactory ensheathing cells (OEC) SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract CT 9th International Symposium on NeuroVirology CY JUN 02-06, 2009 CL Miami Beach, FL C1 [Yao, Karen; OKeefe, Erin; Ohayon, Joan; Jacobson, Steven] NINDS, Viral Immunol Sect, Bethesda, MD 20892 USA. [Maric, Dragin] NINDS, FACS Core Facil, Bethesda, MD 20892 USA. [Henkin, Robert] Ctr Mol Nutr & Sensory Disorders, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PY 2009 VL 15 MA P221 BP 106 EP 106 PG 1 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 500DT UT WOS:000270278700222 ER PT J AU Yao, K Hoest, C Stuve, O Jacobson, S AF Yao, Karen Hoest, Christel Stuve, Olaf Jacobson, Steven TI Reactivation of Human Herpesvirus after Natalizumab Treatment in Patients with Multiple Sclerosis SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract CT 9th International Symposium on NeuroVirology CY JUN 02-06, 2009 CL Miami Beach, FL C1 [Yao, Karen; Hoest, Christel; Jacobson, Steven] NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. [Yao, Karen] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. [Stuve, Olaf] Univ Texas SW Med Ctr Dallas, Dept Neurol, Dallas, TX 75390 USA. [Stuve, Olaf] Univ Texas SW Med Ctr Dallas, Ctr Immunol, Dallas, TX 75390 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PY 2009 VL 15 MA P222 BP 107 EP 107 PG 1 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 500DT UT WOS:000270278700223 ER PT J AU Mohan, KVK Zhang, CX Atreya, CD AF Mohan, Ketha V. K. Zhang, Cheryl X. Atreya, Chintamani D. TI The proteoglycan bamacan is a host cellular ligand of vaccinia virus neurovirulence factor N1L SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE chondroitin sulfate; CSPG6; GFP; poxvirus; SMC3; WR strain ID SURFACE HEPARAN-SULFATE; CHONDROITIN-SULFATE; PROTEIN BINDS; CDNA CLONING; IN-VITRO; SMALLPOX; BRAIN; CELLS; GENE; OVEREXPRESSION AB Neurovirulence is one of the pathological complications associated with vaccinia virus (VV) infection/vaccination. Although the viral N1L protein has been identified as the neurovirulence factor, none of the host N1L-interacting factors have been identified so far. In the present study, we identified N1L-interacting proteins by screening a human brain cDNA expression library with N1L as a bait protein in a yeast two-hybrid analysis. The analysis revealed that N1L interacts with human brain-originated cellular basement membrane-associated chondroitin sulfate proteoglycan ( bamacan). The N1L-binding domain of bamacan was mapped to its C-terminal 227 amino acids. The N1L-bamacan interaction was further confirmed in both VV-infected and N1L-transfected mammalian cells. Following the confirmation of the protein interactions by coimmunoprecipitation experiments, confocal microscopic analysis revealed that N1L colocalizes with bamacan both in VV-infected B-SC-1 cells as well as in mice neuronal tissue. Furthermore, a human neural cell line, which expresses bamacan to moderately elevated levels relative to a non-neural cell line, supported enhanced viral growth. Overall, these studies clearly suggest that bamacan interacts with the VV-N1L and such interactions seem to play a positive role in promoting the viral growth and perhaps contribute to the virulence of VV in neural cells. Journal of NeuroVirology (2009) 15, 229-237. C1 [Mohan, Ketha V. K.; Zhang, Cheryl X.] US FDA, CBER, Div Viral Prod, Bethesda, MD 20892 USA. [Mohan, Ketha V. K.; Atreya, Chintamani D.] US FDA, Div Hematol, Lab Cellular Hematol, Sect Cell Biol, Bethesda, MD 20892 USA. RP Mohan, KVK (reprint author), US FDA, CBER, Div Viral Prod, Bldg 29A,Room 2C-15,HFM-335,NIH Campus,8800 Rockv, Bethesda, MD 20892 USA. EM krishna.ketha391534@fda.hhs.gov FU CBER; FDA CounterTerrorism (CT) Unmet Needs FX The authors gratefully acknowledge Dr. Bernard Moss and Norman Cooper, NIAID, for kind gift of WR strain; Dr. Geoffrey Smith, University of Oxford, UK, for anti-N1L antibody; and Dr. Dorothy Scott, CBER, for VIG serum. Manuscript review by Drs. Ronald Lundquist and Zhiping Ye, DVP, CBER, FDA, is duly acknowledged. Funds from CBER and FDA CounterTerrorism (CT) Unmet Needs in the past partly supported this study. NR 30 TC 3 Z9 4 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PY 2009 VL 15 IS 3 BP 229 EP 237 DI 10.1080/13550280902913636 PG 9 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 479SJ UT WOS:000268680900003 PM 19444697 ER PT J AU Liow, JS Kreisl, W Zoghbi, SS Lazarova, N Seneca, N Gladding, RL Taku, A Herscovitch, P Pike, VW Innis, RB AF Liow, Jeih-San Kreisl, William Zoghbi, Sami S. Lazarova, Neva Seneca, Nicholas Gladding, Robert L. Taku, Andrew Herscovitch, Peter Pike, Victor W. Innis, Robert B. TI P-Glycoprotein Function at the Blood-Brain Barrier Imaged Using (11)C-N-Desmethyl-Loperamide in Monkeys SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE molecular imaging; radiotracer tissue kinetics; P-glycoprotein; loperamide; PET ID IN-VIVO; MULTIDRUG-RESISTANCE; GENE; TRANSPORTER; INHIBITION; PET AB (11)C-Loperamide is an avid substrate for P-glycoprotein (P-gp), but it is rapidly metabolized to (11)C-N-desmethyl-loperamide ((11)C-dLop), which is also a substrate for P-gp and thereby contaminates the radioactive signal in the brain. Should further demethylation of (11)C-dLop occur, radiometabolites with low entry into the brain are generated. Therefore, we evaluated the ability of (11)C-dLop to quantify the function of P-gp at the blood-brain barrier in monkeys. Methods: Six monkeys underwent 12 PET scans of the brain, 5 at baseline and 7 after pharmacologic blockade of P-gp. A subset of monkeys also underwent PET scans with (15)O-water to measure cerebral blood flow. To determine whether P-gp blockade affected peripheral distribution of (11)C-dLop, we measured whole-body biodistribution in 4 monkeys at baseline and after P-gp blockade. Results: The concentration of (11)C-dLop in the brain was low under baseline conditions and increased 5-fold after P-gp blockade. This increase was primarily caused by an increased rate of entry into the brain rather than a decreased rate of removal from the brain. With P-gp blockade, uptake of radioactivity among brain regions correlated linearly with blood flow, suggesting a high single-pass extraction. After correction for cerebral blood flow, the uptake of (11)C-dLop was fairly uniform among brain regions, suggesting that the function of P-gp is fairly uniformly distributed in the brain. On whole-body imaging, P-gp blockade significantly affected distribution of radioactivity only to the brain and not to other visually identified source organs. The effective dose estimated for humans was approximately 9 mu Sv/MBq. Conclusion: PET with (11)C-dLop can quantify P-gp function at the blood-brain barrier in monkeys. The single-pass extraction of (11)C-dLop is high and requires correction for blood flow to accurately measure the function of this efflux transporter. The low uptake at baseline and markedly increased uptake after P-gp blockade suggest that (11)C-dLop will be useful to measure a wide range of P-gp functions at the blood-brain barrier in humans. C1 [Liow, Jeih-San] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. [Herscovitch, Peter] NIH, Ctr Clin, PET Dept, Bethesda, MD 20892 USA. RP Liow, JS (reprint author), NIMH, Mol Imaging Branch, NIH, 31 Ctr Dr,Room B2B37,MSC 2035, Bethesda, MD 20892 USA. EM liowj@mail.nih.gov FU National Institute of Mental Health [Z01-MH-002795-07] FX We thank Eli Lilly for providing DCPQ; Edward Tuan, Cheryl Morse, and Jinsoo Hong for their assistance in this study; the staff of the National Institutes of Health PET Department for successfully performing the PET studies; and PMOD Technologies (Zurich, Switzerland) for providing its image-analysis software. The Intramural Research Program of the National Institute of Mental Health Supported this research (project Z01-MH-002795-07). A patent application has been filed on behalf of the U.S. government for PET imaging of P-gp function. Sami S. Zoghbi, Victor W. Pike, Neva Lazarova, and Robert B. Innis could personally benefit from this patent. NR 19 TC 52 Z9 54 U1 1 U2 2 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD JAN PY 2009 VL 50 IS 1 BP 108 EP 115 DI 10.2967/jnumed.108.056226 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 393BS UT WOS:000262346500024 PM 19091890 ER PT J AU Ferrucci, LM Cross, AJ Gunter, MJ Ahn, J Mayne, ST Ma, XM Chanock, SJ Yeager, M Graubard, BI Berndt, SI Huang, WY Hayes, RB Sinha, R AF Ferrucci, Leah M. Cross, Amanda J. Gunter, Marc J. Ahn, Jiyoung Mayne, Susan T. Ma, Xiaomei Chanock, Stephen J. Yeager, Meredith Graubard, Barry I. Berndt, Sonja I. Huang, Wen-Yi Hayes, Richard B. Sinha, Rashmi TI Xenobiotic Metabolizing Genes, Meat Intake, and Risk of Advanced Colorectal Adenoma SO JOURNAL OF NUTRIGENETICS AND NUTRIGENOMICS LA English DT Meeting Abstract C1 [Ferrucci, Leah M.; Cross, Amanda J.; Yeager, Meredith; Graubard, Barry I.; Berndt, Sonja I.; Huang, Wen-Yi; Sinha, Rashmi] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Ferrucci, Leah M.; Mayne, Susan T.; Ma, Xiaomei] Yale Univ, Sch Publ Hlth, New Haven, CT USA. [Gunter, Marc J.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, New York, NY USA. [Ahn, Jiyoung; Hayes, Richard B.] NYU, Dept Environm Med, Sch Med, Div Epidemiol, New York, NY 10016 USA. RI Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 NR 0 TC 0 Z9 0 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1661-6499 J9 J NUTRIGENET NUTRIGE JI J. Nutrigenet. Nutrigenomics PY 2009 VL 2 IS 4-5 BP 194 EP 194 PG 1 WC Genetics & Heredity; Nutrition & Dietetics SC Genetics & Heredity; Nutrition & Dietetics GA 610BD UT WOS:000278703300014 ER PT J AU Steer, CD Emmett, PM Smith, GD Hibbeln, JR Davis, JM Golding, J AF Steer, C. D. Emmett, P. M. Smith, G. Davey Hibbeln, J. R. Davis, J. M. Golding, J. TI FADS2 Polymorphisms Modify the Effect of Breastfeeding on Child IQ SO JOURNAL OF NUTRIGENETICS AND NUTRIGENOMICS LA English DT Meeting Abstract C1 [Steer, C. D.; Emmett, P. M.; Golding, J.] Univ Bristol, Ctr Child & Adolescent Hlth, Dept Community Based Med, Bristol, Avon 60612, England. [Smith, G. Davey] Univ Bristol, MRC, Ctr Causal Anal Translat Epidemiol, Bristol, Avon, England. [Hibbeln, J. R.] NIAAA, NIH, Bethesda, MD USA. [Davis, J. M.] Univ Illinois, Dept Psychiat, Chicago, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1661-6499 J9 J NUTRIGENET NUTRIGE JI J. Nutrigenet. Nutrigenomics PY 2009 VL 2 IS 4-5 BP 195 EP 195 PG 1 WC Genetics & Heredity; Nutrition & Dietetics SC Genetics & Heredity; Nutrition & Dietetics GA 610BD UT WOS:000278703300016 ER PT J AU Brody, LC AF Brody, Lawrence C. TI Building the Cairns on the Path to Personalized Medicine SO JOURNAL OF NUTRIGENETICS AND NUTRIGENOMICS LA English DT Meeting Abstract C1 [Brody, Lawrence C.] NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1661-6499 J9 J NUTRIGENET NUTRIGE JI J. Nutrigenet. Nutrigenomics PY 2009 VL 2 IS 4-5 BP 199 EP 199 PG 1 WC Genetics & Heredity; Nutrition & Dietetics SC Genetics & Heredity; Nutrition & Dietetics GA 610BD UT WOS:000278703300027 ER PT J AU Ross, SA AF Ross, Sharon A. TI Dietary Regulation of microRNA Expression in Cancer Cells SO JOURNAL OF NUTRIGENETICS AND NUTRIGENOMICS LA English DT Meeting Abstract C1 [Ross, Sharon A.] NCI, Nutr Sci Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1661-6499 J9 J NUTRIGENET NUTRIGE JI J. Nutrigenet. Nutrigenomics PY 2009 VL 2 IS 4-5 BP 199 EP 200 PG 2 WC Genetics & Heredity; Nutrition & Dietetics SC Genetics & Heredity; Nutrition & Dietetics GA 610BD UT WOS:000278703300028 ER PT J AU Espey, MG Wang, J Cam, M Wang, YH Padayatty, S Eck, P Levine, M AF Espey, Michael Graham Wang, Jin Cam, Maggie Wang, Yahoui Padayatty, Sebastian Eck, Peter Levine, Mark TI Precisely Controlled Human Vitamin C Intake, Genomic Expression Patterns, and Immune Homeostasis SO JOURNAL OF NUTRIGENETICS AND NUTRIGENOMICS LA English DT Meeting Abstract C1 [Espey, Michael Graham; Wang, Jin; Cam, Maggie; Wang, Yahoui; Padayatty, Sebastian; Eck, Peter; Levine, Mark] NIDDK, Mol & Clin Nutr Sect, NIH, Bethesda, MD USA. RI Padayatty, Sebastian/A-8581-2012 OI Padayatty, Sebastian/0000-0001-8758-3170 NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1661-6499 J9 J NUTRIGENET NUTRIGE JI J. Nutrigenet. Nutrigenomics PY 2009 VL 2 IS 4-5 BP 221 EP 222 PG 2 WC Genetics & Heredity; Nutrition & Dietetics SC Genetics & Heredity; Nutrition & Dietetics GA 610BD UT WOS:000278703300076 ER PT J AU Luo, YQ Mughal, M Ouyang, X Jiang, HY Son, TG Mattson, MP AF Luo, Yongquan Mughal, Mohamed Ouyang, Xin Jiang, Haiyang Son, Tae-Gen Mattson, Mark P. TI Plumbagin Promotes the Generation of Astrocytes From Embryonic Rat Neural Progenitors Via Activation of the Transcription Factor Stat3 SO JOURNAL OF NUTRIGENETICS AND NUTRIGENOMICS LA English DT Meeting Abstract C1 [Luo, Yongquan; Mughal, Mohamed; Ouyang, Xin; Jiang, Haiyang; Son, Tae-Gen; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 0 TC 0 Z9 0 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1661-6499 J9 J NUTRIGENET NUTRIGE JI J. Nutrigenet. Nutrigenomics PY 2009 VL 2 IS 4-5 BP 222 EP 222 PG 1 WC Genetics & Heredity; Nutrition & Dietetics SC Genetics & Heredity; Nutrition & Dietetics GA 610BD UT WOS:000278703300077 ER PT J AU Tsai, MY Loria, CM Cao, J Kim, Y Siscovick, D Schreiner, PJ Hanson, NQ AF Tsai, Michael Y. Loria, Catherine M. Cao, Jing Kim, Yongin Siscovick, David Schreiner, Pamela J. Hanson, Naomi Q. TI Clinical Utility of Genotyping the 677C > T Variant of Methylenetetrahydrofolate Reductase in Humans Is Decreased in the Post-Folic Acid Fortification Era SO JOURNAL OF NUTRITION LA English DT Article ID CORONARY-HEART-DISEASE; HOMOCYSTEINE CONCENTRATIONS; CARDIOVASCULAR-DISEASE; PLASMA HOMOCYSTEINE; NATIONAL-HEALTH; COMMON MUTATION; FOLATE; METAANALYSIS; DETERMINANTS; POPULATION AB Moderate hyperhomocysteinemia is associated with many diseases. Major factors affecting plasma total homocysteine (tHcy) concentrations include folate concentrations and polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene. Because U.S.-mandated fortification of grain products with folic acid has improved folate and tHcy status in Americans, we investigated the effect of the MTHFR 677C>T variant before and after fortification. We determined tHcy and folate concentrations in sera from 844 Caucasian and 587 African American participants in the Coronary Artery Risk Development in Young Adults study before and after fortification and we genotyped the MTHFR 677C>T variant. MTHFR 677TT homozygotes had higher (P < 0.01) tHcy concentrations both before and after fortification compared with MTHFR 677CC homozygotes. However, the difference between these 2 genotypes decreased from 2.5 mu mol/L before fortification to <0.7 mu mol/L postfortification (P < 0.01). In addition, the prevalence of moderate hyperhomocysteinemia (tHcy > 13 mu mol/L) in 677TT homozygotes decreased from 33% before fortification to 12% postfortification (P< 0.01). Using a cutoff value of 13 mu mol/L to define moderate hyperhomocysteinemia, the sensitivity of the MTHFR 677TT genotype to predict elevations in homocysteine was low (similar to 30%) both before and after folic acid fortification. Increasing the cutoff from 13 to 19 mu mol/L increased the sensitivity of the assay before fortification to 62% but decreased the sensitivity to 17% postfortification. We conclude that after folic acid fortification in the US, measurement of tHcy rather than genotyping of MTHFR 677TT should be used as the primary assay for the diagnosis and monitoring of moderate hyperhomocysteinemia. J. Nutr. 139: 33-37. 2009. C1 [Tsai, Michael Y.; Cao, Jing; Hanson, Naomi Q.] Univ Minnesota, Sch Publ Hlth, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. [Schreiner, Pamela J.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN 55455 USA. [Loria, Catherine M.] NHLBI, Div Prevent & Populat Sci, Bethesda, MD 20824 USA. [Kim, Yongin] Univ Alabama, Div Prevent Med, Birmingham, AL 35294 USA. [Siscovick, David] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA. RP Tsai, MY (reprint author), Univ Minnesota, Sch Publ Hlth, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. EM tsaix001@tc.umn.edu FU National Heart, Lung, and Blood Institute [N01-HC-95095, N01-HC-48047-48050, N01-HC-05187] FX Supported by the National Heart, Lung, and Blood Institute (N01-HC-95095, N01-HC-48047-48050, and N01-HC-05187). NR 25 TC 11 Z9 12 U1 0 U2 2 PU AMER SOC NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD JAN PY 2009 VL 139 IS 1 BP 33 EP 37 DI 10.3945/jn.108.096511 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 384XI UT WOS:000261777100007 PM 19056652 ER PT J AU Wang, YJ Zhang, L Moslehi, R Ma, JL Pan, KF Zhou, T Liu, WD Brown, LM Hu, YR Pee, D Gail, MH You, WC AF Wang, Ylijue Zhang, Lian Moslehi, Roxana Ma, Junling Pan, Kaifeng Zhou, Tong Liu, Weidong Brown, Linda Morris Hu, Yuangreng Pee, David Gail, Mitchell H. You, Weicheng TI Long-Term Garlic or Micronutrient Supplementation, but Not Anti-Helicobacter pylori Therapy, Increases Serum Folate or Glutathione Without Affecting Serum Vitamin B-12 or Homocysteine in a Rural Chinese Population SO JOURNAL OF NUTRITION LA English DT Article ID PRECANCEROUS GASTRIC-LESIONS; PLASMA GLUTATHIONE; FOLIC-ACID; RANDOMIZED FACTORIAL; ANTIBIOTIC-TREATMENT; ATROPHIC GASTRITIS; CONTROLLED-TRIAL; STOMACH-CANCER; RISK-FACTOR; DEFICIENCY AB The effects of a 7.3-y supplementation with garlic and micronutrients and of anti-Helicobacter pylori treatment with amoxicillin (1 g twice daily) and omeprazole (20 mg twice daily) on serum folate, vitamin B-12, homocysteine, and glutathione concentrations were assessed in a rural Chinese population. A randomized, double-blind, placebo-controlled, factorial trial was conducted to compare the ability of 3 treatments to retard the development of precancerous gastric lesions in 3411 subjects. The treatments were: 7) anti-H. pylori treatment with amoxicillin and omeprazole; 2) 7.3-y supplementation with aged garlic and steam-distilled garlic oil; and 3) 7.3-y supplementation with vitamin C, vitamin E, and selenium. All 3 treatments were given in a 23 factorial design to subjects seropositive for H. pylori infection; only the garlic supplement and vitamin and selenium supplement were given in a 22 factorial design to the other subjects. Thirty-four subjects were randomly selected from each of the 12 treatment strata. Sera were analyzed after 7.3 y to measure effects on folate, vitamin B-12, homocysteine, and glutathione concentrations. Regression analyses adjusted for age, gender, and smoking indicated an increase of 10.2% (95%CI: 2.9-18.1 %) in serum folate after garlic supplementation and an increase of 13.4% (95%CI: 5.3-22.2%) in serum glutathione after vitamin and selenium supplementation. The vitamin and selenium supplement did not affect other analytes and the amoxicillin and omeprazole therapy did not affect any of the variables tested. In this rural Chinese population, 7.3 y of garlic supplementation increased the serum folate concentration and the vitamin and selenium supplement increased that of glutathione, but neither affected serum concentrations of vitamin B-12 or homocysteine. J. Nutr. 139: 106-112, 2009. C1 [Wang, Ylijue; Zhang, Lian; Ma, Junling; Pan, Kaifeng; Zhou, Tong; You, Weicheng] Peking Univ, Sch Oncol, Beijing Canc Hosp & Inst,Key Lab Carcinogenesis &, Dept Epidemiol,Minist Educ, Beijing 100036, Peoples R China. [Moslehi, Roxana] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Liu, Weidong] Linque Publ Hlth Bur, Shandong 262600, Peoples R China. [Pee, David] Informat Management Serv Inc, Rockville, MD 20852 USA. RP You, WC (reprint author), Peking Univ, Sch Oncol, Beijing Canc Hosp & Inst,Key Lab Carcinogenesis &, Dept Epidemiol,Minist Educ, Beijing 100036, Peoples R China. EM weichengyou@yahoo.com FU National Cancer Institute [N01-CP-71103]; Intramural Research Program of the National Cancer Institute Division of Cancer Epidemiology and Genetics; Peking University School of Oncology; Key Laboratory of Carcinogenesis and Translation Research (Ministry of Education) FX Supported by contract number N01-CP-71103 from the National Cancer Institute; the Intramural Research Program of the National Cancer Institute Division of Cancer Epidemiology and Genetics; and Peking University School of Oncology, Key Laboratory of Carcinogenesis and Translation Research (Ministry of Education). NR 47 TC 5 Z9 5 U1 0 U2 4 PU AMER SOC NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD JAN PY 2009 VL 139 IS 1 BP 106 EP 112 DI 10.3945/jn.108.091389 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 384XI UT WOS:000261777100019 PM 19056661 ER PT J AU Park, D Stewart, PA Coble, JB AF Park, Donguk Stewart, Patricia A. Coble, Joseph B. TI A Comprehensive Review of the Literature on Exposure to Metalworking Fluids SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL HYGIENE LA English DT Review DE grinding operation; machining operation; metalworking fluids (MWFs); weighted arithmetic means (WAMs) ID METAL-WORKING FLUIDS; SMALL MACHINE SHOPS; AUTOMOBILE MANUFACTURING-INDUSTRY; OIL MIST CONCENTRATIONS; RESPIRATORY SYMPTOMS; OCCUPATIONAL-EXPOSURE; LUNG-FUNCTION; HYPERSENSITIVITY PNEUMONITIS; GRINDING OPERATIONS; AIRWAY RESPONSIVENESS AB An extensive literature review was conducted of studies with exposure measurements to metalworking fluids (MWFs). A database of 155 arithmetic means based on 9379 aerosol measurements from published studies was compiled. Weighted arithmetic means (WAMs) and their variance calculated across studies were summarized based on decade (prior to 1970s through 2000s), industry (auto, auto parts, small job shops, and others), operation (grinding and machining), and fluid type (straight, soluble, synthetic, and semisynthetic). Total mass and total extractable mass measurements that were simultaneously collected were compared. Average concentrations by size fractions and mass median aerodynamic diameters (MMADs) were also analyzed. Analysis of the WAMs indicated a reduction in exposure levels over time regardless of industry or type of operation or fluid, with mean levels prior to the 1970s of 5.4 mg/m(3), which dropped to 2.5 mg/m(3) in the 1970s, to 1.2 mg/m(3) in the 1980s, and to 0.5 mg/m(3) in the 1990s. No further reduction was seen in the 2000s. A comparison by industry, operation, and fluid type found no consistent patterns in the measurement results. The percent extractable mass in the total aerosol samples varied by fluid type, with an average 84% in straight fluids, 58% in synthetic fluids, 56% in soluble fluids, and 42% in the semisynthetic fluids. Exposure means from the thoracic fraction (0.3-0.5 mg/m(3)) were slightly less than those for total aerosol for both the 1990s and 2000s, the only decades for which thoracic data were available. Respirable means did not change from the 1980s to the 2000s (generally about 0.2-0.3 mg/m(3)). The MMADs of the MWF aerosols averaged 4-6 mu m. These measurement data indicate a clear reduction of exposure levels over time. They will be used for the retrospective assessment of exposure levels to MWFs in a population-based, case-control study of bladder cancer. C1 [Park, Donguk] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD 20852 USA. [Park, Donguk] Korea Natl Open Univ, Dept Environm Hlth, Seoul, South Korea. [Stewart, Patricia A.] Stewart Exposure Assessments LLC, Arlington, VA USA. RP Park, D (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 6120 Execut Blvd,EPS Room 8005, Rockville, MD 20852 USA. EM dongukp@mail.nih.gov FU National Cancer Institute, National Institutes of Health, Department of Health and Human Services FX This research was supported by intramural funds from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services. NR 95 TC 11 Z9 11 U1 1 U2 13 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1545-9624 J9 J OCCUP ENVIRON HYG JI J. Occup. Environ. Hyg. PY 2009 VL 6 IS 9 BP 530 EP 541 DI 10.1080/15459620903065984 PG 12 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 470KU UT WOS:000267974400004 PM 19544177 ER PT J AU Kim, SB Cai, C Faust, MD Trenkle, WC Sweigart, DA AF Kim, Sang Bok Cai, Chen Faust, Marcus D. Trenkle, William C. Sweigart, Dwight A. TI The synthesis and catalytic activity of the iridium(I) hydroquinone complex [(H(2)Q)Ir(COD)](+) SO JOURNAL OF ORGANOMETALLIC CHEMISTRY LA English DT Article DE Iridium; Hydroquinone; Conjugate addition ID ARYL BORONIC ACIDS; HYDROGENATION; ALKYLATION; MICHAEL; CARBON; BONDS AB The eta(6)-hydroquinone iridium complex [(eta(6)-H(2)Q) Ir(COD)]BF(4) undergoes facile double deprotonation to the eta(4)-quinone anionic analogue. The latter has been shown to be the first example of an iridium complex that catalyzes 1,4 conjugate addition reactions of aryl boronic acids to electron deficient olefins. (C) 2008 Elsevier B. V. All rights reserved. C1 [Kim, Sang Bok; Cai, Chen; Faust, Marcus D.; Sweigart, Dwight A.] Brown Univ, Dept Chem, Providence, RI 02912 USA. [Trenkle, William C.] NIDDK, NIH, DHHS, Bethesda, MD 20892 USA. RP Sweigart, DA (reprint author), Brown Univ, Dept Chem, Providence, RI 02912 USA. EM Dwight_Sweigart@Brown.edu FU Petroleum Research Fund; American Chemical Society; NIH; National Institute of Diabetes and Digestive and Kidney Disease (WCT) FX We are pleased to acknowledge the donors of the Petroleum Research Fund, administered by the American Chemical Society, for support of this research. This research was supported in part by the Intramural Research Program of the NIH, National Institute of Diabetes and Digestive and Kidney Disease (WCT). NR 19 TC 5 Z9 5 U1 1 U2 3 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 0022-328X J9 J ORGANOMET CHEM JI J. Organomet. Chem. PD JAN 1 PY 2009 VL 694 IS 1 BP 52 EP 56 DI 10.1016/j.jorganchem.2008.09.066 PG 5 WC Chemistry, Inorganic & Nuclear; Chemistry, Organic SC Chemistry GA 376LB UT WOS:000261184000008 ER PT J AU Montenegro, D Romero, R Kim, SS Tarca, AL Draghici, S Kusanovic, JP Kim, JS Lee, DC Erez, O Gotsch, F Hassan, SS Kim, CJ AF Montenegro, D. Romero, R. Kim, S. S. Tarca, A. L. Draghici, S. Kusanovic, J. P. Kim, J. S. Lee, D. C. Erez, O. Gotsch, F. Hassan, S. S. Kim, C. J. TI Expression patterns of microRNAs in the chorioamniotic membranes: a role for microRNAs in human pregnancy and parturition SO JOURNAL OF PATHOLOGY LA English DT Article DE miR-338; group IVB phospholipase A2; Dicer; development; decidua; labour; preterm birth ID TARGET MESSENGER-RNAS; CAENORHABDITIS-ELEGANS; SPONTANEOUS LABOR; SIGNATURE; AMNION; CANCER; CELLS; DICER; MICE AB MicroRNAs (miRNAs) are involved in the post-transcriptional regulation of gene expression during development. This study was performed to determine gestational age-dependent changes in miRNA expression in the chorioamniotic membranes and to assess the significance of miRNAs in human pregnancy and parturition. The expression profile of 455 miRNAs was compared between patients at term without labour (TNL: n = 10), in labour (TL: n = 10), and preterm labour (PTL: n = 10) using microarrays. A total of 39 miRNAs were differentially expressed between term and preterm cases, of which 31 (79.5%) were down-regulated at term. Expression of ten miRNAs, including miR-338, differentially expressed between PTL and TL groups was decreased at term. Computational analyses using miRBase Targets have identified PLA2G4B, a phospholipase implicated in parturition, as a putative target of miR-338. Inhibition of endogenous miR-338 with anti-MiR-338 increased the mRNA and protein expression of PLA2G4B in decidual cells. Luciferase assay with reporter constructs confirmed that the suppression of PLA2G4B occurs through binding of miR-338 to the 3'UTR of PLA2G4B. Interestingly, the expression of Dicer, a key miRNA-processing enzyme, was markedly decreased at term, particularly with labour in the chorioamniotic membranes. Collectively, the novel findings reported herein strongly suggest that post-transcriptional regulation of genes by miRNAs, coupled with the changes of miRNA processing machinery in the chorioamniotic membranes, plays a role in pregnancy and parturition. Furthermore, the expression level of Dicer it) the chorioamniotic membranes dichotomizes pathological preterm labour and physiological spontaneous labour at term. Published in 2008 by John Wiley & Sons, Ltd. C1 [Montenegro, D.; Romero, R.; Kim, S. S.; Tarca, A. L.; Kusanovic, J. P.; Kim, J. S.; Lee, D. C.; Erez, O.; Gotsch, F.; Hassan, S. S.; Kim, C. J.] Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, Detroit, MI 48201 USA. [Montenegro, D.; Romero, R.; Kim, S. S.; Tarca, A. L.; Kusanovic, J. P.; Kim, J. S.; Lee, D. C.; Erez, O.; Gotsch, F.; Hassan, S. S.; Kim, C. J.] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Romero, R.] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA. [Tarca, A. L.; Draghici, S.] Wayne State Univ, Dept Comp Sci, Detroit, MI 48201 USA. [Kim, J. S.; Kim, C. J.] Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. [Hassan, S. S.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. RP Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, 3990 John R,Box 4, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu; cjkim@med.wayne.edu RI Draghici, Sorin/B-3074-2013 OI Draghici, Sorin/0000-0002-0786-8377 FU Eunice Kennedy Shriver National Institute Of Child Health and Human Development, NIH; DHHS FX This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute Of Child Health and Human Development, NIH. and DHHS. NR 33 TC 42 Z9 42 U1 1 U2 6 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0022-3417 J9 J PATHOL JI J. Pathol. PD JAN PY 2009 VL 217 IS 1 BP 113 EP 121 DI 10.1002/path.2463 PG 9 WC Oncology; Pathology SC Oncology; Pathology GA 389LQ UT WOS:000262094500013 PM 18991333 ER PT J AU Keil, MF Stratakis, CA AF Keil, Margaret F. Stratakis, Constantine A. TI Facial Metrics in Children with Corticotrophin-Producing Pituitary Adenomas Suggest Abnormalities in Midface Development SO JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM LA English DT Article DE Cushing's disease; anthropometrics; middle face; pituitary gland; development ID HORMONE DEFICIENCY PATIENTS; CUSHING-DISEASE; HYPOPITUITARISM; FEATURES; DEFECTS; REGIONS; PROP-1; GENE AB Background: Tumors of the hypothalamic-pituitary unit have been linked to genetic syndromes that are associated with midfacial abnormalities. Aim: We hypothesized that mutations of genes that affect the development of the face (and consequently of the anterior pituitary) may be present in children with ACTH-producing pituitary adenomas, and if this is true then facial measurements would be different from those predicted by parental features. Methods: We studied 20 children with cortico-tropinomas and a control group and their parents. All facial measurements were expressed according to standard deviation scores. Results: Significant differences were seen between the children with pituitary adenomas and their parents for vertical facial height measures: nasal length (p <0.001), lower facial height (p <0.03) and overall facial height (p <0.01). Conclusion: We conclude that some of the indices of midline craniofacial development, in particular those affecting the vertical axis, are different in children with corticotroph adenomas producing ACTH. C1 [Keil, Margaret F.; Stratakis, Constantine A.] NICHHD, Pediat Endocrinol Inter Inst Training Program, NIH, Bethesda, MD 20892 USA. [Stratakis, Constantine A.] NICHHD, Sect Endocrinol & Genet, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Stratakis, CA (reprint author), NICHD, Sect Endocrinol & Genet SEGEN, Pediat Endocrinol Training Program, DEB,NIH, Bldg 10 CRC,Room 1-3330,10 Ctr Dr,MSC1103, Bethesda, MD 20892 USA. EM stratakc@mail.nih.gov FU National Institute of Child Health & Human Development (NICHD); NIH [Z01-HD-000642-04] FX This study was supported by the National Institute of Child Health & Human Development (NICHD), NIH intramural project Z01-HD-000642-04 to Dr. C.A. Stratakis. We would like to thank Cara Olsen, Uniformed-Services University of the Health Sciences, for her assistance with statistical review. NR 34 TC 0 Z9 0 U1 0 U2 0 PU FREUND PUBLISHING HOUSE LTD PI TEL AVIV PA PO BOX 35010, TEL AVIV 61350, ISRAEL SN 0334-018X J9 J PEDIATR ENDOCR MET JI J. Pediatr. Endocrinol. Metab. PD JAN PY 2009 VL 22 IS 1 BP 47 EP 53 PG 7 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 415UD UT WOS:000263960200008 PM 19344074 ER PT J AU Nansel, TR Rovner, AJ Haynie, D Iannotti, RJ Simons-Morton, B Wysocki, T Anderson, B Weissberg-Benchell, J Laffel, L AF Nansel, Tonja R. Rovner, Alisha J. Haynie, Denise Iannotti, Ronald J. Simons-Morton, Bruce Wysocki, Timothy Anderson, Barbara Weissberg-Benchell, Jill Laffel, Lori TI Development and Validation of the Collaborative Parent Involvement Scale for Youths with Type 1 Diabetes SO JOURNAL OF PEDIATRIC PSYCHOLOGY LA English DT Article ID QUALITY-OF-LIFE; METABOLIC-CONTROL; SELF-MANAGEMENT; LONGITUDINAL ANALYSIS; HEALTH-STATUS; ADOLESCENTS; FAMILY; ADHERENCE; MELLITUS; SUPPORT AB Objective To develop and test a youth-report measure of collaborative parent involvement in type 1 diabetes management. Methods Initial item development and testing were conducted with 81 youths; scale refinement and validation were conducted with 122 youths from four geographic regions. Descriptive statistics, Cronbachs , and factor analyses were conducted to select items comprising the scale. Correlations with parenting style and parent diabetes responsibility were examined. Multiple regression analyses examining associations with quality of life, adherence, and glycemic control were conducted to assess concurrent validity. Results The measure demonstrated strong internal consistency. It was modestly associated with parenting style, but not with parent responsibility for diabetes management. A consistent pattern of associations with quality of life and adherence provide support for the measures concurrent validity. Conclusions This brief youth-report measure of parent collaborative involvement assesses a unique dimension of parent involvement in diabetes management associated with important youth outcomes. C1 [Nansel, Tonja R.; Rovner, Alisha J.; Haynie, Denise; Iannotti, Ronald J.; Simons-Morton, Bruce] Eunice Kennedy Shriver NICHHD, Div Epidemiol Stat & Prevent Res, NIH, DHHS, Bethesda, MD 20892 USA. [Anderson, Barbara] Baylor Coll Med, Houston, TX 77030 USA. [Weissberg-Benchell, Jill] Childrens Mem Hosp, Chicago, IL 60614 USA. [Laffel, Lori] Joslin Diabet Ctr, Boston, MA 02215 USA. RP Nansel, TR (reprint author), 6100 Execut Blvd,Rm 7B13R,MSC 7510, Bethesda, MD 20892 USA. EM nanselt@mail.nih.gov OI Nansel, Tonja/0000-0002-8298-7595; Simons-Morton, Bruce/0000-0003-1099-6617; Haynie, Denise/0000-0002-8270-6079 FU Intramural NIH HHS [Z01 HD008741-06]; NICHD NIH HHS [N01-HD-4-3361, N01-HD-4-3362, N01 HD003364, N01-HD-4-3363, N01-HD-4-3364, N01-HD-3-3360] NR 42 TC 24 Z9 26 U1 7 U2 11 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0146-8693 J9 J PEDIATR PSYCHOL JI J. Pediatr. Psychol. PD JAN-FEB PY 2009 VL 34 IS 1 BP 30 EP 40 DI 10.1093/jpepsy/jsn058 PG 11 WC Psychology, Developmental SC Psychology GA 392WW UT WOS:000262333900006 PM 18567926 ER PT J AU Alexander, D Boat, T Britto, M Burke, A Homes, A Sectish, T Stanton, B Stevenson, D AF Alexander, Duane Boat, Thomas Britto, Maria Burke, Ann Homes, Alison Sectish, Theodore Stanton, Bonita Stevenson, David TI Federation of Pediatric Organizations Task Force on Women in Pediatrics: Considerations for Part-Time Training and Employment for Research-Intensive Fellows and Faculty SO JOURNAL OF PEDIATRICS LA English DT Editorial Material C1 Childrens Hosp Boston, Boston, MA 02115 USA. [Alexander, Duane] NICHHD, NIH, Bethesda, MD 20892 USA. [Boat, Thomas; Britto, Maria] Cincinnati Childrens Hosp, Cincinnati, OH USA. [Britto, Maria; Burke, Ann; Homes, Alison; Sectish, Theodore; Stanton, Bonita] Wright State Univ, Federat Pediat Org Task Force Women Pediat, Dayton, OH 45435 USA. [Homes, Alison] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Hanover, NH 03756 USA. [Sectish, Theodore] Harvard Univ, Boston, MA 02115 USA. [Stanton, Bonita] Wayne State Univ, Detroit, MI USA. [Stevenson, David] Stanford Univ, Stanford, CA 94305 USA. RP Sectish, T (reprint author), Childrens Hosp Boston, 300 Longwood Ave, Boston, MA 02115 USA. EM theodore.sectish@childrens.harvard.edu NR 0 TC 8 Z9 8 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD JAN PY 2009 VL 154 IS 1 BP 1 EP 3 DI 10.1016/j.jpeds.2008.08.010 PG 3 WC Pediatrics SC Pediatrics GA 391ZK UT WOS:000262272500001 PM 19187728 ER PT J AU Lee, J Seong, HS Kim, BJ Jun, JK Romero, R Yoon, BH AF Lee, JoonHo Seong, Hyo Suk Kim, Byoung Jae Jun, Jong Kwan Romero, Roberto Yoon, Bo Hyun TI Evidence to support that spontaneous preterm labor is adaptive in nature: neonatal RDS is more common in "indicated'' than in "spontaneous'' preterm birth SO JOURNAL OF PERINATAL MEDICINE LA English DT Article DE Indicated preterm birth; neonatal respiratory distress syndrome (RDS); spontaneous preterm birth ID RESPIRATORY-DISTRESS-SYNDROME; HYALINE-MEMBRANE DISEASE; FETAL LUNG MATURITY; INTRAAMNIOTIC ENDOTOXIN; ANTENATAL CORTICOSTEROIDS; AMNIOTIC-FLUID; MATURATION; EPIDEMIOLOGY; CLASSIFICATION; INTERLEUKIN-6 AB Objectives: The onset of preterm labor has been proposed to have survival value and to be adaptive in nature. This hypothesis would predict that induced preterm birth may be associated with higher rates of complications than spontaneous preterm birth. The purpose of this study was to determine if there is a difference in the frequency of neonatal respiratory distress syndrome (RDS), the most common neonatal complication, according to the etiology of preterm birth (e. g., preterm labor [PTL], preterm PROM, or pregnancies which ended because of maternal-fetal indications). Study design: The relationship between the occurrence of RDS and the obstetrical circumstances leading to preterm birth was examined in 257 consecutive singleton preterm births (gestational age: 24-32 weeks). Cases with major congenital anomalies were excluded. The study population was divided into two groups according to the cause of preterm birth: 1) preterm birth due to PTL with intact membranes or preterm PROM (spontaneous preterm birth group); and 2) preterm birth due to maternal or fetal indications (indicated preterm birth group). Results: 1) RDS was diagnosed in 47% of cases; 2) RDS was more common in patients with indicated preterm birth than in those with spontaneous preterm birth group (58.1% vs. 38.4%, P = 0.002); 3) Patients with indicated preterm birth had a significantly higher mean gestational age at birth, but lower mean birth weight, lower rate of histological chorioamnionitis and higher rates of cesarean delivery, 5 min Apgar score of <7, and umbilical arterial blood pH of <7.15 than those with spontaneous preterm birth (P<0.05 for each); 4) Antenatal corticosteroids were used in 73.4% of cases with indicated preterm birth and in 76.9% of those with spontaneous preterm birth; 5) Multivariate analysis demonstrated that indicated preterm birth was associated with an increased risk of RDS after adjusting for confounding variables (OR = 2.29, 95% CI 1.22-4.29). Conclusions: 1) The rate of RDS is greater following "indicated'' rather than spontaneous preterm birth; 2) This observation supports the view that spontaneous preterm labor is adaptive in nature. C1 [Lee, JoonHo; Seong, Hyo Suk; Jun, Jong Kwan; Yoon, Bo Hyun] Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul 110744, South Korea. [Kim, Byoung Jae] Seoul Natl Univ, Boramae Hosp, Dept Obstet & Gynecol, Seoul 110744, South Korea. [Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Detroit, MI USA. RP Yoon, BH (reprint author), Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul 110744, South Korea. EM Yoonbh@snu.ac.kr RI Jun, Jong Kwan/D-5776-2012; Yoon, Bo Hyun/H-6344-2011 OI Jun, Jong Kwan/0000-0002-0242-1736; FU Korea government [R01-2006-000-10607-0]; Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS FX This research was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (No. R01-2006-000-10607-0) and also, in part, by the Intramural Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. NR 27 TC 16 Z9 16 U1 0 U2 1 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 0300-5577 J9 J PERINAT MED JI J. Perinat. Med. PD JAN PY 2009 VL 37 IS 1 BP 53 EP 58 DI 10.1515/JPM.2009.036 PG 6 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 411OL UT WOS:000263658800010 PM 19099368 ER PT J AU Gallo, IS Keil, A McCulloch, KC Rockstroh, B Gollwitzer, PM AF Gallo, Inge Schweiger Keil, Andreas McCulloch, Kathleen C. Rockstroh, Brigitte Gollwitzer, Peter M. TI Strategic Automation of Emotion Regulation SO JOURNAL OF PERSONALITY AND SOCIAL PSYCHOLOGY LA English DT Article DE emotion regulation; implementation intentions; disgust; fear; event-related potentials ID IMPLEMENTATION INTENTIONS; BRAIN POTENTIALS; GOAL ACHIEVEMENT; PLANNED BEHAVIOR; ATTENTION; MOTIVATION; CONSEQUENCES; METAANALYSIS; PERFORMANCE; PHYSIOLOGY AB As implementation intentions are a powerful self-regulation tool for thought and action (meta-analysis by P. M. Gollwitzer & P. Sheeran, 2006), the present studies were conducted to address their effectiveness in regulating emotional reactivity. Disgust-(Study 1) and fear-(Study 2) eliciting stimuli were viewed under 3 different self-regulation instructions: the goal intention to not get disgusted or frightened, respectively, this goal intention furnished with an implementation intention (i.e., an if-then plan), and a no-self-regulation control group. Only implementation-intention participants succeeded in reducing their disgust and fear reactions as compared to goal-intention and control participants. In Study 3, electro-cortical correlates (using dense-array electroencephalography) revealed differential early visual activity in response to spider slides in ignore implementation-intention participants, as reflected in a smaller Pl. Theoretical and applied implications of the present findings for emotion regulation via implementation intentions are discussed. C1 [Gallo, Inge Schweiger] Univ Complutense Madrid, Dept Psicol Social, Fac Ciencias Polit & Sociol, Madrid 28223, Spain. [Keil, Andreas] Univ Florida, NIMH, Ctr Study Emot & Attent, Gainesville, FL 32611 USA. [McCulloch, Kathleen C.] Univ Illinois, Dept Psychol, Urbana, IL 61801 USA. [Rockstroh, Brigitte; Gollwitzer, Peter M.] Univ Konstanz, Fachgrp Psychol, Constance, Germany. [Gollwitzer, Peter M.] NYU, Dept Psychol, New York, NY 10003 USA. RP Gallo, IS (reprint author), Univ Complutense Madrid, Dept Psicol Social, Fac Ciencias Polit & Sociol, Campus Somosaguas, Madrid 28223, Spain. EM ingesg@cps.ucm.es; peter.gollwitzer@nyu.edu RI Keil, Andreas/F-9427-2011; OI Keil, Andreas/0000-0002-4064-1924; McCulloch, Kathleen/0000-0002-0795-8065 FU PHS HHS [R01-67100] NR 86 TC 53 Z9 54 U1 1 U2 31 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-3514 J9 J PERS SOC PSYCHOL JI J. Pers. Soc. Psychol. PD JAN PY 2009 VL 96 IS 1 BP 11 EP 31 DI 10.1037/a0013460 PG 21 WC Psychology, Social SC Psychology GA 388WD UT WOS:000262049800002 PM 19210061 ER PT J AU Sanghvi, R Mogalian, E Machatha, SG Narazaki, R Karlage, KL Jain, P Tabibi, SE Glaze, E Myrdal, PB Yalkowsky, SH AF Sanghvi, Ritesh Mogalian, Erik Machatha, Stephen G. Narazaki, Ryuichi Karlage, Kelly L. Jain, Parijat Tabibi, S. Esmail Glaze, Elizabeth Myrdal, Paul B. Yalkowsky, Samuel H. TI Preformulation and Pharmacokinetic Studies on Antalarmin: A Novel Stress Inhibitor SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE solubility; antalarmin; cosolvent; surfactant; complexing agents; lipid-based formulation ID LIPID-BASED FORMULATIONS; DRUG-DELIVERY SYSTEMS; RECEPTOR ANTAGONIST; IN-VITRO; SOLUBILIZATION; ABSORPTION; COMPLEXATION; LABRASOL; VIVO AB The preformulation, solubilization and pharmacokinetic evaluation of antalarmin, a stress inhibitor, have been conducted. Antalarmin has a poor water solubility of less than 1 mu g/mL and is weakly basic with an experimentally determined pK(a) of 5.0. Multiple solubilization approaches including pH-control either alone or in combination with cosolvents, surfactants and complexing agents have been investigated. The applicability of lipid-based systems has also been explored. Four formulations, each with a targeted drug loading capacity of 100 mg/mL, show potential for oral administration. Three of these formulations are aqueous solutions (10% ethanol+40% propylene glycol; 20% cremophor EL; 20% sulfobutylether-beta-cyclodextrin) each buffered at pH 1. The fourth formulation is a lipid-based formulation comprising of 20% oleic acid, 40% cremophor EL and 40% Labrasol. No precipitation was observed following dilution of the four formulations with water and enzyme free simulated gastric fluid. However, only the lipid-based formulation successfully resisted drug precipitation following dilution with enzyme free simulated intestinal fluid. Pharmacokinetic analysis conducted in rats revealed that the 20% cremophor EL solution formulation has a fivefold higher oral bioavailability compared to a suspension formulation. The lipid-based formulation resulted in over 12-fold higher bioavailability as compared to the suspension formulation, the highest amongst the formulations examined. (C) 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:205-214, 2009 C1 [Sanghvi, Ritesh; Mogalian, Erik; Karlage, Kelly L.; Jain, Parijat; Myrdal, Paul B.; Yalkowsky, Samuel H.] Univ Arizona, Coll Pharm, Tucson, AZ 85721 USA. [Machatha, Stephen G.] Cydex Inc, Lenexa, KS 66214 USA. [Narazaki, Ryuichi] Eisai & Co Ltd, Formulat Res Lab, Gifu 5016195, Japan. [Tabibi, S. Esmail; Glaze, Elizabeth] NCI, Bethesda, MD 20892 USA. RP Sanghvi, R (reprint author), Univ Arizona, Coll Pharm, Tucson, AZ 85721 USA. EM rsanghvi@pharmacy.arizona.edu NR 27 TC 9 Z9 9 U1 2 U2 8 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD JAN PY 2009 VL 98 IS 1 BP 205 EP 214 DI 10.1002/jps.21421 PG 10 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 391JC UT WOS:000262228600017 PM 18428980 ER PT J AU Kitazawa, T Asakawa, K Teraoka, H Unno, T Komori, S Yamada, M Wess, J AF Kitazawa, Takio Asakawa, Koichi Teraoka, Hiroki Unno, Toshihiro Komori, Sei-ichi Yamada, Masahisa Wess, Jurgen TI Opposite inotropic action induced by activation of M2 and M3 muscarinic receptors in mouse atrium SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 82nd Annual Meeting of the Japanese-Pharmacological-Society CY MAR 16-18, 2009 CL Yokohama, JAPAN SP Japanese Pharmacol Soc C1 [Kitazawa, Takio; Asakawa, Koichi] Rakuno Gakuen Univ, Sch Vet Med, Dept Pharmacol, Ebetsu, Hokkaido 0698501, Japan. [Teraoka, Hiroki] Rakuno Gakuen Univ, Sch Vet Med, Dept Toxicol, Ebetsu, Hokkaido 0698501, Japan. [Unno, Toshihiro; Komori, Sei-ichi] Gifu Univ, Fac Appl Biol Sci, Pharmacol Lab, Gifu 5011193, Japan. [Yamada, Masahisa] RIKEN Brain Sci Inst, Yamada Res Unit, Wako, Saitama 3510198, Japan. [Wess, Jurgen] NIDDKD, Bioorgan Chem Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2009 VL 109 BP 86P EP 86P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 422BV UT WOS:000264402900294 ER PT J AU Tanabe, M Chiba, Y Kimura, H Misawa, M AF Tanabe, Miki Chiba, Yoshihiko Kimura, Hioko Misawa, Miwa TI Pharmacological studies on the respiratory tract (Rpt. 319): Possible involvement of CPI-17 in augmented contraction of bronchial smooth muscle in mice with allergic bronchial asthma SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 82nd Annual Meeting of the Japanese-Pharmacological-Society CY MAR 16-18, 2009 CL Yokohama, JAPAN SP Japanese Pharmacol Soc C1 [Tanabe, Miki; Chiba, Yoshihiko; Misawa, Miwa] Hoshi Univ, Sch Pharm, Dept Pharmacol, Shinagawa Ku, Tokyo 1428501, Japan. [Kimura, Hioko] NCI, Endorinol Sec, Lab Metab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2009 VL 109 BP 113P EP 113P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 422BV UT WOS:000264402900402 ER PT J AU Tanahashi, Y Waki, N Unno, T Matsuyama, H Yamada, M Jurgen, W Komori, S AF Tanahashi, Yasuyuki Waki, Naoko Unno, Toshihiro Matsuyama, Hayato Yamada, Masahisa Jurgen, Wess Komori, Seiichi TI Roles of M-2 and M-3 muscarinic receptors involved in the generation of peristaltic movements in mouse ileum SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 82nd Annual Meeting of the Japanese-Pharmacological-Society CY MAR 16-18, 2009 CL Yokohama, JAPAN SP Japanese Pharmacol Soc C1 [Tanahashi, Yasuyuki] Gifu Univ, Dept Patho Vet Sci, Unite Grad Sch Vet Sci, Gifu 5011193, Japan. [Waki, Naoko; Unno, Toshihiro; Matsuyama, Hayato; Komori, Seiichi] Gifu Univ, Pharmacol Lab, Dept Vet Med, Gifu 5011193, Japan. [Yamada, Masahisa] RIKEN, Yamada Res Unit, Brain Sci Inst, Wako, Saitama 3510198, Japan. [Jurgen, Wess] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2009 VL 109 SU 1 BP 152P EP 152P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 422BV UT WOS:000264402901048 ER PT J AU Jones, PJ Merrick, EC Batts, TW Hargus, NJ Wang, YS Stables, JP Bertram, EH Brown, ML Patel, MK AF Jones, Paulianda J. Merrick, Ellen C. Batts, Timothy W. Hargus, Nicholas J. Wang, Yuesheng Stables, James P. Bertram, Edward H. Brown, Milton L. Patel, Manoj K. TI Modulation of Sodium Channel Inactivation Gating by a Novel Lactam: Implications for Seizure Suppression in Chronic Limbic Epilepsy SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID RAT HIPPOCAMPAL-NEURONS; SLOW INACTIVATION; NA+ CHANNELS; MOLECULAR-MECHANISMS; ANTIEPILEPTIC DRUGS; LIDOCAINE BLOCK; BRAIN; PHENYTOIN; CURRENTS; STATE AB Epilepsy remains a devastating neurological disorder associated with recurrent, unprovoked, spontaneous epileptic seizures. Current treatments involve seizure suppression using antiepileptic drugs (AEDs); however, many patients remain refractory to current treatments or suffer serious side effects. In view of this continued need for more effective and safer AEDs, we have designed a novel compound, 3-hydroxy-3-(4-methoxyphenyl)1-methyl-1,3-dihydro-indol-2-one (YWI92), based on a lactam structural class, and evaluated its modulation of human neuronal sodium channel isoform (hNa(v)) 1.2 currents and hippocampal neuron action potential firing. Furthermore, we have tested its AED activity using a chronic and acute rat seizure model. In a similar manner to lamotrigine, a clinically used AED, YWI92 exhibited tonic block of hNav 1.2 channels and caused a hyperpolarizing shift in the steady-state inactivation curve when using a 30-s inactivating prepulse. YWI92 also delayed the time constants of channel repriming after a 30-s inactivating prepulse and exhibited use-dependent block at 20-Hz stimulation frequency. In membrane excitability experiments, YWI92 inhibited burst firing in CA1 neurons of animals with temporal lobe epilepsy at concentrations that had little effect on CA1 neurons from control animals. These actions on neuronal activity translated into AED activity in the maximal electroshock acute seizure model (ED(50) = 22.96 mg/kg), and importantly, in a chronic temporal lobe epilepsy model, in which the mean number of seizures was reduced. Notably, YWI92 exhibited no sedative/ataxic side effects at concentrations up to 500 mg/kg. In summary, greater affinity for inactivated sodium channels, particularly after long depolarizing prepulses, may be important for both anticonvulsant activity and drug tolerability. C1 [Hargus, Nicholas J.; Bertram, Edward H.; Patel, Manoj K.] Univ Virginia, Grad Program Neurosci, Charlottesville, VA USA. [Jones, Paulianda J.; Merrick, Ellen C.; Batts, Timothy W.; Hargus, Nicholas J.; Patel, Manoj K.] Univ Virginia, Dept Anesthesiol, Charlottesville, VA USA. [Bertram, Edward H.] Univ Virginia, Dept Neurol, Charlottesville, VA USA. [Wang, Yuesheng] Univ Virginia, Dept Chem, Charlottesville, VA USA. [Brown, Milton L.] Georgetown Univ, Med Ctr, Dept Oncol, Washington, DC 20007 USA. [Brown, Milton L.] Georgetown Univ, Med Ctr, Dept Neurosci, Washington, DC 20007 USA. [Stables, James P.] NINDS, ASP Program, Rockville, MD USA. RP Patel, MK (reprint author), Univ Virginia Hlth Syst, Dept Anesthesiol, Old Med Sch, 1 Hosp Dr, Charlottesville, VA 22908 USA. EM mkp5u@virginia.edu OI Schill, Ellen/0000-0003-2803-0132 FU National Institutes of Health [R01 CA 105435-01, 5 T32 GM008328]; United Negro College Fund/Merck Science Initiative FX This work was supported by the National Institutes of Health [Grants NIH R01 CA 105435-01, 5 T32 GM008328]; and the United Negro College Fund/Merck Science Initiative. NR 40 TC 12 Z9 12 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JAN PY 2009 VL 328 IS 1 BP 201 EP 212 DI 10.1124/jpet.108.144709 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 385AC UT WOS:000261784300022 PM 18952887 ER PT J AU Godlewski, G Offertaler, L Osei-Hyiaman, D Mo, FM Harvey-White, J Liu, J Davis, MI Zhang, L Razdan, RK Milman, G Pacher, P Mukhopadhyay, P Lovinger, DM Kunos, G AF Godlewski, Grzegorz Offertaler, Laszlo Osei-Hyiaman, Douglas Mo, Fong Ming Harvey-White, Judith Liu, Jie Davis, Margaret I. Zhang, Li Razdan, Raj K. Milman, Garry Pacher, Pal Mukhopadhyay, Partha Lovinger, David M. Kunos, George TI The Endogenous Brain Constituent N-Arachidonoyl L-Serine Is an Activator of Large Conductance Ca2+-Activated K+ Channels SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID ANANDAMIDE-INDUCED VASORELAXATION; POTASSIUM CHANNELS; CORONARY-ARTERIES; BKCA CHANNELS; LIPID RAFTS; RECEPTORS; CELLS; ACID; KINASE; PHOSPHORYLATION AB The novel endocannabinoid-like lipid N-arachidonoyl L-serine (ARA-S) causes vasodilation through both endothelium-dependent and -independent mechanisms. We have analyzed the vasorelaxant effect of ARA-S in isolated vascular preparations and its effects on Ca2+-activated K+ currents in human embryonic kidney cells stably transfected with the alpha-subunit of the human, large conductance Ca2+- activated K+ (BKCa) channel [human embryonic kidney (HEK) 293hSlo cells]. ARA-S caused relaxation of rat isolated, intact and denuded, small mesenteric arteries preconstricted with (R)-(-)-1-(3-hydroxyphenyl)-2-methylaminoethanol hydrochloride (pEC(50), 5.49 and 5.14, respectively), whereas it caused further contraction of vessels preconstricted with KCI (pEC(50), 5.48 and 4.82, respectively). Vasorelaxation by ARA-S was inhibited by 100 nM iberiotoxin. In human embryonic kidney cells stably transfected with the alpha-subunit of the human BKCa channel cells, ARA-S and its enantiomer, N-arachidonoyl-D-serine, enhanced the whole-cell outward K+ current with similar potency (pEC(50), 5.63 and 5.32, respectively). The potentiation was not altered by the beta(1) subunit or mediated by ARA-S metabolites, stimulation of known cannabinoid receptors, G proteins, protein kinases, or Ca2+-dependent processes; it was lost after patch excision or after membrane cholesterol depletion but was restored after cholesterol reconstitution. BKCa currents were also enhanced by N-arachidonoyl ethanolamide (pEC(50), 5.27) but inhibited by another endocannabinoid, O-arachidonoyl ethanolamine (pIC(50), 6.35), or by the synthetic cannabinoid O-1918 [(-)-1,3-dimethoxy- 2-(3-3,4-trans-p-menthadien-(1,8)-yl)-orcinol] (pIC(50), 6.59), which blocks ARA-S- induced vasodilation. We conclude the following. 1) ARA-S directly activates BKCa channels. 2) This interaction does not involve cannabinoid receptors or cytosolic factors but is dependent on the presence of membrane cholesterol. 3) Direct BKCa channel activation probably contributes to the endothelium-independent component of ARA-S-induced mesenteric vasorelaxation. 4) O-1918 is a BKCa channel inhibitor. C1 [Godlewski, Grzegorz; Offertaler, Laszlo; Osei-Hyiaman, Douglas; Mo, Fong Ming; Harvey-White, Judith; Liu, Jie; Pacher, Pal; Mukhopadhyay, Partha; Kunos, George] NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. [Davis, Margaret I.; Zhang, Li; Lovinger, David M.] NIAAA, Lab Integrat Neurosci, NIH, Bethesda, MD 20892 USA. [Razdan, Raj K.] Organix Inc, Woburn, MA USA. [Milman, Garry] Hebrew Univ Jerusalem, Dept Med Chem, Jerusalem, Israel. RP Godlewski, G (reprint author), NIAAA, Lab Physiol Studies, NIH, 5625 Fishers Lane, Bethesda, MD 20892 USA. EM godlewskig@mail.nih.gov RI Davis, Margaret/F-4165-2010; MUKHOPADHYAY, PARTHA/G-3890-2010; Pacher, Pal/B-6378-2008; OI MUKHOPADHYAY, PARTHA/0000-0002-1178-1274; Pacher, Pal/0000-0001-7036-8108; Davis, Margaret/0000-0002-0489-8351 FU Intramural Research Program of the National Institutes of Health; National Institute on Alcohol Abuse and Alcoholism FX This study was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism. NR 40 TC 20 Z9 20 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JAN PY 2009 VL 328 IS 1 BP 351 EP 361 DI 10.1124/jpet.108.144717 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 385AC UT WOS:000261784300038 PM 18923087 ER PT J AU Cidlowski, JA AF Cidlowski, John A. TI THE GLUCOCORTICOID RECEPTOR: ONE GENE, MANY PROTEINS - AN INTRACELLULAR SENSOR FOR GLUCOCORTICOIDS SO JOURNAL OF PHYSIOLOGICAL SCIENCES LA English DT Meeting Abstract C1 [Cidlowski, John A.] Natl Inst Environm Hlth Sci, Lab Signal Transduct, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER TOKYO PI TOKYO PA 1-11-11 KUDAN-KITA, CHIYODA-KU, TOKYO, 102-0073, JAPAN SN 1880-6546 J9 J PHYSIOL SCI JI J. Physiol. Sci. PY 2009 VL 59 SU 1 BP 39 EP 39 PG 1 WC Physiology SC Physiology GA 509MX UT WOS:000271023100153 ER PT J AU Hikosaka, O AF Hikosaka, Okihide TI BIASING, LEARNING, AND SWITCHING OF BEHAVIOR BY THE BASAL GANGLIA SO JOURNAL OF PHYSIOLOGICAL SCIENCES LA English DT Meeting Abstract C1 [Hikosaka, Okihide] NEI, Sensorimotor Res Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER TOKYO PI TOKYO PA 1-11-11 KUDAN-KITA, CHIYODA-KU, TOKYO, 102-0073, JAPAN SN 1880-6546 J9 J PHYSIOL SCI JI J. Physiol. Sci. PY 2009 VL 59 SU 1 BP 48 EP 48 PG 1 WC Physiology SC Physiology GA 509MX UT WOS:000271023100209 ER PT J AU Donaldson, JG AF Donaldson, Julie G. TI G PROTEINS IN ENDOSOMAL TRAFFICKING PATHWAYS SO JOURNAL OF PHYSIOLOGICAL SCIENCES LA English DT Meeting Abstract C1 [Donaldson, Julie G.] NHLBI, Cell Biol Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU SPRINGER TOKYO PI TOKYO PA 1-11-11 KUDAN-KITA, CHIYODA-KU, TOKYO, 102-0073, JAPAN SN 1880-6546 J9 J PHYSIOL SCI JI J. Physiol. Sci. PY 2009 VL 59 SU 1 BP 56 EP 56 PG 1 WC Physiology SC Physiology GA 509MX UT WOS:000271023100254 ER PT J AU Maltsev, VA Lakatta, EG AF Maltsev, Victor A. Lakatta, Edward G. TI NOVEL PERSPECTIVES ON CARDIAC PACEMAKER REGULATION BASED ON NUMERICAL MODELING OF COUPLED SUBCELLULAR Ca AND MEMBRANE VOLTAGE OSCILLATORS SO JOURNAL OF PHYSIOLOGICAL SCIENCES LA English DT Meeting Abstract C1 [Maltsev, Victor A.; Lakatta, Edward G.] NIA, Cardiovasc Sci Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER TOKYO PI TOKYO PA 1-11-11 KUDAN-KITA, CHIYODA-KU, TOKYO, 102-0073, JAPAN SN 1880-6546 J9 J PHYSIOL SCI JI J. Physiol. Sci. PY 2009 VL 59 SU 1 BP 66 EP 66 PG 1 WC Physiology SC Physiology GA 509MX UT WOS:000271023100309 ER PT J AU Petit, C Michalski, N Michel, V Verpy, E Caberlotto, E Gaelle, L Leibovici, M Weil, D Hardelin, JP Richardson, GP Martin, P Avan, P AF Petit, Christine Michalski, Nicolas Michel, Vincent Verpy, Elisabeth Caberlotto, Elisa Gaelle, Lefevre Leibovici, Michel Weil, Dominique Hardelin, Jean-Pierre Richardson, Guy P. Martin, Pascal Avan, Paul TI LINKING DEAFNESS GENES TO HAIR-BUNDLE DEVELOPMENT AND PHYSIOLOGY: THE ROLE OF HAIR-BUNDLE LINKS AND ASSOCIATED PROTEINS SO JOURNAL OF PHYSIOLOGICAL SCIENCES LA English DT Meeting Abstract C1 [Gaelle, Lefevre] UPMC, Inst Pasteur, INSERM, Unite Genet & Physiol Audit,UMRS587, Paris, France. [Gaelle, Lefevre] NIDKK, NIH, Bethesda, MD USA. [Richardson, Guy P.] Univ Sussex, Sch Life Sci, Brighton, E Sussex, England. [Martin, Pascal] Inst Curie, Lab Physicochim, CNRS, UMR 168, F-75231 Paris, France. [Avan, Paul] Univ Auvergne, Lab Biophys Sensorielle, Auvergne, France. RI AVAN, Paul/J-6878-2015 NR 0 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER TOKYO PI TOKYO PA 1-11-11 KUDAN-KITA, CHIYODA-KU, TOKYO, 102-0073, JAPAN SN 1880-6546 J9 J PHYSIOL SCI JI J. Physiol. Sci. PY 2009 VL 59 SU 1 BP 76 EP 76 PG 1 WC Physiology SC Physiology GA 509MX UT WOS:000271023100370 ER PT J AU Sakaguchi, H Tokita, J Fujita, T Suzuki, T Kachar, B Hisa, Y AF Sakaguchi, Hirofumi Tokita, Joshua Fujita, Tomoki Suzuki, Toshihiro Kachar, Bechara Hisa, Yasuo TI THE MOLECULAR ASSEMBLY OF THE TIP-LINK FILAMENTS IN SENSORY HAIR CELLS SO JOURNAL OF PHYSIOLOGICAL SCIENCES LA English DT Meeting Abstract C1 [Sakaguchi, Hirofumi; Fujita, Tomoki; Suzuki, Toshihiro; Hisa, Yasuo] Kyoto Prefectural Univ Med, Dept Otolaryngol Head & Neck Surg, Kyoto 602, Japan. [Tokita, Joshua; Kachar, Bechara] NIDCD, Lab Cell Struct & Dynam, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER TOKYO PI TOKYO PA 1-11-11 KUDAN-KITA, CHIYODA-KU, TOKYO, 102-0073, JAPAN SN 1880-6546 J9 J PHYSIOL SCI JI J. Physiol. Sci. PY 2009 VL 59 SU 1 BP 76 EP 76 PG 1 WC Physiology SC Physiology GA 509MX UT WOS:000271023100371 ER PT J AU Cumming, BG Haefner, R Tanabe, S AF Cumming, Bruce Gordon Haefner, Ralf Tanabe, Seiji TI HOW CORTICAL NEURONS REPRESENT NATURALLY OCCURRING DISPARITIES SO JOURNAL OF PHYSIOLOGICAL SCIENCES LA English DT Meeting Abstract C1 [Cumming, Bruce Gordon; Haefner, Ralf; Tanabe, Seiji] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER TOKYO PI TOKYO PA 1-11-11 KUDAN-KITA, CHIYODA-KU, TOKYO, 102-0073, JAPAN SN 1880-6546 J9 J PHYSIOL SCI JI J. Physiol. Sci. PY 2009 VL 59 SU 1 BP 79 EP 79 PG 1 WC Physiology SC Physiology GA 509MX UT WOS:000271023100390 ER PT J AU Krug, K Cumming, BG Dodd, JV Parker, AJ AF Krug, Kristine Cumming, Bruce G. Dodd, Jon V. Parker, Andrew J. TI NEURONS IN VISUAL AREA V5/MT IN THE AWAKE RHESUS MONKEY ARE SELECTIVE FOR THE RELATIVE DISPARITY BETWEEN TWO TRANSPARENT PLANES SO JOURNAL OF PHYSIOLOGICAL SCIENCES LA English DT Meeting Abstract C1 [Krug, Kristine; Dodd, Jon V.; Parker, Andrew J.] Univ Oxford, Dept Physiol Anat & Genet, Oxford OX1 2JD, England. [Cumming, Bruce G.] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD USA. RI Parker, Andrew/I-7867-2013 OI Parker, Andrew/0000-0001-5800-0407 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER TOKYO PI TOKYO PA 1-11-11 KUDAN-KITA, CHIYODA-KU, TOKYO, 102-0073, JAPAN SN 1880-6546 J9 J PHYSIOL SCI JI J. Physiol. Sci. PY 2009 VL 59 SU 1 BP 79 EP 79 PG 1 WC Physiology SC Physiology GA 509MX UT WOS:000271023100391 ER PT J AU Putney, JW AF Putney, James W. TI REGULATION OF STORE-OPERATED CALCIUM ENTRY SO JOURNAL OF PHYSIOLOGICAL SCIENCES LA English DT Meeting Abstract C1 [Putney, James W.] Natl Inst Environm Hlth Sci, Lab Signal Transduct, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER TOKYO PI TOKYO PA 1-11-11 KUDAN-KITA, CHIYODA-KU, TOKYO, 102-0073, JAPAN SN 1880-6546 J9 J PHYSIOL SCI JI J. Physiol. Sci. PY 2009 VL 59 SU 1 BP 91 EP 91 PG 1 WC Physiology SC Physiology GA 509MX UT WOS:000271023100459 ER PT J AU Puertollano, R Martina, J Vergarajauregui, S Lelouvier, B AF Puertollano, Rosa Martina, Jose Vergarajauregui, Silvia Lelouvier, Benjamin TI TRPMLs REGULATE TRAFFICKING OF LIPIDS AND PROTEINS ALONG THE ENDOSOMAL/LYSOSOMAL PATHWAY SO JOURNAL OF PHYSIOLOGICAL SCIENCES LA English DT Meeting Abstract C1 [Puertollano, Rosa; Martina, Jose; Vergarajauregui, Silvia; Lelouvier, Benjamin] NIH, Cell Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER TOKYO PI TOKYO PA 1-11-11 KUDAN-KITA, CHIYODA-KU, TOKYO, 102-0073, JAPAN SN 1880-6546 J9 J PHYSIOL SCI JI J. Physiol. Sci. PY 2009 VL 59 SU 1 BP 104 EP 104 PG 1 WC Physiology SC Physiology GA 509MX UT WOS:000271023100540 ER PT J AU Allard, JS de Cabo, R Mattison, J Pearson, K Minor, R Ingram, D AF Allard, Joanne Stacey de Cabo, Rafael Mattison, Julie Pearson, Kevin Minor, Robin Ingram, Donald TI CALORIE RESTRICTION MIMETICS: DEVELOPING INTERVENTIONS FOR HEALTHY AGING AND LONGEVITY SO JOURNAL OF PHYSIOLOGICAL SCIENCES LA English DT Meeting Abstract C1 [Allard, Joanne Stacey; de Cabo, Rafael; Mattison, Julie; Minor, Robin] NIA, Lab Expt Gerontol, Bethesda, MD 20892 USA. [Pearson, Kevin] Univ Kentucky, Lexington, KY USA. [Ingram, Donald] Pennington Biomed Res Ctr, Baton Rouge, LA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER TOKYO PI TOKYO PA 1-11-11 KUDAN-KITA, CHIYODA-KU, TOKYO, 102-0073, JAPAN SN 1880-6546 J9 J PHYSIOL SCI JI J. Physiol. Sci. PY 2009 VL 59 SU 1 BP 111 EP 111 PG 1 WC Physiology SC Physiology GA 509MX UT WOS:000271023100580 ER PT J AU Bortner, CD Sifre, MI Cidlowski, JA AF Bortner, Carl David Sifre, Maria I. Cidlowski, John A. TI CATIONIC GRADIENT REVERSAL AND CYTOSKELETAL INDEPENDENT VOLUME REGULATORY PATHWAYS DEFINE AN EARLY STAGE OF APOPTOSIS IN LYMPHOID CELLS SO JOURNAL OF PHYSIOLOGICAL SCIENCES LA English DT Meeting Abstract C1 [Bortner, Carl David; Sifre, Maria I.; Cidlowski, John A.] NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER TOKYO PI TOKYO PA 1-11-11 KUDAN-KITA, CHIYODA-KU, TOKYO, 102-0073, JAPAN SN 1880-6546 J9 J PHYSIOL SCI JI J. Physiol. Sci. PY 2009 VL 59 SU 1 BP 153 EP 153 PG 1 WC Physiology SC Physiology GA 509MX UT WOS:000271023100822 ER PT J AU Tanahashi, Y Waki, N Unno, T Matsuyama, H Yamada, M Wess, J Komori, S AF Tanahashi, Yasuyuki Waki, Naoko Unno, Toshihiro Matsuyama, Hayato Yamada, Masahisa Wess, Jurgen Komori, Seiichi TI MYENTERIC INTERSTITIAL CELLS OF CAJAL AND M-3 MUSCARINIC RECEPTORS REGULATE THE PERIODICITY OF PERISTALTIC MOVEMENTS IN MOUSE SMALL INTESTINE SO JOURNAL OF PHYSIOLOGICAL SCIENCES LA English DT Meeting Abstract C1 [Waki, Naoko; Unno, Toshihiro; Matsuyama, Hayato; Komori, Seiichi] Gifu Univ, Fac Appl Biol Sci, Dept Vet Med, Pharmacol Lab, Gifu, Japan. [Yamada, Masahisa] RIKEN, Brain Sci Inst, Yamada Res Unit, Wako, Saitama, Japan. [Wess, Jurgen] NIDDKD, Bioorgan Chem Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER TOKYO PI TOKYO PA 1-11-11 KUDAN-KITA, CHIYODA-KU, TOKYO, 102-0073, JAPAN SN 1880-6546 J9 J PHYSIOL SCI JI J. Physiol. Sci. PY 2009 VL 59 SU 1 BP 345 EP 345 PG 1 WC Physiology SC Physiology GA 509MX UT WOS:000271023102330 ER PT J AU Ueyama, T Morand, S Tsujibe, S Korzeniowska, A Saito, N Leto, TL AF Ueyama, Takehiko Morand, Stanislas Tsujibe, Satoshi Korzeniowska, Agnieszka Saito, Naoaki Leto, Thomas L. TI DUAL OXIDASES (DUOXS) FORM CELL SURFACE COMPLEXES WITH DUOX ACTIVATORS (DUOXAS) AFFECTING THE SPECIFICITY OF ROS GENERATION SO JOURNAL OF PHYSIOLOGICAL SCIENCES LA English DT Meeting Abstract C1 [Ueyama, Takehiko; Tsujibe, Satoshi; Saito, Naoaki] Kobe Univ, Mol Pharmacol Lab, Biosignal Res Ctr, Kobe, Hyogo, Japan. [Morand, Stanislas; Korzeniowska, Agnieszka; Leto, Thomas L.] NIAID, Host Def Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER TOKYO PI TOKYO PA 1-11-11 KUDAN-KITA, CHIYODA-KU, TOKYO, 102-0073, JAPAN SN 1880-6546 J9 J PHYSIOL SCI JI J. Physiol. Sci. PY 2009 VL 59 SU 1 BP 347 EP 347 PG 1 WC Physiology SC Physiology GA 509MX UT WOS:000271023102339 ER PT J AU Phillips, DJ French, S Aponte, A Boja, E Blinova, K Balaban, RS AF Phillips, Darci Joelle French, Stephanie Aponte, Angel Boja, Emily Blinova, Ksenia Balaban, Robert S. TI MITOCHONDRIAL OXIDATIVE PHOSPHORYLATION ACTIVITY PER MOLE OF ENZYME COMPLEX IS DIFFERENTIALLY CONTROLLED IN HEART AND LIVER SO JOURNAL OF PHYSIOLOGICAL SCIENCES LA English DT Meeting Abstract C1 [Phillips, Darci Joelle; French, Stephanie; Aponte, Angel; Boja, Emily; Blinova, Ksenia; Balaban, Robert S.] NHLBI, Cardiac Energet Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER TOKYO PI TOKYO PA 1-11-11 KUDAN-KITA, CHIYODA-KU, TOKYO, 102-0073, JAPAN SN 1880-6546 J9 J PHYSIOL SCI JI J. Physiol. Sci. PY 2009 VL 59 SU 1 BP 348 EP 348 PG 1 WC Physiology SC Physiology GA 509MX UT WOS:000271023102345 ER PT J AU Tomida, M Yamashita, S Onozuka, M Hirano, Y Tachibana, A Ando, H Asanuma, N AF Tomida, Mihoko Yamashita, Shuichiro Onozuka, Minoru Hirano, Yoshiyuki Tachibana, Atsumichi Ando, Hiroshi Asanuma, Naokazu TI REDUCING EFFECTS OF ADDITIONAL SENSORY STIMULI ON PERCEPTION OF PAIN SO JOURNAL OF PHYSIOLOGICAL SCIENCES LA English DT Meeting Abstract C1 [Tomida, Mihoko; Ando, Hiroshi; Asanuma, Naokazu] Matsumoto Dent Univ, Dept Oral Physiol, Matsumoto, Nagano, Japan. [Yamashita, Shuichiro] Matsumoto Dent Univ, Dept Oral & Maxillofacial Biol, Matsumoto, Nagano, Japan. [Onozuka, Minoru] Kanagawa Dent Coll, Dept Physiol & Neurosci, Kanagawa, Japan. [Hirano, Yoshiyuki] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER TOKYO PI TOKYO PA 1-11-11 KUDAN-KITA, CHIYODA-KU, TOKYO, 102-0073, JAPAN SN 1880-6546 J9 J PHYSIOL SCI JI J. Physiol. Sci. PY 2009 VL 59 SU 1 BP 374 EP 374 PG 1 WC Physiology SC Physiology GA 509MX UT WOS:000271023102501 ER PT J AU Zemkova, H Jindrichova, M Vavra, V Obsil, T Stojilkovic, SS AF Zemkova, Hana Jindrichova, Marie Vavra, Vojtech Obsil, Tomas Stojilkovic, Stanko S. TI CONTRIBUTION OF AROMATIC RESIDUES IN THE FIRST TRANSMEMBRANE DOMAIN TO FUNCTION OF P2X RECEPTORS SO JOURNAL OF PHYSIOLOGICAL SCIENCES LA English DT Meeting Abstract C1 [Stojilkovic, Stanko S.] NICHD, Sect Cellular Signaling, Program Dev Neurosci, NIH, Bethesda, MD USA. RI Jindrichova, Marie/H-4320-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER TOKYO PI TOKYO PA 1-11-11 KUDAN-KITA, CHIYODA-KU, TOKYO, 102-0073, JAPAN SN 1880-6546 J9 J PHYSIOL SCI JI J. Physiol. Sci. PY 2009 VL 59 SU 1 BP 394 EP 394 PG 1 WC Physiology SC Physiology GA 509MX UT WOS:000271023102620 ER PT J AU Chatsudthipong, V Meetam, P Srimaroeng, C Soodvilai, S AF Chatsudthipong, Varanuj Meetam, Paranee Srimaroeng, Chutima Soodvilai, Sunhapas TI REGULATION OF RENAL ORGANIC CATION TRANSPORT BY TESTOSTERONE IN MICE SO JOURNAL OF PHYSIOLOGICAL SCIENCES LA English DT Meeting Abstract C1 [Chatsudthipong, Varanuj; Meetam, Paranee; Soodvilai, Sunhapas] Mahidol Univ, Bangkok 10700, Thailand. [Srimaroeng, Chutima] NIEHS, Pharmacol Lab, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER TOKYO PI TOKYO PA 1-11-11 KUDAN-KITA, CHIYODA-KU, TOKYO, 102-0073, JAPAN SN 1880-6546 J9 J PHYSIOL SCI JI J. Physiol. Sci. PY 2009 VL 59 SU 1 BP 434 EP 434 PG 1 WC Physiology SC Physiology GA 509MX UT WOS:000271023103045 ER PT J AU Shiono, H Ogawa, S Chen, HM Okada, T Okada, Y Maruoka, H Ito, Y AF Shiono, Hiroyuki Ogawa, Shintaro Chen, Hong M. Okada, Tadashi Okada, Yasunori Maruoka, Hiroki Ito, Yoichiro TI NOVEL FLOW-THROUGH DENSITY GRADIENT CELL SEPARATION VERSUS FICOLL DENSITY GRADIENT METHOD IN SEPARATION OF HEMATOPOIETIC PROGENITOR CELLS SO JOURNAL OF PHYSIOLOGICAL SCIENCES LA English DT Meeting Abstract C1 [Shiono, Hiroyuki; Ogawa, Shintaro; Chen, Hong M.; Okada, Tadashi] Aichi Med Univ, Dept Physiol, Sch Med, Aichi, Japan. [Okada, Yasunori] Kutuwa Sangyo Co Ltd, Hiroshima, Japan. [Maruoka, Hiroki] Kurabo Ind Ltd, Tech Res Lab, Osaka, Japan. [Ito, Yoichiro] NHLBI, Bioseparat Technol Lab, Biochem & Biophys Ctr, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER TOKYO PI TOKYO PA 1-11-11 KUDAN-KITA, CHIYODA-KU, TOKYO, 102-0073, JAPAN SN 1880-6546 J9 J PHYSIOL SCI JI J. Physiol. Sci. PY 2009 VL 59 SU 1 BP 438 EP 438 PG 1 WC Physiology SC Physiology GA 509MX UT WOS:000271023103070 ER PT J AU Yazawa, I O'Donovan, MJ AF Yazawa, Itaru O'Donovan, Michael J. TI NEURONAL ACTIVITY ORIGINATING IN THE BRAINSTEM CAN TRIGGER LOCOMOTOR-LIKE ACTIVITY VIA DESCENDING PATHWAYS IN THE LOWER SPINAL CORD SO JOURNAL OF PHYSIOLOGICAL SCIENCES LA English DT Meeting Abstract C1 [Yazawa, Itaru; O'Donovan, Michael J.] NINDS, Sect Dev Neurobiol, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER TOKYO PI TOKYO PA 1-11-11 KUDAN-KITA, CHIYODA-KU, TOKYO, 102-0073, JAPAN SN 1880-6546 J9 J PHYSIOL SCI JI J. Physiol. Sci. PY 2009 VL 59 SU 1 BP 450 EP 450 PG 1 WC Physiology SC Physiology GA 509MX UT WOS:000271023103144 ER PT J AU Toda, K Mizuhiki, T Sugase-Miyamoto, Y Inaba, K Ozaki, S Richmond, BJ Shidara, M AF Toda, Koji Mizuhiki, Takashi Sugase-Miyamoto, Yasuko Inaba, Kiyonori Ozaki, Shigeru Richmond, Barry J. Shidara, Munetaka TI NEURAL SIGNALS IN THE ROSTRAL PART OF THE ANTERIOR CINGULATE CORTEX MODULATED BY THE REWARD PROXIMITY AND AMOUNT SO JOURNAL OF PHYSIOLOGICAL SCIENCES LA English DT Meeting Abstract C1 [Toda, Koji; Mizuhiki, Takashi; Inaba, Kiyonori; Ozaki, Shigeru; Shidara, Munetaka] Univ Tsukuba, Grad Sch Comprehens Human Sci, Tsukuba, Ibaraki 305, Japan. [Sugase-Miyamoto, Yasuko] AIST, Neurosci Res Inst, Tsukuba, Ibaraki, Japan. [Richmond, Barry J.] NIMH, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER TOKYO PI TOKYO PA 1-11-11 KUDAN-KITA, CHIYODA-KU, TOKYO, 102-0073, JAPAN SN 1880-6546 J9 J PHYSIOL SCI JI J. Physiol. Sci. PY 2009 VL 59 SU 1 BP 508 EP 508 PG 1 WC Physiology SC Physiology GA 509MX UT WOS:000271023103490 ER PT J AU Tuck, MK Chan, DW Chia, D Godwin, AK Grizzle, WE Krueger, KE Rom, W Sanda, M Sorbara, L Stass, S Wang, W Brenner, DE AF Tuck, Melissa K. Chan, Daniel W. Chia, David Godwin, Andrew K. Grizzle, William E. Krueger, Karl E. Rom, William Sanda, Martin Sorbara, Lynn Stass, Sanford Wang, Wendy Brenner, Dean E. TI Standard Operating Procedures for Serum and Plasma Collection: Early Detection Research Network Consensus Statement Standard Operating Procedure Integration Working Group SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE Consensus; Serum collection; Plasma collection; Standard Operating Procedures; Biomarkers; Sample handling AB Specimen collection is an integral component of clinical research. Specimens from subjects with various stages of cancers or other conditions, as well as those without disease, are critical tools in the hunt for biomarkers, predictors, or tests that will detect serious diseases earlier or more readily than currently possible. Analytic methodologies evolve quickly. Access to high-quality specimens, collected and handled in standardized ways that minimize potential bias or confounding factors, is key to the "bench to bedside" aim of translational research. It is essential that standard operating procedures, "the how" of creating the repositories, be defined prospectively when designing clinical trials. Small differences in the processing or handling of a specimen can have dramatic effects in analytical reliability and reproducibility, especially when multiplex methods are used. A representative working group, Standard Operating Procedures Internal Working Group (SOPIWG), comprised of members from across Early Detection Research Network (EDRN) was formed to develop standard operating procedures (SOPs) for various types of specimens collected and managed for our biomarker discovery and validation work. This report presents our consensus on SOPs for the collection, processing, handling, and storage of serum and plasma for biomarker discovery and validation. C1 [Tuck, Melissa K.; Brenner, Dean E.] Univ Michigan, Canc & Geriatr Ctr 2150, Div Hematol Oncol, Ann Arbor, MI 48109 USA. [Chan, Daniel W.] Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21231 USA. [Chia, David] Univ Calif Los Angeles, Immunogenet Ctr, Los Angeles, CA 90095 USA. [Godwin, Andrew K.] Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA. [Grizzle, William E.] Univ Alabama, Birmingham, AL 35233 USA. [Krueger, Karl E.; Sorbara, Lynn; Wang, Wendy] NCI, Canc Biomarkers Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. [Rom, William] NYU, Sch Med, New York, NY 10016 USA. [Sanda, Martin] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Stass, Sanford] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA. RP Tuck, MK (reprint author), Univ Michigan, Canc & Geriatr Ctr 2150, Div Hematol Oncol, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM mtuck@umich.edu RI Sanda, Martin/A-6202-2013; Sanda, Martin/B-2023-2015 FU NCI NIH HHS [U01 CA086400, U01 CA086400-05] NR 12 TC 148 Z9 152 U1 0 U2 27 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD JAN PY 2009 VL 8 IS 1 BP 113 EP 117 DI 10.1021/pr800545q PG 5 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 390NN UT WOS:000262171100012 PM 19072545 ER PT J AU Bigos, KL Folan, MM Jones, MR Haas, GL Kroboth, FJ Kroboth, PD AF Bigos, K. L. Folan, M. M. Jones, M. R. Haas, G. L. Kroboth, F. J. Kroboth, P. D. TI Dysregulation of neurosteroids in obsessive compulsive disorder SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Letter DE Obsessive compulsive disorder; OCD; DHEA; Dehydroepiandrosterone; Cortisol; Hormones ID DEXAMETHASONE SUPPRESSION TEST; GABA-A RECEPTOR; NEUROACTIVE STEROIDS; DEHYDROEPIANDROSTERONE-SULFATE; PLASMA-CONCENTRATIONS; CEREBROSPINAL-FLUID; ANXIETY DISORDERS; HEALTHY CONTROLS; DEPRESSION; CORTISOL AB Alterations in hormone concentrations, including adrenocorticotropin, corticotropin releasing hormone, and cortisol have been reported in patients with obsessive compulsive disorder (OCD). Dehydroepiandrosterone (DHEA) and its sulfated metabolite, DHEA-S, have not been assessed in patients with OCD. We report 24-h serum DHEA, DHEA-S, and cortisol concentrations in a young man with OCD and 15 healthy young men. Circadian patterns of DHEA and cortisol were markedly different in the subject with OCD than in the control subjects. DHEA and DHEA-S concentrations were substantially higher in the OCD subject than in the control subjects. In contrast, cortisol concentrations were similar in the OCD subject and the control subjects. Future clinical studies are needed to evaluate the significance of DHEA and DHEA-S in OCD. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Bigos, K. L.; Folan, M. M.; Kroboth, P. D.] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15260 USA. [Jones, M. R.; Haas, G. L.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15260 USA. [Kroboth, F. J.] Univ Pittsburgh, Sch Med, Dept Gen Internal Med, Pittsburgh, PA 15260 USA. RP Bigos, KL (reprint author), NIMH, Unit Clin Neuroimaging Genes Cognit & Psychosis P, NIH, 10 Ctr Dr,10-3C101, Bethesda, MD 20892 USA. EM bigosk@mail.nih.gov RI Bigos, Kristin/E-9768-2010 FU Intramural NIH HHS [Z99 MH999999] NR 25 TC 14 Z9 14 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 EI 1879-1379 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD JAN PY 2009 VL 43 IS 4 BP 442 EP 445 DI 10.1016/j.jpsychires.2008.04.007 PG 4 WC Psychiatry SC Psychiatry GA 406QF UT WOS:000263309300011 PM 18514738 ER PT J AU Fobair, P Stearns, N Christ, G Dozier-Hall, D Newman, NW Zabora, J Schnipper, HH Kennedy, V Loscalzo, M Stensland, S Hedlund, S Lauria, M Fife, M Herschl, J Marcusen, C Vaitones, V BrintzenhofeSzoc, K Walsh, K Lawson, K DeSonier, M AF Fobair, Patricia Stearns, Naomi 'Noni' Christ, Grace Dozier-Hall, Deborah Newman, Nancy W. Zabora, James Schnipper, Hester Hill Kennedy, Vicki Loscalzo, Matthew Stensland, Susan M. Hedlund, Susan Lauria, Marie M. Fife, Michael Herschl, Joyce Marcusen, Carol P. Vaitones, Virginia Brintzenhofeszoc, Karlynn Walsh, Katherine Lawson, Kimberly Desonier, Marcia TI Historical Threads in the Development of Oncology Social Work SO JOURNAL OF PSYCHOSOCIAL ONCOLOGY LA English DT Article ID SURVIVING ADULT CANCERS; BREAST-CANCER; RADICAL-MASTECTOMY; HODGKINS-DISEASE; GROUP-THERAPY; PERSPECTIVE; HEALTH; ADAPTATION; BARRIERS; OUTCOMES AB As the Association of Oncology Social Work celebrates its 25th year, we pause to reflect on the many historical threads that contributed to its development and hear from each of the presidents who helped create the organization, as we know it today. Set within hospitals, medical social work was born in the early 20th century. In the 1940s medical social work became necessary for hospital accreditation. Two additional historical shifts, one in medical improvements in treating cancer, the other a shift to a consumer-oriented American Cancer Society, contributed to the push for a greater role for the federal government in funding cancer research. Oncology social work came to full blossom in the 1970s, a result of the physicians' need for a member of the health care team who understood cancer, its treatment, and the patient's need to address his or her psychosocial needs resulting from cancer. Today, oncology social work is a fully developed profession with a national organization providing education and support to oncology social workers' in their use of psychosocial interventions and research in behalf of cancer patients and their families. C1 [Fobair, Patricia] Stanford Univ Hosp, Supportive Care program, Ctr Canc, Stanford, CA 94305 USA. [Stearns, Naomi 'Noni'] Dana Farber Canc Inst, Boston, MA 02115 USA. [Christ, Grace] Columbia Univ, Sch Social Work, New York, NY USA. [Dozier-Hall, Deborah] NIH, Dept Social Work, Bethesda, MD 20892 USA. [Newman, Nancy W.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Schnipper, Hester Hill] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Kennedy, Vicki] Wellness Community Natl, Program Dev & Qual Assurance, Indianapolis, IN USA. [Loscalzo, Matthew] Sheri & Les Biller Patient & Family Resource Ctr, Duarte, CA USA. [Stensland, Susan M.] Nebraska Med Ctr, Omaha, NE USA. [Hedlund, Susan] Hosp & Palliat Care Washington Cty, Hillsboro, OR USA. [Lauria, Marie M.] Univ N Carolina, Chapel Hill, NC USA. [Fife, Michael] Univ Texas MD Anderson Canc Ctr, Dept Social Work, Houston, TX 77030 USA. [Herschl, Joyce] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [Vaitones, Virginia] Penobscot Bay Med Ctr, Rockport, ME USA. [Brintzenhofeszoc, Karlynn] Catholic Univ Amer, Natl Catholic Sch Social Serv, Washington, DC 20064 USA. [Walsh, Katherine] Springfield Coll, Sch Social Work, Springfield, MA USA. [Lawson, Kimberly] Siteman Canc Ctr, Dept Educ & Qual, St Louis, MO USA. [Desonier, Marcia] Baptist Hosp, Canc Support Serv, Pensacola, FL USA. [Loscalzo, Matthew] Dept Populat Sci, Dept Support Care Med, Duarte, CA USA. [Hedlund, Susan] Oregon Hlth & Sci Univ, Sch Med, Hillsboro, OR USA. [Hedlund, Susan] Portland State Univ, Grad Sch Social Work, Hillsboro, OR USA. RP Fobair, P (reprint author), 1943 Mt Vernon Court,203, Mountain View, CA 94040 USA. EM fobair@sbcglobal.net FU Intramural NIH HHS [Z99 CL999999] NR 78 TC 4 Z9 4 U1 0 U2 2 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0734-7332 EI 1540-7586 J9 J PSYCHOSOC ONCOL JI J. Psychosoc. Oncol. PY 2009 VL 27 IS 2 BP 155 EP 215 AR PII 910064540 DI 10.1080/07347330902775301 PG 61 WC Psychology, Social SC Psychology GA 428BV UT WOS:000264823900001 PM 19337929 ER PT J AU Rybalchenko, V Grillo, MA Gastinger, MJ Rybalchenko, N Payne, AJ Koulen, P AF Rybalchenko, Volodymyr Grillo, Michael A. Gastinger, Matthew J. Rybalchenko, Nataliya Payne, Andrew J. Koulen, Peter TI The unliganded long isoform of estrogen receptor beta stimulates brain ryanodine receptor single channel activity alongside with cytosolic Ca2+ SO JOURNAL OF RECEPTORS AND SIGNAL TRANSDUCTION LA English DT Article DE 17 beta-estradiol; neuron; intracellular calcium stores; electrophysiology; endocrinology; nervous system ID BREAST-CANCER CELLS; ELEMENT-BINDING PROTEIN; INTRACELLULAR CALCIUM; ER-BETA; INDUCED NEUROPROTECTION; HIPPOCAMPAL-NEURONS; INDUCED INCREASES; CORTICAL-NEURONS; ESTRADIOL; ALPHA AB Ca2+ release from intracellular stores mediated by endoplasmic reticulum membrane ryanodine receptors (RyR) plays a key role in activating and synchronizing downstream Ca2+-dependent mechanisms, in different cells varying from apoptosis to nuclear transcription and development of defensive responses. Recently discovered, atypical "nongenomic" effects mediated by estrogen receptors (ER) include rapid Ca2+ release upon estrogen exposure in conditions implicitly suggesting involvement of RyRs. In the present study, we report various levels of colocalization between RyR type 2 (RyR2) and ER type beta (ER beta) in the neuronal cell line HT-22, indicating a possible functional interaction. Electrophysiological analyses revealed a significant increase in single-channel ionic currents generated by mouse brain RyRs after application of the soluble monomer of the long form ER beta (ER beta 1). The effect was due to a strong increase in open probability of RyR higher open channel sublevels at cytosolic [Ca2+] concentrations of 100 nM, suggesting a synergistic action of ER beta 1 and Ca2+ in RyR activation, and a potential contribution to Ca2+-induced Ca2+ release rather than to basal intracellular Ca2+ concentration level at rest. This RyR/ER beta interaction has potential effects on cellular physiology, including roles of shorter ER beta isoforms and modulation of the RyR/ER beta complexes by exogenous estrogens. C1 [Koulen, Peter] Univ Missouri, Sch Med, Vis Res Ctr, Kansas City, MO 64108 USA. [Rybalchenko, Volodymyr] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Gastinger, Matthew J.] NIAID, NIH, Bethesda, MD 20892 USA. [Rybalchenko, Nataliya] Univ N Texas, Hlth Sci Ctr, Ft Worth, TX USA. RP Koulen, P (reprint author), Univ Missouri, Sch Med, Vis Res Ctr, 6th Floor,Room HHC649,2300 Holmes St, Kansas City, MO 64108 USA. EM koulenp@umkc.edu FU NIH/NEI [EY014227]; NIH/NCRR [RR022570]; NIH/NIA [AG010485, AG022550, AG027956]; The Garvey Texas Foundation FX This study was supported in part by grants EY014227 from NIH/NEI, RR022570 from NIH/NCRR and AG010485, AG022550, and AG027956 from NIH/NIA as well as by The Garvey Texas Foundation (P.K.). We thank Margaret, Richard, and Sara Koulen for their generous support and encouragement. NR 68 TC 4 Z9 4 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1079-9893 J9 J RECEPT SIG TRANSD JI J. Recept. Signal Transduct. PY 2009 VL 29 IS 6 BP 326 EP 341 DI 10.3109/10799890903295168 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 536ML UT WOS:000273048400005 PM 19899956 ER PT J AU Kupersmith, J Lew, HL Ommaya, AK Jaffee, M Koroshetz, WJ AF Kupersmith, Joel Lew, Henry L. Ommaya, Alex K. Jaffee, Michael Koroshetz, Walter J. TI Traumatic brain injury research opportunities: Results of Department of Veterans Affairs Consensus Conference SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Editorial Material ID POSTTRAUMATIC-STRESS-DISORDER; BLAST INJURY; INDUCED NEUROTRAUMA; SEVERITY; POPULATION; PREVALENCE; PLASTICITY; DAMAGE; RISK; IRAQ C1 [Kupersmith, Joel; Ommaya, Alex K.] US EPA, Off Res & Dev, Dept Vet Affairs VA, Washington, DC 20460 USA. [Lew, Henry L.] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Jaffee, Michael] VA Boston Healthcare Syst, Boston, MA USA. [Jaffee, Michael] Walter Reed Army Med Ctr, Def & Vet Brain injury Ctr, Washington, DC 20307 USA. [Koroshetz, Walter J.] NINDS, NIH, Bethesda, MD 20892 USA. RP Kupersmith, J (reprint author), US EPA, Off Res & Dev, Dept Vet Affairs VA, Washington, DC 20460 USA. EM henry.lew@va.gou NR 33 TC 3 Z9 3 U1 0 U2 3 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2009 VL 46 IS 6 BP VII EP XV DI 10.1682/JRRD.2009.06.0079 PG 9 WC Rehabilitation SC Rehabilitation GA 531BQ UT WOS:000272638100001 PM 20104393 ER PT J AU Ward, MM AF Ward, Michael M. TI Changes in the Incidence of Endstage Renal Disease Due to Lupus Nephritis in the United States, 1996-2004 SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE SYSTEMIC LUPUS ERYTHEMATOSUS; LUPUS NEPHRITIS; ENDSTAGE RENAL DISEASE; INCIDENCE AB Objective. To determine if the incidence of endstage renal disease (ESRD) due to lupus nephritis has decreased from 1996 to 2004. Methods. Patients age 15 years or older with incident ESRD due to lupus nephritis in 1996-2004 and living in one of the 50 United States or the District Of Columbia were identified using the US Renal Data System, a national population-based registry of all patients receiving renal replacement therapy for ESRD. Incidence rates were computed for each calendar year, using population estimates of the US census as denominators. Results. Over the 9-year study period, 9199 new cases of ESRD due to lupus nephritis were observed. Incidence rates, adjusted to the age, sex, and race composition of the US population in 2000, were 4.4 per million in 1996 and 4.9 per million in 2004. Compared to the pooled incidence rate in 1996-1998, the relative risk of ESRD due to lupus nephritis in 1999-2000 was 0.99 (95% CI 0.93-1.06). in 2001-2002 was 0.99 (95% CI 0.92-1.06), and in 2003-2004 was 0.96 (95%, CI 0.89-1.02). Findings were similar in analyses stratified by sex, age group, race, and socioeconomic status. Conclusion. There was no decrease in the incidence of ESRD due to lupus nephritis between 1996 and 2004. This may reflect the limits of effectiveness Of Current treatments, or limitations in access. use, or adherence to treatment. (First Release Nov 1 2008; J Rheumatol 2009;36:63-67; doi: 10.3999/jrheum.090625) C1 [Ward, Michael M.] NIAMSD, Intramural Res Program, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Ward, MM (reprint author), NIAMS, NIH, IRP, Bldg 10 CRC,Room 4-1339,10 Ctr Dr,MSC 1468, Bethesda, MD 20892 USA. EM wardm1@mail.nih.gov FU National Institute of Arthritis and Musculoskeletal and Skin Diseases; National Institutes of Health FX Supported by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health. The data reported here have been supplied by the United States Renal Data System (USRDS). The interpretation and reporting of these data are the responsibility of the author and in no way should be seen as an official policy or interpretation of the U.S. federal government. The funding agency had no role in the design and conduct of this study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. The author had full access to all data in the, study and takes full responsibility for the integrity of the data and the accuracy of the data analysis. There are no relevant conflicts of interest to disclose. NR 12 TC 53 Z9 58 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD JAN PY 2009 VL 36 IS 1 BP 63 EP 67 DI 10.3899/jrheum.080625 PG 5 WC Rheumatology SC Rheumatology GA 395PF UT WOS:000262535300012 PM 19004042 ER PT J AU Rapoport, J Chavez, A Greenstein, D Addington, A Gogtay, N AF Rapoport, Judith Chavez, Alex Greenstein, Deanna Addington, Anjene Gogtay, Nitin TI Autism Spectrum Disorders and Childhood-Onset Schizophrenia: Clinical and Biological Contributions to a Relation Revisited SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Review DE schizophrenia; childhood; autism; genetics; brain development ID COMPLEX DEVELOPMENTAL DISORDER; BIRTH COHORT; NEURODEVELOPMENTAL DISORDERS; PSYCHIATRIC-DISORDERS; STRUCTURAL VARIANTS; BRAIN-DEVELOPMENT; GENE-EXPRESSION; CORTICAL GRAY; RISK-FACTORS; PDD-NOS AB Objective: To highlight emerging evidence for clinical and biological links between autism/pervasive developmental disorder (PDD) and schizophrenia, with particular attention to childhood-onset schizophrenia (COS). Method: Clinical, demographic, and brain developmental data from the National Institute of Mental Health (and other) COS studies and selected family, imaging, and genetic data from studies of autism, PDD, and schizophrenia were reviewed. Results: In the two large studies that have examined this systematically, COS is preceded by and comorbid with PDD in 30% to 50% of cases. Epidemiological and family studies find association between the disorders. Both disorders have evidence of accelerated trajectories of anatomic brain development at ages near disorder onset. A growing number of risk genes and/or rare small chromosomal variants (microdeletions or duplications) are shared by schizophrenia and autism. Conclusions: Biological risk does not closely follow DSM phenotypes, and core neurobiological processes are likely common for subsets of these two heterogeneous clinical groups. Long-term prospective follow-up of autistic populations and greater diagnostic distinction between schizophrenia spectrum and autism spectrum disorders in adult relatives are needed. J. Am. Acad. Child Adolesc. Psychiatry, 2009;48(1):10-18. C1 [Rapoport, Judith; Chavez, Alex; Greenstein, Deanna; Addington, Anjene; Gogtay, Nitin] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RP Gogtay, N (reprint author), NIMH, Child Psychiat Branch, Bldg 10,Room 3N202,10 Ctr Dr,MSC 1600, Bethesda, MD 20892 USA. EM gogtayn@mail.nih.gov OI Chavez, Alexis/0000-0003-1322-4532 FU Intramural NIH HHS [Z01 MH002581-17] NR 81 TC 134 Z9 136 U1 6 U2 33 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JAN PY 2009 VL 48 IS 1 BP 10 EP 18 DI 10.1097/CHI.0b013e31818b1c63 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 386PF UT WOS:000261894400003 PM 19218893 ER PT J AU Shreeram, S He, JP Kalaydjian, A Brothers, S Merikangas, KR AF Shreeram, Srirangam He, Jian-Ping Kalaydjian, Amanda Brothers, Shannon Merikangas, Kathleen Ries TI Prevalence of Enuresis and Its Association With Attention-Deficit/Hyperactivity Disorder Among US Children: Results From a Nationally Representative Study SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE enuresis; prevalence; health care use; comorbidities; ADHD ID DEFICIT-HYPERACTIVITY DISORDER; PRIMARY NOCTURNAL ENURESIS; BEHAVIORAL-PROBLEMS; CHILDHOOD ENURESIS; PSYCHIATRIC-DISORDERS; ENURETIC CHILDREN; CHINESE CHILDREN; EPIDEMIOLOGY; ADOLESCENCE; ADULTS AB Objective: There are no published nationally representative prevalence estimates of enuresis among children in the United States using standardized diagnostic criteria. This study sets out to describe the prevalence, demographic correlates, comorbidities, and service patterns for enuresis in a representative sample of U.S. children. Method: The diagnosis of enuresis was derived from parent-reported data for "enuresis, nocturnal" collected using the computerized version of the Diagnostic Interview Schedule for Children (C-DISC 4.0) from a nationally representative sample of 8- to 11-year-old children (n = 1,136) who participated in the 2001-2004 National Health and Nutrition Examination Surveys. Results: The overall 12-month prevalence of enuresis was 4.45%. The prevalence in boys (6.21%) was significantly greater than that in girls (2,51%). Enuresis was more common at younger ages and among black youth. Attention-deficit/hyperactivity disorder (ADHD) was strongly associated with enuresis (odds ratio 2.88: 95% confidence interval 1.26-6.57). Only 36% of the enuretic children had received health services for enuresis. Conclusions: Enuresis is a common condition among children in the United States. Few families seek treatment for enuresis despite the potential for adverse effects on emotional health. Child health care professionals should routinely screen for enuresis and its effects on the emotional health of the child and the family. Assessment of ADHD should routinely include evaluation for enuresis and vice versa, Research on the explanations for the association between enuresis and ADHD is indicated. J. Am. Acad. Child Adolesc. Psychiatry. 2009 48(1):35-41. C1 [Shreeram, Srirangam; He, Jian-Ping; Kalaydjian, Amanda; Brothers, Shannon; Merikangas, Kathleen Ries] NIMH, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Shreeram, S (reprint author), NIMH, Intramural Res Program, NIH, 35 Convent Dr,1A-202,MSC 3720, Bethesda, MD 20892 USA. EM s.shreeram@dc.gov FU Intramural NIH HHS [Z01 MH002870-02, Z01 MH002870-03] NR 53 TC 41 Z9 48 U1 2 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JAN PY 2009 VL 48 IS 1 BP 35 EP 41 DI 10.1097/CHI.0b013e318190045c PG 7 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 386PF UT WOS:000261894400006 PM 19096296 ER PT J AU Dunton, GF Atienza, AA AF Dunton, Genevieve Fridlund Atienza, Audie A. TI The Need for Time-Intensive Information in Healthful Eating and Physical Activity Research: A Timely Topic SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Editorial Material ID ECOLOGICAL MOMENTARY ASSESSMENT; FEELING STATES; PERSONALITY ARCHITECTURE; VEGETABLE CONSUMPTION; DECISION-MAKING; DIETARY-INTAKE; UNITED-STATES; BRISK WALKING; WEIGHT-LOSS; EXERCISE C1 [Atienza, Audie A.] NCI, Hlth Promot Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Dunton, GF (reprint author), NCI, Hlth Promot Res Branch, Behav Res Program, Div Canc Control & Populat Sci, 6130 Execut Blvd,EPN 4051C,MSC 7365, Bethesda, MD 20892 USA. EM duntong@mail.nih.gov NR 94 TC 31 Z9 31 U1 3 U2 7 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD JAN PY 2009 VL 109 IS 1 BP 30 EP 35 DI 10.1016/j.jada.2008.10.019 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 394ZY UT WOS:000262492900009 PM 19103320 ER PT J AU Ceresini, G Lauretani, F Maggio, M Ceda, GP Morganti, S Usberti, E Chezzi, C Valcavi, R Bandinelli, S Guralnik, JM Cappola, AR Valenti, G Ferrucci, L AF Ceresini, Graziano Lauretani, Fulvio Maggio, Marcello Ceda, Gian Paolo Morganti, Simonetta Usberti, Elisa Chezzi, Carlo Valcavi, Rita Bandinelli, Stefania Guralnik, Jack M. Cappola, Anne R. Valenti, Giorgio Ferrucci, Luigi TI Thyroid Function Abnormalities and Cognitive Impairment in Elderly People: Results of the Invecchiare in Chianti Study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE thyroid function; aging; cognition ID SUBCLINICAL HYPOTHYROIDISM; ALZHEIMERS-DISEASE; DEMENTIA; RISK; PREVALENCE; THYROTROPIN; DYSFUNCTION; POPULATION; ANTIBODIES; ROTTERDAM AB To investigate thyroid function testing abnormalities in older persons and to explore the relationship between thyroid dysfunction and cognition. Cross-sectional. Community-based. One thousand one hundred seventy-one men and women aged 23 to 102. Thyroid function was evaluated by measuring plasma concentrations of thyrotropin (TSH), free thyroxine (FT4), and free triiodothyronine (FT3). Cognition was evaluated using the Mini-Mental State Examination (MMSE). Prevalence of overt and subclinical thyroid dysfunction was evaluated in different age groups (< 65 vs >= 65). Age trends in TSH, FT4, and FT3 were examined in euthyroid participants. The cross-sectional association between thyroid dysfunction and MMSE score was evaluated adjusting for confounders. Subclinical hypothyroidism and subclinical hyperthyroidism were more prevalent in older than in younger participants (subclinical hypothyroidism, 3.5% vs 0.4%, P <.03; subclinical hyperthyroidism, 7.8% vs 1.9%, P <.002). In euthyroid participants, TSH and FT3 declined with age, whereas FT4 increased. Older participants with subclinical hyperthyroidism had lower MMSE scores than euthyroid subjects (22.61 +/- 6.88 vs 24.72 +/- 4.52, P <.03). In adjusted analyses, participants with subclinical hyperthyroidism were significantly more likely to have cognitive dysfunction (hazard rate=2.26, P=.003). Subtle age-related changes in FT3, FT4, and TSH occur in individuals who remain euthyroid. Subclinical hyperthyroidism is the most prevalent thyroid dysfunction in Italian older persons and is associated with cognitive impairment. C1 [Ceresini, Graziano; Maggio, Marcello; Ceda, Gian Paolo; Morganti, Simonetta; Usberti, Elisa; Valcavi, Rita; Cappola, Anne R.; Valenti, Giorgio] Univ Parma, Dept Geriatr, Endocrine Unit, I-43100 Parma, Italy. [Chezzi, Carlo] Univ Parma, Dept Pathol, I-43100 Parma, Italy. [Chezzi, Carlo] Univ Parma, Lab Med, I-43100 Parma, Italy. [Lauretani, Fulvio] ARS Toscana, Florence, Italy. [Bandinelli, Stefania] Azienda Sanitaria Toscana, Geriatr Unit, Florence, Italy. [Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Baltimore, MD 21224 USA. [Cappola, Anne R.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA. [Ferrucci, Luigi] NIA, Clin Res Branch, Longitudinal Studies Sect, Baltimore, MD 21224 USA. RP Ceresini, G (reprint author), Sect Geriatr, Dept Internal Med & Biomed Sci, Endocrine Unit, Via Gramsci 14, I-43100 Parma, Italy. EM ceresini@unipr.it RI Lauretani, Fulvio/K-5115-2016; OI Lauretani, Fulvio/0000-0002-5287-9972; Ceda, Gian Paolo/0000-0002-9648-8295 FU Italian Ministry of Health [ICS 110.1| RS97.71]; U. S. National Institute on Aging [263_ MD_ 9164_ 13, 263_ MD_ 821336]; Ministero dell'Universitae della Ricerca, Rome [FIL0774249] FX Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this manuscript. Author Contributions: All the listed authors contributed to all aspects of the research and the manuscript. Sponsor's Role: None. NR 30 TC 73 Z9 77 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JAN PY 2009 VL 57 IS 1 BP 89 EP 93 DI 10.1111/j.1532-5415.2008.02080.x PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 389YD UT WOS:000262130600013 PM 19054181 ER PT J AU Coyle, JL Davis, LA Easterling, C Graner, DE Langmore, S Leder, SB Lefton-Greif, MA Leslie, P Logemann, JA Mackay, L Martin-Harris, B Murray, JT Sonies, B Steele, CM AF Coyle, James L. Davis, Lori A. Easterling, Caryn Graner, Darlene E. Langmore, Susan Leder, Steven B. Lefton-Greif, Maureen A. Leslie, Paula Logemann, Jeri A. Mackay, Linda Martin-Harris, Bonnie Murray, Joseph T. Sonies, Barbara Steele, Catriona M. TI Oropharyngeal Dysphagia Assessment and Treatment Efficacy: Setting the Record Straight (Response to Campbell-Taylor) SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Article DE Dysphagia; swallowing; videofluoroscopy; evidence-based medicine ID COMMUNITY-ACQUIRED PNEUMONIA; ASPIRATION PNEUMONIA; STROKE; INTERVENTIONS; HOSPITALIZATION; ADULTS; CARE AB In September 2008, an article was published in the Journal of the American Medical Directors Association criticizing current dysphagia assessment and management practices performed by speech-language pathologists in Long-Term Care (LTC) settings. In the same issue, an editorial invited dialogue on the points raised by Campbell-Taylor. We are responding to this call for dialogue. We find Campbell-Taylor's interpretation of the literature to be incomplete and one-sided, leading to misleading and pessimistic conclusions. We offer a complementary perspective to balance this discussion on the 4 specific questions raised: (1) is the use of videofluoroscopy warranted for evaluating dysphagia in the LTC population? (2) How effective are thickened liquids and other interventions for preventing aspiration and do they contribute to reduction of morbidity? (3) Can aspiration be prevented and is its prevention important? and (4) Is there sufficient evidence to justify dysphagia intervention by speech language pathologists? (C) 2009 American Medical Directors Association. Published by Elsevier Inc. All rights reserved. C1 [Coyle, James L.; Leslie, Paula] Univ Pittsburgh, Pittsburgh, PA USA. [Davis, Lori A.] Univ Tulsa, Dept Commun Disorders, Tulsa, OK 74104 USA. [Easterling, Caryn] Univ Wisconsin, Dept Commun Sci & Disorders, Milwaukee, WI 53201 USA. [Easterling, Caryn] Vet Adm Med Ctr, Milwaukee, WI 53295 USA. [Graner, Darlene E.] Mayo Clin, Rochester, MN USA. [Langmore, Susan] Boston Med Ctr, Dept Otolaryngol Head & Neck Surg, Boston, MA USA. [Langmore, Susan] Boston Univ, Dept Speech & Hearing Sci, Boston, MA 02215 USA. [Leder, Steven B.] Yale Univ, Sch Med, New Haven, CT USA. [Lefton-Greif, Maureen A.] Johns Hopkins Univ, Dept Pediat, Baltimore, MD 21218 USA. [Logemann, Jeri A.] Northwestern Univ, Dept Otolaryngol Head & Neck Surg, Evanston, IL USA. [Logemann, Jeri A.] Northwestern Univ, Dept Neurol, Evanston, IL USA. [Logemann, Jeri A.] Northwestern Univ, Dept Commun Sci & Disorders, Evanston, IL USA. [Mackay, Linda] St Francis Hosp & Med Ctr, Hartford, CT USA. [Mackay, Linda] Specialty Board Swallowing & Swallowing Disorders, Hartford, CT USA. [Martin-Harris, Bonnie] Med Univ S Carolina, Evelyn Trammell Inst Voice & Swallowing, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA. [Martin-Harris, Bonnie] Med Univ S Carolina, Evelyn Trammell Inst Voice & Swallowing, Dept Commun Sci & Disorders, Charleston, SC 29425 USA. [Murray, Joseph T.] Vet Adm Ann Arbor Healthcare Syst, Audiol Speech Pathol Serv, Ann Arbor, MI USA. [Sonies, Barbara] Univ Maryland, Dept Hearing & Speech Sci, College Pk, MD 20742 USA. [Sonies, Barbara] Univ Maryland, NIH, Ctr Clin, College Pk, MD 20742 USA. [Steele, Catriona M.] Univ Toronto, Dept Speech Language Pathol, Toronto, ON, Canada. [Steele, Catriona M.] Toronto Rehabil Inst, Toronto, ON M5G 2A2, Canada. RP Steele, CM (reprint author), Toronto Rehabil Inst, 550 Univ Ave 12030, Toronto, ON M5G 2A2, Canada. EM catriona.steele@utoronto.ca RI Leslie, Paula/G-9623-2013; OI Langmore, Susan/0000-0003-0521-7375; Steele, Catriona/0000-0002-4294-6561 NR 35 TC 13 Z9 14 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-8610 EI 1538-9375 J9 J AM MED DIR ASSOC JI J. Am. Med. Dir. Assoc. PD JAN PY 2009 VL 10 IS 1 BP 62 EP 66 DI 10.1016/j.jamda.2008.10.003 PG 5 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 399IZ UT WOS:000262794900010 PM 19111855 ER PT J AU Corn, M AF Corn, Milton TI Archiving the Phenome: Clinical Records Deserve Long-term Preservation SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article; Proceedings Paper CT International Symposium on Digital Curation Focus CT International Symposium on Digital Curation Focus CY APR 18-20, 2007 CY APR 20, 2007 CL Univ N Carolina, Chapel Hill, NC CL Chapel Hill, NC HO Univ N Carolina ID HEALTH AB Retention policies for clinical records are set primarily by the states, although the federal government mandates minimum maintenance periods for certain classes of patients and selected types of information. State policies vary considerably, but most jurisdictions permit many types of data to be destroyed after some period usually shorter than 10 years. Many health care organizations hold records longer than mandated, but over time much clinical data are discarded or become difficult to access. For improved care of patients and for support of research, the nation should recognize that clinical information, both paper and electronic, constitutes a valuable asset, the national phenome, that deserves long-term storage in archives that preserve both the records and access to the information. The technical and social problems of establishing archiving are formidable but offer an opportunity to exploit the potential of clinical information for public good. C1 [Corn, Milton] Natl Lib Med, NIH, Bethesda, MD USA. RP Corn, M (reprint author), 6705 Rockledge Dr,Suite 301, Bethesda, MD 20892 USA. EM cornm@mail.nih.gov NR 18 TC 5 Z9 5 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1067-5027 EI 1527-974X J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD JAN-FEB PY 2009 VL 16 IS 1 BP 1 EP 6 DI 10.1197/jamia.M2925 PG 6 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics SC Computer Science; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics GA 396UB UT WOS:000262615600001 PM 18952936 ER PT J AU Kilicoglu, H Demner-Fushman, D Rindflesch, TC Wilczynski, NL Haynes, RB AF Kilicoglu, Halil Demner-Fushman, Dina Rindflesch, Thomas C. Wilczynski, Nancy L. Haynes, R. Brian TI Towards Automatic Recognition of Scientifically Rigorous Clinical Research Evidence SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID TEXT CATEGORIZATION; STACKED GENERALIZATION; BIOMEDICAL TEXT; SYSTEM AB The growing numbers of topically relevant biomedical publications readily available due to advances in document retrieval methods pose a challenge to clinicians practicing evidence-based medicine. It is increasingly time consuming to acquire and critically appraise the available evidence. This problem could be addressed in part if methods were available to automatically recognize rigorous studies immediately applicable in a specific clinical situation. We approach the problem of recognizing studies containing useable clinical advice from retrieved topically relevant articles as a binary classification problem. The gold standard used in the development of PubMed clinical query filters forms the basis of our approach. We identify scientifically rigorous studies using supervised machine learning techniques (Naive Bayes, support vector machine (SVM), and boosting) trained on high-level semantic features. We combine these methods using an ensemble learning method (stacking). The performance of learning methods is evaluated using precision, recall and F, score, in addition to area under the receiver operating characteristic (ROC) curve (AUC). Using a training set of 10,000 manually annotated MEDLINE citations, and a test set of an additional 2,000 citations, we achieve 73.7% precision and 61.5% recall in identifying rigorous, clinically relevant studies, with stacking over five feature-classifier combinations and 82.5% precision and 84.3% recall in recognizing rigorous studies with treatment focus using stacking over word + metadata feature vector. Our results demonstrate that a high quality gold standard and advanced classification methods can help clinicians acquire best evidence from the medical literature. C1 [Kilicoglu, Halil] Concordia Univ, Dept Comp Sci & Software Engn, Montreal, PQ H3G 1M8, Canada. [Kilicoglu, Halil; Demner-Fushman, Dina; Rindflesch, Thomas C.] Natl Lib Med, NIH, Bethesda, MD USA. [Wilczynski, Nancy L.; Haynes, R. Brian] McMaster Univ, Hlth Informat Res Unit, Hamilton, ON, Canada. RP Kilicoglu, H (reprint author), Concordia Univ, Dept Comp Sci & Software Engn, 1515 Ste Catherine W, Montreal, PQ H3G 1M8, Canada. EM h_kilico@cse.concordia.ca OI Haynes, Robert Brian/0000-0002-1453-3196 FU Intramural Research Program of the National Institutes of Health; National Library of Medicine FX Supported in part by the Intramural Research Program of the National Institutes of Health, National Library of Medicine. NR 24 TC 30 Z9 30 U1 0 U2 6 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD JAN-FEB PY 2009 VL 16 IS 1 BP 25 EP 31 DI 10.1197/jamia.M2996 PG 7 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 396UB UT WOS:000262615600005 PM 18952929 ER PT J AU Lu, ZY Kim, W Wilbur, WJ AF Lu, Zhiyong Kim, Won Wilbur, W. John TI Evaluating Relevance Ranking Strategies for MEDLINE Retrieval SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID AUTOMATIC TEXT RETRIEVAL AB This paper evaluates the retrieval effectiveness of relevance ranking strategies on a collection of 55 queries and about 160,000 MEDLINE (R) citations used in the 2006 and 2007 Text Retrieval Conference (TREC) Genomics Tracks. The authors study two relevance ranking strategies: term frequency-inverse document frequency (TF-IDF) weighting and sentence-level co-occurrence, and examine their ability to rank retrieved MEDLINE documents given user queries. Furthermore, the authors use the reverse chronological order-PubMed's default display option-as a baseline for comparison. Retrieval effectiveness is assessed using both mean average precision and mean rank precision. Experimental results show that retrievals based on the two strategies had improved performance over the baseline performance, and that TF-IDF weighting is more effective in retrieving relevant documents based on the comparison between the two strategies. C1 [Lu, Zhiyong; Kim, Won; Wilbur, W. John] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Lu, ZY (reprint author), NCBI, Natl Lib Med, NIH, 8600 Rockville Pike, Rockville, MD 20852 USA. EM luzh@ncbi.nlm.nih.gov FU Intramural Research Program of NIH; National Library of Medicine FX Supported by the Intramural Research Program of NIH, National Library of Medicine. The authors are grateful to the TREC organizers for their efforts in producing and making the text collection and relevance judgments publicly available. NR 29 TC 18 Z9 19 U1 0 U2 8 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD JAN-FEB PY 2009 VL 16 IS 1 BP 32 EP 36 DI 10.1197/jamia.M2935 PG 5 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 396UB UT WOS:000262615600006 PM 18952932 ER PT J AU Collins, SA Currie, LM Bakken, S Cimino, JJ AF Collins, Sarah A. Currie, Leanne M. Bakken, Suzanne Cimino, James J. TI Information Needs, Infobutton Manager Use, and Satisfaction by Clinician Type: A Case Study SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID CARE AB To effectively meet clinician information needs at the point of care, we must understand how their needs are dependent on both context and clinician type. The Infobutton Manager (IM), accessed through a clinical information system, anticipates the clinician's questions and provides links to pertinent electronic resources. We conducted an observational usefulness case study of medical residents (MDs), nurse practitioners (NPs), registered nurses (RNs), and a physician assistant (PA), using the IM in a laboratory setting. Generic question types and success rates for each clinician's information needs were characterized. Question type frequency differed by clinician type. All clinician types asked for institution-specific protocols. The MDs asked about unfamiliar domains, RNs asked about physician order rationales, and NPs asked questions similar to both MDs and RNs. Observational data suggest that IM success rates may be improved by tailoring anticipated questions to clinician type. Clinicians reported that a more visible Infobutton may increase use. C1 [Collins, Sarah A.; Currie, Leanne M.; Bakken, Suzanne] Columbia Univ, Sch Nursing, New York, NY 10032 USA. [Currie, Leanne M.; Bakken, Suzanne; Cimino, James J.] Columbia Univ, Dept Biomed Informat, New York, NY 10032 USA. [Currie, Leanne M.] New York Presbyterian Hosp, New York, NY USA. [Cimino, James J.] NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Collins, SA (reprint author), Columbia Univ, Sch Nursing, 630 W 168th St,Mailbox 6, New York, NY 10032 USA. EM sac2125@columbia.edu OI Cimino, James/0000-0003-4101-1622 FU National Institute for Nursing Research [732NR00769]; National Library of Medicine [1R01LM07593]; National Institutes of Health Clinical Center; National Library of Medicine FX Supported by the National Institute for Nursing Research 732NR00769 and National Library of Medicine 1R01LM07593. Dr. Cimino is supported in part by intramural research funds from the National Institutes of Health Clinical Center and the National Library of Medicine. NR 8 TC 21 Z9 21 U1 0 U2 4 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD JAN-FEB PY 2009 VL 16 IS 1 BP 140 EP 142 DI 10.1197/jamia.M2746 PG 3 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 396UB UT WOS:000262615600019 PM 18952943 ER PT J AU Neveol, A Deserno, TM Darmoni, SJ Guld, MO Aronson, AR AF Neveol, Aurelie Deserno, Thomas M. Darmoni, Stefan J. Gueld, Mark Oliver Aronson, Alan R. TI Natural Language Processing Versus Content-Based Image Analysis for Medical Document Retrieval SO JOURNAL OF THE AMERICAN SOCIETY FOR INFORMATION SCIENCE AND TECHNOLOGY LA English DT Article ID TEXTURAL FEATURES; SYSTEMS; CLASSIFICATION; FUTURE; SEARCH AB One of the most significant recent advances in health information systems has been the shift from paper to electronic documents. While research on automatic text and image processing has taken separate paths, there is a growing need for joint efforts, particularly for electronic health records and biomedical literature databases. This work aims at comparing text-based versus image-based access to multimodal medical documents using state-of-the-art methods of processing text and image components. A collection of 180 medical documents containing an image accompanied by a short text describing it was divided into training and test sets. Content-based image analysis and natural language processing techniques are applied individually and combined for multimodal document analysis. The evaluation consists of an indexing task and a retrieval task based on the "gold standard" codes manually assigned to corpus documents. The performance of text-based and image-based access, as well as combined document features, is compared. Image analysis proves more adequate for both the indexing and retrieval of the images. In the indexing task, multimodal analysis outperforms both independent image and text analysis. This experiment shows that text describing images can be usefully analyzed in the framework of a hybrid text/image retrieval system. C1 [Neveol, Aurelie; Deserno, Thomas M.; Aronson, Alan R.] NIH, US Natl Lib Med, Bethesda, MD 20894 USA. [Deserno, Thomas M.; Gueld, Mark Oliver] Rhein Westfal TH Aachen, Rhein Westfal TH Aachen, Dept Med Informat, D-52057 Aachen, Germany. [Darmoni, Stefan J.] Univ Rouen, CISMeF Grp, Rouen Univ Hosp, F-76031 Rouen, France. [Darmoni, Stefan J.] Univ Rouen, GCSIS, LITIS EA 4051, Inst Biomed Res, F-76031 Rouen, France. RP Neveol, A (reprint author), NIH, US Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM neveola@nlm.nih.gov; tdesemo@mi.rwth-aachen.de; Stefan.Darmoni@chu-rouen.fr; mgueld@mi.rwth-aachen.de; alan@nlm.nih.org RI Stefan, Darmoni/H-4554-2016; OI darmoni, stefan/0000-0002-7162-318X FU National Library of Medicine FX This research was supported in part by an appointment of A. Neveol to the Lister Hill Center Fellows Program and an appointment of T.M. Deserno, ne Lehmann, to the Lister Hill Center Visitor Program both sponsored by the National Library of Medicine and administered by the Oak Ridge Institute for Science and Education. The authors would like to thank Jean-Nicolas Dasher for his insight in creating the imaging-angle dictionary for text analysis, Filip Florea for supplying the corpus data used in this work, and Bastian Ott for supplying IRMA reference coding for the dataset. NR 39 TC 11 Z9 11 U1 2 U2 10 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 JAN PY 2009 VL 60 IS 1 BP 123 EP 134 DI 10.1002/asi.20955 PG 12 WC Computer Science, Information Systems; Information Science & Library Science SC Computer Science; Information Science & Library Science GA 394DD UT WOS:000262424900012 ER PT J AU Ishani, A Xue, JL Himmelfarb, J Eggers, PW Kimmel, PL Molitoris, BA Collins, AJ AF Ishani, Areef Xue, Jay L. Himmelfarb, Jonathan Eggers, Paul W. Kimmel, Paul L. Molitoris, Bruce A. Collins, Allan J. TI Acute Kidney Injury Increases Risk of ESRD among Elderly SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID ACUTE-RENAL-FAILURE; CRITICALLY-ILL PATIENTS; ACUTE TUBULAR-NECROSIS; LONG-TERM PROGNOSIS; REPLACEMENT THERAPY; REQUIRING DIALYSIS; INTENSIVE-CARE; RECOVERY; DISEASE; INSUFFICIENCY AB Risk for ESRD among elderly patients with acute kidney injury (AKI) has not been studied in a large, representative sample. This study aimed to determine incidence rates and hazard ratios for developing ESRD in elderly individuals, with and without chronic kidney disease (CKD), who had AKI. In the 2000 5% random sample of Medicare beneficiaries, clinical conditions were identified using Medicare claims; ESRD treatment information was obtained from ESRD registration during 2 yr of follow-up. Our cohort of 233,803 patients were hospitalized in 2000, were aged >= 67 yr on discharge, did not have previous ESRD or AKI, and were Medicare-entitled for >= 2 yr before discharge. In this cohort, 3.1% survived to discharge with a diagnosis of AKI, and 5.3 per 1000 developed ESRD. Among patients who received treatment for ESRD, 25.2% had a previous history of AKI. After adjustment for age, gender, race, diabetes, and hypertension, the hazard ratio for developing ESRD was 41.2 (95% confidence interval [CI] 34.6 to 49.1) for patients with AKI and CKD relative to those without kidney disease, 13.0 (95% Cl 10.6 to 16.0) for patients with AKI and without previous CKD, and 8.4 (95% Cl 7.4 to 9.6) for patients with CKD and without AKI. In summary, elderly individuals with AKI, particularly those with previously diagnosed CKD, are at significantly increased risk for ESRD, suggesting that episodes of AKI may accelerate progression of renal disease. C1 [Ishani, Areef; Xue, Jay L.; Collins, Allan J.] Univ Minnesota, Sch Med, United States Renal Data Syst Coordinating Ctr, Minneapolis, MN 55455 USA. [Ishani, Areef; Xue, Jay L.; Collins, Allan J.] Univ Minnesota, Sch Med, Dept Med, Minneapolis, MN 55455 USA. [Himmelfarb, Jonathan] Maine Med Ctr, Div Nephrol, Portland, ME 04102 USA. [Eggers, Paul W.; Kimmel, Paul L.] NIDDK, NIH, Bethesda, MD USA. [Kimmel, Paul L.] George Washington Univ, Med Ctr, Dept Med, Div Renal Dis & Hypertens, Washington, DC 20037 USA. [Molitoris, Bruce A.] Indiana Univ, Sch Med, Div Nephrol, Indianapolis, IN USA. RP Collins, AJ (reprint author), United States Renal Data Syst, 914 S 8th St,Suite S-406, Minneapolis, MN 55404 USA. EM acollins@usrds.org FU National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD [HHSN267200715002C] FX We thank USRDS colleagues Beth Forrest and Shane Nygaard for manuscript preparation and Nan Booth, MSW, MPH, for Manuscript editing. NR 31 TC 429 Z9 455 U1 5 U2 20 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 JAN PY 2009 VL 20 IS 1 BP 223 EP 228 DI 10.1681/ASN.2007080837 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 397QM UT WOS:000262677200030 PM 19020007 ER PT J AU Meya, D Spacek, LA Tibenderana, H John, L Namugga, I Magero, S Dewar, R Quinn, TC Colebunders, R Kambugu, A Reynolds, SJ AF Meya, David Spacek, Lisa A. Tibenderana, Hilda John, Laurence Namugga, Irene Magero, Stephen Dewar, Robin Quinn, Thomas C. Colebunders, Robert Kambugu, Andrew Reynolds, Steven J. TI Development and evaluation of a clinical algorithm to monitor patients on antiretrovirals in resource-limited settings using adherence, clinical and CD4 cell count criteria SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY LA English DT Article ID FIXED-DOSE COMBINATION; IMMUNODEFICIENCY-VIRUS-INFECTION; SELF-REPORTED ADHERENCE; HIV-1-INFECTED PATIENTS; VIROLOGICAL EFFICACY; TREATMENT RESPONSE; DRUG-RESISTANCE; HIV-1 INFECTION; POOR SETTINGS; COTE-DIVOIRE AB Background: Routine viral load monitoring of patients on antiretroviral therapy (ART) is not affordable in most resource-limited settings. Methods: A cross-sectional study of 496 Ugandans established on ART was performed at the Infectious Diseases Institute, Kampala, Uganda. Adherence, clinical and laboratory parameters were assessed for their relationship with viral failure by multivariate logistic regression. A clinical algorithm using targeted viral load testing was constructed to identify patients for second-line ART. This algorithm was compared with the World Health Organization (WHO) guidelines, which use clinical and immunological criteria to identify failure in the absence of viral load testing. Results: Forty-nine (10%) had a viral load of >400 copies/mL and 39 (8%) had a viral load of >1000 copies/mL. An algorithm combining adherence failure (interruption > 2 days) and CD4 failure (30% fall from peak) had a sensitivity of 67% for a viral load of > 1000 copies/mL, a specificity of 82%, and identified 22% of patients for viral load testing. Sensitivity of the WHO-based algorithm was 31%, specificity was 87%, and would result in 14% of those with viral suppression (<400 copies/mL) being switched inappropriately to second-line ART. Conclusion: Algorithms using adherence, clinical and CD4 criteria may better allocate viral load testing, reduce the number of patients continued on failing ART, and limit the development of resistance. C1 [Meya, David; Tibenderana, Hilda; John, Laurence; Namugga, Irene; Magero, Stephen; Kambugu, Andrew; Reynolds, Steven J.] Makerere Univ, Infect Dis Inst, Kampala, Uganda. [Spacek, Lisa A.; Quinn, Thomas C.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Dewar, Robin; Reynolds, Steven J.] SAIC Frederick, Frederick, MD USA. [Quinn, Thomas C.] NIAID, NIH, Bethesda, MD 20892 USA. [Colebunders, Robert] Inst Trop Med, B-2000 Antwerp, Belgium. [Colebunders, Robert] Univ Antwerp, B-2020 Antwerp, Belgium. RP John, L (reprint author), Makerere Univ, Infect Dis Inst, Kampala, Uganda. EM david.meya@gmail.com; lspacek@jhmi.edu; htibenderana@yahoo.com; laurence.karen@btinternet.com; irenenamugga@yahoo.com; smagero@idi.co.ug; rdewar@mail.nih.gov; tquinn@jhmi.edu; bcoleb@itg.be; akambugu@idi.co.ug; sjr@jhmi.edu OI Meya, David/0000-0002-4138-240X FU Division of Intramural Research of the National Institute of Allergy and Infectious Diseases; National Institutes of Health, USA; Career Development Award [K23 AI060384] FX The study was funded by the Division of Intramural Research of the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, USA. We also acknowledge support from the Career Development Award K23 AI060384 (LAS). NR 46 TC 22 Z9 22 U1 0 U2 2 PU INT AIDS SOCIETY PI GENEVA PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND SN 1758-2652 J9 J INT AIDS SOC JI J. Int. AIDS Soc. PY 2009 VL 12 AR 3 DI 10.1186/1758-2652-12-3 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA V19YA UT WOS:000208106500003 PM 19261189 ER PT J AU Hofman, KJ Kanyengo, CW Rapp, BA Kotzin, S AF Hofman, Karen J. Kanyengo, Christine W. Rapp, Barbara A. Kotzin, Sheldon TI Mapping the health research landscape in Sub-Saharan Africa: a study of trends in biomedical publications SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article C1 [Hofman, Karen J.] NIH, John E Fogarty Int Ctr, Div Int Sci Policy Planning & Evaluat, Bethesda, MD 20892 USA. [Kanyengo, Christine W.] Univ Zambia, Sch Med, Med Lib, Lusaka, Zambia. [Rapp, Barbara A.] NIH, Off Planning & Anal, Off Hlth Informat Programs Dev, Natl Lib Med, Bethesda, MD 20894 USA. [Kotzin, Sheldon] NIH, Lib Operat, Natl Lib Med, Bethesda, MD 20894 USA. RP Hofman, KJ (reprint author), NIH, John E Fogarty Int Ctr, Div Int Sci Policy Planning & Evaluat, 16 Ctr Dr,MSC 6705, Bethesda, MD 20892 USA. EM hofmank@mail.nih.gov; ckanyengo@yahoo.com; rappb@mail.nlm.nih.gov; kotzins@mail.nlm.nih.gov NR 15 TC 20 Z9 20 U1 0 U2 2 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 JAN PY 2009 VL 97 IS 1 BP 44 EP 44 DI 10.3163/1536-5050.97.1.007 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA 398NK UT WOS:000262738600009 PM 19158994 ER PT J AU Yu, BB Huang, L Tiwari, RC Feuer, EJ Johnson, KA AF Yu, Binbing Huang, Lan Tiwari, Ram C. Feuer, Eric J. Johnson, Karen A. TI Modelling population-based cancer survival trends by using join point models for grouped survival data SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES A-STATISTICS IN SOCIETY LA English DT Article DE Annual percentage change; Bayesian information criterion; Join point model; Proportional hazards; Relative survival; Surveillance; epidemiology and end results programme ID HIGH-RISK; SEGMENTED REGRESSION; ADJUVANT THERAPY; LIKELIHOOD RATIO; LINEAR-MODELS; MELANOMA; IMPROVEMENTS; GEMCITABINE; SELECTION; BENEFIT AB In the USA cancer as a whole is the second leading cause of death and a major burden to health care; thus medical progress against cancer is a major public health goal. There are many individual studies to suggest that cancer treatment breakthroughs and early diagnosis have significantly improved the prognosis of cancer patients. To understand better the relationship between medical improvements and the survival experience for the patient population at large, it is useful to evaluate cancer survival trends on the population level, e.g. to find out when and how much the cancer survival rates changed. We analyse population-based grouped cancer survival data by incorporating join points into the survival models. A join point survival model facilitates the identification of trends with significant change-points in cancer survival, when related to cancer treatments or interventions. The Bayesian information criterion is used to select the number of join points. The performance of the join point survival models is evaluated with respect to cancer prognosis, join point locations, annual percentage changes in death rates by year of diagnosis and sample sizes through intensive simulation studies. The model is then applied to grouped relative survival data for several major cancer sites from the 'Surveillance, epidemiology and end results' programme of the National Cancer Institute. The change-points in the survival trends for several major cancer sites are identified and the potential driving forces behind such change-points are discussed. C1 [Yu, Binbing] NIH, Bethesda, MD 20892 USA. [Huang, Lan; Tiwari, Ram C.; Feuer, Eric J.; Johnson, Karen A.] NCI, Bethesda, MD 20892 USA. RP Yu, BB (reprint author), Suite 3C309,7201 Wisconsin Ave, Bethesda, MD 20892 USA. EM yubi@mail.nih.gov FU National Cancer Institute; National Institute on Aging FX The research of the first author was carried out in part at Information Management Services, Inc., Silver Spring, Maryland, and was supported in part by the contract with the National Cancer Institute and by the intramural research programme of the National Institute on Aging.; The view of Dr Tiwari is solely his own and does not reflect that of his current affiliation, the Food and Drug Administration. NR 42 TC 6 Z9 7 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0964-1998 EI 1467-985X J9 J R STAT SOC A STAT JI J. R. Stat. Soc. Ser. A-Stat. Soc. PY 2009 VL 172 BP 405 EP 425 DI 10.1111/j.1467-985X.2009.00580.x PN 2 PG 21 WC Social Sciences, Mathematical Methods; Statistics & Probability SC Mathematical Methods In Social Sciences; Mathematics GA 417OX UT WOS:000264086900006 PM 22211005 ER PT J AU Baker, SG Cook, NR Vickers, A Kramer, BS AF Baker, Stuart G. Cook, Nancy R. Vickers, Andrew Kramer, Barnett S. TI Using relative utility curves to evaluate risk prediction SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES A-STATISTICS IN SOCIETY LA English DT Article DE Decision analysis; Decision curve; Receiver operating characteristic curve; Utility ID DIAGNOSTIC-TESTS; ROC CURVE; MARKER; RECLASSIFICATION; ABILITY; MODELS; AREA AB Because many medical decisions are based on risk prediction models that are constructed from medical history and results of tests, the evaluation of these prediction models is important. This paper makes five contributions to this evaluation: the relative utility curve which gauges the potential for better prediction in terms of utilities, without the need for a reference level for one utility, while providing a sensitivity analysis for misspecification of utilities, the relevant region, which is the set of values of prediction performance that are consistent with the recommended treatment status in the absence of prediction, the test threshold, which is the minimum number of tests that would be traded for a true positive prediction in order for the expected utility to be non-negative, the evaluation of two-stage predictions that reduce test costs and connections between various measures of performance of prediction. An application involving the risk of cardiovascular disease is discussed. C1 [Baker, Stuart G.] NCI, Canc Prevent Div, Biometry Res Grp, Bethesda, MD 20892 USA. [Cook, Nancy R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Vickers, Andrew] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Kramer, Barnett S.] NIH, Bethesda, MD 20892 USA. RP Baker, SG (reprint author), NCI, Canc Prevent Div, Biometry Res Grp, EPN 3131,6130 Execut Blvd,MSC 7354, Bethesda, MD 20892 USA. EM sb16i@nih.gov OI Vickers, Andrew/0000-0003-1525-6503 FU Donald W. Reynolds Foundation (Las Vegas, Nevada); National Heart, Lung and Blood Institute [HL043851, CA047988]; National Cancer Institute FX The authors thank Laurence Freedman, Mitchell Gail, Ruth Pfeiffer and Margaret Pepe for helpful comments. Dr Cook was supported by a research grant from the Donald W. Reynolds Foundation (Las Vegas, Nevada), and theWomen's Health Study cohort is supported by grants (HL043851 and CA047988) from the National Heart, Lung and Blood Institute and National Cancer Institute. NR 16 TC 59 Z9 59 U1 2 U2 11 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0964-1998 J9 J R STAT SOC A STAT JI J. R. Stat. Soc. Ser. A-Stat. Soc. PY 2009 VL 172 BP 729 EP 748 PN 4 PG 20 WC Social Sciences, Mathematical Methods; Statistics & Probability SC Mathematical Methods In Social Sciences; Mathematics GA 499QE UT WOS:000270238700003 PM 20069131 ER PT J AU Maity, A Carroll, RJ Mammen, E Chatterjee, N AF Maity, Arnab Carroll, Raymond J. Mammen, Enno Chatterjee, Nilanjan TI Testing in semiparametric models with interaction, with applications to gene-environment interactions SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY LA English DT Article DE Additive models; Diplotypes; Function estimation; Non-parametric regression; Omnibus hypothesis testing; Partially linear model; Repeated measures; Score test; Semiparametric models; Smooth backfitting; Tukey's 1 degree-of-freedom model ID REGRESSION; SPLINES AB Motivated from the problem of testing for genetic effects on complex traits in the presence of gene-environment interaction, we develop score tests in general semiparametric regression problems that involves Tukey style 1 degree-of-freedom form of interaction between parametrically and non-parametrically modelled covariates. We find that the score test in this type of model, as recently developed by Chatterjee and co-workers in the fully parametric setting, is biased and requires undersmoothing to be valid in the presence of non-parametric components. Moreover, in the presence of repeated outcomes, the asymptotic distribution of the score test depends on the estimation of functions which are defined as solutions of integral equations, making implementation difficult and computationally taxing. We develop profiled score statistics which are unbiased and asymptotically efficient and can be performed by using standard bandwidth selection methods. In addition, to overcome the difficulty of solving functional equations, we give easy interpretations of the target functions, which in turn allow us to develop estimation procedures that can be easily implemented by using standard computational methods. We present simulation studies to evaluate type I error and power of the method proposed compared with a naive test that does not consider interaction. Finally, we illustrate our methodology by analysing data from a case-control study of colorectal adenoma that was designed to investigate the association between colorectal adenoma and the candidate gene NAT2 in relation to smoking history. C1 [Maity, Arnab] Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA. [Mammen, Enno] Univ Mannheim, D-6800 Mannheim 1, Germany. [Chatterjee, Nilanjan] NCI, Rockville, MD USA. RP Carroll, RJ (reprint author), Texas A&M Univ, Dept Stat, Room 447,Blocker Bldg,3143 TAMU, College Stn, TX 77843 USA. EM carroll@stat.tamu.edu RI Mammen, Enno/A-1552-2014; MAITY, ARNAB/M-8142-2016 OI Mammen, Enno/0000-0001-7348-5588; MAITY, ARNAB/0000-0002-3364-8933 FU National Cancer Institute [CA-57030, CA104620]; Deutsche Forschungsgemeinschaft [MA 1026/7-3] FX Maity and Carroll's research was supported by grants from the National Cancer Institute (CA-57030 and CA104620). Mammen's research was supported by the Deutsche Forschungsgemeinschaft project MA 1026/7-3. Chatterjee's research was supported by a 'Gene-environment initiative' grant from the National Heart, Lung and Blood Institute and by the intramural research programme of the National Cancer Institute. NR 15 TC 17 Z9 17 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1369-7412 J9 J ROY STAT SOC B JI J. R. Stat. Soc. Ser. B-Stat. Methodol. PY 2009 VL 71 BP 75 EP 96 DI 10.1111/j.1467-9868.2008.00671.x PG 22 WC Statistics & Probability SC Mathematics GA 391LS UT WOS:000262235400005 PM 19838317 ER PT J AU Cheng, J Qin, J Zhang, BA AF Cheng, Jing Qin, Jing Zhang, Biao TI Semiparametric estimation and inference for distributional and general treatment effects SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY LA English DT Article DE Causal effect; Empirical likelihood; Exponential tilt model; Instrumental variable; Mixture model; Non-compliance; Randomized trials ID INSTRUMENTAL VARIABLES; EMPIRICAL LIKELIHOOD; CONFIDENCE-INTERVALS; MIXTURE MODEL; IDENTIFICATION; NONCOMPLIANCE; TRIAL AB There is a large literature on methods of analysis for randomized trials with noncompliance which focuses on the effect of treatment on the average outcome. The paper considers evaluating the effect of treatment on the entire distribution and general functions of this effect. For distributional treatment effects, fully non-parametric and fully parametric approaches have been proposed. The fully non-parametric approach could be inefficient but the fully parametric approach is not robust to the violation of distribution assumptions. We develop a semiparametric instrumental variable method based on the empirical likelihood approach. Our method can be applied to general outcomes and general functions of outcome distributions and allows us to predict a subject's latent compliance class on the basis of an observed outcome value in observed assignment and treatment received groups. Asymptotic results for the estimators and likelihood ratio statistic are derived. A simulation study shows that our estimators of various treatment effects are substantially more efficient than the currently used fully non-parametric estimators. The method is illustrated by an analysis of data from a randomized trial of an encouragement intervention to improve adherence to prescribed depression treatments among depressed elderly patients in primary care practices. C1 [Cheng, Jing] Univ Florida, Coll Med, Div Biostat, Gainesville, FL 32610 USA. [Qin, Jing] NIAID, Bethesda, MD 20892 USA. [Zhang, Biao] Univ Toledo, Toledo, OH USA. RP Cheng, J (reprint author), Univ Florida, Coll Med, Div Biostat, Suite 5130,1329 SW 16th St,POB 100177, Gainesville, FL 32610 USA. EM jcheng@biostat.ufl.edu FU National Science Foundation [DMS-0603873] FX We are grateful to the Joint Editor, an Associate Editor and two referees for their careful reading and for some helpful comments and suggestions that have greatly improved our paper. We also thank Dylan S. Small and Thomas R. Ten Have for providing the PROSPECT data and helpful discussions. B. Zhang thanks the National Science Foundation for partial support through grant DMS-0603873. NR 29 TC 13 Z9 13 U1 1 U2 7 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1369-7412 J9 J ROY STAT SOC B JI J. R. Stat. Soc. Ser. B-Stat. Methodol. PY 2009 VL 71 BP 881 EP 904 PG 24 WC Statistics & Probability SC Mathematics GA 480EA UT WOS:000268713700006 ER PT J AU Ramalingam, SS Belani, CP Ruel, C Frankel, P Gitlitz, B Koczywas, M Espinoza-Delgado, I Gandara, D AF Ramalingam, Suresh S. Belani, Chandra. P. Ruel, Christopher Frankel, Paul Gitlitz, Barbara Koczywas, Marianna Espinoza-Delgado, Igor Gandara, David TI Phase II Study of Belinostat (PXD101), a Histone Deacetylase Inhibitor, for Second Line Therapy of Advanced Malignant Pleural Mesothelioma SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Mesothelioma; Histone deacetylase inhibition; Belinostat; PXD 101 ID SUBEROYLANILIDE HYDROXAMIC ACID; SOLID TUMORS; CANCER; GROWTH; EXPERIENCE; TRIAL AB Background: Belinostat (PXD 101) is a novel inhibitor of class I and II histone deacetylases. This class of compounds has demonstrated anticancer activity in malignant mesothelioma. We conducted a phase II study of belinostat in patients with relapsed malignant pleural mesothelioma. Methods: Patients with advanced mesothelioma, progression with one prior chemotherapy regimen and Eastern Cooperative Oncology Group performance status 0-2 were eligible. Belinostat was administered at 1000 mg/m(2) intravenously over 30 Minutes oil days 1-5 of every 3 week cycle. The primary end point was response rate. The Simon two-stage design was used. Disease assessments were performed every two cycles. Results: Thirteen patients were enrolled. Baseline characteristics were: median age of 73 years; Eastern Cooperative Oncology Group performance status 0 (n = 4), 1 (8) and 2 (1). A median of two cycles of therapy were administered. Disease stabilization was seen in two patients. No objective responses were noted and the study did not meet criteria to proceed to the second stage of accrual. Median survival was 5 months with a median progression-free survival of 1 month. Salient toxicities included nausea, emesis, fatigue, and constipation. One patient died as a consequence of cardiac arrhythmia which was deemed 'possibly' related to therapy. Conclusions: Belinostat is not active as monotherapy against recurrent malignant pleural mesothelioma. Evaluation of combination strategies or alternate dosing schedules may be necessary for further development of this novel agent in mesothelioma. C1 [Ramalingam, Suresh S.] Emory Univ, Sch Med, Winship Canc Ctr, Dept Hematol & Med Oncol, Atlanta, GA 30322 USA. [Belani, Chandra. P.] Penn State Univ, Milton S Hershey Med Ctr, Dept Med, Hershey, PA 17033 USA. [Ruel, Christopher; Frankel, Paul; Koczywas, Marianna] City Hope Natl Med Ctr, Dept Biostat, Duarte, CA 91010 USA. [Gitlitz, Barbara] City Hope Natl Med Ctr, Dept Med, Duarte, CA 91010 USA. [Espinoza-Delgado, Igor] Univ So Calif, Med Ctr, Dept Med, Los Angeles, CA USA. [Gandara, David] NCI, Canc Therapy Evaluat Program, Rockville, MD USA. Univ Calif Davis, Med Ctr, Dept Med, Sacramento, CA 95817 USA. RP Ramalingam, SS (reprint author), Emory Univ, Sch Med, Winship Canc Ctr, Dept Hematol & Med Oncol, 1365 Clifton Rd,Rm C-5090, Atlanta, GA 30322 USA. EM suresh.ramalingam@emory.edu FU NCI [NO1 CM-62209] FX Supported by NCI NO1 CM-62209. NR 20 TC 83 Z9 84 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JAN PY 2009 VL 4 IS 1 BP 97 EP 101 PG 5 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 390XH UT WOS:000262196500016 PM 19096314 ER PT J AU Li, WJ Chiang, H Kuo, TF Lee, HS Jiang, CC Tuan, RS AF Li, Wan-Ju Chiang, Hongsen Kuo, Tzong-Fu Lee, Hsuan-Shu Jiang, Ching-Chuan Tuan, Rocky S. TI Evaluation of articular cartilage repair using biodegradable nanofibrous scaffolds in a swine model: a pilot study SO Journal of Tissue Engineering and Regenerative Medicine LA English DT Article DE cartilage tissue engineering; cartilage repair; nanofibre; mesenchymal stem cell; chondrocyte; in vivo model ID MESENCHYMAL STEM-CELLS; AUTOLOGOUS CHONDROCYTE TRANSPLANTATION; HISTOLOGICAL ASSESSMENT; REGENERATIVE MEDICINE; BIPHASIC INDENTATION; BONE-MARROW; DEFECTS; MATRIX; IMPLANTATION; THICKNESS AB The aim of this study was to evaluate a cell-seeded nanofibrous scaffold for cartilage repair in vivo. We used a biodegradable poly(e-caprolactone) (PCL) nanofibrous scaffold seeded with allogeneic chondrocytes or xenogeneic human mesenchymal stem cells (MSCs), or acellular PCL scaffolds, with no implant as a control to repair iatrogenic, 7 mm full-thickness cartilage defects in a swine model. Six months after implantation, MSC-seeded constructs showed the most complete repair in the defects compared to other groups. Macroscopically, the MSC-seeded constructs regenerated hyaline cartilage-like tissue and restored a smooth cartilage surface, while the chondrocyte-seeded constructs produced mostly fibrocartilage-like tissue with a discontinuous superficial cartilage contour. Incomplete repair containing fibrocartilage or fibrous tissue was found in the acellular constructs and the no-implant control group. Quantitative histological evaluation showed overall higher scores for the chondrocyte- and MSC-seeded constructs than the acellular construct and the no-implant groups. Mechanical testing showed the highest equilibrium compressive stress of 1.5 MPa in the regenerated cartilage produced by the MSC-seeded constructs, compared to 1.2 MPa in the chondrocyte-seeded constructs, 1.0 MPa in the acellular constructs and 0.2 MPa in the no-implant group. No evidence of immune reaction to the allogeneically- and xenogeneically-derived regenerated cartilage was observed, possibly related to the immunosuppressive activities of MSCs, suggesting the feasibility of allogeneic or xenogeneic transplantation of MSCs for cell-based therapy. Taken together, our results showed that biodegradable nanofibrous scaffolds seeded with MSCs effectively repair cartilage defects in vivo, and that the current approach is promising for cartilage repair. Copyright (C) 2008 John Wiley & Sons, Ltd. C1 [Chiang, Hongsen; Jiang, Ching-Chuan] Natl Taiwan Univ Hosp, Dept Orthoped Surg, Taipei 100, Taiwan. [Li, Wan-Ju; Tuan, Rocky S.] NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Kuo, Tzong-Fu] Natl Taiwan Univ Vet Hosp, Taipei, Taiwan. [Lee, Hsuan-Shu] Natl Taiwan Univ, Dept Internal Med, Taipei 10764, Taiwan. RP Jiang, CC (reprint author), Natl Taiwan Univ Hosp, Dept Orthoped Surg, 7 Chung Shan S Rd, Taipei 100, Taiwan. EM ccj@ccms.ntu.edu.tw; tuanr@mail.nih.gov OI Jiang, Ching-Chuan/0000-0001-7954-0875; LEE, HSUAN-SHU/0000-0002-8017-0434; Chiang, Hongsen/0000-0001-8781-5146; KUO, TZONG-FU/0000-0002-6328-8967 FU NIAMS; NIH [Z01 AR 41131]; National Taiwan University Hospital [NTUH-92A07]; Industrial Technology Research Institute [ITRI-IR91-1003] FX The authors thank Dr Bin-Ru She and Mei-Chiao Lin for providing technical assistance in cell culture work. This work was supported by the Intramural Research Programme of NIAMS, NIH (Z01 AR 41131), the National Taiwan University Hospital (NTUH-92A07), and in part by the Industrial Technology Research Institute (ITRI-IR91-1003). NR 35 TC 82 Z9 83 U1 0 U2 21 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1932-6254 J9 J TISSUE ENG REGEN M JI J. Tissue Eng. Regen. Med. PD JAN PY 2009 VL 3 IS 1 BP 1 EP 10 DI 10.1002/term.127 PG 10 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Engineering, Biomedical SC Cell Biology; Biotechnology & Applied Microbiology; Engineering GA 395AM UT WOS:000262494400001 PM 19004029 ER PT J AU Lang, I Scarlett, A Guralnik, J Depledge, M Melzer, D Galloway, T AF Lang, Iain A. Scarlett, Alan Guralnik, Jack M. Depledge, Michael H. Melzer, David Galloway, Tamara S. TI Age-Related Impairments of Mobility Associated with Cobalt and Other Heavy Metals: Data from NHANES 1999-2004 SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES LA English DT Article ID HARD METAL; OXIDATIVE STRESS; ALPHA-SYNUCLEIN; IN-VITRO; EXPOSURE; TOXICITY; IONS; POPULATION; PARTICLES; URINE AB Exposure to heavy metals promotes oxidative stress and damage to cellular components, and may accelerate age-related disease and disability. Physical mobility is a validated biomarker of age-related disability and is predictive of hospitalization and mortality. Our study examined associations between selected heavy metals and impaired lower limb mobility in a representative older human population. Data for 1615 adults aged 60 yr from the National Health and Nutrition Examination Survey (NHANES) 1999 to 2004 were used to identify associations between urinary concentrations of 10 metals with self-reported and measured significant walking impairments. Models were adjusted for confounding factors, including smoking. In models adjusted for age, gender, and ethnicity, elevated levels of cadmium, cobalt, and uranium were associated with impairment of the ability to walk a quarter mile. In fully adjusted models, cobalt was the only metal that remained associated: the odds ratio (OR) for reporting walking problems with a 1-unit increase in logged cobalt concentration (g/L) was 1.43 (95% CI 1.12 to 1.84). Cobalt was also the only metal associated with a significant increased measured time to walk a 20-ft course. In analyses of disease categories to explain the mobility finding, cobalt was associated with physician diagnosed arthritis (1-unit increase OR = 1.22 (95% CI 1.00 to 1.49). Low-level cobalt exposure, assessed through urinary concentrations of this essential heavy metal, may be a risk factor for age-related physical impairments. Independent replication is needed to confirm this association. C1 [Scarlett, Alan; Galloway, Tamara S.] Univ Exeter, Sch Biosci, Exeter EX4 4AS, Devon, England. [Lang, Iain A.; Melzer, David] Peninsula Med Sch, Epidemiol & Publ Hlth Grp, Exeter, Devon, England. [Guralnik, Jack M.] NIA, EDB Lab, Bethesda, MD 20892 USA. [Depledge, Michael H.] Peninsula Med Sch, Environm & Human Hlth Grp, Exeter, Devon, England. RP Galloway, T (reprint author), Univ Exeter, Sch Biosci, Prince Wales Rd, Exeter EX4 4AS, Devon, England. EM t.s.galloway@exeter.ac.uk RI Lang, Iain/B-8255-2008; Galloway, Tamara/C-1662-2009; OI Scarlett, Alan/0000-0002-9559-2154; Lang, Iain/0000-0002-8473-2350; Melzer, David/0000-0002-0170-3838 FU International Research Program; National Institute on Ageing, NIH FX Supported in part by the International Research Program, National Institute on Ageing, NIH. NR 41 TC 8 Z9 9 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1528-7394 J9 J TOXICOL ENV HEAL A JI J. Toxicol. Env. Health Part A PY 2009 VL 72 IS 6 BP 402 EP 409 AR PII 908546399 DI 10.1080/15287390802647336 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 404HX UT WOS:000263143500006 PM 19199147 ER PT J AU Sears, CLG Wright, J O'Brien, J Jezior, JR Hernandez, SL Albright, TS Siddique, S Fischer, JR AF Sears, Christine L. Gray Wright, Johnnie O'Brien, Jennie Jezior, James R. Hernandez, Sandra L. Albright, Todd S. Siddique, Sohail Fischer, John R. TI The Racial Distribution of Female Pelvic Floor Disorders in an Equal Access Health Care System SO JOURNAL OF UROLOGY LA English DT Article DE urinary incontinence; prolapse; epidemiology; continental population groups; female ID URINARY-INCONTINENCE; ORGAN PROLAPSE; SOCIOECONOMIC-STATUS; STRESS-INCONTINENCE; UNITED-STATES; RISK-FACTORS; PREVALENCE; RACE; POPULATION AB Purpose: We examined ethnic differences in female pelvic disorders in an equal access health care system. Materials and Methods: An electronic medical record review was performed for patients with pelvic floor disorders at a military female pelvic medicine and reconstructive surgery division for a 1-year period. Primary diagnosis codes and patient reported race were reviewed. Results: Mean +/- SD cohort age was 55 +/- 16.3 years, A total of 720 patients were identified, of whom 68.8% were white and 18.6% were black. Pelvic organ prolapse was the primary diagnosis in 34.2% of the women, while 19.7% had stress urinary incontinence and 10.8% had urge urinary incontinence. There was no difference in the prevalence of prolapse between black and white women. However, of patients with incontinence there was a statistically significant difference with urge incontinence in more black women (51.2%) and stress incontinence in more white women (66.2%) (chi-square p <0.05). Conclusions: There is a similar ethnic distribution of pelvic organ prolapse in an equal access health care system. Of women with incontinence there was a higher prevalence of urge urinary incontinence in black women and a higher prevalence of stress urinary incontinence in white women. C1 [Sears, Christine L. Gray] NIH, Natl Capital Consortium Fellowship Program, Dept Obstet & Gynecol, Div Urogynecol,Walter Reed Army Med Ctr, Washington, DC 20307 USA. [Sears, Christine L. Gray; Jezior, James R.] Walter Reed Army Med Ctr, Dept Urol, Washington, DC 20307 USA. RP Sears, CLG (reprint author), NIH, Natl Capital Consortium Fellowship Program, Dept Obstet & Gynecol, Div Urogynecol,Walter Reed Army Med Ctr, 6900 Georgia Ave NW, Washington, DC 20307 USA. EM Christine.Sears@na.amedd.army.mil NR 21 TC 14 Z9 14 U1 0 U2 1 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 JAN PY 2009 VL 181 IS 1 BP 187 EP 192 DI 10.1016/j.juro.2008.09.035 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 383WU UT WOS:000261705900110 PM 19013607 ER PT J AU Cooke, J AF Cooke, John TI THE ROLE OF ADMA IN VASCULAR DISEASE SO JOURNAL OF VASCULAR RESEARCH LA English DT Meeting Abstract CT 10th International Symposium on Mechanisms of Vasodilation CY JUN 01-03, 2009 CL Miyagi, JAPAN C1 [Cooke, John] Stanford Cardiovasc Inst, Stanford, CA USA. [Cooke, John] Stanford Univ, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA. [Cooke, John] NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-1172 J9 J VASC RES JI J. Vasc. Res. PY 2009 VL 46 BP 50 EP 50 PG 1 WC Physiology; Peripheral Vascular Disease SC Physiology; Cardiovascular System & Cardiology GA 452WR UT WOS:000266572400050 ER PT J AU Gauthier, KM Chawengsub, Y Zeldin, DC Campbell, WB AF Gauthier, Kathryn M. Chawengsub, Yuttana Zeldin, Darryl C. Campbell, William B. TI ROLE OF SOLUBLE EPOXIDE HYDROLASE IN FLOW-INDUCED DILATIONS OF MOUSE MESENTERIC ARTERIES SO JOURNAL OF VASCULAR RESEARCH LA English DT Meeting Abstract CT 10th International Symposium on Mechanisms of Vasodilation CY JUN 01-03, 2009 CL Miyagi, JAPAN C1 [Gauthier, Kathryn M.; Chawengsub, Yuttana; Campbell, William B.] Med Coll Wisconsin, Milwaukee, WI USA. [Zeldin, Darryl C.] Natl Inst Environm Hlth Sci, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-1172 J9 J VASC RES JI J. Vasc. Res. PY 2009 VL 46 BP 154 EP 154 PG 1 WC Physiology; Peripheral Vascular Disease SC Physiology; Cardiovascular System & Cardiology GA 452WR UT WOS:000266572400151 ER PT J AU Yang, XY Chen, EY Jiang, HG Muszynski, K Harris, RD Giardina, SL Gromeier, M Mitra, G Soman, G AF Yang, Xiaoyi Chen, Eying Jiang, Hengguang Muszynski, Karen Harris, Raymond D. Giardina, Steven L. Gromeier, Matthias Mitra, Gautam Soman, Gopalan TI Evaluation of IRES-mediated, cell-type-specific cytotoxicity of poliovirus using a colorimetric cell proliferation assay SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE Cytopathogenicity; Cytotoxicity; Poliovirus; MTS-based assay; CD155; Gliomas ID ONCOLYTIC RECOMBINANT POLIOVIRUS; RIBOSOME ENTRY SITE; NEOPLASTIC MENINGITIS; CANCER-CELLS; C-MYC; GROWTH; GLIOMA; NEUROVIRULENCE; REPLICATION; ACTIVATION AB PVS-RIPO is it recombinant oncolytic poliovirus designed for clinical application to target CD155 expressing malignant gliomas and other malignant diseases. PVS-RIPO does not replicate in healthy neurons and is therefore non-pathogenic in rodent and non-human primate models of poliomyelitis. A tetrazolium salt dye-based cellular assay was developed and qualified to define the cytotoxicity of virus preparations on susceptible cells and to explore the target cell specificity of PVS-RIPO. In this assay, PVS-RIPO inhibited proliferation of U87-MG astrocytoma cells in a dose-dependent manner. However, HEK293 cells were much less susceptible to cell killing by PVS-RIPO. In contrast, the Sabin type 1 live attenuated poliovirus vaccine strain (PV(1)S) was cytotoxic to both HEK293 and U87-MG cells. The correlation between expression of CD155 and cytotoxicity was also explored using six different cell lines. There was little or no expression of CD155 and PVS-RIPO-induced cytotoxicity in Jurkat and Daudi cells. HEK293 was the only cell line tested that showed CD155 expression and resistance to PVS-RIPO cytotoxicity. The results indicate that differential cytotoxicity measured by the colorimetric assay can be used to evaluate the cytotoxicity and cell-type specificity of recombinant strains of poliovirus and to demonstrate lot to lot consistency during the manufacture of viruses intended for clinical use. (c) 2008 Elsevier B.V. All rights reserved. C1 [Yang, Xiaoyi; Chen, Eying; Jiang, Hengguang; Harris, Raymond D.; Giardina, Steven L.; Mitra, Gautam; Soman, Gopalan] SAIC Frederick Inc, Bioanalyt Dev Lab, Biopharmaceut Dev Program, NCI Frederick, Frederick, MD 21702 USA. [Muszynski, Karen] Natl Canc Inst, Biol Resource Branch, Frederick, MD 21702 USA. [Gromeier, Matthias] Duke Univ, Med Ctr, Div Neurosurg, Dept Surg, Durham, NC 27710 USA. RP Soman, G (reprint author), SAIC Frederick Inc, Bioanalyt Dev Lab, Biopharmaceut Dev Program, NCI Frederick, POB B, Frederick, MD 21702 USA. EM somang@mail.nih.gov FU National Cancer Institute, National Institutes of Health [N01-CO-12400]; Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health FX This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract N01-CO-12400; and also supported [in part] through the NCI-RAID Program of the Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 36 TC 14 Z9 14 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD JAN PY 2009 VL 155 IS 1 BP 44 EP 54 DI 10.1016/j.jviromet.2008.09.020 PG 11 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 396DW UT WOS:000262573400007 PM 18951922 ER PT J AU Chen, ZY Santos, C Aspelund, A Gillim-Ross, L Jin, H Kemble, G Subbarao, K AF Chen, Zhongying Santos, Celia Aspelund, Amy Gillim-Ross, Laura Jin, Hong Kemble, George Subbarao, Kanta TI Evaluation of Live Attenuated Influenza A Virus H6 Vaccines in Mice and Ferrets SO JOURNAL OF VIROLOGY LA English DT Article ID CROSS-PROTECTIVE IMMUNITY; TEMPERATURE SENSITIVITY; B/ANN ARBOR/1/66; H5N1 VIRUSES; INFECTION; POULTRY; GENES; REASSORTMENT; GENERATION; VIRULENCE AB Avian influenza A virus A/teal/HK/W312/97 (H6N1) possesses seven gene segments that are highly homologous to those of highly pathogenic human influenza H5N1 viruses, suggesting that a W312-like H6N1 virus might have been involved in the generation of the A/HK/97 H5N1 viruses. The continuous circulation and reassortment of influenza H6 subtype viruses in birds highlight the need to develop an H6 vaccine to prevent potential influenza pandemics caused by the H6 viruses. Based on the serum antibody cross-reactivity data obtained from 14 different H6 viruses from Eurasian and North American lineages, A/duck/HK/182/77, A/teal/HK/W312/97, and A/mallard/Alberta/89/85 were selected to produce live attenuated H6 candidate vaccines. Each of the H6 vaccine strains is a 6:2 reassortant ca virus containing HA and NA gene segments from an H6 virus and the six internal gene segments from cold-adapted A/Ann Arbor/6/60 (AA ca), the master donor virus that is used to make live attenuated influenza virus FluMist (intranasal) vaccine. All three H6 vaccine candidates exhibited phenotypic properties of temperature sensitivity (ts), ca, and attenuation (att) conferred by the internal gene segments from AA ca. Intranasal administration of a single dose of the three H6 ca vaccine viruses induced neutralizing antibodies in mice and ferrets and fully protected mice and ferrets from homologous wild-type (wt) virus challenge. Among the three H6 vaccine candidates, the A/teal/HK/W312/97 ca virus provided the broadest cross-protection against challenge with three antigenically distinct H6 wt viruses. These data support the rationale for further evaluating the A/teal/HK/W312/97 ca vaccine in humans. C1 [Santos, Celia; Gillim-Ross, Laura; Subbarao, Kanta] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Chen, Zhongying; Aspelund, Amy; Jin, Hong; Kemble, George] MedImmune, Mountain View, CA 94043 USA. RP Subbarao, K (reprint author), NIAID, Infect Dis Lab, NIH, Bldg 33,Room 3E13C-1,33 North Dr,MSC 3203, Bethesda, MD 20892 USA. EM ksubbarao@niaid.nih.gov FU NIAID; NIH FX This work was performed under a Cooperative Research and Development Agreement (CRADA no. AI-0155) between the Laboratory of Infectious Diseases, NIAID, and MedImmune and was supported in part by the Intramural Research Program of the NIAID, NIH. NR 42 TC 38 Z9 43 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 JAN 1 PY 2009 VL 83 IS 1 BP 65 EP 72 DI 10.1128/JVI.01775-08 PG 8 WC Virology SC Virology GA 381TP UT WOS:000261559100006 PM 18945773 ER PT J AU Jia, R Liu, XF Tao, MF Kruhlak, M Guo, M Meyers, C Baker, CC Zheng, ZM AF Jia, Rong Liu, Xuefeng Tao, Mingfang Kruhlak, Michael Guo, Ming Meyers, Craig Baker, Carl C. Zheng, Zhi-Ming TI Control of the Papillomavirus Early-to-Late Switch by Differentially Expressed SRp20 SO JOURNAL OF VIROLOGY LA English DT Article ID BINDING PROTEIN YB-1; EXONIC SPLICING SUPPRESSOR; LATE MESSENGER-RNAS; EPITHELIAL-CELLS; SR PROTEINS; CERVICAL-CARCINOMA; GENE-EXPRESSION; EARLY PROMOTER; RAFT CULTURES; TYPE-16 AB The viral early-to-late switch of papillomavirus infection is tightly linked to keratinocyte differentiation and is mediated in part by alternative mRNA splicing. Here, we report that SRp20, a cellular splicing factor, controls the early-to-late switch via interactions with A/C-rich RNA elements. An A/C-rich SE4 element regulates the selection of a bovine papillomavirus type 1 (BPV-1) late-specific splice site, and binding of SRp20 to SE4 suppresses this selection. Expression of late BPV-1 L1 or human papillomavirus (HPV) L1, the major capsid protein, inversely correlates with SRp20 levels in the terminally differentiated keratinocytes. In HPV type 16, a similar SRp20-interacting element also controls the viral early-to-late switch. Keratinocytes in raft cultures, which support L1 expression, make considerably less SRp20 than keratinocytes in monolayer cultures, which do not support L1 expression. Conversely, abundant SRp20 in cancer cells or undifferentiated keratinocytes is important for the expression of the viral early E6 and E7 by promoting the expression of cellular transcription factor SP1 for transactivation of viral early promoters. C1 [Jia, Rong; Liu, Xuefeng; Tao, Mingfang; Zheng, Zhi-Ming] NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Kruhlak, Michael] NCI, Expt Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Baker, Carl C.] NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Guo, Ming] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Meyers, Craig] Penn State Univ, Coll Med, Dept Microbiol & Immunol, Hershey, PA 17033 USA. RP Zheng, ZM (reprint author), NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, NIH, 10 Ctr Dr 6N106, Bethesda, MD 20892 USA. EM zhengt@exchange.nih.gov FU Intramural Research Program of the Center for Cancer Research; National Cancer Institute; NIH [R01 AI057988-01] FX This study was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, NIH, and NIH grant R01 AI057988-01 to C. M. NR 61 TC 42 Z9 42 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 JAN 1 PY 2009 VL 83 IS 1 BP 167 EP 180 DI 10.1128/JVI.01719-08 PG 14 WC Virology SC Virology GA 381TP UT WOS:000261559100017 PM 18945760 ER PT J AU Doria-Rose, NA Klein, RM Manion, MM O'Dell, S Phogat, A Chakrabarti, B Hallahan, CW Migueles, SA Wrammert, J Ahmed, R Nason, M Wyatt, RT Mascola, JR Connors, M AF Doria-Rose, Nicole A. Klein, Rachel M. Manion, Maura M. O'Dell, Sijy Phogat, Adhuna Chakrabarti, Bimal Hallahan, Claire W. Migueles, Stephen A. Wrammert, Jens Ahmed, Rafi Nason, Martha Wyatt, Richard T. Mascola, John R. Connors, Mark TI Frequency and Phenotype of Human Immunodeficiency Virus Envelope-Specific B Cells from Patients with Broadly Cross-Neutralizing Antibodies SO JOURNAL OF VIROLOGY LA English DT Article ID LONG-TERM NONPROGRESSORS; PRIMARY HIV-1 INFECTION; TO-CHILD TRANSMISSION; MONOCLONAL-ANTIBODIES; ANTIRETROVIRAL THERAPY; PROTECTIVE IMMUNITY; ELITE SUPPRESSORS; TYPE-1 INFECTION; PLASMA-CELLS; ENV CLONES AB Induction of broadly cross-reactive neutralizing antibodies (NAb) is an important goal for a prophylactic human immunodeficiency virus type 1 (HIV-1) vaccine. Some HIV-infected patients make a NAb response that reacts with diverse strains of HIV-1, but most candidate vaccines have induced NAb only against a subset of highly sensitive isolates. To better understand the nature of broad NAb responses that arise during natural infection, we screened patients for sera able to neutralize diverse HIV strains and explored the frequency and phenotype of their peripheral Envelope-specific B cells. We screened 113 HIV-infected patients of various clinical statuses for the prevalence of broad NAb. Sera able to neutralize at least four of five viral isolates were found in over one-third of progressors and slow progressors, but much less frequently in aviremic long-term nonprogressors. Most Env-specific antibody-secreting B cells were CD27(hi) CD38(hi) plasmablasts, and the total plasmablast frequency was higher in HIV-infected patients than in uninfected donors. We found that 0.0031% of B cells and 0.047% of plasmablasts secreted Env-specific immunoglobulin G (IgG) in an enzyme-linked immunospot (ELISPOT) assay. We developed a novel staining protocol to label HIV-specific B cells with Env gp140 protein. A total of 0.09% of B cells were found to be Env-specific by this method, a frequency far higher than that indicated by ELISPOT assay. gp140-labeled B cells were predominantly CD27(+) and surface IgG(+). These data describe the breadth and titer of serum NAb and the frequency and phenotype of HIV-specific B cells in a cohort of patients with broad cross-neutralizing antibody responses that are potential goals for vaccines for HIV. C1 [Connors, Mark] NIAID, LIR, NIH, Immunoregulat Lab, Bethesda, MD 20892 USA. [O'Dell, Sijy; Phogat, Adhuna; Chakrabarti, Bimal; Wyatt, Richard T.; Mascola, John R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Hallahan, Claire W.; Nason, Martha] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. [Wrammert, Jens; Ahmed, Rafi] Emory Univ, Emory Vaccine Ctr, Atlanta, GA 30329 USA. RP Connors, M (reprint author), NIAID, LIR, NIH, Immunoregulat Lab, Bldg 10,Rm 7N246,10 Ctr Dr, Bethesda, MD 20892 USA. EM mconnors@niaid.nih.gov FU National Institute of Allergy and Infectious Diseases; National Institutes of Health FX This research was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health, and a grant from the NIH Intramural AIDS Targeted Antiviral Program. NR 89 TC 184 Z9 187 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN 1 PY 2009 VL 83 IS 1 BP 188 EP 199 DI 10.1128/JVI.01583-08 PG 12 WC Virology SC Virology GA 381TP UT WOS:000261559100019 PM 18922865 ER PT J AU Ambagala, AP Bosma, T Ali, MA Poustovoitov, M Chen, JJ Gershon, MD Adams, PD Cohen, JI AF Ambagala, Aruna P. Bosma, Trent Ali, Mir A. Poustovoitov, Maxim Chen, Jason J. Gershon, Michael D. Adams, Peter D. Cohen, Jeffrey I. TI Varicella-Zoster Virus Immediate-Early 63 Protein Interacts with Human Antisilencing Function 1 Protein and Alters Its Ability To Bind Histones H3.1 and H3.3 SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN TRIGEMINAL GANGLIA; REPLICATION IN-VITRO; NUCLEOSOME ASSEMBLY PATHWAY; LATENCY-ASSOCIATED PROTEIN; DNA-DAMAGE CHECKPOINT; CHAPERONE ASF1; S-PHASE; SACCHAROMYCES-CEREVISIAE; GENE-EXPRESSION; HIR PROTEINS AB Varicella-zoster virus (VZV) immediate-early 63 protein (IE63) is abundantly expressed during both acute infection in vitro and latent infection in human ganglia. Using the yeast two-hybrid system, we found that VZV IE63 interacts with human antisilencing function 1 protein (ASF1). ASF1 is a nucleosome assembly factor which is a member of the H3/H4 family of histone chaperones. IE63 coimmunoprecipitated and colocalized with ASF1 in transfected cells expressing IE63 and in VZV-infected cells. IE63 also colocalized with ASF1 in both lytic and latently VZV-infected enteric neurons. ASF1 exists in two isoforms, ASF1a and ASF1b, in mammalian cells. IE63 preferentially bound to ASF1a, and the amino-terminal 30 amino acids of ASF1a were critical for its interaction with IE63. VZV IE63 amino acids 171 to 208 and putative phosphorylation sites of IE63, both of which are critical for virus replication and latency in rodents, were important for the interaction of IE63 with ASF1. Finally, we found that IE63 increased the binding of ASF1 to histone H3.1 and H3.3, which suggests that IE63 may help to regulate levels of histones in virus-infected cells. Since ASF1 mediates eviction and deposition of histones during transcription, the interaction of VZV IE63 with ASF1 may help to regulate transcription of viral or cellular genes during lytic and/or latent infection. C1 [Ambagala, Aruna P.; Bosma, Trent; Ali, Mir A.; Cohen, Jeffrey I.] NIH, Lab Clin Infect Dis, Bethesda, MD 20892 USA. [Poustovoitov, Maxim; Adams, Peter D.] Fox Chase Canc Ctr, Dept Basic Sci, Philadelphia, PA 19111 USA. [Chen, Jason J.; Gershon, Michael D.] Columbia Univ, Dept Pathol & Cell Biol, Coll Phys & Surg, New York, NY 10032 USA. RP Cohen, JI (reprint author), NIH, Lab Clin Infect Dis, 10 Ctr Dr,Bldg 10,Room 11N234, Bethesda, MD 20892 USA. EM jcohen@niaid.nih.gov FU National Institute of Allergy and Infectious Diseases; NIH [RO1 GM062281] FX This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases and NIH RO1 GM062281 to Peter D. Adams. NR 61 TC 23 Z9 24 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN 1 PY 2009 VL 83 IS 1 BP 200 EP 209 DI 10.1128/JVI.00645-08 PG 10 WC Virology SC Virology GA 381TP UT WOS:000261559100020 PM 18971269 ER PT J AU Buonaguro, L Tornesello, ML Gallo, RC Marincola, FM Lewis, GK Buonaguro, FM AF Buonaguro, L. Tornesello, M. L. Gallo, R. C. Marincola, Franco M. Lewis, G. K. Buonaguro, F. M. TI Th2 Polarization in Peripheral Blood Mononuclear Cells from Human Immunodeficiency Virus (HIV)-Infected Subjects, as Activated by HIV Virus-Like Particles SO JOURNAL OF VIROLOGY LA English DT Article ID CHRONIC HEPATITIS-C; PLASMACYTOID DENDRITIC CELLS; INTERFERON-GAMMA-PRODUCTION; CYTOTOXIC T-LYMPHOCYTES; GENE-EXPRESSION PROFILE; INFECTED INDIVIDUALS; ANTIGEN PRESENTATION; NEUTRALIZING ANTIBODIES; CLADE-A; INHIBITION AB We have recently shown that human immunodeficiency virus type 1 (HIV-1) Pr55(gag) virus-like particles (HIV-VLPs), produced in a baculovirus expression system and presenting a gp120 molecule from a Ugandan HIV-1 isolate of clade A, induce maturation and activation of monocyte-derived dendritic cells (MDDCs) with a production of Th1- and Th2-specific cytokines. Furthermore, HIV-VLP-loaded MDDCs are able to induce a primary and secondary response in autologous human CD4(+) T cells in an ex vivo immunization assay. In the present study, we show that similar data can be obtained directly with fresh peripheral blood mononuclear cells (PBMCs), and the HIV-1 seropositivity status, with either low or high viremia, does not significantly impair the immune activation status and the responsiveness of circulating monocyte CD14(+) cell populations to an immunogenic stimulus. Some HIV-1-seropositive subjects, however, show a complete lack of maturation induced by HIV-VLPs in CD14(+) circulating cells, which does not consistently correlate with an advanced status of HIV-1 infection. The established Th2 polarization in both HIV-seropositive groups is efficiently boosted by HIV-VLP induction and does not switch into a Th1 pattern, strongly suggesting that specific Th1 adjuvants would be required for therapeutic effectiveness in HIV-1-infected subjects. These results indicate the possibility of screening PBMCs for donor susceptibility to an immunogen treatment, which would greatly simplify the identification of "responsive" vaccinees as well as the understanding of eventual failures in individuals enrolled in clinical trials. C1 [Buonaguro, L.; Tornesello, M. L.; Buonaguro, F. M.] Ist Nazl Tumori Fond G Pascale, Mol Biol Lab, I-80131 Naples, Italy. [Buonaguro, L.; Tornesello, M. L.; Buonaguro, F. M.] Ist Nazl Tumori Fond G Pascale, Viral Oncogenesis & AIDS Reference Ctr, I-80131 Naples, Italy. [Buonaguro, L.; Gallo, R. C.; Lewis, G. K.] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA. [Marincola, Franco M.] NIH, IDIS, Dept Transfus Med, Ctr Clin, Bethesda, MD USA. RP Buonaguro, FM (reprint author), Ist Nazl Tumori Fond G Pascale, Mol Biol Lab, Via Mariano Semmola 1, I-80131 Naples, Italy. EM irccsvir@unina.it RI Tornesello, Maria Lina/A-1564-2009; OI Tornesello, Maria Lina/0000-0002-3523-3264; Buonaguro, Luigi/0000-0002-6380-7114 FU Ministero Italiano Universita e Ricerca; Ministero Italiano della Sanita; Institute of Human Virology; NIH FX This study was supported by grants from the Ministero Italiano Universita e Ricerca ( MIUR, 2004), the Ministero Italiano della Sanita ( Ricerca Corrente and Progetto Finalizzato AIDS 2006), the Institute of Human Virology, and the NIH ( NIH grants to G. K. L.). NR 56 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 0022-538X J9 J VIROL JI J. Virol. PD JAN 1 PY 2009 VL 83 IS 1 BP 304 EP 313 DI 10.1128/JVI.01606-08 PG 10 WC Virology SC Virology GA 381TP UT WOS:000261559100029 PM 18945779 ER PT J AU Sheliga, BM FitzGibbon, EJ Miles, FA AF Sheliga, B. M. FitzGibbon, E. J. Miles, F. A. TI The initial torsional Ocular Following Response (tOFR) in humans: A response to the total motion energy in the stimulus? SO JOURNAL OF VISION LA English DT Review DE cycloversion; winner-take-all; normalization; visual motion ID VERGENCE EYE-MOVEMENTS; PRIMARY VISUAL-CORTEX; OPTIC FLOW STIMULI; SUPERIOR TEMPORAL SULCUS; TAKE-ALL MECHANISM; OPTOKINETIC NYSTAGMUS; MACAQUE MONKEY; MST NEURONS; AREA MT; STRIATE CORTEX AB We recorded the initial torsional Ocular Following Responses (tOFRs) elicited at short latency by visual images that occupied the frontal plane and rotated about the lines of sight. Using 1-D radial gratings, the local spatio-temporal characteristics of these tOFRs closely resembled those we previously reported for the hOFRs to horizontal motion with 1-D vertical gratings. When the 1-D radial grating was subdivided into a number of concentric annuli, each with the same radial thickness, tOFRs were less than predicted from the sum of the responses to the individual annuli: spatial normalization. However, the normalization was much weaker than that which we previously reported for the hOFRs. Further, when the number, thickness and contrast of these concentric annuli were varied systematically, the latency and magnitude of the tOFRs were well described by single monotonic functions when plotted against the product of the total area of the annuli and the square of their Michelson contrast ("A(star)C(2)"), consistent with the hypothesis that the onset and magnitude of the initial tOFR are determined by the total motion energy in the stimulus. When our previously published hOFR data were plotted against A(star)C(2), a single monotonic function sufficed to describe the latency but not the magnitude. C1 [Sheliga, B. M.; FitzGibbon, E. J.; Miles, F. A.] NEI, Sensorimotor Res Lab, Bethesda, MD 20892 USA. RP Sheliga, BM (reprint author), NEI, Sensorimotor Res Lab, Bldg 49,Room 2A50, Bethesda, MD 20892 USA. EM bms@lsr.nei.nih.gov FU National Eye Institute at the National Institutes of Health FX This research was supported by the Intramural Research Program of the National Eye Institute at the National Institutes of Health. NR 109 TC 6 Z9 6 U1 1 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 1534-7362 J9 J VISION JI J. Vision PY 2009 VL 9 IS 12 AR 2 DI 10.1167/9.12.2 PG 38 WC Ophthalmology SC Ophthalmology GA 539TP UT WOS:000273281300002 ER PT J AU Whitcomb, BW Schisterman, EF Luo, XP Chegini, N AF Whitcomb, Brian W. Schisterman, Enrique F. Luo, Xiaoping Chegini, Nasser TI Maternal Serum Granulocyte Colony-Stimulating Factor Levels and Spontaneous Preterm Birth SO JOURNAL OF WOMENS HEALTH LA English DT Article ID HUMAN PLACENTA; PREGNANCY; EXPRESSION; PREDICTION; INFLAMMATION; INFECTIONS; CYTOKINES; DELIVERY; RECEPTOR; BIASES AB Objective: Preterm birth (PTB) remains a cause of substantial morbidity with an elusive etiology. Previous studies suggested an association of PTB with elevated serum levels of granulocyte colony-stimulating factor (GCSF) at 28 weeks gestation. G-CSF, a hematopoietic cytokine, mediates the increase in leukocytes in pregnancy and may play a role in placentation. We evaluated the association between maternal serum G-CSF in the first and second trimesters and PTB. Methods: Serum samples collected for the Collaborative Perinatal Project (CPP) from women with normal pregnancy (n = 394) and PTB (n = 31), defined as delivery before 37 weeks gestation, were used to assess G-CSF levels. Linear regression was used to evaluate the relation of G-CSF with gestational age (GA) at birth. Logistic regression, conditional on GA at sample provision, was used to model the association between G-CSF and PTB. Results: G-CSF was significantly associated with gestational age at birth (p = 0.02). In conditional logistic regression models, G-CSF was significantly associated with PTB, with an adjusted odds ratio (AOR) of 1.52 (95% confidence interval [CI] 1.07, 2.16) per standard deviation (SD) increase. Conclusions: Acute effects of G-CSF on PTB have been suggested. In our study we observed an association of higher serum G-CSF levels early in the second trimester with PTB, suggesting PTB as the culmination process beginning early in, if not before, pregnancy. C1 [Whitcomb, Brian W.; Schisterman, Enrique F.] NICHD, Epidemiol Branch, DESPR, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Rockville, MD USA. [Luo, Xiaoping; Chegini, Nasser] Univ Florida, Dept Obstet & Gynecol, Gainesville, FL 32611 USA. RP Whitcomb, BW (reprint author), Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Div Biostat & Epidemiol, 408 Arnold House,715 N Pleasant St, Amherst, MA 01003 USA. EM bwhitcomb@schoolph.umass.edu OI Schisterman, Enrique/0000-0003-3757-641X FU Epidemiology Branch of the Division of Epidemiology; Statistics and Prevention Research at the Eunice Kennedy Shriver National Institute of Child Health and Human Development FX This research was funded by an intramural grant from the Epidemiology Branch of the Division of Epidemiology, Statistics and Prevention Research at the Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 32 TC 7 Z9 9 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD JAN PY 2009 VL 18 IS 1 BP 73 EP 78 DI 10.1089/jwh.2008.0883 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 395AX UT WOS:000262495500010 PM 19105692 ER PT J AU Peterson, MJ Giuliani, C Morey, MC Pieper, CF Evenson, KR Mercer, V Cohen, HJ Visser, M Brach, JS Kritchevsky, SB Goodpaster, BH Rubin, S Satterfield, S Newman, AB Simonsick, EM AF Peterson, Matthew J. Giuliani, Carol Morey, Miriam C. Pieper, Carl F. Evenson, Kelly R. Mercer, Vicki Cohen, Harvey J. Visser, Marjolein Brach, Jennifer S. Kritchevsky, Stephen B. Goodpaster, Bret H. Rubin, Susan Satterfield, Suzanne Newman, Anne B. Simonsick, Eleanor M. CA Hlth Aging & Body Composition Stud TI Physical Activity as a Preventative Factor for Frailty: The Health, Aging, and Body Composition Study SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Aging; Exercise; Frail elderly; Longitudinal studies ID LOWER-EXTREMITY FUNCTION; OLDER-ADULTS; LIFE-STYLE; SUBSEQUENT DISABILITY; PERFORMANCE BATTERY; FUNCTIONAL DECLINE; RANDOMIZED-TRIAL; ELDERLY-PEOPLE; EXERCISE; FITNESS AB Background. It is unclear if physical activity (PA) can prevent or reverse frailty. We examined different doses and types of PA and their association with the onset and severity of frailty. Methods. Health, Aging and Body Composition (Health ABC) study participants (N = 2,964) were followed for 5 years, with frailty defined as a gait speed of less than 0.60 m/s and/or inability to rise from a chair without using one's arms. Individuals with one impairment were considered moderately frail and those with both severely frail. We examined PA doses of volume and intensity, activity types (eg, lifestyle vs exercise activities), and their associations with incident frailty and transition to severe frailty in those who became frail. Results. Adjusted models indicated that sedentary individuals had significantly increased odds of developing frailty compared with the exercise active group (adjusted odds ratio [OR] = 1.45; 95% confidence interval [CI]: 1.04-2.01), whereas the lifestyle active did not. Number of diagnoses was the strongest predictor of incident frailty. In those who became frail during follow-up (n = 410), there was evidence that the sedentary (adjusted OR = 2.80; 95% CI: 0.98-8.02) and lifestyle active (adjusted OR = 2.81; 95% CI: 1.22-6.43) groups were more likely to have worsening frailty over time. Conclusions. Despite the strong relationship seen between comorbid conditions and onset of frailty, this observational study suggests that participation in self-selected exercise activities is independently associated with delaying the onset and the progression of frailty. Regular exercise should be further examined as a potential factor in frailty prevention for older adults. C1 [Peterson, Matthew J.; Morey, Miriam C.; Pieper, Carl F.; Cohen, Harvey J.] Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Durham, NC USA. [Peterson, Matthew J.; Morey, Miriam C.; Pieper, Carl F.; Cohen, Harvey J.] Duke Univ, Ctr Study Aging & Human Dev, Durham, NC USA. [Giuliani, Carol; Mercer, Vicki] Univ N Carolina, Curriculum Human Movement Sci, Chapel Hill, NC USA. [Evenson, Kelly R.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Visser, Marjolein] Vrije Univ Amsterdam Med Ctr, Inst Res Extramural Med, Amsterdam, Netherlands. [Brach, Jennifer S.] Univ Pittsburgh, Dept Phys Therapy, Pittsburgh, PA 15260 USA. [Kritchevsky, Stephen B.] Wake Forest Univ, Bowman Gray Sch Med, Sticht Ctr Aging, Winston Salem, NC USA. [Goodpaster, Bret H.; Newman, Anne B.] Univ Pittsburgh, Med Ctr, Dept Med, Pittsburgh, PA 15260 USA. [Rubin, Susan] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Satterfield, Suzanne] Univ Tennessee, Dept Prevent Med, Memphis, TN USA. [Simonsick, Eleanor M.] NIA, Clin Res Branch, Baltimore, MD USA. [Simonsick, Eleanor M.] Johns Hopkins Univ, Sch Med, Div Geriatr Med & Gerontol, Baltimore, MD USA. RP Peterson, MJ (reprint author), Durham VA Med Ctr, GRECC 182, 508 Fulton St, Durham, NC 27705 USA. EM peter076@mc.duke.edu RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Kritchevsky, Stephen/0000-0003-3336-6781 FU Intramural Research Program of the National Institutes of Health; National Institute of Aging [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106] FX This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute of Aging, Contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106. NR 38 TC 99 Z9 104 U1 3 U2 26 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JAN PY 2009 VL 64 IS 1 BP 61 EP 68 DI 10.1093/gerona/gln001 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 418ZY UT WOS:000264190100006 PM 19164276 ER PT J AU Shardell, M Hicks, GE Miller, RR Kritchevsky, S Andersen, D Bandinelli, S Cherubini, A Ferrucci, L AF Shardell, Michelle Hicks, Gregory E. Miller, Ram R. Kritchevsky, Stephen Andersen, Daniel Bandinelli, Stefania Cherubini, Antonio Ferrucci, Luigi TI Association of Low Vitamin D Levels With the Frailty Syndrome in Men and Women SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Vitamin D; Frailty syndrome; Parathyroid hormone; InCHIANTI ID GROWTH-FACTOR-I; MUSCLE STRENGTH; SKELETAL-MUSCLE; PHYSICAL PERFORMANCE; HYPOVITAMINOSIS D; CHRONIC DISEASES; ELDERLY PERSONS; OLDER-ADULTS; SERUM-LEVELS; D DEFICIENCY AB Background. Although both vitamin D (25-hydroxyvitamin D[25(OH)D]) insufficiency and the frailty syndrome are more prevalent in women than men, sex-specific associations have not been explored. We estimated sex-specific associations of low 25(OH)D with frailty. Vitamin D insufficiency can result in hyperparathyroidism, and thus, parathyroid hormone (PTH) was explored as a potential mediator in the relationship between 25(OH)D levels and frailty. Methods. The sample included 444 male and 561 female participants aged 65 years and older from the InCHIANTI study for whom 25(OH)D levels and frailty information were available. Frailty was defined as the presence of at least three of the five following criteria: slowness, weakness, low energy expenditure, exhaustion, and weight loss. Logistic regression models estimated the association between serum levels of 25(OH)D and PTH with frailty, controlling for potential confounders. Results. Independent of covariates, men with 25(OH)D <50 nmol/L had greater odds of frailty than those with 25(OH) D >= 50 nmol/L (odds ratio [OR] = 4.94, 95% confidence interval [CI] = 1.80-13.61). In women, the adjusted OR for frailty (95% CI) was 1.43 (0.58-3.56). The 25(OH)D ORs differed between men and women (p = .041). ORs changed little after controlling for PTH. However, when low energy expenditure was excluded from the frailty definition, adjusted OR for frailty in men (95% CI) was 2.18 (0.59-8.04); controlling for PTH attenuated this OR by 32%. In women, the OR (95% CI) for frailty (low energy expenditure excluded) was 1.54 (0.31-7.58) and was attenuated by 6% after controlling for PTH. Conclusions. Vitamin D insufficiency was associated with frailty in men, but not in women. Results suggest that PTH mediates the relationship between 25(OH)D and nonenergy expenditure aspects of frailty. C1 [Shardell, Michelle; Miller, Ram R.; Andersen, Daniel] Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. [Hicks, Gregory E.] Univ Delaware, Dept Phys Therapy, Newark, DE USA. [Kritchevsky, Stephen] Wake Forest Univ, Bowman Gray Sch Med, Sticht Ctr Aging, Winston Salem, NC USA. [Bandinelli, Stefania] Tuscany Reg Hlth Agcy, Florence, Italy. [Cherubini, Antonio] Univ Perugia, Inst Gerontol & Geriatr, I-06100 Perugia, Italy. [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD USA. RP Shardell, M (reprint author), Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, 660 W Redwood St,Room 119, Baltimore, MD 21201 USA. EM mshardel@epi.umaryland.edu OI Kritchevsky, Stephen/0000-0003-3336-6781; Cherubini, Antonio/0000-0003-0261-9897 FU National Institutes of Health (NIH) [R37 AG09901, 1 R01 AI6085901A1, K23 AG019161]; Building Interdisciplinary Research Careers in Women's Health; NIH [K12 HD43489] FX This research was partly supported by an unrestricted grant from Procter and Gamble, SrL, Italy. Authors were supported by grants from the National Institutes of Health (NIH) : R37 AG09901, 1 R01 AI6085901A1, K23 AG019161, Building Interdisciplinary Research Careers in Women's Health. Dr. Hicks, a BIRCWH scholar at the time of this work, was supported by NIH K12 HD43489 NR 40 TC 77 Z9 82 U1 2 U2 8 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 JAN PY 2009 VL 64 IS 1 BP 69 EP 75 DI 10.1093/gerona/gln007 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 418ZY UT WOS:000264190100007 PM 19164273 ER PT J AU Vestergaard, S Nayfield, SG Patel, KV Eldadah, B Cesari, M Ferrucci, L Ceresini, G Guralnik, JM AF Vestergaard, Sonja Nayfield, Susan G. Patel, Kushang V. Eldadah, Basil Cesari, Matteo Ferrucci, Luigi Ceresini, Graziano Guralnik, Jack M. TI Fatigue in a Representative Population of Older Persons and Its Association With Functional Impairment, Functional Limitation, and Disability SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article; Proceedings Paper CT Workshop on Unexplained Fatigue in the Elderly CY JUN 25-26, 2007-5007 CL Bethesda, MD DE Fatigue; Aging; Disability; Physical function ID PHYSICAL PERFORMANCE BATTERY; LOWER-EXTREMITY FUNCTION; SUBSEQUENT DISABILITY; WALKING LIMITATIONS; GENERAL-POPULATION; THYROID-DISEASE; ADULTS; TIREDNESS; INCHIANTI; AGE AB Background. Older persons often complain of fatigue, but the functional consequences of this symptom are unclear. The aim of the present study was to evaluate fatigue and its association with measures of physical function and disability in a representative sample of the older population. Methods. Cross-sectional data from a population-based sample of 1,055 Italian men and women aged 65 and older were analyzed. Fatigue was defined according to two questions evaluating whether participants felt that "everything was an effort" and/or they "could not get going" on three or more days in the past week. Objective measures of physical function were handgrip strength, the Short Physical Performance Battery (SPPB), and 400-m walking speed. Disability was defined as the inability to complete the 400-m walk test and self-reported difficulty in activities of daily living (ADL) and instrumental activities of daily living (IADL). Results. The prevalence of fatigue was higher in women (29%) than in men (15%). In age-adjusted analyses, fatigued men and women had weaker handgrip strength, lower SPPB score, slower walking speed, and higher mobility, ADL, and IADL disability than nonfatigued persons. Further adjustment for health behaviors, diseases, inflammatory markers, and thyroid function generally reduced the relationship between fatigue and functional outcomes, but fatigue remained significantly associated with SPPB score, walking speed, and mobility and IADL disability. Conclusions. Older persons who report fatigue had significantly poorer functional status than those who did not report this symptom. The causal link between fatigue and these outcomes should be further investigated. C1 [Vestergaard, Sonja; Patel, Kushang V.; Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. [Nayfield, Susan G.; Eldadah, Basil] NIA, Geriatr Branch, NIH, Bethesda, MD 20892 USA. [Cesari, Matteo] Univ Florida, Inst Aging, Dept Aging & Geriatr Res, Gainesville, FL USA. [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA. [Ceresini, Graziano] Univ Parma, Dept Internal Med & Biomed Sci, I-43100 Parma, Italy. RP Vestergaard, S (reprint author), NIA, Lab Epidemiol Demog & Biometry, NIH, 7201 Wisconsin Ave,Gateway Bldg,Suite 3C309, Bethesda, MD 20892 USA. EM vestergaards@mail.nih.gov RI Cesari, Matteo/A-4649-2008 OI Cesari, Matteo/0000-0002-0348-3664 FU Intramural NIH HHS; NIA NIH HHS [1 P30 AG028740]; NIMHD NIH HHS [263 MD 821336, 263 MD 9164 13] NR 37 TC 75 Z9 75 U1 1 U2 12 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 JAN PY 2009 VL 64 IS 1 BP 76 EP 82 DI 10.1093/gerona/gln017 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 418ZY UT WOS:000264190100008 PM 19176328 ER PT J AU Penninx, BWJH Nicklas, BJ Newman, AB Harris, TB Goodpaster, BH Satterfield, S de Rekeneire, N Yaffe, K Pahor, M Kritchevsky, SB AF Penninx, Brenda W. J. H. Nicklas, Barbara J. Newman, Anne B. Harris, Tamara B. Goodpaster, Bret H. Satterfield, Suzanne de Rekeneire, Nathalie Yaffe, Kristine Pahor, Marco Kritchevsky, Stephen B. CA Hlth ABC Study TI Metabolic Syndrome and Physical Decline in Older Persons: Results from the Health, Aging and Body Composition Study SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Metabolic syndrome; Obesity; Glucose; Mobility limitation; Older; Diabetes; Cerebrovascular disease ID C-REACTIVE PROTEIN; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; ASSOCIATION; OBESITY; RISK; COHORT; WOMEN; MEN; STRENGTH AB Background. The metabolic syndrome includes dyslipidemia, abdominal obesity, insulin resistance, and hypertension and is associated with an increased risk of diabetes and cerebrovascular disease (CVD), but consequences beyond these outcomes have not been examined extensively. We investigated whether metabolic abnormalities have independent consequences on loss of mobility function of older persons. Methods. Data are from 2,920 men and women, 70-79 years, participating in the Health ABC study without mobility limitations at baseline. Metabolic syndrome was defined as >= 3 of the following: (a) waist circumference >102 (men) or >88 cm (women); (b) triglycerides >= 150 mg/dL; (c) high-density lipoprotein cholesterol <40 mg/dL (men) or <50 mg/dL (women); (d) blood pressure >= 130/85 mm Hg or antihypertensive medication; and (d) fasting glucose >= 110 mg/dL or antidiabetic medication. Mobility limitation was defined as difficulty or inability walking mile or climbing 10 steps during two consecutive semiannual assessments over 4.5 years. Results. The prevalence of metabolic syndrome was 38.6%. The metabolic syndrome was associated with an adjusted relative risk (RR) of 1.46 (95% confidence interval [CI] = 1.30-1.63) for developing mobility limitations. The risk increased when more metabolic syndrome components were present (p trend > .001). All metabolic syndrome components were significantly associated with incident mobility limitations with the highest RRs for abdominal obesity (RR = 1.54, 95% CI = 1.35-1.75) and hyperglycemia (RR = 1.44, 95% CI = 1.27-1.63). Findings were unchanged when persons with baseline, or incident, CVD, stroke, or diabetes were excluded. Conclusions. Metabolic syndrome abnormalities, especially abdominal obesity and hyperglycemia, are predictive of mobility limitations in the elderly, independent of CVD or diabetes. C1 [Penninx, Brenda W. J. H.] Vrije Univ Amsterdam Med Ctr, EMGO Inst, Dept Psychiat, NL-1081 HL Amsterdam, Netherlands. [Nicklas, Barbara J.; Kritchevsky, Stephen B.] Wake Forest Univ, Bowman Gray Sch Med, Sticht Ctr Aging, Winston Salem, NC USA. [Newman, Anne B.; Goodpaster, Bret H.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Harris, Tamara B.] NIA, Bethesda, MD 20892 USA. [Satterfield, Suzanne] Univ Tennessee, Memphis, TN USA. [de Rekeneire, Nathalie] Ctr Dis Control, Atlanta, GA 30333 USA. [Yaffe, Kristine] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Pahor, Marco] Univ Florida, Gainesville, FL USA. RP Penninx, BWJH (reprint author), Vrije Univ Amsterdam Med Ctr, EMGO Inst, Dept Psychiat, AJ Ernststr 887, NL-1081 HL Amsterdam, Netherlands. EM b.penninx@vumc.nl RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Kritchevsky, Stephen/0000-0003-3336-6781 FU Intramural NIH HHS; NHLBI NIH HHS [1R01-HL72972, R01 HL072972]; NIA NIH HHS [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, P30 AG021332, P30 AG028740] NR 30 TC 35 Z9 36 U1 0 U2 2 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 JAN PY 2009 VL 64 IS 1 BP 96 EP 102 DI 10.1093/gerona/gln005 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 418ZY UT WOS:000264190100011 PM 19164274 ER PT J AU Dalal, M Ferrucci, L Sun, K Beck, J Fried, LP Semba, RD AF Dalal, Mansi Ferrucci, Luigi Sun, Kai Beck, Justine Fried, Linda P. Semba, Richard D. TI Elevated Serum Advanced Glycation End Products and Poor Grip Strength in Older Community-Dwelling Women SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Advanced glycation end products; Aging; Inflammation; Muscle; Sarcopenia ID NONENZYMATIC GLYCATION; MUSCLE STRENGTH; SKELETAL-MUSCLE; SELENIUM CONCENTRATIONS; PHYSICAL-DISABILITY; HANDGRIP STRENGTH; SOLUBLE RECEPTOR; BODY-COMPOSITION; RISK-FACTOR; SARCOPENIA AB Background. Advanced glycation end products (AGEs) have been implicated in the pathogenesis of diabetes, heart disease, and kidney failure and may potentially affect skeletal muscle. Whether AGEs are associated with poor muscle strength is unknown. Methods. Serum carboxymethyl-lysine (CML), a dominant AGE, circulating soluble form of receptor for advanced glycation end products (sRAGE), and endogenous secretory receptor for advanced glycation end product (esRAGE) and grip strength were measured in 559 moderately to severely disabled women, age 65 and older, in the Women's Health and Aging Study I in Baltimore, Md. Results. Mean (standard deviation) grip strength among women in the highest quartile of serum CML compared with women in the lower three quartiles was 18.6 and 20.0 kg, respectively (p = .002), adjusting for age, race, body mass index, cognitive dysfunction, depression, and diabetes. Serum sRAGE and esRAGE were not significantly associated with grip strength. Conclusions. Women with high serum AGEs have greater muscle weakness. Further studies are needed to determine whether AGEs, a potentially modifiable risk factor, are associated with physical performance and disability in older adults. C1 [Dalal, Mansi; Sun, Kai; Beck, Justine; Fried, Linda P.; Semba, Richard D.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA. RP Semba, RD (reprint author), 550 N Broadway,Suite 700, Baltimore, MD 21205 USA. EM rdsemba@jhmi.edu FU National Institute on Aging [R01 AG027012, AG11703-01A1]; National Institutes of Health - National Center for Research Resources; Outpatient Department General Clinical Research Center [RR00722]; NIA [N01-AG12112]; Intramural Research Program; National Institute on Aging, National Institutes of Health FX This work was supported by National Institute on Aging grant R01 AG027012, AG11703-01A1, National Institutes of Health - National Center for Research Resources, Outpatient Department General Clinical Research Center grant RR00722, NIA Contract N01-AG12112, and the Intramural Research Program, National Institute on Aging, National Institutes of Health. NR 44 TC 29 Z9 29 U1 0 U2 4 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 JAN PY 2009 VL 64 IS 1 BP 132 EP 137 DI 10.1093/gerona/gln018 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 418ZY UT WOS:000264190100016 PM 19182228 ER PT J AU Spencer, SM Schulz, R Rooks, RN Albert, SM Thorpe, RJ Brenes, GA Harris, TB Koster, A Satterfield, S Ayonayon, HN Newman, AB AF Spencer, S. Melinda Schulz, Richard Rooks, Ronica N. Albert, Steven M. Thorpe, Roland J., Jr. Brenes, Gretchen A. Harris, Tamara B. Koster, Annemarie Satterfield, Suzanne Ayonayon, Hilsa N. Newman, Anne B. TI Racial Differences in Self-Rated Health at Similar Levels of Physical Functioning: An Examination of Health Pessimism in the Health, Aging, and Body Composition Study SO JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES LA English DT Article DE Self-rated health; Health pessimism; Objective measures; Physical functioning ID WHITE ADULTS; OLDER ADULTS; MORTALITY; ASSOCIATION; ETHNICITY; RATINGS; ELDERS; RACE AB Background. The health pessimism hypothesis suggests that Black elders are more pessimistic about health than Whites and therefore tend to report lower self-rated health (SRH) at comparable health status. The current analysis examined the factors associated with SRH and tested the health pessimism hypothesis among older adults at similar levels of physical functioning. Methods. The study example included 2,729 Health, Aging, and Body Composition study participants aged 70-79 years. We used hierarchical logistic regression to examine the association between race and SRH while adjusting for demographic, physical health, and psychosocial factors. The analyses were repeated for participants at similar levels of objective functioning to test the health pessimism hypothesis. Results. The association between race and SRH remained independent of physical and psychosocial health variables, with Whites being 3.7 times more likely than Black elders to report favorable SRH. This association was significant at each level of physical functioning and greater at the higher (odds ratio [OR] = 5.5) versus lower ( OR = 2.2) levels of functioning. Conclusions. The results suggest greater health pessimism among Black elders and expand previous work by including objective functioning in multidimensional models to deconstruct race variations in the SRH of older adults C1 [Spencer, S. Melinda] Univ S Carolina, Arnold Sch Publ Hlth, Dept Hlth Promot Educ & Behav, Columbia, SC 29208 USA. [Spencer, S. Melinda] Univ S Carolina, Inst So Studies, Columbia, SC 29208 USA. [Schulz, Richard] Univ Pittsburgh, Univ Ctr Social & Urban Res, Pittsburgh, PA 15260 USA. [Rooks, Ronica N.] Univ Colorado, Dept Hlth & Behav Sci, Denver, CO 80202 USA. [Albert, Steven M.] Univ Pittsburgh, Dept Behav & Community Hlth Sci, Pittsburgh, PA 15260 USA. [Thorpe, Roland J., Jr.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Johns Hopkins Ctr Hlth Dispar Solut, Baltimore, MD USA. [Brenes, Gretchen A.] Wake Forest Univ, Bowman Gray Sch Med, Dept Psychiat & Behav Med, Winston Salem, NC USA. [Harris, Tamara B.; Koster, Annemarie] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Koster, Annemarie] Univ Maastricht, Dept Hlth Care Studies, Maastricht, Netherlands. [Satterfield, Suzanne] Univ Tennessee, Dept Prevent Med, Knoxville, TN USA. [Ayonayon, Hilsa N.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Ctr Aging & Populat Hlth, Pittsburgh, PA 15260 USA. RP Spencer, SM (reprint author), Univ S Carolina, Arnold Sch Publ Hlth, Dept Hlth Promot Educ & Behav, 800 Sumter St,Room 216, Columbia, SC 29208 USA. EM mspencer@sc.edu RI Koster, Annemarie/E-7438-2010; Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Albert, Steven/0000-0001-6786-9956 FU Kellogg Health Scholars Program; W. K. Kellogg Foundation [P0117943]; University of Pittsburgh Center for Minority Health [NIH-5-P60MD000207-07]; National Institutes of Health; National Institute on Aging; [N01-AG-6-2101]; [N01-AG-6-2103]; [N01-AG-6-2106]; [R01 AG18037] FX Postdoctoral support for Dr. S. M. S. is provided by the Kellogg Health Scholars Program, funded by the W. K. Kellogg Foundation (P0117943), University of Pittsburgh Center for Minority Health site (NIH-5-P60MD000207-07). Health ABC is funded by N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, and R01 AG18037. This research was supported in part by the Intramural Research program of the National Institutes of Health, National Institute on Aging. NR 26 TC 25 Z9 26 U1 1 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5014 J9 J GERONTOL B-PSYCHOL JI J. Gerontol. Ser. B-Psychol. Sci. Soc. Sci. PD JAN PY 2009 VL 64 IS 1 BP 87 EP 94 DI 10.1093/geronb/gbn007 PG 8 WC Geriatrics & Gerontology; Gerontology; Psychology; Psychology, Multidisciplinary SC Geriatrics & Gerontology; Psychology GA 419AD UT WOS:000264190600012 PM 19176485 ER PT J AU Brindle, TJ Mizelle, JC Lebiedowska, MK Miller, JL Stanhope, SJ AF Brindle, Timothy J. Mizelle, J. C. Lebiedowska, Maria K. Miller, Jeri L. Stanhope, Steven J. TI Visual and proprioceptive feedback improves knee joint position sense SO KNEE SURGERY SPORTS TRAUMATOLOGY ARTHROSCOPY LA English DT Article DE Kinesthesia; Lower extremity; Motor learning; Sensorimotor; Somatosensory ID ANKLE SPRAINS; BALANCE; KINESTHESIA AB Joint position sense (JPS), one method to assess proprioception, is the ability to replicate a target limb position. Feedback is commonly used to improve motor performance but it has not been demonstrated to improve JPS. The purpose of this study was to determine if feedback decreases error associated with knee JPS at three movement velocities. Healthy volunteers sat with their hip and knees flexed. The knee was passively extended at three velocities (0.5, 2, and 10A degrees/s). Subjects were instructed to stop knee motion, via a thumb switch, at a 20A degrees knee flexion target. Following movement, each subject received visual and proprioceptive feedback indicating final leg position relative to the target position. Movement velocities and times (4 s, 5 s, 6 s) were randomly presented so subjects could not predict the target position. Measures of JPS included constant error (CE), absolute error (AE), variable error (VE), and percent correct (%CORR). Significant decreases in CE, AE, and VE as well as an increase in %CORR were demonstrated. The majority of JPS improvement (85%) occurred by the tenth trial. Short-term improvements in JPS may be the result of temporary CNS adaptations via feedback that was provided to subjects. Long-term learning of JPS enhancement needs further investigation. C1 [Brindle, Timothy J.; Lebiedowska, Maria K.; Miller, Jeri L.] NIH, Biomech Lab, Bethesda, MD 20892 USA. [Mizelle, J. C.] Georgia Inst Technol, Sch Appl Physiol, Atlanta, GA 30332 USA. [Stanhope, Steven J.] Univ Delaware, Coll Hlth Sci, Newark, DE 19716 USA. RP Brindle, TJ (reprint author), NIH, Biomech Lab, Bldg 10 CRC,Room 1-1469 10 Ctr Dr,MCS 1604, Bethesda, MD 20892 USA. EM Tbrindle@cc.nih.gov FU NICHD NIH HHS [R13 HD063283] NR 23 TC 5 Z9 5 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0942-2056 J9 KNEE SURG SPORT TR A JI Knee Surg. Sports Traumatol. Arthrosc. PD JAN PY 2009 VL 17 IS 1 BP 40 EP 47 DI 10.1007/s00167-008-0638-3 PG 8 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 394HV UT WOS:000262438700008 PM 18839143 ER PT J AU Kralj, JG Player, A Sedrick, H Munson, MS Petersen, D Forry, SP Meltzer, P Kawasaki, E Locascio, LE AF Kralj, Jason G. Player, Audrey Sedrick, Hope Munson, Matthew S. Petersen, David Forry, Samuel P. Meltzer, Paul Kawasaki, Ernest Locascio, Laurie E. TI T7-based linear amplification of low concentration mRNA samples using beads and microfluidics for global gene expression measurements SO LAB ON A CHIP LA English DT Article ID POLYMER SURFACE; CDNA; QUANTITIES; PROCESSOR; PLASMA AB We have demonstrated in vitro transcription (IVT) of cDNA sequences from purified Jurkat T-cell mRNA immobilized on microfluidic packed beds down to single-cell quantities. The microfluidically amplified antisense-RNA (aRNA) was nearly identical in length and quantity compared with benchtop reactions using the same starting sample quantities. Microarrays were used to characterize the number and population of genes in each sample, allowing comparison of the microfluidic and benchtop processes. For both benchtop and microfluidic assays, we measured the expression of approximately 4000 to 9000 genes for sample amounts ranging from 20 pg to 10 ng (2 to 1000 cell equivalents), corresponding to 41 to 93% of the absolute number of genes detected from a 100 ng total RNA control sample. Concordance of genes detected between methods (benchtop vs. microfluidic) and repeats (microfluidic vs. microfluidic) typically exceeded 90%. Validation of microarray by Real-time PCR of a panel of five genes suggests transcription of genes present is approximately six times more efficient with the microfluidic IVT compared with benchtop processing. Microfluidic IVT introduces no bias to the gene expression profile of the sample and provides more efficient transcription of mRNA sequences present at the single-cell level. C1 [Kralj, Jason G.; Sedrick, Hope; Munson, Matthew S.; Forry, Samuel P.; Locascio, Laurie E.] Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA. [Player, Audrey; Petersen, David; Meltzer, Paul; Kawasaki, Ernest] NCI, NIH, Gaithersburg, MD USA. RP Kralj, JG (reprint author), Natl Inst Stand & Technol, 100 Bur Dr MS 8313, Gaithersburg, MD 20899 USA. EM jason.kralj@nist.gov FU Intramural Research Program of the NIH; National Cancer Institute; Center for Cancer Research FX This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. The authors thank Dr. Yonghong Wang for depositing the microarray data into NCBI Gene Expression Omnibus (GEO) repository. NR 18 TC 15 Z9 15 U1 0 U2 8 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1473-0197 J9 LAB CHIP JI Lab Chip PY 2009 VL 9 IS 7 BP 917 EP 924 DI 10.1039/b811714d PG 8 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA 419YS UT WOS:000264256200009 PM 19294302 ER PT J AU Sun, S Ossandon, M Kostov, Y Rasooly, A AF Sun, Steven Ossandon, Miguel Kostov, Yordan Rasooly, Avraham TI Lab-on-a-chip for botulinum neurotoxin a (BoNT-A) activity analysis SO LAB ON A CHIP LA English DT Article ID LINKED-IMMUNOSORBENT-ASSAY; ARRAY BIOSENSOR; NEUROTRANSMITTER RELEASE; FLUORESCENCE DETECTION; PROTEOLYTIC CLEAVAGE; SENSITIVE DETECTION; MASS-SPECTROMETRY; MEMBRANE-PROTEIN; RAPID DETECTION; MOUSE BIOASSAY AB A Lab-on-a-chip (LOC) was designed, fabricated and tested for the in vitro detection of botulinum neurotoxin serotype A (BoNT-A) activity using an assay that measures cleavage of a fluorophore-tagged peptide substrate specific for BoNT-A (SNAP-25) by the toxin light chain (LcA). LcA cleavage was detected by Forster Resonance Energy Transfer (FRET) fluorescence. FRET fluorescence was measured by a newly developed portable charge-coupled device (CCD) fluorescent detector equipped with multi-wavelength light-emitting diodes (LED) illumination. An eight V-junction microchannel device for BoNTs activity assays was constructed using Laminated Object Manufacturing (LOM) technology. The six-layer device was fabricated with a Poly(methyl methacrylate (PMMA) core and five polycarbonate (PC) layers micromachined by CO(2) laser. The LOC is operated by syringe and is equipped with reagents, sample wells, reaction wells, diffusion traps (to avoid cross contamination among channels) and waste reservoirs. The system was detected LcA at concentrations as low as 0.5 nM, which is the reported sensitivity of the SNAP-25 in vitro cleavage assay. Combined with our CCD detector, the simple point of care system enables the detection of BoNTs activity and may be useful for the performance of other complex medical assays without a laboratory. This approach may realize the potential to enhance the quality of health care delivery for underserved populations. C1 [Sun, Steven; Rasooly, Avraham] NCI, Div Biol, Off Sci & Engn Labs, FDA,NIH, Silver Spring, MD 20993 USA. [Sun, Steven; Kostov, Yordan] Univ Maryland Baltimore Cty, Ctr Adv Sensor Technol, Baltimore, MD 21250 USA. [Ossandon, Miguel; Rasooly, Avraham] Natl Canc Inst, Canc Diag Program, Rockville, MD 20892 USA. RP Rasooly, A (reprint author), NCI, Div Biol, Off Sci & Engn Labs, FDA,NIH, Silver Spring, MD 20993 USA. EM rasoolya@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 54 TC 36 Z9 36 U1 3 U2 18 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1473-0197 J9 LAB CHIP JI Lab Chip PY 2009 VL 9 IS 22 BP 3275 EP 3281 DI 10.1039/b912097a PG 7 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA 512JH UT WOS:000271243600014 PM 19865736 ER PT J AU Armani, M Rodriguez-Canales, J Gillespie, J Tangrea, M Erickson, H Emmert-Buck, MR Shapiro, B Smela, E AF Armani, Michael Rodriguez-Canales, Jaime Gillespie, John Tangrea, Michael Erickson, Heidi Emmert-Buck, Michael R. Shapiro, Benjamin Smela, Elisabeth TI 2D-PCR: a method of mapping DNA in tissue sections SO LAB ON A CHIP LA English DT Article ID POLYMERASE-CHAIN-REACTION; GENE-EXPRESSION PATTERNS; IN-SITU HYBRIDIZATION; QUANTITATIVE RT-PCR; TYRAMIDE SIGNAL AMPLIFICATION; LASER CAPTURE MICRODISSECTION; MESSENGER-RNA; MICROFLUIDIC DEVICES; BIOLOGICAL SAMPLES; MOUSE EMBRYO AB A novel approach was developed for mapping the location of target DNA in tissue sections. The method combines a high-density, multi-well plate with an innovative single-tube procedure to directly extract, amplify, and detect the DNA in parallel while maintaining the two-dimensional (2D) architecture of the tissue. A 2D map of the gene glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was created from a tissue section and shown to correlate with the spatial area of the sample. It is anticipated that this approach may be easily adapted to assess the status of multiple genes within tissue sections, yielding a molecular map that directly correlates with the histology of the sample. This will provide investigators with a new tool to interrogate the molecular heterogeneity of tissue specimens. C1 [Armani, Michael; Shapiro, Benjamin; Smela, Elisabeth] Univ Maryland, Bioengn Grad Program, College Pk, MD 20742 USA. [Armani, Michael; Shapiro, Benjamin] Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA. [Smela, Elisabeth] Univ Maryland, Dept Mech Engn, College Pk, MD 20742 USA. [Armani, Michael; Tangrea, Michael; Emmert-Buck, Michael R.] NCI, Pathogenet Unit, Pathol Lab, Bethesda, MD 20892 USA. [Gillespie, John] SAIC Frederick Inc, Frederick, MD USA. [Erickson, Heidi] Univ Texas MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA. RP Smela, E (reprint author), Univ Maryland, Bioengn Grad Program, College Pk, MD 20742 USA. EM smela@umd.edu RI Shapiro, Benjamin/H-6176-2011; Smela, Elisabeth/B-9911-2011; OI Smela, Elisabeth/0000-0003-3921-2265; Rodriguez-Canales, Jaime/0000-0002-0885-2377 FU NIH; National Cancer Institute; Center for Cancer Research FX We thank Rodrigo Chuaqui and Jeffrey Hanson at the NCI for their support for this project. This work was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 59 TC 3 Z9 3 U1 0 U2 3 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1473-0197 J9 LAB CHIP JI Lab Chip PY 2009 VL 9 IS 24 BP 3526 EP 3534 DI 10.1039/b910807f PG 9 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA 524KM UT WOS:000272142200009 PM 20024032 ER PT J AU Alberti, N Val, D Vicens, J Garijo, MF Val-Bernal, JF de Agustin, P Merino, MJ AF Alberti, N. Val, D. Vicens, J. Garijo, M. F. Val-Bernal, J. F. de Agustin, P. Merino, M. J. TI Molecular Profile of Breast Cancer Metastases to the Central Nervous System SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 NCI, Bethesda, MD 20892 USA. Marques Valdecilla Univ Hosp, Santander, Spain. 12 Octubre Univ Hosp, Madrid, Spain. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2009 VL 89 MA 105 BP 26A EP 26A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 394XK UT WOS:000262486300106 ER PT J AU Sherman, ME Gaudet, MM Campan, M Yang, XR Figueroa, JD Lissowska, J Peplonska, B Brinton, LA Garcia-Closas, M Laird, PW AF Sherman, M. E. Gaudet, M. M. Campan, M. Yang, X. R. Figueroa, J. D. Lissowska, J. Peplonska, B. Brinton, L. A. Garcia-Closas, M. Laird, P. W. TI DNA Methylation of ESR1 and PGR in Breast Cancer: Relationship to Pathologic and Epidemiologic Features SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 NCI, Rockville, MD USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ So Calif, Los Angeles, CA USA. Canc Ctr & M Sklodowska Curie Inst Oncol, Warsaw, Poland. Nofer Inst Occupat Med, Lodz, Poland. RI Peplonska, Beata/F-6004-2010 NR 0 TC 0 Z9 0 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2009 VL 89 MA 292 BP 67A EP 68A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 394XK UT WOS:000262486300293 ER PT J AU Liu, Q Wrathall, L Galli, S Vicens, J Linehan, WM Tsokos, M Merino, MJ AF Liu, Q. Wrathall, L. Galli, S. Vicens, J. Linehan, W. M. Tsokos, M. Merino, M. J. TI Renal Medullary Carcinoma: Molecular, IHC, and Pathologic Correlation SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 [Liu, Q.; Wrathall, L.; Galli, S.; Vicens, J.; Linehan, W. M.; Tsokos, M.; Merino, M. J.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2009 VL 89 MA 809 BP 179A EP 179A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 394XK UT WOS:000262486300810 ER PT J AU Chowdhuri, SR Vicens, J Teller, L Linehan, WM Merino, MJ AF Chowdhuri, S. Roy Vicens, J. Teller, L. Linehan, W. M. Merino, M. J. TI Renal Cancer in Tuberous Sclerosis: An Underdiagnosed Disease? Molecular, IHC and Pathologic Correlation SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 [Chowdhuri, S. Roy; Vicens, J.; Teller, L.; Linehan, W. M.; Merino, M. J.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2009 VL 89 MA 866 BP 191A EP 191A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 394XK UT WOS:000262486300867 ER PT J AU Vicens, J Pinto, P Linehan, WM Merino, MJ AF Vicens, J. Pinto, P. Linehan, W. M. Merino, M. J. TI Percutaneous Core Needle Biopsy; a Helpful Tool in the Diagnosis of Hereditary Kidney Tumors SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 [Vicens, J.; Pinto, P.; Linehan, W. M.; Merino, M. J.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2009 VL 89 MA 907 BP 200A EP 200A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 394XK UT WOS:000262486300908 ER PT J AU Bechert, CJ Shively, SB Yuldasheva, N Glasker, S Vortmeyer, A AF Bechert, C. J. Shively, S. B. Yuldasheva, N. Glasker, S. Vortmeyer, A. TI VHL Deficiency in the Female Genital Tract SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Univ Texas Med Branch, Galveston, TX USA. Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. NCI, Bethesda, MD 20892 USA. Univ Freiburg, Freiburg, Germany. Yale Univ, Sch Med, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2009 VL 89 SU 1 MA 941 BP 207A EP 207A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 394XK UT WOS:000262486300942 ER PT J AU Castellar, ERP Merino, MJ Diaz-Montes, TP AF Castellar, E. R. Parrilla Merino, M. J. Diaz-Montes, T. P. TI Cross-Sectional Study of Ovarian Tumors among Hispanic Women Living in the United States SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 NIH, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2009 VL 89 MA 1052 BP 231A EP 231A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 394XK UT WOS:000262486301053 ER PT J AU Garcia, A Villamor, N Gaulard, P Jaffe, E Campo, E Martinez, A AF Garcia, A. Villamor, N. Gaulard, P. Jaffe, E. Campo, E. Martinez, A. TI Characterization of TCR delta Expression in Paraffin Embedded Tissue Sections: A New Diagnostic Tool for gamma delta T-Cell Lymphomas SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Hosp Clin Barcelona, Barcelona, Spain. Hosp Henri Mondor, Creteil, France. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2009 VL 89 MA 1195 BP 263A EP 263A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 394XK UT WOS:000262486301196 ER PT J AU Kovach, AE Humsi, MK Jaffe, ES Calvo, KR AF Kovach, A. E. Humsi, M. K. Jaffe, E. S. Calvo, K. R. TI Basal Activation of NFkB Protein Signaling Pathway in Follicular Lymphoma In Vivo SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 [Kovach, A. E.; Humsi, M. K.; Jaffe, E. S.; Calvo, K. R.] NCI, NIH, Bethesda, MD 20892 USA. RI Calvo, Katherine/A-8109-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2009 VL 89 MA 1239 BP 273A EP 273A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 394XK UT WOS:000262486301239 ER PT J AU Maric, I Giri, N Arthur, D Noel, P Alter, BP AF Maric, I. Giri, N. Arthur, D. Noel, P. Alter, B. P. TI Distinct Patterns of Marrow Fibrosis in Patients with Inherited Bone Marrow Failure Syndromes SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 NIH, CC, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2009 VL 89 MA 1254 BP 276A EP 276A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 394XK UT WOS:000262486301254 ER PT J AU Meyer, PN Weisenburger, DD Choi, WL Smith, LM Greiner, TC Aoun, P Delabie, J Braziel, RM Vose, JM Lenz, G Staudt, LM Chan, WC Fu, K AF Meyer, P. N. Weisenburger, D. D. Choi, W. L. Smith, L. M. Greiner, T. C. Aoun, P. Delabie, J. Braziel, R. M. Vose, J. M. Lenz, G. Staudt, L. M. Chan, W. C. Fu, K. TI LMO2 Expression and the Hans Algorithm in Predicting Germinal Center Phenotype and Survival in Diffuse Large B-Cell Lymphoma Treated with Rituximab SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Univ Nebraska, Med Ctr, Omaha, NE USA. Univ Hong Kong, Fac Med, Hong Kong, Hong Kong, Peoples R China. Univ Oslo, Med Ctr, Oslo, Norway. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2009 VL 89 MA 1258 BP 277A EP 277A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 394XK UT WOS:000262486301258 ER PT J AU Schrager, JA Pittaluga, S Raffeld, M Jaffe, ES AF Schrager, J. A. Pittaluga, S. Raffeld, M. Jaffe, E. S. TI EBV Reactivation Syndromes in Adults without Known Immunodeficiency SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 [Schrager, J. A.; Pittaluga, S.; Raffeld, M.; Jaffe, E. S.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2009 VL 89 MA 1291 BP 285A EP 285A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 394XK UT WOS:000262486301291 ER PT J AU Slotta-Huspenina, J Koch, I de Leval, L Keller, G Bink, K Kremer, M Raffeld, M Fend, F Quintanilla-Martinez, L AF Slotta-Huspenina, J. Koch, I. de Leval, L. Keller, G. Bink, K. Kremer, M. Raffeld, M. Fend, F. Quintanilla-Martinez, L. TI High Proliferation Rate in Mantle Cell Lymphoma Is Associated with p53 Mutations and Blastoid Morphology, but Not with 3'UTR Deficient Cyclin D1 mRNA or High Total Cyclin D1 mRNA Levels SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Tech Univ Munich, Inst Pathol, Munich, Germany. Helmholtz Ctr, Inst Pathol, Munich, Germany. Univ Tubingen, Inst Pathol 3, Tubingen, Germany. Univ Liege, Liege, Belgium. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2009 VL 89 MA 1298 BP 287A EP 287A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 394XK UT WOS:000262486301298 ER PT J AU Taylor, J Huang, W Facchetti, F Jaffe, E Chang, C AF Taylor, J. Huang, W. Facchetti, F. Jaffe, E. Chang, C. TI Genomic Profiling of Plasmablastic Lymphoma Using BAC Array CGH - Revealing Significant Overlapping Genomic Lesions with DLBCL SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Methodist Hosp TMHRI, Houston, TX USA. Chang Gung Mem Hosp, Kaohsiung, Taiwan. Univ Brescia, Brescia, Italy. NCI, NIH, Bethesda, MD 20892 USA. RI Facchetti, Fabio/E-7190-2010 OI Facchetti, Fabio/0000-0003-4975-2388 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2009 VL 89 MA 1303 BP 288A EP 288A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 394XK UT WOS:000262486301303 ER PT J AU Mani, H Saxena, R Hoofnagle, JH Kleiner, DE AF Mani, H. Saxena, R. Hoofnagle, J. H. Kleiner, D. E. TI Temporal Evolution of Amoxicillin-Clavulanate Induced Liver Injury SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 NCI, NIH, Bethesda, MD 20892 USA. Indiana Univ, Indianapolis, IN 46204 USA. NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2009 VL 89 MA 1430 BP 316A EP 316A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 394XK UT WOS:000262486301430 ER PT J AU Galli, S Li, G Ren, Y Tsokos, M AF Galli, S. Li, G. Ren, Y. Tsokos, M. TI Expression of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) Receptor DR5 in Ewing Sarcoma Family Tumors (ESFT) SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 [Galli, S.; Li, G.; Ren, Y.; Tsokos, M.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2009 VL 89 SU 1 MA 1569 BP 346A EP 346A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 394XK UT WOS:000262486301569 ER PT J AU Galli, S Perlman, E Tsokos, M AF Galli, S. Perlman, E. Tsokos, M. TI Survivin, Bcl-2 and Caspase 8 Expression in Wilms Tumors with Favorable Histology Does Not Correlate with Clinical Stage SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 NCI, NIH, Bethesda, MD 20892 USA. Childrens Mem Med Ctr, Chicago, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2009 VL 89 SU 1 MA 1568 BP 346A EP 346A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 394XK UT WOS:000262486301568 ER PT J AU Valera, VA Walter, BA Linehan, WM Sobel, ME Merino, MJ AF Valera, V. A. Walter, B. A. Linehan, W. M. Sobel, M. E. Merino, M. J. TI microRNA Regulation of VHL Gene in Clear Cell Renal Cell Carcinomas SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 NCI, Bethesda, MD 20892 USA. Amer Soc Investigat Pathol, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2009 VL 89 MA 1709 BP 377A EP 377A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 394XK UT WOS:000262486301708 ER PT J AU Osman, JM Fliedner, SF Abu-Asab, M Pacak, K Tsokos, M AF Osman, J. M. Fliedner, S. F. Abu-Asab, M. Pacak, K. Tsokos, M. TI Unique Ultrastructural Features in Pheochromocytoma from Patients with Mutations in the Succinate Dehydrogenase B and D Genes SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 [Osman, J. M.; Fliedner, S. F.; Abu-Asab, M.; Pacak, K.; Tsokos, M.] NIH, Bethesda, MD 20892 USA. RI Fliedner, Stephanie/D-3406-2012 NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2009 VL 89 MA 1779 BP 392A EP 393A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 394XK UT WOS:000262486301778 ER PT J AU Szefler, SJ Gergen, PJ Mitchell, H Busse, WW AF Szefler, Stanley J. Gergen, Peter J. Mitchell, Herman Busse, William W. CA NIAID Inner City Asthma Consortium TI Clinical use of exhaled nitric oxide measurements Reply SO LANCET LA English DT Letter C1 [Szefler, Stanley J.] Natl Jewish Hlth, Dept Pediat, Denver, CO 80206 USA. [Gergen, Peter J.] NIAID, Bethesda, MD 20892 USA. [Mitchell, Herman] Rho, Chapel Hill, NC USA. [Busse, William W.] Univ Wisconsin, Madison, WI USA. RP Szefler, SJ (reprint author), Natl Jewish Hlth, Dept Pediat, 1400 Jackson St,Room J313, Denver, CO 80206 USA. EM szeflers@njc.org NR 1 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 0140-6736 J9 LANCET JI Lancet PD JAN-FEB PY 2009 VL 373 IS 9661 BP 382 EP 382 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 401BC UT WOS:000262912100027 ER PT J AU Persad, G Wertheimer, A Emanuel, EJ AF Persad, Govind Wertheimer, Alan Emanuel, Ezekiel J. TI Principles for allocation of scarce medical interventions SO LANCET LA English DT Article ID INTENSIVE-CARE-UNIT; HEALTH-CARE; RENAL-TRANSPLANTATION; RESOURCE-ALLOCATION; LIFE EXPECTANCY; PUBLIC-HEALTH; FAIR PROCESS; OF-LIFE; REASONABLENESS; ACCOUNTABILITY AB Allocation of very scarce medical interventions such as organs and vaccines is a persistent ethical challenge. We evaluate eight simple allocation principles that can be classified into four categories: treating people equally, favouring the worst-off, maximising total benefits, and promoting and rewarding social usefulness. No single principle is sufficient to incorporate all morally relevant considerations and therefore individual principles must be combined into multiprinciple allocation systems. We evaluate three systems: the United Network for Organ Sharing points systems, quality-adjusted life-years, and disability-adjusted life-years. We recommend an alternative system-the complete lives system-which prioritises younger people who have not yet lived a complete life, and also incorporates prognosis, save the most lives, lottery, and instrumental value principles. C1 [Persad, Govind; Wertheimer, Alan; Emanuel, Ezekiel J.] NIH, Dept Bioeth, Clin Ctr, Bethesda, MD 20892 USA. RP Emanuel, EJ (reprint author), NIH, Dept Bioeth, Clin Ctr, Bldg 10, Bethesda, MD 20892 USA. EM eemanuel@nih.gov NR 96 TC 183 Z9 186 U1 8 U2 26 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 JAN-FEB PY 2009 VL 373 IS 9661 BP 423 EP 431 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 401BC UT WOS:000262912100034 PM 19186274 ER PT J AU McFarland, HF AF McFarland, Henry F. TI Alemtuzumab versus interferon beta-1a: implications for pathology and trial design SO LANCET NEUROLOGY LA English DT Editorial Material ID MULTIPLE-SCLEROSIS C1 NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. RP McFarland, HF (reprint author), NINDS, Neuroimmunol Branch, NIH, Bldg 10,Room 5C103,9000 Rockville Pike, Bethesda, MD 20892 USA. EM mcfarlandh@ninds.nih.gov NR 4 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1474-4422 J9 LANCET NEUROL JI Lancet Neurol. PD JAN PY 2009 VL 8 IS 1 BP 26 EP 28 DI 10.1016/S1474-4422(08)70280-1 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 386CU UT WOS:000261860700015 PM 19081510 ER PT J AU Chen, Y Roney, C Yuan, SA Jiang, J Li, G Ma, HZ Cable, A Lee, C Summers, R AF Chen, Yu Roney, Celeste Yuan, Shuai Jiang, James Li, Grace Ma, Hongzhou Cable, Alex Lee, Chi Summers, Ronald TI MULTI-MODAL OPTICAL IMAGING OF COLON CANCER SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 29th Annual Conference of the American-Society-for-Laser-Medicine and Surgery CY APR 01-05, 2009 CL National Harbor, MD SP Amer Soc Laser Med & Surg C1 NIH, Bethesda, MD 20892 USA. Univ Maryland, College Pk, MD 20742 USA. Thorlabs Inc, Newton, NJ 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 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2009 BP 15 EP 15 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 464RV UT WOS:000267524700043 ER PT J AU Barrett, AJ Savani, BN AF Barrett, A. J. Savani, B. N. TI Does chemotherapy modify the immune surveillance of hematological malignancies? SO LEUKEMIA LA English DT Review DE lymphocyte recovery; immune surveillance; lymphoma ID STEM-CELL TRANSPLANTATION; CHRONIC MYELOGENOUS LEUKEMIA; EARLY LYMPHOCYTE RECOVERY; CHRONIC MYELOID-LEUKEMIA; BONE-MARROW-TRANSPLANTATION; PREDICTS SUPERIOR SURVIVAL; NATURAL-KILLER-CELLS; NON-HODGKIN-LYMPHOMA; EPSTEIN-BARR-VIRUS; T-CELLS AB Malignant diseases induce immune responses against them which have variable success in controlling progression of disease. A variety of congenital and acquired disorders provide evidence in support of T cell or NK cell immune surveillance mechanisms in human hematological malignancies. Furthermore, clinical experience with stem cell transplantation underlines the potential for both T and NK cell-mediated antileukemia effects. Animal models of tumor surveillance and viral-driven lymphoproliferative diseases in man emphasize the dynamic nature of the equilibrium between tumors and the immune system, which can lead to tumor escape in individuals with normal immune function. In hematological malignancies the implication of a dynamic immune surveillance model is that chemotherapy may disrupt potentially competent immune surveillance mechanisms leading to disease recurrence following successful tumor bulk reduction by chemotherapy. This possibility deserves further investigation with a view to developing strategies to boost immune function following chemotherapy so as to combine the beneficial effect of chemotherapy with an immune response capable of sustaining remissions. C1 [Barrett, A. J.] NHLBI, Stem Cell Allotransplantat Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Savani, B. N.] Vanderbilt Univ, Transplant Program, Nashville, TN USA. [Savani, B. N.] Vet Affairs Med Ctr, Hematol & Stem Cell Transplant Sect, Nashville, TN 37212 USA. RP Barrett, AJ (reprint author), NHLBI, Stem Cell Allogene Transplantat Sect, Hematol Branch, NIH, Bldg 10,Hatfield CRC,Room 3-5330,10 Ctr Dr MSC 12, Bethesda, MD 20892 USA. EM barrettj@nhlbi.nih.gov FU Intramural NIH HHS [ZIA HL002342-16] NR 58 TC 24 Z9 27 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD JAN PY 2009 VL 23 IS 1 BP 53 EP 58 DI 10.1038/leu.2008.273 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA 394TL UT WOS:000262470700006 PM 18830260 ER PT J AU Gillet, JP Molina, TJ Jamart, J Gaulard, P Leroy, K Briere, J Theate, I Thieblemont, C Bosly, A Herin, M Hamels, J Remacle, J AF Gillet, Jean-Pierre Molina, Thierry Jo Jamart, Jacques Gaulard, Philippe Leroy, Karen Briere, Josette Theate, Ivan Thieblemont, Catherine Bosly, Andre Herin, Michel Hamels, Jacques Remacle, Jose TI Evaluation of a low density DNA microarray for small B-cell non-Hodgkin lymphoma differential diagnosis SO LEUKEMIA & LYMPHOMA LA English DT Article DE Small B-cell non-Hodgkin lymphoma; low density DNA microarray; diagnosis ID MARGINAL-ZONE LYMPHOMA; SMALL LYMPHOCYTIC LYMPHOMA; GENE-EXPRESSION; MANTLE CELL; CDNA ARRAYS; CLASSIFICATION; CANCER; TISSUE; IDENTIFICATION; MALIGNANCIES AB Lymphomas are classified according to the World Health Organisation (WHO) classification which defines subtypes on the basis of clinical, morphological, immunophenotypic, molecular and cytogenetic criteria. Differential diagnosis of the subtypes is sometimes difficult, especially for small B-cell lymphoma (SBCL). Standardisation of molecular genetic assays using multiple gene expression analysis by microarrays could be a useful complement to the current diagnosis. The aim of the present study was to develop a low density DNA microarray for the analysis of 107 genes associated with B-cell non-Hodgkin lymphoma and to evaluate its performance in the diagnosis of SBCL. A predictive tool based on Fisher discriminant analysis using a training set of 40 patients including four different subtypes (follicular lymphoma n=15, mantle cell lymphoma n=7, B-cell chronic lymphocytic leukemia n=6 and splenic marginal zone lymphoma n=12) was designed. A short additional preliminary analysis to gauge the accuracy of this signature was then performed on an external set of nine patients. Using this model, eight of nine of those samples were classified successfully. This pilot study demonstrates that such a microarray tool may be a promising diagnostic approach for small B-cell non-Hodgkin lymphoma. C1 [Gillet, Jean-Pierre; Remacle, Jose] Univ Namur FUNDP, Res Unit Cellular Biol URBC, Namur, Belgium. [Molina, Thierry Jo] Univ Paris 05, Hop Hotel Dieu, AP HP, Paris, France. [Jamart, Jacques; Bosly, Andre] Mt Godinne Univ Hosp, Dept Hematol, Yvoir, Belgium. [Gaulard, Philippe; Leroy, Karen] Hop Henri Mondor, AP HP, Dept Pathol, F-94010 Creteil, France. [Gaulard, Philippe; Leroy, Karen] INSERM, U841, Creteil, France. [Gaulard, Philippe; Leroy, Karen] Univ Paris 12, Creteil, France. [Briere, Josette; Thieblemont, Catherine] Hop St Louis, IUH, AP HP, Paris, France. [Theate, Ivan] Univ Louvain, Dept Pathol, Brussels, Belgium. [Herin, Michel] Univ Namur FUNDP, Cell & Tissue Lab LabCeTi, Namur, Belgium. [Herin, Michel; Hamels, Jacques] Inst Pathol & Genet, Gosselies, Belgium. RP Gillet, JP (reprint author), Natl Canc Inst, Cell Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Rm 2112, Bethesda, MD 20892 USA. EM gilletjp@mail.nih.gov RI Leroy, Karen/E-9235-2011; gillet, jean-pierre/A-3714-2012 FU Institut de Pathologie et de Genetique (IPG, Belgium) FX The authors thank George Leiman for valuable editorial assistance. The authors acknowledge Eppendorf Array Technologies Company of Namur (Belgium) for their technical support. This work was financially supported by the Institut de Pathologie et de Genetique (IPG, Belgium). NR 31 TC 3 Z9 3 U1 0 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PY 2009 VL 50 IS 3 BP 410 EP 418 AR PII 909597568 DI 10.1080/10428190902763459 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA 435RN UT WOS:000265361100020 PM 19294557 ER PT J AU Martin, DN Mikhail, IS Landgren, O AF Martin, Damali N. Mikhail, Isis S. Landgren, Ola TI Autoimmunity and hematologic malignancies: associations and mechanisms SO LEUKEMIA & LYMPHOMA LA English DT Review DE Autoimmunity; hematologic cancers; lymphoma; pathogenesis; etiology; mechanisms ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; PRIMARY SJOGRENS-SYNDROME; NON-HODGKINS-LYMPHOMA; HEPATITIS-C VIRUS; CHRONIC LYMPHOCYTIC-LEUKEMIA; EPSTEIN-BARR-VIRUS; RHEUMATOID-ARTHRITIS; CHRONIC INFLAMMATION; MULTIPLE-MYELOMA; CANCER INCIDENCE AB Although the true prevalence of autoimmune diseases remains to be better defined, in Western countries the current estimates indicate that at least 5% of the population is affected by an autoimmune disorder. Over the last few decades, autoimmune diseases have been associated with an elevated risk of developing lymphoproliferative malignancies, particularly non-Hodgkin lymphomas. Some studies have found the relationship between autoimmunity and lymphoproliferative tumors to be bi-directional. Although substantial work has been carried out to characterise the associations between autoimmunity and lymphoproliferation, current insights regarding underlying biological mechanisms remain limited and hence present a gap in the literature. In this article, we review reported main associations between selected common autoimmune diseases and lymphoproliferative neoplasms. We also discuss potential underlying mechanisms that have been proposed to connect these two disorders. Finally, we provide future directions for new research studies aimed to improve our understanding of inflammation and the dysregulated immune system in the development of autoimmunity and hematologic malignancies. C1 [Martin, Damali N.; Mikhail, Isis S.] NCI, Epidemiol & Genet Res Program, Div Canc Control & Populat Sci, Rockville, MD 20852 USA. [Landgren, Ola] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. [Landgren, Ola] NCI, Med Oncol Branch, Ctr Canc Res, Rockville, MD 20852 USA. RP Martin, DN (reprint author), NCI, Epidemiol & Genet Res Program, Div Canc Control & Populat Sci, EPN Room 5105, Rockville, MD 20852 USA. EM martinda@mail.nih.gov FU Division of Cancer Control and Population Sciences; National Cancer Institute; Intramural Research Program of the NIH; Division of Cancer Epidemiology and Genetics FX This work was supported by the Division of Cancer Control and Population Sciences, National Cancer Institute (D. N. Martin, I. S. Mikhail) and the Intramural Research Program of the NIH, National Cancer Institute, Division of Cancer Epidemiology and Genetics (O. Landgren). NR 65 TC 33 Z9 34 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PY 2009 VL 50 IS 4 BP 541 EP 550 AR PII 910513475 DI 10.1080/10428190902780677 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA 435RR UT WOS:000265361500008 PM 19373651 ER PT J AU Wilkinson, ST Fernandez, DR Murphy, SP Braziel, RM Campo, E Chan, WC Delabie, J Gascoyne, RD Staudt, LM Jaffe, ES Rosenwald, A Rimsza, LM AF Wilkinson, Sarah T. Fernandez, Diane R. Murphy, Shawn P. Braziel, Rita M. Campo, Elias Chan, Wing C. Delabie, Jan Gascoyne, Randy D. Staudt, Louis M. Jaffe, Elaine S. Rosenwald, Andreas Rimsza, Lisa M. TI Decreased major histocompatibility complex class II expression in diffuse large B-cell lymphoma does not correlate with CpG methylation of class II transactivator promoters III and IV SO LEUKEMIA & LYMPHOMA LA English DT Letter ID POOR PATIENT SURVIVAL; PROTEIN EXPRESSION; CIITA; GENE; MECHANISM; GAMMA C1 [Wilkinson, Sarah T.; Fernandez, Diane R.; Rimsza, Lisa M.] Univ Arizona, Dept Pathol, Tucson, AZ 85724 USA. [Murphy, Shawn P.] Univ Rochester, Sch Med & Dent, Dept Obstet & Gynecol, Rochester, NY 14642 USA. [Braziel, Rita M.] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97201 USA. [Campo, Elias] Univ Barcelona, Dept Pathol, Hosp Clin, Barcelona, Spain. [Chan, Wing C.] Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE USA. [Delabie, Jan] Radium Hosp, Dept Pathol, Oslo, Norway. [Gascoyne, Randy D.] British Columbia Canc Agcy, Dept Pathol, Vancouver, BC V5Z 4E6, Canada. [Staudt, Louis M.] NCI, Metab Branch, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Jaffe, Elaine S.] NCI, Hematopathol Sect, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Rosenwald, Andreas] Univ Wurzburg, Inst Pathol, D-8700 Wurzburg, Germany. RP Rimsza, LM (reprint author), Univ Arizona, Dept Pathol, 1501 N Campbell Ave,Box 245043, Tucson, AZ 85724 USA. EM lrimsza@email.arizona.edu OI Delabie, Jan/0000-0001-5023-0689; Campo, elias/0000-0001-9850-9793 FU NCI NIH HHS [1-U10-CA-84967-02, P30 CA023074, T32 CA009213, T32 CA009213-32, T32 CA09213, U01 CA084967, U01 CA084967-02] NR 15 TC 6 Z9 6 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PY 2009 VL 50 IS 11 BP 1875 EP U187 DI 10.3109/10428190903297531 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA 524LO UT WOS:000272145000029 PM 19814686 ER PT J AU Tay, K Dunleavy, K Wilson, WH AF Tay, Kevin Dunleavy, Kieron Wilson, Wyndham H. TI Targeting HLA-DR SO LEUKEMIA & LYMPHOMA LA English DT Editorial Material ID ANTIBODY; CELLS; ANTIGEN; HU1D10; EXPRESSION; LYMPHOMA C1 [Tay, Kevin; Dunleavy, Kieron; Wilson, Wyndham H.] NCI, Ctr Canc Res, Metab Branch, Bethesda, MD 20892 USA. RP Wilson, WH (reprint author), NCI, Ctr Canc Res, Metab Branch, Bethesda, MD 20892 USA. EM wilsonw@mail.nih.gov NR 14 TC 1 Z9 1 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PY 2009 VL 50 IS 12 BP 1911 EP 1913 DI 10.3109/10428190903370379 PG 3 WC Oncology; Hematology SC Oncology; Hematology GA 532MO UT WOS:000272753000004 PM 19886843 ER PT S AU Gaskins, AJ Schisterman, EF AF Gaskins, Audrey J. Schisterman, Enrique F. BE Armstrong, D TI The Effect of Lipid Adjustment on the Analysis of Environmental Contaminants and the Outcome of Human Health Risks SO LIPIDOMICS, VOL 2: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Causal modeling; Directed acyclic graphs; Risk estimation; Serum lipids; Organochlorines; Polychlorinated biphenyls ID PLASMA ORGANOCHLORINE LEVELS; BREAST-CANCER RISK; ADIPOSE-TISSUE; POLYCHLORINATED-BIPHENYLS; HUMAN-SERUM; EXPOSURE; WORKERS; BLOOD; US AB Past literature on exposure to lipophilic agents Such as organochlorines (OCs) is conflicting, posing challenges for the interpretation of their potential human health risks. Since blood is often used as a proxy for adipose tissue, it is necessary to model serum lipids when assessing health risks of OCs. Using a simulation study, we evaluated four statistical models (unadjusted, standardized, adjusted, and two-stage) for the analysis of polychlorinated biphenyls (PCBs) exposure, serum lipids, and health outcome risk. Eight candidate true causal scenarios, depicted by directed acyclic graphs, were used to illustrate the ramifications of misspecification of underlying assumptions when interpreting results. Biased results were produced when statistical models that deviated from the underlying causal assumptions were used with the lipid standardization method found to be particularly prone to bias. We concluded that investigators must consider biology, biological medium, laboratory measurement, and other underlying modeling assumptions when devising a statistical model for assessing health outcomes in relation to environmental exposures. C1 [Gaskins, Audrey J.; Schisterman, Enrique F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Rockville, MD USA. RP Gaskins, AJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Rockville, MD USA. OI Schisterman, Enrique/0000-0003-3757-641X FU Intramural NIH HHS [NIH0013951122]; NIDDK NIH HHS [T32 DK007703]; PHS HHS [NIH0013951122] NR 17 TC 17 Z9 17 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60761-324-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2009 VL 580 BP 371 EP 381 DI 10.1007/978-1-60761-325-1_20 D2 10.1007/978-1-60761-325-1 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BMR76 UT WOS:000273425200020 PM 19784610 ER PT J AU Seeff, LB AF Seeff, Leonard B. TI The history of the "natural history" of hepatitis C (1968-2009) SO LIVER INTERNATIONAL LA English DT Review DE cirrhosis; hepatitis C; natural history; prospective study; retrospective-prospective study; retrospective study ID NON-B-HEPATITIS; HUMAN-IMMUNODEFICIENCY-VIRUS; TRANSFUSION-ASSOCIATED HEPATITIS; NORMAL AMINOTRANSFERASE LEVELS; TERM-FOLLOW-UP; STAGE LIVER-DISEASE; CHRONIC NON-A; FIBROSIS PROGRESSION; POSTTRANSFUSION HEPATITIS; VIRAL-HEPATITIS AB In the late 1960's, only types A and B hepatitis were believed to exist, distinguished by circumstances of exposure and incubation periods. In the early 1970's, studies of transfusion recipients were begun with the belief that hepatitis B would be responsible should transfusion-associated hepatitis develop. After discovery of the viruses of hepatitis A and B, neither agent was found responsible, hence non-A, non-B (NANB) hepatitis. Initial follow-up of these cases showed that similar to 50% developed chronic hepatitis based on persistence of serum enzymes for at least 6 months. Approximately 15 years later, after the hepatitis C virus had been identified as the cause for NANB hepatitis, chronic hepatitis was found to develop more frequently as indicated by persistent viral infection in over 80% of infected adults but in only about 50% of infected children or young women. Follow-up over 2 to 4 decades indicated that many infected persons developed progressive hepatic fibrosis, sometimes culminating in cirrhosis and/or liver cancer. Long-term natural history studies have proved to be challenging because disease onset is often silent and progression extremely slow. Differing strategies have been used to determine the natural history, the descriptions and results of which are presented in this review. C1 NIDDKD, NIH, Bethesda, MD 20892 USA. RP Seeff, LB (reprint author), NIDDKD, NIH, 31A Ctr Dr,Room 9A27, Bethesda, MD 20892 USA. EM seeffl@extra.niddk.nih.gov FU Intramural NIH HHS [Z99 DK999999] NR 103 TC 121 Z9 123 U1 1 U2 8 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1478-3223 J9 LIVER INT JI Liver Int. PD JAN PY 2009 VL 29 SU 1 BP 89 EP 99 DI 10.1111/j.1478-3231.2008.01927.x PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 397FB UT WOS:000262646800013 PM 19207971 ER PT B AU Bruno, DA Kirk, AD AF Bruno, David A. Kirk, Allan D. BE Everson, GT Trotter, JF TI Tolerance in Liver Transplantation Just a Promise or an Evolving Reality? SO LIVER TRANSPLANTATION: CHALLENGING CONTROVERSIES AND TOPICS SE Clinical Gastroenterology LA English DT Article; Book Chapter DE Immunosuppression; Interleukin receptor antagonist; Campath; Sirolimus; Hepatitis C; Hepatocellular carcinoma ID SINUSOIDAL ENDOTHELIAL-CELLS; VERSUS-HOST-DISEASE; T-CELLS; DENDRITIC CELLS; IMMUNOSUPPRESSION WITHDRAWAL; ALLOGRAFT TOLERANCE; GRAFT ACCEPTANCE; KUPFFER CELLS; RECIPIENTS; ANTIGEN AB In recent years, a variety of immunosuppressive (IS) agents has emerged. The best application and combination of these new agents along with traditional immunosuppressive agents present challenges and opportunities to transplant physicians. Two anti-IL2 receptor monoclonal antibodies are currently available for clinical use: daclizumab (Zenapax, Roche) and basiliximab (Simulect, Novartis). Both bind to the alpha subunit of the IL-2 receptor (CD-25), which is expressed on activated, but not resting, lymphocytes. These drugs are the most commonly used induction agents in the United States. Campath-1H (C-1H) or alemtuzumab (Ilex Pharmaceuticals) has been used in a limited fashion in liver transplantation recipients with mixed results. The role of sirolimus in liver transplantation remains controversial. However, this agent may offer specific advantages in patients with hepatocellular carcinoma or renal dysfunction. Because hepatitis C is the most common indication for liver transplantation, the application of immunosuppression in these patients is important. However, the best regimen for these patients remains controversial. The role of new immunosuppressive drugs including FTY720, FK778, and LEA29Y offers the promise for better immunosuppression for future liver transplantation recipients. C1 [Bruno, David A.; Kirk, Allan D.] NIDDK, Transplantat Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. RP Bruno, DA (reprint author), NIDDK, Transplantat Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. RI Kirk, Allan/B-6905-2012 NR 65 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-58829-793-8 J9 CLIN GASTROENT-SER PY 2009 BP 1 EP 18 DI 10.1007/978-1-60327-028-1_1 D2 10.1007/978-1-60327-028-1 PG 18 WC Gastroenterology & Hepatology; Transplantation SC Gastroenterology & Hepatology; Transplantation GA BKD77 UT WOS:000267842000001 ER PT B AU Albert, PS Follmann, DA AF Albert, Paul S. Follmann, Dean A. BE Fitzmaurice, G Davidian, M Verbeke, G Molenberghs, G TI Shared-parameter models SO LONGITUDINAL DATA ANALYSIS SE Chapman & Hall-CRC Handbooks of Modern Statistical Methods LA English DT Article; Book Chapter ID LONGITUDINAL BINARY DATA; LOGISTIC-REGRESSION MODELS; LINEAR MIXED MODELS; MISSING DATA; DROP-OUT; INFORMATIVE MISSINGNESS; MIXTURE-MODELS; RESPONSE DATA; DATA SUBJECT; EVENT TIMES C1 [Albert, Paul S.] Natl Canc Inst, Biometr Res Branch, Rockville, MD USA. [Follmann, Dean A.] NIAID, Biostat Res Branch, Bethesda, MD 20892 USA. RP Albert, PS (reprint author), Natl Canc Inst, Biometr Res Branch, Rockville, MD USA. NR 40 TC 18 Z9 18 U1 0 U2 1 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-58488-658-7 J9 CH CRC HANDB MOD STA PY 2009 BP 433 EP 452 PG 20 WC Statistics & Probability SC Mathematics GA BKC26 UT WOS:000267748700019 ER PT S AU Turkbey, B Ravizzini, G Choyke, PL Kobayashi, H AF Turkbey, Baris Ravizzini, Gregory Choyke, Peter L. Kobayashi, Hisataka BE Stacker, SA Achen, MG TI LYMPHANGIOGENESIS AND IMAGING OF THE LYMPHATICS IN CANCER SO LYMPHANGIOGENESIS IN CANCER METASTASIS SE Cancer Metastasis Biology and Treatment LA English DT Article; Book Chapter DE Imaging; Lymphangiogenesis; Cancer; Metastases ID MAGNETIC RESONANCE LYMPHANGIOGRAPHY; NEPHROGENIC SYSTEMIC FIBROSIS; SENTINEL NODE LOCALIZATION; ENDOTHELIAL GROWTH-FACTORS; AMERICAN JOINT COMMITTEE; EARLY-STAGE MELANOMA; BREAST-CANCER; QUANTUM DOTS; TUMOR-METASTASIS; VEGF-C AB Metastatic spread of cancer is one of the major causes of cancer death. The lymphatics contribute to metastatic spread by providing a conduit for the spread of cancer cells. Tumors actively induce new lymphatic formation by deploying growth factors, a process known as lymphangiogenesis. Systemic lymphatic imaging with conventional modalities such as computed tomography, magnetic resonance imaging and ultrasound is limited to morphological evaluation for detection of enlarged lymph nodes; on the other hand, functional lymphatic imaging approaches, including positron emission tomography, dynamic contrast-enhanced MRI, lymphotrophic iron oxide nanoparticle enhanced-MRI have been used to diagnose metastatic cancer in lymph nodes. Recently, new targeted lymphatic imaging techniques including gadolinium-conjugated dendrimer-based MRI, optical imaging using nano-sized molecules based on fluorescence-labeled dendrimers, organic macromolecules, or quantum dots, have been developed. In this chapter, we will explain principles and basic findings of conventional and functional lymphatic imaging and will outline newly developed targeted lymphatic imaging approaches. C1 [Turkbey, Baris; Ravizzini, Gregory; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Bethesda, MD 20892 USA. RP Turkbey, B (reprint author), NCI, Mol Imaging Program, Bethesda, MD 20892 USA. EM turkbeyi@mail.nih.gov; ravizzini@msn.com; pchoyke@mail.nih.gov; kobayash@mail.nih.gov NR 109 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 1568-2102 BN 978-90-481-2246-2 J9 CANCER METAST BIOL T JI Cancer Metastasis-Biol Treat PY 2009 VL 13 BP 159 EP 184 DI 10.1007/978-90-481-2247-9_7 D2 10.1007/978-90-481-2247-9 PG 26 WC Oncology SC Oncology GA BLY23 UT WOS:000271413300007 ER PT J AU Dimitrov, DS AF Dimitrov, Dimiter S. TI Engineered CH2 domains (nanoantibodies) SO MABS LA English DT Review DE CH2; nanoantibodies; scaffold; Fabs; antibodies ID BINDING-PROTEINS; ANTIBODY DOMAIN; SCAFFOLDS; MECHANISM AB Currently, almost all FDA approved therapeutic antibodies (except ReoPro, Lucentis and Cimzia which are Fabs), and the vast majority of those in clinical trials are full-size antibodies mostly in IgG1 format of about 150 kDa size. A fundamental problem for such large molecules is their poor penetration into tissues (e.g., solid tumors) and poor or absent binding to regions on the surface of some molecules (e.g., on the HIV envelope glycoprotein) which are fully accessible only by molecules of smaller size. Therefore, much work especially during the last decade has been aimed at developing novel scaffolds of much smaller size and high stability. Here I briefly describe a proposition to use the immunoglobulin (Ig) constant CH2 domain (CH3 for IgE and IgM) as a scaffold. CH2 is critical for the Ig effector functions. Isolated CH2 is stable monomer in contrast to all other constant domains and most of the variable domains. CH2 and engineered CH2 domains with improved stability can be used as scaffolds for construction of libraries containing diverse binders to various antigens. Such binders based on a CH2 scaffold could also confer some effector functions. Because the CH2 domains are the smallest independently folded antibody domains that can be engineered to contain simultaneously antigen-binding sites and binding sites mediating effector and stability functions, and to distinguish them from domain antibodies which are used to denote engineered VH or VL domains or nanobodies which are used to denote camelid VHH, I termed them nanoantibodies (nAbs). C1 NCI, Prot Interact Grp, Ctr Canc Res Nanobiol Program, NIH, Frederick, MD 21702 USA. RP Dimitrov, DS (reprint author), NCI, Prot Interact Grp, Ctr Canc Res Nanobiol Program, NIH, Bldg 469,Rm 150B, Frederick, MD 21702 USA. EM dimitrov@ncifcrf.gov FU NIH FX This work was supported by the NIH NO CCR intramural program, the NIH intramural AIDS program (IATAP) and the NIH intramural biodefense program. I would like to thank to Dr. Prabakaran Ponraj for helpful discussions and help with the figures. NR 14 TC 26 Z9 27 U1 0 U2 7 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1942-0862 J9 MABS JI mAbs PD JAN-FEB PY 2009 VL 1 IS 1 BP 26 EP 28 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 519ZJ UT WOS:000271809200004 PM 20046570 ER PT J AU Roth, BJ Basser, PJ AF Roth, Bradley J. Basser, Peter J. TI Mechanical Model of Neural Tissue Displacement During Lorentz Effect Imaging SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE magnetic resonance imaging; MRI; Lorentz force; elasticity; displacement; action current ID MAGNETIC-RESONANCE; CURRENT-DENSITY; NEURONAL-ACTIVITY; VOLUME CONDUCTOR; SINGLE AXON; NERVE-FIBER; BRAIN; FIELD; CURRENTS; MRI AB Allen Song and coworkers recently proposed a method for MRI detection of biocurrents in nerves called "Lorentz effect imaging." When exposed to a magnetic field, neural currents are subjected to a Lorentz force that moves the nerve. If the displacement is large enough, an artifact is predicted in the MR signal. In this work, the displacement of a nerve of radius a in a surrounding tissue of radius b and shear modulus mu is analyzed. The nerve carries a current density J and lies in a magnetic field B. The solution to the resulting elasticity problem indicates that the nerve moves a distance BJ/4 mu a(2)In(b/a). Using realistic parameters for a human median nerve in a 4T field, this calculated displacement is 0.013 mu m or less. The distribution of displacement is widespread throughout the tissue, and is not localized near the nerve. This displacement is orders of magnitude too small to be detected by conventional MRI methods. Magn Reson Mad 61:59-64, 2009, (C) 2008 Wiley-Liss, Inc. C1 [Roth, Bradley J.] Oakland Univ, Dept Phys, Rochester, MI 48309 USA. [Basser, Peter J.] Eunice Kennedy Shriver NICHHD, Sect Tissue Biophys & Biomimet, NIH, Bethesda, MD 20892 USA. RP Roth, BJ (reprint author), Oakland Univ, Dept Phys, Rochester, MI 48309 USA. EM roth@oakland.edu RI Roth, Bradley/A-4920-2008; Basser, Peter/H-5477-2011 FU National Institutes of Health (NIH) [R01EB008421]; Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH FX National Institutes of Health (NIH); Grant number: R01EB008421; Grant sponsor; Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH. NR 30 TC 15 Z9 15 U1 0 U2 1 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 JAN PY 2009 VL 61 IS 1 BP 59 EP 64 DI 10.1002/mrm.21772 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 386WT UT WOS:000261914000009 PM 19097218 ER PT J AU Blaimer, M Gutberlet, M Kellman, P Breuer, FA Kostler, H Griswold, MA AF Blaimer, Martin Gutberlet, Marcel Kellman, Peter Breuer, Felix A. Koestler, Herbert Griswold, Mark A. TI Virtual Coil Concept for Improved Parallel MRI Employing Conjugate Symmetric Signals SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE parallel MRI; conjugate symmetry; SENSE; GRAPPA ID SPATIAL HARMONICS SMASH; SIMULTANEOUS ACQUISITION; RESOLUTION ENHANCEMENT; RECONSTRUCTION; GRAPPA; SENSE AB A new approach for utilizing conjugate k-space symmetry for improved parallel MRI performance is presented. By generating virtual coils containing conjugate symmetric k-space signals from actual coils, additional image- and coil-phase information can be incorporated into the reconstruction process for parallel acquisition techniques. In that way the reconstruction conditions are improved, resulting in less noise enhancement. In particular in combination with generalized autocalibrating partially parallel acquisitions (GRAPPA), the virtual coil concept represents a practical approach since no explicit spatial phase information is required. In addition, the influence of phase variations originating from the complex receiver coils as well as from the background is investigated. It is shown that there exist background phase distributions yielding an optimized pMRI reconstruction. Magn Reson Med 61:93-102, 2009. (C) 2009 Wiley-Liss, Inc. C1 [Blaimer, Martin; Breuer, Felix A.] Res Ctr Magnet Resonance Bavaria, D-97074 Wurzburg, Germany. [Blaimer, Martin; Griswold, Mark A.] Univ Hosp Cleveland, Dept Radiol, Cleveland, OH 44106 USA. [Blaimer, Martin; Griswold, Mark A.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Gutberlet, Marcel; Koestler, Herbert] Univ Wurzburg, Inst Rontgendiagnost, Wurzburg, Germany. [Kellman, Peter] NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RP Blaimer, M (reprint author), Res Ctr Magnet Resonance Bavaria, D-97074 Wurzburg, Germany. EM blaimer@mr-bavaria.de RI Kostler, Herbert /B-2089-2010 OI Kostler, Herbert /0000-0001-6207-9226 NR 26 TC 20 Z9 21 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD JAN PY 2009 VL 61 IS 1 BP 93 EP 102 DI 10.1002/mrm.21652 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 386WT UT WOS:000261914000013 PM 19097211 ER PT J AU Kellman, P Hernando, D Shah, S Zuehlsdorff, S Jerecic, R Mancini, C Liang, ZP Arai, AE AF Kellman, Peter Hernando, Diego Shah, Saurabh Zuehlsdorff, Sven Jerecic, Renate Mancini, Christine Liang, Zhi-Pei. Arai, Andrew E. TI Multiecho Dixon Fat and Water Separation Method for Detecting Fibrofatty Infiltration in the Myocardium SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE MRI; heart; fat; chronic myocardial infarction; arrhythmogenic right ventricular dysplasia; ARVD; arrhythmogenic right ventricular cardiomyopathy; ARVC; lipoma; phase-sensitive inversion recovery; PSIR ID RIGHT-VENTRICULAR CARDIOMYOPATHY; MAGNETIC-RESONANCE; DECOMPOSITION; MAP AB Conventional approaches for fat and water discrimination based on chemical-shift fat suppression have reduced ability to characterize fatty infiltration due to poor contrast of microscopic fat. The multiecho Dixon approach to water and fat separation has advantages over chemical-shift fat suppression: 1) water and fat images can be acquired in a single breathhold, avoiding misregistration; 2) fat has positive contrast; 3) the method is compatible with precontrast and late-enhancement imaging, 4) less susceptible to partial-volume effects, and 5) robust in the presence of background field variation; and 6) for the bandwidth implemented, chemical-shift artifact is decreased. The proposed technique was applied successfully in all 28 patients studied. This included 10 studies with indication of coronary artery disease (CAD), of which four cases with chronic myocardial infarction (MI) exhibited fatty infiltration; 13 studies to rule out arrhythmogenic right ventricular cardiomyopathy (ARVC), of which there were three cases with fibrofatty infiltration and two confirmed with ARVC; and five cases of cardiac masses (two lipomas). The precontrast contrast-to-noise ratio (CNR) of intramyocardial fat was greatly improved, by 240% relative to conventional fat suppression. For the parameters implemented, the signal-to-noise ratio (SNR) was decreased by 30% relative to conventional late enhancement. The multiecho Dixon method for fat and water separation provides a sensitive means of detecting intramyocardial fat with positive signal contrast. Magn Reson Med 61:215-221, 2009. (C) 2008 Wiley-Liss, Inc. C1 [Kellman, Peter; Mancini, Christine; Arai, Andrew E.] NHLBI, Cardiac Energet Lab, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Hernando, Diego; Liang, Zhi-Pei.] Univ Illinois, Dept Elect & Comp Engn, Urbana, IL 61801 USA. [Shah, Saurabh; Zuehlsdorff, Sven; Jerecic, Renate] Siemens Med Solut, MR Res & Dev, Chicago, IL USA. RP Kellman, P (reprint author), NHLBI, Cardiac Energet Lab, NIH, US Dept HHS, Room B1D416,Bldg 10,MSC-1061,10 Ctr Dr, Bethesda, MD 20892 USA. EM kellman@nih.gov FU National Institutes of Health (NIH) [P41-EB03631-16, R01-CA098717]; Intramural Research Program of the NIH; National Heart, Lung and Blood Institute (NHLBI) FX Grant sponsor: National Institutes of Health (NIH); Grant numbers; P41-EB03631-16, R01-CA098717; Grant sponsor: Intramural Research Program of the NIH, National Heart, Lung and Blood Institute (NHLBI). NR 21 TC 50 Z9 50 U1 0 U2 3 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 JAN PY 2009 VL 61 IS 1 BP 215 EP 221 DI 10.1002/mrm.21657 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 386WT UT WOS:000261914000025 PM 19097213 ER PT J AU Truong, D Dressler, D Hallett, M AF Truong, Daniel Dressler, Dirk Hallett, Mark BE Truong, D Dressler, D Hallett, M TI Botulinum toxin: history of clinical development SO MANUAL OF BOTULINUM TOXIN THERAPY LA English DT Article; Book Chapter ID SPASMODIC TORTICOLLIS; DOUBLE-BLIND; A TOXIN; BLEPHAROSPASM; STRABISMUS; NEUROTOXINS; INJECTION; DYSTONIA; MUSCLES; NEURONS C1 [Truong, Daniel] Orange Coast Mem Med Ctr, Parkinsons & Movement Disorder Inst, Fountain Valley, CA 92708 USA. [Dressler, Dirk] Hannover Med Sch, Dept Neurol, Hannover, NH, Germany. [Hallett, Mark] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. RP Truong, D (reprint author), Orange Coast Mem Med Ctr, Parkinsons & Movement Disorder Inst, Fountain Valley, CA 92708 USA. NR 28 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-69442-1 PY 2009 BP 9 EP 12 DI 10.1017/CBO9780511575761.004 D2 10.1017/CBO9780511575761 PG 4 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BDI45 UT WOS:000313441000004 ER PT J AU Truong, D Dressler, D Hallett, M AF Truong, Daniel Dressler, Dirk Hallett, Mark BE Truong, D Dressler, D Hallett, M TI Manual of Botulinum Toxin Therapy Preface SO MANUAL OF BOTULINUM TOXIN THERAPY LA English DT Editorial Material; Book Chapter C1 [Truong, Daniel] Orange Coast Mem Med Ctr, Parkinsons & Movement Disorder Inst, Fountain Valley, CA 92708 USA. [Dressler, Dirk] Hannover Med Sch, Dept Neurol, Hannover, NH, Germany. [Hallett, Mark] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. RP Truong, D (reprint author), Orange Coast Mem Med Ctr, Parkinsons & Movement Disorder Inst, Fountain Valley, CA 92708 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-69442-1 PY 2009 BP XV EP XVI DI 10.1017/CBO9780511575761.002 D2 10.1017/CBO9780511575761 PG 2 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BDI45 UT WOS:000313441000002 ER PT J AU Das, CP Truong, D Hallett, M AF Das, Chandi Prasad Truong, Daniel Hallett, Mark BE Truong, D Dressler, D Hallett, M TI Treatment of focal hand dystonia SO MANUAL OF BOTULINUM TOXIN THERAPY LA English DT Article; Book Chapter ID BOTULINUM TOXIN; WRITERS CRAMP; MUSICIANS; PATHOPHYSIOLOGY; PREVALENCE C1 [Das, Chandi Prasad] Postgrad Inst Med Educ & Res, Dept Neurol, Chandigarh 160012, India. [Truong, Daniel] Orange Coast Mem Med Ctr, Parkinsons & Movement Disorder Inst, Fountain Valley, CA USA. [Hallett, Mark] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. RP Das, CP (reprint author), Postgrad Inst Med Educ & Res, Dept Neurol, Chandigarh 160012, India. NR 36 TC 2 Z9 2 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-69442-1 PY 2009 BP 61 EP 75 DI 10.1017/CBO9780511575761.011 D2 10.1017/CBO9780511575761 PG 15 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BDI45 UT WOS:000313441000011 ER PT J AU Dressler, D Truong, D Hallett, M AF Dressler, Dirk Truong, Daniel Hallett, Mark BE Truong, D Dressler, D Hallett, M TI Developing the next generation of botulinum toxin drugs SO MANUAL OF BOTULINUM TOXIN THERAPY LA English DT Article; Book Chapter ID CERVICAL DYSTONIA; ANTIBODY; EFFICACY; SPASM C1 [Dressler, Dirk] Hannover Med Sch, Dept Neurol, Hannover, NH, Germany. [Truong, Daniel] Orange Coast Mem Med Ctr, Parkinsons & Movement Disorder Inst, Fountain Valley, CA USA. [Hallett, Mark] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. RP Dressler, D (reprint author), Hannover Med Sch, Dept Neurol, Hannover, NH, Germany. NR 11 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-69442-1 PY 2009 BP 205 EP 208 DI 10.1017/CBO9780511575761.026 D2 10.1017/CBO9780511575761 PG 4 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BDI45 UT WOS:000313441000026 ER PT J AU Fogg, JM Catanese, DJ Randall, GL Swick, MC Zechiedrich, L AF Fogg, Jonathan M. Catanese, Daniel J., Jr. Randall, Graham L. Swick, Michelle C. Zechiedrich, Lynn BE Benham, CJ Harvey, S Olson, WK Sumners, DWL Swigon, D TI DIFFERENCES BETWEEN POSITIVELY AND NEGATIVELY SUPERCOILED DNA THAT TOPOISOMERASES MAY DISTINGUISH SO MATHEMATICS OF DNA STRUCTURE, FUNCTION AND INTERACTIONS SE IMA Volumes in Mathematics and its Applications LA English DT Proceedings Paper CT Workshop on Mathematics of DNA Structure, Function and Interactions CY SEP 16-21, 2007 CL Minneapolis, MN SP Inst Math & Applicat ID MOLECULAR-DYNAMICS SIMULATIONS; LOCAL JUXTAPOSITION GEOMETRY; ARCHAEAL HISTONE HMF; N-TERMINAL FRAGMENT; SINGLE-STRANDED-DNA; ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; TORSIONAL RIGIDITY; II TOPOISOMERASES; SUPERHELICAL DNA AB In all living cells, DNA is homeostatically underwound relative to its lowest energy conformation, resulting in negative supercoiling. This underwinding of DNA is critical to the metabolism of DNA and, thus, is vital to cell survival. Enzymes called topoisomerases regulate and maintain the supercoiled state of DNA and are critical to the successful replication of the genome. These enzymes are major targets for drugs used in the treatment of bacterial infections and cancer. One puzzling phenomenon of the topoisomerase mechanism is how these enzymes, orders of magnitude smaller than their subs :rate, can search, recognize and act at a local level to affect global DNA topology. While the homeostatic state of DNA supercoiling in cells is negative, both positive;aid negative supercoils exist transiently. Because of the right-handed nature of the DNA helix, the positive and negative supercoils are not equivalent. Several computational and theoretical models have been developed in an effort to describe the features of both positively and negatively supercoiled DNA. These models have accurately predicted some of the phenomena observed in vivo. However, the over-simplifying assumptions cannot, account for the different biological activities of positively and negatively supercoiled DNA. This review will discuss the models in place and the mathematical and energetic properties of this elegant molecule and the "machines that push it around." C1 [Fogg, Jonathan M.; Catanese, Daniel J., Jr.; Zechiedrich, Lynn] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. [Randall, Graham L.; Zechiedrich, Lynn] Baylor Coll Med, Inst Program Struct & Comp Biol & Mol Biophys, Houston, TX 77030 USA. [Swick, Michelle C.; Zechiedrich, Lynn] Baylor Coll Med, Interdept Program Cell & Mol Biol, Houston, TX 77030 USA. [Zechiedrich, Lynn] NIH, Bethesda, MD USA. RP Zechiedrich, L (reprint author), Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. EM elz@bcm.edu FU Program in Mathematics and Molecular Biology at Florida State University; Burroughs Wellcome Fund Interfaces Program; National Institutes of Health (NIH); Pharmacoinformatics Training Program; Computational and Structural Biology of the Gulf Coast Consortia; NIH [T90 DK070109]; Infection and Immunity NIH [T32 AI55413]; Computational Biology and Medicine Program; NLM [T15 LM07093]; [RO1 A1054830] FX Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030. JMF: Formerly funded by a post-doctoral fellowship from the Program in Mathematics and Molecular Biology at Florida State University, with funding from the Burroughs Wellcome Fund Interfaces Program; currently funded by National Institutes of Health (NIH) grant to LZ. DJC: Formerly funded by the Pharmacoinformatics Training Program of the W.M. Keck Center for Computational and Structural Biology of the Gulf Coast Consortia; NIH T90 DK070109; currently funded by the Infection and Immunity NIH Grant T32 AI55413. Institutional Program in Structural and Computational Biology and Molecular Bio-physics, Baylor College of Medicine, Houston, TX 77030. GLR: Formerly funded by the Computational Biology and Medicine Program of the W.M. Keck Center for Computational and Structural Biology of the Gulf Coast Consortia, NLM T15 LM07093. Interdepartmental Program in Cell and Molecular Biology, Baylor College of Medicine, Houston, TX 77030. MCS: Funded by the Pharmacoinformatics Training Program of the W.M. Keck Center for Computational and Structural Biology of the Gulf Coast Consortia, NIH T90 DK070109. LZ: Funded by NIH Grant RO1 A1054830. (Corresponding Author, elz@bcm.edu.) NR 222 TC 9 Z9 9 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES J9 IMA VOL MATH APPL PY 2009 VL 150 BP 73 EP + DI 10.1007/978-1-4419-0670-0_5 PG 11 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA BPW22 UT WOS:000280141500005 ER PT J AU Packard, BZ Artym, VV Komoriya, A Yamada, KM AF Packard, Beverly Z. Artym, Vira V. Komoriya, Akira Yamada, Kenneth M. TI Direct visualization of protease activity on cells migrating in three-dimensions SO MATRIX BIOLOGY LA English DT Article DE Cell motility; Collagenase; Invasion; Metastasis; MMP; TIMP; MT1-MMP ID TYPE-1 MATRIX-METALLOPROTEINASE; PERICELLULAR PROTEOLYSIS; LIVING CELLS; MODEL; TRANSITION; INVASION; OPINION AB Determining the specific role(s) of proteases in cell migration and invasion will require high-resolution imaging of sites of protease activity during live-cell migration through extracellular matrices. We have designed a novel fluorescent biosensor to detect localized extracellular sites of protease activity and to test requirements for matrix metalloprotease (MMP) function as cells migrate and invade three-dimensional collagen matrices. This probe fluoresces after cleavage of a peptide site present in interstitial collagen by a variety of proteases including MMP-2,-9, and -14 (MT1-MMP) without requiring transfection or modification of the cells being characterized. Using matrices derivatized with this biosensor, we show that protease activity is localized at the polarized leading edge of migrating tumor cells rather than further back on the cell body. This protease activity is essential for cell migration in native cross-linked but not pepsin-treated collagen matrices. The new type of high-resolution probe described in this study provides site-specific reporting of protease activity and insights into mechanisms by which cells migrate through extracellular matrices; it also helps to clarify discrepancies between previous studies regarding the contributions of proteases to metastasis. (C) 2008 Elsevier B.V. All rights reserved. C1 [Packard, Beverly Z.; Komoriya, Akira] Oncolmmunin Inc, Gaithersburg, MD 20877 USA. [Artym, Vira V.; Yamada, Kenneth M.] NIDCR, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA. [Artym, Vira V.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. RP Packard, BZ (reprint author), Oncolmmunin Inc, 207A Perry Pkwy,Suite 6, Gaithersburg, MD 20877 USA. EM BPackard@PhiPhiLux.com; kenneth.yamada@nih.gov OI Yamada, Kenneth/0000-0003-1512-6805 FU NIDCR; NIH FX This work was supported in part by the intramural research program of the NIDCR, NIH. We thank Thomas Bugge for helpful suggestions on the manuscript. NR 21 TC 48 Z9 48 U1 3 U2 18 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD JAN PY 2009 VL 28 IS 1 BP 3 EP 10 DI 10.1016/j.matbio.2008.10.001 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 405HZ UT WOS:000263215200002 PM 19010413 ER PT J AU Pawelec, G Bohr, V Campisi, J AF Pawelec, G. Bohr, V. Campisi, J. TI Special issue on cancer and ageing SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Editorial Material C1 [Pawelec, G.] Univ Tubingen, Med Res Ctr, ZMF, D-72072 Tubingen, Germany. [Bohr, V.] NIA, Mol Gerontol Branch, Biomed Res Ctr, NIH, Baltimore, MD 21224 USA. [Campisi, J.] Lawrence Berkeley Natl Lab, Berkeley, CA USA. RP Pawelec, G (reprint author), Univ Tubingen, Med Res Ctr, ZMF, Waldhornlestr 22, D-72072 Tubingen, Germany. EM graham.pawelec@uni-tuebingen.de FU Intramural NIH HHS [ZIA AG000729-22] NR 0 TC 3 Z9 4 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD JAN-FEB PY 2009 VL 130 IS 1-2 BP 1 EP 2 DI 10.1016/j.mad.2008.11.002 PG 2 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 407XT UT WOS:000263398300001 PM 19059279 ER PT S AU Stojilkovic, SS Murano, T Gonzalez-Iglesias, AE Andric, SA Popovic, MA Van Goor, F Tomic, M AF Stojilkovic, Stanko S. Murano, Takayo Gonzalez-Iglesias, Arturo E. Andric, Silvana A. Popovic, Marko A. Van Goor, Fredrick Tomic, Melanija BE Zorec, R Vardjan, N Chowdhury, HH Kreft, M Rupnik, M TI Multiple Roles of G(i/o) Protein-coupled Receptors in Control of Action Potential Secretion Coupling in Pituitary Lactotrophs SO MECHANISMS OF EXOCYTOSIS SE Annals of the New York Academy of Sciences LA English DT Article DE action potential; calcium; cAMP; GPCR; lactotrophs; gonadotrophs; dopamine D-2 receptors; endothelin ETA receptors; PI3-kinase; GSK-3 ID RAT ANTERIOR-PITUITARY; PROLACTIN-RELEASE; CA2+ OSCILLATIONS; ELECTRICAL-ACTIVITY; DOPAMINE-RECEPTORS; CALCIUM INFLUX; D2-DOPAMINE RECEPTOR; SIGNAL-TRANSDUCTION; POTASSIUM CHANNELS; CYTOSOLIC CALCIUM AB G(i/o) protein-coupled receptors, signaling through G protein-dependent and protein-independent pathways, have prominent effects on secretion by modulating calcium signaling and regulating the size of the releasable secretory pool, the rates of exocytosis and endocytosis, and de novo synthesis. Pituitary cells fire action potentials spontaneously, and the associated calcium influx is sufficient to maintain prolactin (PRL) release but not gonadotropin release at high and steady levels for many hours. Such secretion, termed intrinsic, spontaneous, or basal, reflects fusion of secretory vesicles triggered by the cell type-specific pattern of action potentials. In lactotrophs, activation of endothelin ETA and dopamine D-2 receptors causes inhibition of spontaneous electrical activity and basal adenylyl cyclase activity accompanied with inhibition of basal PRL release. Agonist-induced inhibition of cAMP production and firing of action potentials is abolished in cells with blocked pertussis toxin (PTX)-sensitive G(i/o) signaling pathway. However, agonist-induced inhibition of PRL release is only partially relieved in such treated cells, indicating that both receptors also inhibit exocytosis downstream of cAMP/calcium signaling. The PTX-insensitive step in agonist-induced inhibition of PRL release is not affected by inhibition of phosphoinositide 3-kinase and glycogen synthase kinase-3 but is partially rescued by downregulation of the G(z)alpha expression. Thus, ETA and D-2 receptors inhibit basal PRL release not only by blocking electrical activity but also by desensitizing calcium-secretion coupling. C1 [Stojilkovic, Stanko S.; Murano, Takayo; Gonzalez-Iglesias, Arturo E.; Andric, Silvana A.; Popovic, Marko A.; Van Goor, Fredrick; Tomic, Melanija] NICHHD, Sect Cellular Signaling, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA. RP Stojilkovic, SS (reprint author), NICHD, Bldg 49,Room 6A-36,49 Convent Dr, Bethesda, MD 20892 USA. EM stankos@helix.nih.gov RI Tomic, Melanija/C-3371-2016 FU National Institute of Child Health and Human Development, National Institutes of Health FX This research was supported by the Intramural Research Program of the National Institute of Child Health and Human Development, National Institutes of Health. NR 67 TC 9 Z9 9 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN 02148, MA USA SN 0077-8923 BN 978-1-57331-735-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2009 VL 1152 BP 174 EP 186 DI 10.1111/j.1749-6632.2008.03994.x PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA BIW14 UT WOS:000263265600018 PM 19161388 ER PT S AU Irfanoglu, MO Koay, CG Pajevic, S Machiraju, R Basser, PJ AF Irfanoglu, Mustafa Okan Koay, Cheng Guan Pajevic, Sinisa Machiraju, Raghu Basser, Peter J. BE Yang, GZ Hawkes, D Rueckert, D Nobel, A Taylor, C TI Diffusion Tensor Field Registration in the Presence of Uncertainty SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION - MICCAI 2009, PT I, PROCEEDINGS SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 12th International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI2009) CY SEP 20-24, 2009 CL Imperial Coll, London, ENGLAND HO Imperial Coll ID FRAMEWORK; IMAGES; MRI AB We propose a novel method for deformable tensor-to-tensor registration of Diffusion Tensor Imaging (DTI) data. Our registration method considers estimated diffusion tensors as normally distributed random variables whose covariance matrices describe Uncertainties in the mean estimated tensor chic to factors such m noise in diffusion weighted images (DWIs), tissue diffusion properties, and experimental design. The dissimilarity between distributions of tensors in two different voxels is computed using the Kullback-Leibler divergence to drive a, deformable registration process, which is not only affected by principal diffusivities and principal directions, but also the underlying DWI properties. We in general do not assume the positive definite nature of the tensor space given the pervasive influence of noise and other factors. Results indicate that: the proposed metric weights voxels more heavily whose diffusion tensors are estimated with greater certainty and exhibit anisotropic diffusion behavior thus intrinsically favoring coherent white matter regions whose tensors are estimated with high confidence. C1 [Irfanoglu, Mustafa Okan; Machiraju, Raghu] Ohio State Univ, Columbus, OH 43210 USA. [Irfanoglu, Mustafa Okan; Koay, Cheng Guan; Pajevic, Sinisa; Basser, Peter J.] NICHD, NIH, Bethesda, MD 20892 USA. RP Irfanoglu, MO (reprint author), Ohio State Univ, Columbus, OH 43210 USA. NR 14 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-642-04267-6 J9 LECT NOTES COMPUT SC PY 2009 VL 5761 BP 181 EP + PG 3 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BMU82 UT WOS:000273617300023 ER PT S AU Yao, JH Summers, RM AF Yao, Jianhua Summers, Ronald M. BE Yang, GZ Hawkes, D Rueckert, D Nobel, A Taylor, C TI Statistical Location Model for Abdominal Organ Localization SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION - MICCAI 2009, PT II, PROCEEDINGS SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 12th International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI2009) CY SEP 20-24, 2009 CL Imperial Coll, London, ENGLAND HO Imperial Coll ID CONSTRUCTION; SEGMENTATION AB Initial placement of the models is an essential pre-processing step for model-based organ segmentation. Based oil the observation that organs move along with the spine and their relative locations remain relatively stable, we built a statistical location model (SLM) and applied it to abdominal organ localization. The model is a point distribution model which learns the pattern of variability of organ locations relative to the spinal column from a training set of normal individuals. The localization is achieved in three stages: spine alignment, model optimization and location refinement. The SLM is optimized through maximum a posteriori estimation of a probabilistic density model constructed for each organ. Our model includes five organs: liver, left kidney, right kidney, spleen and pancreas. We validated our method on 12 abdominal CTs using leave-one-out experiments. The SLM enabled reduction ill the overall localization error from 62.0 +/- 28.5 min to 5.8 +/- 1.5 min. Experiments showed that the SLM was robust to the reference model selection. C1 [Yao, Jianhua; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bethesda, MD 20892 USA. RP Yao, JH (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. NR 8 TC 7 Z9 7 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-642-04270-6 J9 LECT NOTES COMPUT SC PY 2009 VL 5762 BP 9 EP 17 PG 9 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BMU84 UT WOS:000273617500002 ER PT S AU Linguraru, MG Sandberg, JK Li, ZX Pura, JA Summers, RM AF Linguraru, Marius George Sandberg, Jesse K. Li, Zhixi Pura, John A. Summers, Ronald M. BE Yang, GZ Hawkes, D Rueckert, D Nobel, A Taylor, C TI Atlas-Based Automated Segmentation of Spleen and Liver Using Adaptive Enhancement Estimation SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION - MICCAI 2009, PT II, PROCEEDINGS SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 12th International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI2009) CY SEP 20-24, 2009 CL Imperial Coll, London, ENGLAND HO Imperial Coll ID ABDOMINAL CT; IMAGES; KIDNEY; VOLUME; SPACE AB The paper presents the automated segmentation of spleen and liver from contrast-enhanced CT images of normal and hepato/splenomegaly populations. The method used 4 steps: (i) a mean organ model was registered to the patient CT; (ii) the first estimates of the organs were improved by a geodesic active contour; (iii) the contrast enhancements of liver and spleen were estimated to adjust to patient image characteristics, and an adaptive convolution refined the segmentations; (iv) lastly, a normalized probabilistic atlas corrected for shape and location for the precise computation of each organ's volume and height (mid-hepatic liver height and cephalocaudal spleen height). Results from test data demonstrated the method's ability to accurately segment the spleen (RMS error = 1.09mm; DICE/Tanimoto overlaps = 95.2/91) and liver (RMS error = 2.3mm, and DICE/Tanimoto overlaps = 96.2/92.7). The correlations (R(2)) with clinical/manual height measurements were 0.97 and 0.93 for the spleen and liver respectively. C1 [Linguraru, Marius George; Sandberg, Jesse K.; Li, Zhixi; Pura, John A.; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bethesda, MD 20892 USA. RP Linguraru, MG (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM lingurarum@mail.nih.gov NR 22 TC 11 Z9 11 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-642-04270-6 J9 LECT NOTES COMPUT SC PY 2009 VL 5762 BP 1001 EP 1008 PG 8 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BMU84 UT WOS:000273617500121 ER PT S AU Chen, WJ Wagner, RF Yousef, WA Gallas, BD AF Chen, Weijie Wagner, Robert F. Yousef, Waleed A. Gallas, Brandon D. BE Sahiner, B Manning, DJ TI Comparison of classifier performance estimators: a simulation study SO MEDICAL IMAGING 2009: IMAGE PERCEPTION, OBSERVER PERFORMANCE, AND TECHNOLOGY ASSESSMENT SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Image Perception, Observer Performance, and Technology Assessment CY FEB 11-12, 2009 CL CAD, Lake Buena Vista, FL SP SPIE HO CAD DE bias-variance trade-off; training variability; classification; AUC; bootstrap; resampling; cross-validation ID ROC CURVE; AREA AB We aim to compare resampling-based estimators of the area under the ROC curve (AUC) of a classifier with a Monte Carlo simulation study. The comparison is in terms of bias, variance, and mean square error. We also examine the corresponding variance estimators of these AUC estimators. We compared three AUC estimators: the hold-out (HO) estimator, the leave-one-out cross validation (LOOCV) estimator, and the leave-pair-out bootstrap (LPOB) estimator. Each performance estimator has its own variability estimator. In our simulations, in terms of the mean square error, HO is always the worst and the ranking of the other two estimators depends on the interplay of sample size, dimensionality, and the population separability. In terms of estimators variability, the LPOB is the least variable estimator and the HO is the most variable estimator. The results also show that the estimation of the variance of LPOB using the influence function approach with a finite data set is unbiased or conservatively biased whereas the estimation of the variance of the LOOCV or the HO is downwardly (i.e., anti-consevatively) biased. C1 [Chen, Weijie; Wagner, Robert F.; Yousef, Waleed A.; Gallas, Brandon D.] US FDA, NIBIB CDRH Joint Lab Assessment Med Imaging Syst, Div Imaging & Appl Math, OSEL,CDRH, Silver Spring, MD 20993 USA. RP Chen, WJ (reprint author), US FDA, NIBIB CDRH Joint Lab Assessment Med Imaging Syst, Div Imaging & Appl Math, OSEL,CDRH, Silver Spring, MD 20993 USA. EM weijie.chen@fda.hhs.gov OI Gallas, Brandon/0000-0001-7332-1620 NR 9 TC 0 Z9 0 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7514-5 J9 PROC SPIE PY 2009 VL 7263 AR 72630X DI 10.1117/12.811584 PG 11 WC Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BAZ41 UT WOS:000306174400032 ER PT S AU Paquerault, S Samuelson, FW Myers, KJ Smith, RC AF Paquerault, Sophie Samuelson, Frank W. Myers, Kyle J. Smith, Robert C. BE Sahiner, B Manning, DJ TI Non-Localization and Localization ROC Analyses Using Clinically-Based Scoring SO MEDICAL IMAGING 2009: IMAGE PERCEPTION, OBSERVER PERFORMANCE, AND TECHNOLOGY ASSESSMENT SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Image Perception, Observer Performance, and Technology Assessment CY FEB 11-12, 2009 CL CAD, Lake Buena Vista, FL SP SPIE HO CAD DE Multiple reader multiple case (MRMC) analysis; location-specific and non-location-specific receiver operating characteristic; Computer-aided detection ID IMAGING-SYSTEMS; PERFORMANCE AB We are investigating the potential for differences in study conclusions when assessing the estimated impact of a computer-aided detection (CAD) system on readers' performance. The data utilized in this investigation were derived from a multi-reader multi-case observer study involving one hundred mammographic background images to which fixed-size and fixed-intensity Gaussian signals were added, generating a low-and high-intensity signal sets. The study setting allowed CAD assessment in two situations: when CAD sensitivity was 1) superior or 2) lower than the average reader. Seven readers were asked to review each set in the unaided and CAD-aided reading modes, mark and rate their findings. Using this data, we studied the effect on study conclusion of three clinically-based receiver operating characteristic (ROC) scoring definitions. These scoring definitions included both location-specific and non-location-specific rules. The results showed agreement in the estimated impact of CAD on the overall reader performance. In the study setting where CAD sensitivity is superior to the average reader, the mean difference in AUC between the CAD-aided read and unaided read was 0.049 (95% CIs: -0.027; 0.130) for the image scoring definition that is based on non-location-specific rules, and 0.104 (95% CIs: 0.036; 0.174) and 0.090 (95% CIs: 0.031; 0.155) for image scoring definitions that are based on location-specific rules. The increases in AUC were statistically significant for the location-specific scoring definitions. It was further observed that the variance on these estimates was reduced when using the location-specific scoring definitions compared to that using a non-location-specific scoring definition. In the study setting where CAD sensitivity is equivalent or lower than the average reader, the mean differences in AUC are slightly above 0.01 for all image scoring definitions. These increases in AUC were not statistical significant for any of the image scoring definitions. The results on the variance analysis differed from those observed in the other study setting. This investigation furthers our understanding of the relationships between non-localization-specific and localization-specific ROC assessment methodologies and their relevance to clinical practice. C1 [Paquerault, Sophie; Samuelson, Frank W.; Myers, Kyle J.; Smith, Robert C.] CDRH NIBIB, Lab Assessment Med Imaging Syst, Food & Drug Adm, Rockville, MD 20852 USA. RP Paquerault, S (reprint author), CDRH NIBIB, Lab Assessment Med Imaging Syst, Food & Drug Adm, Rockville, MD 20852 USA. NR 9 TC 1 Z9 1 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7514-5 J9 PROC SPIE PY 2009 VL 7263 AR 72630U DI 10.1117/12.813761 PG 9 WC Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BAZ41 UT WOS:000306174400029 ER PT J AU Roilides, E Simitsopoulou, M Katragkou, A Walsh, TJ AF Roilides, Emmanuel Simitsopoulou, Maria Katragkou, Aspasia Walsh, Thomas J. TI Host immune response against Scedosporium species SO MEDICAL MYCOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Adolescent-Medicine CY MAR 26-29, 2008 CL Greensboro, NC DE innate immune response; scedosporiosis; cytokines; phagocytes ID COLONY-STIMULATING FACTOR; HUMAN POLYMORPHONUCLEAR LEUKOCYTES; PHAGOCYTIC CELL RESPONSES; LIPOSOMAL AMPHOTERICIN-B; NADPH OXIDASE COMPONENTS; ASPERGILLUS-FUMIGATUS; PSEUDALLESCHERIA-BOYDII; INTERFERON-GAMMA; DISSEMINATED INFECTION; PATTERN-RECOGNITION AB Scedosporium apiospermum and Scedosporium prolificans cause therapy-refractory infections in immuocompromised and immunocompetent hosts. While innate immune response is believed to be critical for the host defense against these fungi, its role has only recently been elucidated. Undefined pathogen-associated molecular patterns on the surface of conidia and hyphae are recognized by pattern-recognition receptors (PRRs) on the membrane of phagocytes, and the signal is transmitted intracellularly. PRRs that are important in the recognition of both fungal species are human Toll-like receptors (or Toll receptors in Drosophila melanogaster) and dectin-1. These induce signals responsible for the activation of genes leading to an effective host defense, especially those encoding pro-inflammatory cytokines. Both species are efficiently phagocytosed and elicit an oxidative burst by neutrophils and monocytes. While cytokines, such as interleukin-15, granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor and interferon-, have been found in vitro to variably modulate antifungal activity of human phagocytes, cytokines in vivo activities are less well documented. Certain antifungal agents exert immunopharmacological effects on phagocytes against S. apiospermum and S. prolificans. Translation of these in vitro findings to appropriate in vivo systems and into clinical trials may lead to improved strategies for augmenting innate host defenses in patients infected with these emerging pathogens. C1 [Roilides, Emmanuel] Aristotle Univ Thessaloniki, Sch Med, Dept Pediat 3, Hippokrat Hosp, GR-54642 Thessaloniki, Greece. [Roilides, Emmanuel; Walsh, Thomas J.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Roilides, E (reprint author), Aristotle Univ Thessaloniki, Sch Med, Dept Pediat 3, Hippokrat Hosp, Konstantinoupoleos 49, GR-54642 Thessaloniki, Greece. EM roilides@med.auth.gr NR 52 TC 8 Z9 8 U1 0 U2 5 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1369-3786 J9 MED MYCOL JI Med. Mycol. PY 2009 VL 47 IS 4 BP 433 EP 440 AR PII 908416530 DI 10.1080/13693780902738006 PG 8 WC Infectious Diseases; Mycology; Veterinary Sciences SC Infectious Diseases; Mycology; Veterinary Sciences GA 435TY UT WOS:000265367400012 PM 19184770 ER PT J AU Pyrgos, V Ratanavanich, K Donegan, N Veis, J Walsh, TJ Shoham, S AF Pyrgos, Vasilios Ratanavanich, Kathryn Donegan, Nancy Veis, Judith Walsh, Thomas J. Shoham, Shmuel TI Candida bloodstream infections in hemodialysis recipients SO MEDICAL MYCOLOGY LA English DT Article DE Candidemia; hemodialysis; infection; epidemiology ID INTENSIVE-CARE-UNIT; TOTAL PARENTERAL-NUTRITION; RISK-FACTORS; ACTIVE SURVEILLANCE; EPIDEMIOLOGY; FUNGEMIA; ALBICANS; THERAPY; GROWTH; STATES AB Candidemia is a major cause of morbidity and mortality in patients undergoing hemodialysis but it has not been well defined in this patient population. We performed a retrospective case-control study to characterize the epidemiology, microbiology, and outcomes of hemodialysis-associated candidemia. All cases of candidemia at our institution were evaluated from 1 January 2000 until 1 September 2004. For each case, two non-candidemic dialysis patients served as controls. Among 350 cases of candidemia, 78 (22%) occurred in adult hemodialysis patients. Cases and controls were similar with respect to age, corticosteroid, antibiotics use, prevalence of diabetes mellitus, liver cirrhosis, surgical procedures, and cancer. Multivariate analysis found total parenteral nutrition (TPN) (19.5% vs. 1.3%; P<0.0001) and dialysis through a vascular catheter (74% vs. 46.8%; P = 0.0001) to be independently associated with candidemia. Non-C. albicans Candida spp. particularly C. glabrata and C. krusei were more common in hemodialysis recipients than in candidemic patients not receiving hemodialysis (31% vs. 17% p = 0.009). In-hospital mortality was significantly elevated for candidemic vs. non-candidemic hemodialysis recipients (51.9% vs. 7.8%; P<0.0001). Candidemia in hemodialysis recipients is frequently caused by non-C. albicans Candida species, is associated with TPN and dialysis via a vascular catheter (vs. shunt or fistula) and carries a high mortality rate. C1 [Pyrgos, Vasilios; Shoham, Shmuel] Washington Hosp Ctr, Infect Dis Sect, Washington, DC 20010 USA. [Ratanavanich, Kathryn; Veis, Judith] Washington Hosp Ctr, Nephrol Sect, Washington, DC 20010 USA. [Donegan, Nancy] Washington Hosp Ctr, Dept Infect Control, Washington, DC 20010 USA. [Walsh, Thomas J.] NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Pyrgos, V (reprint author), Washington Hosp Ctr, Infect Dis Sect, Rm 2A56, Washington, DC 20010 USA. EM vasilpyrgos@yahoo.com NR 40 TC 14 Z9 15 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1369-3786 J9 MED MYCOL JI Med. Mycol. PY 2009 VL 47 IS 5 BP 463 EP 467 DI 10.1080/13693780802369332 PG 5 WC Infectious Diseases; Mycology; Veterinary Sciences SC Infectious Diseases; Mycology; Veterinary Sciences GA 482IM UT WOS:000268878800003 PM 18798046 ER PT J AU Meyer, W Aanensen, DM Boekhout, T Cogliati, M Diaz, MR Esposto, MC Fisher, M Gilgado, F Hagen, F Kaocharoen, S Litvintseva, AP Mitchell, TG Simwami, SP Trilles, L Viviani, MA Kwon-Chung, J AF Meyer, Wieland Aanensen, David M. Boekhout, Teun Cogliati, Massimo Diaz, Mara R. Esposto, Maria Carmela Fisher, Matthew Gilgado, Felix Hagen, Ferry Kaocharoen, Sirada Litvintseva, Anastasia P. Mitchell, Thomas G. Simwami, Sitali P. Trilles, Luciana Viviani, Maria Anna Kwon-Chung, June TI Consensus multi-locus sequence typing scheme for Cryptococcus neoformans and Cryptococcus gattii SO MEDICAL MYCOLOGY LA English DT Review DE Cryptococcus neoformans; Cryptococcus gattii; Genotyping; Multi Locus Sequence Typing ID PATHOGENIC YEAST; SPECIES COMPLEX; POLYMORPHIC DNA; VAR. GRUBII; RANDOM AMPLIFICATION; RFLP ANALYSIS; MATING TYPES; SEROTYPE-A; IDENTIFICATION; GENE AB This communication describes the consensus multi-locus typing scheme established by the Cryptococcal Working Group I (Genotyping of Cryptococcus neoformans and C. gattii) of the International Society for Human and Animal Mycology (ISHAM) using seven unlinked genetic loci for global strain genotyping. These genetic loci include the housekeeping genes CAP59, GPD1, LAC1, PLB1, SOD1, URA5 and the IGS1 region. Allele and sequence type information are accessible at http://www.mlst.net/. C1 [Kwon-Chung, June] NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Meyer, Wieland; Gilgado, Felix; Kaocharoen, Sirada; Trilles, Luciana] Univ Sydney, Westmead Hosp, Western Clin Sch,Westmead Millennium Inst, Mol Mycol Res Lab,Ctr Infect Dis & Microbiol, Westmead, NSW 2145, Australia. [Aanensen, David M.; Fisher, Matthew; Simwami, Sitali P.] Univ London Imperial Coll Sci Technol & Med, Fac Med, Dept Infect Dis Epidemiol, London, England. [Boekhout, Teun; Hagen, Ferry] CBS Fungal Biodivers Ctr, Utrecht, Netherlands. [Cogliati, Massimo; Esposto, Maria Carmela; Viviani, Maria Anna] Univ Milan, Dip Sanita Pubbl Microbiol Virol, Med Mycol Lab, Milan, Italy. [Diaz, Mara R.] Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, Miami, FL 33149 USA. [Kaocharoen, Sirada] Chulalongkorn Univ, Grad Sch, Interdept Med Microbiol, Bangkok, Thailand. [Litvintseva, Anastasia P.; Mitchell, Thomas G.] Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC USA. [Trilles, Luciana] Fundacao Oswaldo Cruz, Inst Pesquisa Clin Evandro Chargas, Lab Micol, Rio De Janeiro, Brazil. RP Kwon-Chung, J (reprint author), NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. EM june_kwon-chung@nih.go RI Boekhout, Teun/F-1552-2010; Mitchell, Thomas/A-2356-2008; Fisher, Matthew/B-9094-2011; Hagen, Ferry/B-9044-2009; Meyer, Wieland/G-1204-2015 OI Fisher, Matthew/0000-0002-1862-6402; Boekhout, Teun/0000-0002-0476-3609; Hagen, Ferry/0000-0002-5622-1916; Meyer, Wieland/0000-0001-9933-8340 FU NHMRC [352303]; National Institute of Allergy and Infectious Diseases; National Institutes of Health, USA; Wellcome Trust; BBSRC, UK; Odo van Vloten Foundation; US Public Health Service NIH [AI 25783]; CAPES; Ministerio da Educacao, Brazil; Chulalongkorn University Graduate Scholarship FX The authors would like to thank Matthew O'Sullivan for allowing us to use the software page developed as part of his PhD to determine the number of gene loci to be essential for an MLST scheme based on the Simpson's index of diversity. This work was supported by an NH&MRC project grant #352303 to Wieland Meyer. June Kwon-Chung was supported by funds from the intramural program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health, USA. Matthew Fisher and David Aanensen were supported by the Wellcome Trust. Sitali Simwami was supported by the BBSRC, UK. Ferry Hagen was supported by funds from the Odo van Vloten Foundation. Anastasia P. Litvintseva and Thomas G. Mitchell were supported by a US Public Health Service NIH grant AI 25783. Luciana Trilles was supported by CAPES scholarship from the Ministerio da Educacao, Brazil. Sirada Kaocharoen was supported by the Chulalongkorn University Graduate Scholarship to commemorate the 72th anniversary of his majesty King Bhumibol Adulyadej, Thailand. NR 47 TC 169 Z9 175 U1 2 U2 15 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1369-3786 J9 MED MYCOL JI Med. Mycol. PY 2009 VL 47 IS 6 BP 561 EP 570 DI 10.1080/13693780902953886 PG 10 WC Infectious Diseases; Mycology; Veterinary Sciences SC Infectious Diseases; Mycology; Veterinary Sciences GA 495YY UT WOS:000269933700001 PM 19462334 ER PT J AU Kwon-Chung, KJ Sugui, JA AF Kwon-Chung, Kyung J. Sugui, Janyce A. TI What do we know about the role of gliotoxin in the pathobiology of Aspergillus fumigatus? SO MEDICAL MYCOLOGY LA English DT Article DE gliotoxin; virulence determinants; immunosuppressive regimen; invasive aspergillosis ID NONRIBOSOMAL PEPTIDE SYNTHETASE; CELL TRANSPLANT RECIPIENTS; INVASIVE ASPERGILLOSIS; GENE-CLUSTER; VIRULENCE; METABOLITE; GLIP; BIOSYNTHESIS; APOPTOSIS; CONTRIBUTES AB Gliotoxin is a member of the epipolythiodioxopiperazine class of toxins and is both the major and the most potent toxin produced by Aspergillus fumigatus. Since the discovery of the putative gliotoxin biosynthetic 12-gene cluster in the genome of A. fumigatus, five different laboratories have attempted to determine the role of this toxin in the virulence of A. fumigatus. The genes in the cluster that have been disrupted to study the pathobiological importance of gliotoxin include gliZ that encodes a transcription factor and gliP that encodes a nonribosomal peptide synthase. Two of the five laboratories have reported gliotoxin to be an important virulence determinant of A. fumigatus, while the other three laboratories have shown it to be unimportant. Comparisons of the data generated among the five laboratories revealed that the immunosuppressive regimen used for mice was the key factor that contributed to the observed disparity. Regardless of either the mouse strains used or the route of infection, immunosuppression with a combination of cyclophosphamide and corticosteroids (neutropenic mice) showed gliotoxin to be unimportant. The mice immunosuppressed with corticosteroids alone, however, revealed that gliotoxin is an important virulence determinant of A. fumigatus. These studies indicate that the neutropenic mice model is inadequate to reveal the pathobiological importance of fungal secondary metabolites in invasive pulmonary aspergillosis. C1 [Kwon-Chung, Kyung J.; Sugui, Janyce A.] NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Kwon-Chung, KJ (reprint author), NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM june_kwon-chung@nih.gov FU National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA FX This study was supported by funds from the intramural program of the National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. NR 38 TC 48 Z9 52 U1 1 U2 7 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1369-3786 J9 MED MYCOL JI Med. Mycol. PY 2009 VL 47 BP S97 EP S103 AR PII 792857645 DI 10.1080/13693780802056012 PG 7 WC Infectious Diseases; Mycology; Veterinary Sciences SC Infectious Diseases; Mycology; Veterinary Sciences GA 435RZ UT WOS:000265362300013 PM 18608908 ER PT J AU Walsh, TJ Petraitis, V Petraitiene, R Solomon, J Bacher, JD Greene, L Cotton, M Groll, A Roilides, E Avila, N Pyrgos, V Shoham, S AF Walsh, Thomas J. Petraitis, Vidmantas Petraitiene, Ruta Solomon, Jeffrey Bacher, John D. Greene, Lora Cotton, Margaret Groll, Andreas Roilides, Emmanuel Avila, Nilo Pyrgos, Vasilios Shoham, Shmuel TI Diagnostic imaging of experimental invasive pulmonary aspergillosis SO MEDICAL MYCOLOGY LA English DT Article DE Invasive pulmonary aspergillosis; computed tomographic scanning; ultrafast CT scanning; multidimensional volumetric imagin; antifungal therapy ID PERSISTENTLY NEUTROPENIC RABBITS; GALACTOMANNAN ANTIGENEMIA; ANTIFUNGAL THERAPY; AMPHOTERICIN-B; PHARMACOKINETICS; EFFICACY; PATHOGENESIS; TOMOGRAPHY AB Pulmonary infiltrates in neutropenic hosts with invasive aspergillosis are caused by organism-mediated tissue injury, vascular invasion, and hemorrhagic infarction. Ultrafast computed tomography (UFCT) scanning reproducibly measures these lesions in experimental invasive pulmonary aspergillosis in persistently neutropenic rabbits. The pulmonary lesion score from UFCT scanning is a useful outcome variable for measuring differences in efficacy of antifungal compounds alone and in combination, as well as the virulence of different strains and species of Aspergillus. Several studies demonstrate that the course of pulmonary lesions treated with amphotericin B, lipid formulations of amphotericin B, triazoles, echinocandins, and combination therapy measured by serial UFCT scans correlate with those measured by survival, histopathological resolution of lesions, microbiological clearance of Aspergillus fumigatus, and resolution of galactomannan index. We further developed a multidimensional volumetric imaging (MDVI) method for analysis of the volume of pulmonary infiltrates over time in response to antifungal therapy. Volumetric data by MDVI correlate with UFCT pulmonary lesion scores and validated biological endpoints. A recent pilot clinical study demonstrated the applicability of MDVI to human pulmonary fungal infections. MDVI also improves objectivity of radiological assessment of therapeutic response to antifungal therapy and merits more extensive evaluation in patients with invasive aspergillosis, as well as other fungal and bacterial pneumonias. C1 [Walsh, Thomas J.; Petraitis, Vidmantas; Petraitiene, Ruta; Greene, Lora; Cotton, Margaret; Roilides, Emmanuel; Pyrgos, Vasilios; Shoham, Shmuel] NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Petraitiene, Ruta] SAIC Frederick, Lab Anim Sci Program, Frederick, MD USA. [Solomon, Jeffrey] Med Numer, Germantown, MD USA. [Bacher, John D.] NIH, Surg Serv, Div Vet Resources, Off Res Serv, Bethesda, MD USA. [Groll, Andreas] Univ Childrens Hosp, Infect Dis Res Program, Ctr Bone Marrow Transplantat, Munster, Germany. [Groll, Andreas] Univ Childrens Hosp, Dept Paediat Hematol Oncol, Munster, Germany. [Avila, Nilo] NIH, Dept Diagnost Imaging, Ctr Clin, Bethesda, MD USA. [Shoham, Shmuel] Washington Hosp Ctr, Infect Dis Sect, Washington, DC 20010 USA. RP Walsh, TJ (reprint author), NCI, Immunocompromised Host Sect, Pediat Oncol Branch, 10 Ctr Dr,CRC 1-5750, Bethesda, MD 20892 USA. EM walsht@mail.nih.gov NR 22 TC 4 Z9 5 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1369-3786 J9 MED MYCOL JI Med. Mycol. PY 2009 VL 47 BP S138 EP S145 AR PII 909138719 DI 10.1080/13693780802665879 PG 8 WC Infectious Diseases; Mycology; Veterinary Sciences SC Infectious Diseases; Mycology; Veterinary Sciences GA 435RZ UT WOS:000265362300019 PM 19253145 ER PT J AU Yang, D Oppenheim, JJ AF Yang, D. Oppenheim, J. J. TI Alarmins and antimicrobial immunity SO MEDICAL MYCOLOGY LA English DT Article DE Alarmins; aspergillosis; dendritic cell; immunity; antimicrobial ID EOSINOPHIL-DERIVED NEUROTOXIN; MOBILITY GROUP BOX-1; PEPTIDE ANTIBIOTIC LL-37/HCAP-18; HUMAN NEUTROPHIL DEFENSINS; CHROMATIN PROTEIN HMGB1; INNATE HOST-DEFENSE; RECEPTOR-LIKE 1; DENDRITIC CELLS; HUMAN BETA-DEFENSIN-3; ALPHA-DEFENSINS AB Alarmins are endogenous mediators capable of enhancing innate and adaptive immune response through induction of concomitant recruitment and activation of antigen-presenting cells. Here we provide a brief overview of various alarmins, highlight their critical roles in innate and adaptive antimicrobial immunity, and speculate on potential usage of alarmins in combating aspergillosis. C1 [Yang, D.] NCI, Basic Res Program, SAIC Frederick Inc, Ctr Canc Res,NIH, Frederick, MD 21702 USA. [Oppenheim, J. J.] NIH, Mol Immunoregulat Lab, Ctr Canc Res, Frederick, MD USA. RP Yang, D (reprint author), NCI, Basic Res Program, SAIC Frederick Inc, Ctr Canc Res,NIH, 1050 Boyles St, Frederick, MD 21702 USA. EM dyang@ncifcrf.gov FU National Cancer Institute, National Institutes of Health [N01-CO-12400] FX This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract N01-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U. S. Government. This Research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 91 TC 10 Z9 10 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1369-3786 J9 MED MYCOL JI Med. Mycol. PY 2009 VL 47 BP S146 EP S153 AR PII 909145160 DI 10.1080/13693780902721416 PG 8 WC Infectious Diseases; Mycology; Veterinary Sciences SC Infectious Diseases; Mycology; Veterinary Sciences GA 435RZ UT WOS:000265362300020 PM 19253139 ER PT J AU Li, J Huang, A Yao, J Liu, JM Van Uitert, RL Petrick, N Summers, RM AF Li, Jiang Huang, Adam Yao, Jack Liu, Jiamin Van Uitert, Robert L. Petrick, Nicholas Summers, Ronald M. TI Optimizing computer-aided colonic polyp detection for CT colonography by evolving the Pareto front SO MEDICAL PHYSICS LA English DT Article; Proceedings Paper CT European Congress of Radiology CY 2007 CL Vienna, AUSTRIA DE computer-aided detection; pattern recognition; statistical methods; multiobjective evolution; genetic algorithm ID TOMOGRAPHIC VIRTUAL COLONOSCOPY; FALSE POSITIVES; REDUCTION; OPTIMIZATION; METAANALYSIS; ALGORITHM; FEATURES; CANCER; SCHEME; CAD AB A multiobjective genetic algorithm is designed to optimize a computer-aided detection (CAD) system for identifying colonic polyps. Colonic polyps appear as elliptical protrusions on the inner surface of the colon. Curvature-based features for colonic polyp detection have proved to be successful in several CT colonography (CTC) CAD systems. Our CTC CAD program uses a sequential classifier to form initial polyp detections on the colon surface. The classifier utilizes a set of thresholds on curvature-based features to cluster suspicious colon surface regions into polyp candidates. The thresholds were previously chosen experimentally by using feature histograms. The chosen thresholds were effective for detecting polyps sized 10 mm or larger in diameter. However, many medium-sized polyps, 6-9 mm in diameter, were missed in the initial detection procedure. In this paper, the task of finding optimal thresholds as a multiobjective optimization problem was formulated, and a genetic algorithm to solve it was utilized by evolving the Pareto front of the Pareto optimal set. The new CTC CAD system was tested on 792 patients. The sensitivities of the optimized system improved significantly, from 61.68% to 74.71% with an increase of 13.03% (95% CI [6.57%, 19.5%], p = 7.78 X 10(-5) ) for the size category of 6-9 mm polyps, from 65.02% to 77.4% with an increase of 12.38% (95% CI [6.23%, 18.53%], p = 7.95 X 10(-5) ) for polyps 6 mm or larger, and from 82.2% to 90.58% with an increase of 8.38% (95% CI [0.75%, 16%], p = 0.03) for polyps 8 mm or larger at comparable false positive rates. The sensitivities of the optimized system are nearly equivalent to those of expert radiologists. (C) 2009 American Association of Physicists in Medicine. [DOI: 10.1118/1.3040177] C1 [Li, Jiang; Huang, Adam; Yao, Jack; Liu, Jiamin; Van Uitert, Robert L.; Summers, Ronald M.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Li, Jiang] Old Dominion Univ, Dept Elect & Comp Engn, VMASC, Norfolk, VA 23529 USA. [Petrick, Nicholas] FDA CDRH OSEL, Div Imaging & Appl Math, LAMIS Image Anal Lab, Silver Spring, MD 20993 USA. RP Summers, RM (reprint author), NIH, Ctr Clin, Bethesda, MD 20892 USA. EM rms@nih.gov FU Intramural NIH HHS [Z01 CL040003-05] NR 40 TC 12 Z9 13 U1 0 U2 2 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JAN PY 2009 VL 36 IS 1 BP 201 EP 212 DI 10.1118/1.3040177 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 389OU UT WOS:000262105200023 PM 19235388 ER PT S AU Buhler, C Shroff, R Lichten, M AF Buhler, Cyril Shroff, Robert Lichten, Michael BE Keeney, S TI Genome-Wide Mapping of Meiotic DNA Double-Strand Breaks in Saccharomyces cerevisiae SO MEIOSIS, VOL 1: MOLECULAR AND GENETIC METHODS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Double-strand break; Spo11; DMC1; rad50S; chromatin immunoprecipitation; single-strand DNA; BND cellulose; microarray; background normalization; quantitative PCR ID RECOMBINATION HOTSPOTS; CHROMOSOME-III; YEAST MEIOSIS; REVEALS; INITIATION; SYNAPSIS; SPO11; RATES AB DNA double-strand breaks (DSBs) initiate meiotic recombination in eukaryotes. We describe two strategies that Use microarrays to determine the genome-wide distribution Of meiotic DSBs in the yeast Saccharomyces cerevisiae. The first is a chromatin immunoprecipitation (ChIP) approach that targets the Spo11 protein, which remains covalently attached to DSB ends in certain mutant backgrounds. The second approach involves BND cellulose enrichment of the single-strand DNA (ssDNA) recombination intermediate formed by end-resection at DSB sites following Spo11 removal. C1 [Buhler, Cyril; Lichten, Michael] NCI, Biochem & Mol Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Buhler, C (reprint author), NCI, Biochem & Mol Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RI Lichten, Michael/C-5795-2013; OI Lichten, Michael/0000-0001-9707-2956; Buhler, Cyril/0000-0003-0397-7653 NR 25 TC 8 Z9 8 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-934115-66-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2009 VL 557 BP 143 EP 164 DI 10.1007/978-1-59745-527-5_10 D2 10.1007/978-1-59745-527-5 PG 22 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BKN72 UT WOS:000268721200010 PM 19799181 ER PT S AU Qin, J Subramanian, J Arnheim, N AF Qin, Jian Subramanian, Jaichandar Arnheim, Norman BE Keeney, S TI Detection of Meiotic DNA Breaks in Mouse Testicular Germ Cells SO MEIOSIS, VOL 1: MOLECULAR AND GENETIC METHODS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Meiosis; mouse recombination hot spots; DNA double-strand breaks; terminal deoxynucleotidyl transferase ID DOUBLE-STRAND BREAKS; RECOMBINATION HOT-SPOTS; SACCHAROMYCES-CEREVISIAE; HOMOLOGOUS RECOMBINATION; INITIATION SITE; MEIOSIS; HOTSPOTS; GENE; PATHWAYS; STRAINS AB The study of location and intensity of double-strand breaks (DSBs) in mammalian systems is more challenging than in yeast because, unlike yeast, the progression through meiosis is not synchronous and only a small fraction of all testis cells are actually at the stage where DSB formation is initiated. We devised a quantitative approach that is sensitive enough to detect the position of rare DNA strand breaks in mouse germ cell-enriched testicular cell populations. The method can detect DNA breaks at any desired location in the genome but is not specific for DSBs-overhangs, nicks, or gaps with a free 3' OH group arc also detected. The method was successfully used to compare testicular cells from mouse strains that possess or lack an active recombination hot spot at the H2-Ea gene. Breaks that were due to meiotic hot spot activity, could be distinguished from the background of DNA breaks. This highly sensitive approach could be used to study other biological processes where rare DNA breaks are generated. C1 [Qin, Jian] Fluidigm Corp, San Francisco, CA USA. [Subramanian, Jaichandar] NIH, Bethesda, MD 20892 USA. [Arnheim, Norman] Univ So Calif, Mol & Computat Biol Program, Los Angeles, CA USA. RP Qin, J (reprint author), Fluidigm Corp, San Francisco, CA USA. FU NIGMS NIH HHS [GM36745] NR 30 TC 0 Z9 0 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-934115-66-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2009 VL 557 BP 165 EP 181 DI 10.1007/978-1-59745-527-5_11 D2 10.1007/978-1-59745-527-5 PG 17 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BKN72 UT WOS:000268721200011 PM 19799182 ER PT S AU Oh, SD Jessop, L Lao, JP Allers, T Lichten, M Hunter, N AF Oh, Steve D. Jessop, Lea Lao, Jessica P. Allers, Thorsten Lichten, Michael Hunter, Neil BE Keeney, S TI Stabilization and Electrophoretic Analysis of Meiotic Recombination Intermediates in Saccharomyces cerevisiae SO MEIOSIS, VOL 1: MOLECULAR AND GENETIC METHODS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Meiosis; homologous recombination; double-strand break; joint molecule; Holliday junction; D-loop; strand-exhange; electrophoresis ID DOUBLE-STRAND-BREAK; JOINT MOLECULES; DNA; MEIOSIS; YEAST; IDENTIFICATION; TRANSITION; EXCHANGE; JUNCTION; REPAIR AB Joint Molecule (JM) recombination intermediates result from DNA strand-exchange between homologous chromosomes. Physical monitoring of JM formation in budding yeast has provided a wealth of information about the timing and mechanism of meiotic recombination. These assays arc especially informative when applied to the analysis of mutants for which genetic analysis of recombination is impossible, i.e. mutants that die during meiosis. This chapter describes three distinct methods to stabilize JMs against thermally driven dissolution as well as electrophoretic approaches to resolve and detect JMs at two well-characterized recombination hotspots. C1 [Oh, Steve D.; Lao, Jessica P.; Hunter, Neil] Univ Calif Davis, Dept Microbiol, Davis, CA 95616 USA. [Oh, Steve D.; Lao, Jessica P.; Hunter, Neil] Univ Calif Davis, Dept Mol & Cellular Biol, Davis, CA 95616 USA. [Jessop, Lea; Allers, Thorsten; Lichten, Michael] NCI, Biochem & Mol Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Oh, SD (reprint author), Univ Calif Davis, Dept Microbiol, Davis, CA 95616 USA. RI Allers, Thorsten/G-5503-2010; Lichten, Michael/C-5795-2013 OI Allers, Thorsten/0000-0002-7308-3332; Lichten, Michael/0000-0001-9707-2956 FU Intramural NIH HHS; NIGMS NIH HHS [GM074223] NR 21 TC 21 Z9 21 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-934115-66-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2009 VL 557 BP 209 EP 234 DI 10.1007/978-1-59745-527-5_14 D2 10.1007/978-1-59745-527-5 PG 26 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BKN72 UT WOS:000268721200014 PM 19799185 ER PT B AU Khalsa, JH Vocci, F AF Khalsa, Jag H. Vocci, Frank BE Katlin, LJ TI MANAGEMENT OF HUMAN IMMUNODEFICIENCY VIRUS AND HEPATITIS C VIRUS CO-INFECTIONS IN DRUG ABUSERS SO MEN AND ADDICTIONS: NEW RESEARCH SE Substance Abuse Assessment Interventions and Treatment LA English DT Article; Book Chapter ID METHADONE-MAINTENANCE TREATMENT; HIV-INFECTED PATIENTS; SEXUALLY-TRANSMITTED INFECTIONS; POTENT ANTIRETROVIRAL THERAPY; SEVERE MENTAL-ILLNESS; TYPE-1 INFECTION; HCV INFECTION; SAN-FRANCISCO; LIVER-DISEASE; RISK-FACTORS C1 [Khalsa, Jag H.; Vocci, Frank] Natl Inst Drug Abuse, NIH, Bethesda, MD 20892 USA. RP Khalsa, JH (reprint author), Natl Inst Drug Abuse, NIH, Bethesda, MD 20892 USA. NR 133 TC 0 Z9 0 U1 0 U2 0 PU NOVA SCIENCE PUBLISHERS, INC PI HAUPPAUGE PA 400 OSER AVE, STE 1600, HAUPPAUGE, NY 11788-3635 USA BN 978-1-60692-098-5 J9 SUBST ABUS ASSESS IN PY 2009 BP 177 EP 201 PG 25 WC Substance Abuse SC Substance Abuse GA BKU81 UT WOS:000269297300010 ER PT J AU Lee, S Kil, WJ Chun, M Jung, YS Kang, SY Kang, SH Oh, YT AF Lee, Sunyoung Kil, Whoon Jong Chun, Mison Jung, Yong-Sik Kang, Seok Yun Kang, Seung-Hee Oh, Young-Taek TI Chemotherapy-related amenorrhea in premenopausal women with breast cancer SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE Adjuvant endocrine therapy; Breast cancer; Chemotherapy; Chemotherapy-related amenorrhea ID ADJUVANT CHEMOTHERAPY; RANDOMIZED-TRIALS; CYCLOPHOSPHAMIDE; SURVIVAL; THERAPY; TAXANE AB Objective: To report the incidence of chemotherapy-related amenorrhea (CRA) from chemotherapy with/without adjuvant endocrine therapy in premenopausal women with breast cancer and to analyze the related factors. Design: From January 2000 to August 2006, 326 premenopausal women (<= 50 y old) who completed chemotherapy were available for analysis. The CRA definitional criterion in this study was no menstruation for 6 months in a woman who was premenopausal at diagnosis. As risk factors for CRA, woman's age, the type of chemotherapy regimen, adjuvant endocrine therapy use, and body mass index were evaluated. Results: The median age was 42 years (range, 22-50 y). The median follow-up period was 37 months (range, 12-80 mo). Women were divided into two groups by age at diagnosis: 128 women in group I (less than 40 years old) and 198 women in group 2 (age :40 y). CRA occurred in a total of 223 (68%) women: 43% in group 1 and 85% in group 2 (P < 0.001). Despite CRA, 14% resumed menstruation: 24% in group 1 and 11% in group 2. Another 40 (12%) women had less than 6 months of menstruation interruption. Permanent CRA was related with age at diagnosis and use of adjuvant endocrine therapy (P < 0.05). In this study, there were four pregnancies, two of which resulted in therapeutic abortion due to ongoing chemotherapy. Conclusions: This Study confirmed that the rate of CRA depends on age at diagnosis and the use of adjuvant endocrine therapy. It is essential to inform young women of reproductive age of the possibility of amenorrhea, or resumption of menstruation and contraceptive options. C1 [Lee, Sunyoung; Chun, Mison; Kang, Seung-Hee; Oh, Young-Taek] Ajou Univ, Sch Med, Dept Radiat Oncol, Suwon 443721, South Korea. [Kil, Whoon Jong] NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. [Jung, Yong-Sik] Ajou Univ, Sch Med, Dept Surg, Suwon 443721, South Korea. [Kang, Seok Yun] Ajou Univ, Sch Med, Dept Hematol Oncol, Suwon 443721, South Korea. RP Chun, M (reprint author), Ajou Univ, Sch Med, Dept Radiat Oncol, San 5, Suwon 443721, South Korea. EM chunm@ajou.ac.kr OI Jung, Yongsik/0000-0002-2011-1459 NR 28 TC 21 Z9 22 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD JAN-FEB PY 2009 VL 16 IS 1 BP 98 EP 103 DI 10.1097/gme.0b013e3181844877 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 392WO UT WOS:000262333100018 PM 18849877 ER PT S AU Hailey, DW Lippincott-Schwartz, J AF Hailey, Dale W. Lippincott-Schwartz, Jennifer BE Klionsky, DJ TI USING PHOTOACTIVATABLE PROTEINS TO MONITOR AUTOPHAGOSOME LIFETIME SO METHODS IN ENZYMOLOGY: AUTOPHAGY IN MAMMALIAN SYSTEMS, VOL 452, PT B SE Methods in Enzymology LA English DT Review; Book Chapter ID FLUORESCENT PROTEINS; LYSOSOMES; FUSION; LC3; MATURATION; MARKER; SYSTEM; CELLS; GFP AB Many conditions are now known to cause autophagosome proliferation in cells and organisms including amino acid and serum starvation, ER and oxidative stress, and pathogen infection. Autophagosome proliferation is also observed in disease states and developmental programs. The widespread use of GFP-Atg8 fusion molecules has provided a simple way to visualize the proliferation of autophagosomes in cells. However, GFP-Atg8 markers do not reveal the underlying cause of autophagosome proliferation. Two processes regulate the number of autophagosomes present in cells: (1) formation of the structures and (2) their turnover through fusion with lysosomes. Here we describe the use of photoactivatable proteins to decouple the processes of autophagosome formation from autophagosome turnover. Photoactivatable proteins fused to Atg8 homologs make it possible to pulse-label existing populations of autophagosomes in living cells. The fate of those pulse-labeled autophagosomes can then be monitored to determine autophagosome lifetime. This assay is applicable to both engineered tissue culture models and transgenic organisms expressing photoactivatable proteins fused to Atg8 homologs. C1 [Hailey, Dale W.; Lippincott-Schwartz, Jennifer] NICHD, NIH, Cell Biol & Metab Branch, Sect Organelle Biol, Bethesda, MD 20892 USA. RP Hailey, DW (reprint author), NICHD, NIH, Cell Biol & Metab Branch, Sect Organelle Biol, Bethesda, MD 20892 USA. NR 30 TC 8 Z9 8 U1 0 U2 3 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-374547-7 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2009 VL 452 BP 25 EP 45 DI 10.1016/S0076-6879(08)03603-3 PG 21 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BIW12 UT WOS:000263265400003 PM 19200874 ER PT S AU Seleverstov, O Phang, JM Zabirnyk, O AF Seleverstov, Oleksandr Phang, James M. Zabirnyk, Olga BE Klionsky, DJ TI SEMICONDUCTOR NANOCRYSTALS IN AUTOPHAGY RESEARCH: METHODOLOGY IMPROVEMENT AT NANOSIZED SCALE SO METHODS IN ENZYMOLOGY: AUTOPHAGY IN MAMMALIAN SYSTEMS, VOL 452, PT B SE Methods in Enzymology LA English DT Review; Book Chapter ID SENSITIVE FUSOGENIC PEPTIDE; IN-SITU HYBRIDIZATION; QUANTUM DOTS; LIVING CELLS; PHARMACEUTICAL NANOCARRIERS; NANOPARTICLE PROBES; WESTERN-BLOT; GENE-THERAPY; RAT-LIVER; DELIVERY AB Our recent findings establish a functional link between foreign nanosized bodies and autophagy. We find that nanoparticles (NP) within a certain size range act as potent autophagy activators, and that autophagic flux is an underlying physiological process of the cellular clearance of the NP. Therefore, NP may be used to study and to monitor autophagy. We provide a detailed description of laboratory protocols designed for studying NP-mediated autophagy. In addition, we review available methods of nanotechnotogy, which may benefit autophagy research. C1 [Seleverstov, Oleksandr] Univ Wyoming, Dept Anim Sci, Coll Agr, Laramie, WY 82071 USA. [Phang, James M.; Zabirnyk, Olga] NCI, Metab & Canc Susceptibil Sect, Comparat Carcinogenesis Lab, Ctr Canc Res, Frederick, MD 21701 USA. RP Seleverstov, O (reprint author), Univ Wyoming, Dept Anim Sci, Coll Agr, Laramie, WY 82071 USA. FU Intramural NIH HHS NR 68 TC 7 Z9 8 U1 1 U2 9 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-374547-7 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2009 VL 452 BP 277 EP 296 DI 10.1016/S0076-6879(08)03618-5 PG 20 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BIW12 UT WOS:000263265400018 PM 19200889 ER PT S AU Shnyrova, AV Zimmerberg, J AF Shnyrova, Anna V. Zimmerberg, Joshua BE Duzgunes, N TI RECONSTITUTION OF MEMBRANE BUDDING WITH UNILAMELLAR VESICLES SO METHODS IN ENZYMOLOGY; LIPOSOMES, PT F SE Methods in Enzymology LA English DT Review; Book Chapter ID NEWCASTLE-DISEASE VIRUS; VESICULAR STOMATITIS-VIRUS; MATRIX PROTEIN; CURVATURE; LIPOSOMES; ENVELOPE; CELLS AB Enveloped virus particles select their lipid-protein components and egress by budding from the host cell membranes. The matrix protein of many enveloped viruses has been proposed as a crucial element for viral budding; however, molecular mechanisms behind membrane remodeling by the matrix protein are yet to be unraveled. Here, we describe a set of in vitro functional reconstitution assays that allow quantitative evaluation of both, membrane binding and creation of membrane curvature by the matrix protein isolated from Newcastle Disease Virus. Individual budding events orchestrated by the matrix protein can be resolved in real time. The assays may be applied for direct reconstitution of the on-membrane action of cellular proteins involved in membrane curvature induction upon binding in vivo. C1 [Shnyrova, Anna V.; Zimmerberg, Joshua] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cellular & Mol Biol Lab, Program Phys Biol, Bethesda, MD USA. RP Shnyrova, AV (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cellular & Mol Biol Lab, Program Phys Biol, Bethesda, MD USA. FU Intramural NIH HHS [ZIA HD001415-20] NR 31 TC 2 Z9 2 U1 0 U2 4 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-374969-7 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2009 VL 464 BP 55 EP 75 DI 10.1016/S0076-6879(09)64004-0 PG 21 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BMH89 UT WOS:000272400600005 PM 19903550 ER PT S AU Lenardo, MJ McPhee, CK Yu, L AF Lenardo, Michael J. McPhee, Christina K. Yu, Li BE Klionsky, DJ TI AUTOPHAGIC CELL DEATH SO METHODS IN ENZYMOLOGY VOL 453: AUTOPHAGY IN DISEASE AND CLINICAL APPLICATIONS, PT C SE Methods in Enzymology LA English DT Review; Book Chapter ID PROTEIN TARGETING PATHWAY; SACCHAROMYCES-CEREVISIAE; MUTANTS; DEGRADATION; CYTOPLASM; APOPTOSIS AB In this chapter we discuss methods to study autophagic cell death. A large body of evidence demonstrates that autophagy is a cell survival mechanism in response to starvation. The role of autophagy in cell death, however, has long been controversial. Recently, molecular approaches have provided direct evidence that autophagy contributes to cell death in certain contexts. We begin this chapter by outlining methods to quantify cell death, for example by assaying for cell viability. Next, we discuss methods to measure processes involved in cell death, such as caspase activation and autophagy. Finally, we discuss methods to genetically or chemically perturb autophagy to test whether autophagy is required for cell death. Together, these approaches provide a guide to investigate the relationship between autophagy and cell death. C1 [Lenardo, Michael J.; Yu, Li] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. [McPhee, Christina K.] Univ Manchester, Sch Med, Dept Canc Biol, Worcester, MA USA. [McPhee, Christina K.] Univ Maryland, Dept Mol Genet & Cell Biol, Maryville, MO USA. RP Lenardo, MJ (reprint author), NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. FU Intramural NIH HHS [ZIA AI000718-16] NR 19 TC 13 Z9 13 U1 0 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-374936-9 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2009 VL 453 BP 17 EP 31 DI 10.1016/S0076-6879(08)04002-0 PG 15 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BIY80 UT WOS:000263827100002 PM 19216900 ER PT S AU Raben, N Shea, L Hill, V Plotz, P AF Raben, Nina Shea, Lauren Hill, Victoria Plotz, Paul BE Klionsky, DJ TI MONITORING AUTOPHAGY IN LYSOSOMAL STORAGE DISORDERS SO METHODS IN ENZYMOLOGY VOL 453: AUTOPHAGY IN DISEASE AND CLINICAL APPLICATIONS, PT C SE Methods in Enzymology LA English DT Review; Book Chapter ID CATHEPSIN-D DEFICIENCY; PICK-C-DISEASE; NEURONAL CEROID-LIPOFUSCINOSIS; MULTIPLE SULFATASE DEFICIENCY; MUCOLIPIDOSIS TYPE-IV; LIPID TRAFFICKING DEFECTS; CHOLESTEROL HOMEOSTASIS; SKELETAL-MUSCLE; POMPE-DISEASE; MOUSE MODEL AB Lysosomes are the final destination of the autophagic pathway. It is in the acidic milieu of the lysosomes that autophagic cargo is metabolized and recycled. One would expect that diseases with primary lysosomal defects would be among the first systems in which autophagy would be studied. In reality, this is not the case. Lysosomal storage diseases, a group of more than 60 diverse inherited disorders, have only recently become a focus of autophagic research. Studies of these clinically severe conditions promise not only to clarify pathogenic mechanisms, but also to expand our knowledge of autophagy itself. In this chapter, we will describe the lysosomal storage diseases in which autophagy has been explored, and present the approaches used to evaluate this essential cellular pathway. C1 [Raben, Nina; Shea, Lauren; Hill, Victoria; Plotz, Paul] NIAMS, Arrhritis & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. RP Raben, N (reprint author), NIAMS, Arrhritis & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 AR999999] NR 78 TC 46 Z9 47 U1 1 U2 14 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-374936-9 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2009 VL 453 BP 417 EP 449 DI 10.1016/S0076-6879(08)04021-4 PG 33 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BIY80 UT WOS:000263827100021 PM 19216919 ER PT S AU Yu, LD Yang, SQ Yin, Y Cen, XW Zhou, F Xia, D Yu, CA AF Yu, Linda Yang, Shaoqing Yin, Ying Cen, Xiaowei Zhou, Fei Xia, Di Yu, Chang-An BE Allison, WS TI ANALYSIS OF ELECTRON TRANSFER AND SUPEROXIDE GENERATION IN THE CYTOCHROME bc(1) Complex SO METHODS IN ENZYMOLOGY, VOL 456: MITOCHONDRIAL FUNCTION, PART A: MITOCHONDRIAL ELECTRON TRANSPORT COMPLEXES AND REACTIVE OXYGEN SPECIES SE Methods in Enzymology LA English DT Review; Book Chapter ID IRON-SULFUR PROTEIN; BOVINE HEART-MITOCHONDRIA; C REDUCTASE; Q(O) SITE; Q-CYCLE; RHODOBACTER-SPHAEROIDES; QUINOL OXIDATION; MECHANISM; ANION; CHEMILUMINESCENCE AB During the electron transfer through the cytochrome bc(1) complex (ubiquinol-cytochrome c oxidoreductase or complex III), protons are translocated across the membrane, and production of superoxide anion radicals (O-2(center dot-)) is observed. The bc(1) complex is purified from broken mitochondrial preparation prepared from frozen heart muscles by repeated detergent solubilization and salt fractionation. The electron transfer of the purified complex is determined spectrophotometrically. The activity depends on the choice of detergent, protein concentration, and ubiquinol derivatives used. The proton translocation activity of 2H(+)/e(-) is determined in the reconstituted bc(1)-PL vesicles. The O-2(center dot-) production by bc(1) is determined by measuring the chemiluminescence of the 2-methyl-6-(p-methoxyphenyl)-3,7-dihydroimidazol[1,2-1]pyrazin-3-one hydrochloride (MCLA)-O-2(center dot-) adduct during a single turnover of bc(1) complex, with the Applied Photophysics stopped-flow reaction analyzer SX.18MV, by leaving the excitation light source off and registering the light emission. Production of O-2(center dot-) bc(1) is in an inverse relationship to its electron transfer activity. Inactivation of the bc(1) complex by incubating at elevated temperature (37 degrees C) or by treatment with proteinase K results in an increase in O-2(center dot-)-generating activity to the same level as that of the antimycin A-inhibited complex. These results suggest that the structural integrity of protein subunits is not required for O-2(center dot-) generating activity in the bc(1) complex. C1 [Yu, Linda; Yang, Shaoqing; Yin, Ying; Cen, Xiaowei; Zhou, Fei; Yu, Chang-An] Oklahoma State Univ, Dept Biochem & Mol Biol, Stillwater, OK 74078 USA. [Xia, Di] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Yu, LD (reprint author), Oklahoma State Univ, Dept Biochem & Mol Biol, Stillwater, OK 74078 USA. RI yang, shaoqing/C-9761-2012 FU Intramural NIH HHS; NIGMS NIH HHS [GM 30721] NR 38 TC 7 Z9 7 U1 1 U2 10 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-08-087776-1 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2009 VL 456 BP 459 EP 473 DI 10.1016/S0076-6879(08)04425-X PG 15 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BJG35 UT WOS:000265605300025 PM 19348904 ER PT S AU Aponte, AM Phillips, D Harris, RA Blinova, K French, S Johnson, DT Balaban, RS AF Aponte, Angel M. Phillips, Darci Harris, Robert A. Blinova, Ksenia French, Stephanie Johnson, D. Thor Balaban, Robert S. BE Allison, WS Murphy, AN TI P-32 LABELING OF PROTEIN PHOSPHORYLATION AND METABOLITE ASSOCIATION IN THE MITOCHONDRIA MATRIX SO METHODS IN ENZYMOLOGY, VOL 457: MITOCHONDRIAL FUNCTION, PARTB MITOCHONDRIAL PROTEIN KINASES, PROTEIN PHOSPHATASES AND MITOCHONDRIAL DISEASES SE Methods in Enzymology LA English DT Review; Book Chapter ID CYTOCHROME-C-OXIDASE; PYRUVATE-DEHYDROGENASE; OXIDATIVE-PHOSPHORYLATION; MASS-SPECTROMETRY; MECHANISM; MEMBRANE; CAMP; PHOSPHOLAMBAN; KINASE; HEARTS AB Protein phosphorylations, as well as phosphate metabolite binding, are well characterized post-translational mechanisms that regulate enzyme activity in the cytosol, but remain poorly defined in mitochondria. Recently extensive matrix protein phosphorylation sites have been discovered but their functional significance is unclear. Herein we describe methods of using P-32 labeling of intact mitochondria to determine the dynamic pools of protein phosphorylation as well as phosphate metabolite association. This screening approach may be useful in not only characterizing the dynamics of these pools, but also provide insight into which phosphorylation sites have a functional significance. Using the mitochondrial ATP synthetic capacity under appropriate conditions, inorganic P-32 was added to energized mitochondria to generate high specific activity gamma-P-32-ATP in the matrix. In general, SDS denaturing and gel electrophoresis was used to primarily follow protein phosphorylation, whereas native gel techniques were used to observe weaker metabolite associations since the structure of mitochondrial complexes was minimally affected. The protein phosphorylation and metabolite association within the matrix was found to be extensive using these approaches. (32)p labeling in 2D gels was detected in over 40 proteins, including most of the complexes of the cytochrome chain and proteins associated with intermediary metabolism, biosynthetic pathways, membrane transport, and reactive oxygen species metabolism. (32)p pulse-chase experiments further revealed the overall dynamics of these processes that included phosphorylation site turnover as well as phosphate-protein pool size alterations. The high sensitivity of P-32 resulted in many proteins being intensely labeled, but not identified due to the sensitivity limitations of mass spectrometry. These low concentration proteins may represent signaling proteins within the matrix. These results demonstrate that the mitochondrial matrix phosphoproteome is both extensive and dynamic. The use of this, in situ, labeling approach is extremely valuable in confirming protein phosphorylation sites as well as examining the dynamics of these processes under near physiological conditions. C1 [Aponte, Angel M.; French, Stephanie; Johnson, D. Thor] NHLBI, Prote Core Facil, DHHS, Bethesda, MD 20892 USA. [Phillips, Darci; Blinova, Ksenia; Balaban, Robert S.] NHLBI, Cardiac Energet Lab, DHHS, Bethesda, MD 20892 USA. [Harris, Robert A.; Johnson, D. Thor] Indiana Univ, Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN USA. RP Aponte, AM (reprint author), NHLBI, Prote Core Facil, DHHS, Bldg 10, Bethesda, MD 20892 USA. FU Intramural NIH HHS [ZIA HL004601-25] NR 31 TC 21 Z9 21 U1 0 U2 8 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-374622-1 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2009 VL 457 BP 63 EP 80 DI 10.1016/S0076-6879(09)05004-6 PG 18 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BJJ78 UT WOS:000266544100004 PM 19426862 ER PT S AU Hunsicker-Wang, L Vogt, M DeRose, VJ AF Hunsicker-Wang, Laura Vogt, Matthew DeRose, Victoria J. BE Herschalag, D TI EPR METHODS TO STUDY SPECIFIC METAL-ION BINDING SITES IN RNA SO METHODS IN ENZYMOLOGY, VOL 468: BIOPHYSICAL, CHEMICAL, AND FUNCTIONAL PROBES OF RNA STRUCTURE, INTERACTIONS AND FOLDING, PT A SE Methods in Enzymology LA English DT Review; Book Chapter ID ENVELOPE MODULATION SPECTROSCOPY; DOUBLE-RESONANCE SPECTROSCOPY; HAMMERHEAD RIBOZYME; PULSED EPR; STRUCTURAL-ANALYSIS; FROZEN SOLUTION; NUCLEIC-ACIDS; BAND ENDOR; MN2+; COMPLEXES AB The properties of metal-ion interactions with RNA can be explored by spectroscopic methods. in this chapter, we describe the use of paramagnetic Mn(2+) ions and electron paramagnetic resonance (EPR)-based techniques to monitor the association of Mn(2+) with RNA and related nucleotides. Solution EPR methods are used to determine the numbers of Mn(2+) ions associating with RNA. For RNA poised with a single-bound Mn(2+), low-temperature EPR characteristics provide information about the asymmetry of the Mn(2+) coordination site. To identify the RNA groups coordinating to the Mn(2+) ion, ENDOR (electron nuclear double resonance) and ESEEM (electron spin echo envelope modulation) methods are applied. Both continuous-wave (CW) and electron spin echo (ESE)-detected ENDOR methods are described. This chapter includes practical details for RNA sample preparation, including isotope substitution and cryoprotection, and an overview of data acquisition and analysis methods used in these techniques, as well as examples from the current literature. C1 [Hunsicker-Wang, Laura] Trinity Univ, Dept Chem, San Antonio, TX 78212 USA. [Vogt, Matthew] NCI, Pathol Lab, Bethesda, MD 20892 USA. [DeRose, Victoria J.] Univ Oregon, Dept Chem, Eugene, OR 97403 USA. RP Hunsicker-Wang, L (reprint author), Trinity Univ, Dept Chem, San Antonio, TX 78212 USA. FU NIGMS NIH HHS [GM58096] NR 50 TC 27 Z9 27 U1 1 U2 14 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-374399-2 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2009 VL 468 BP 335 EP 367 DI 10.1016/S0076-6879(09)68016-2 PG 33 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BMI33 UT WOS:000272435500017 PM 20946777 ER PT J AU Bailey, KR Crawley, JN AF Bailey, Kathleen R. Crawley, Jacqueline N. BE Buccafusco, JJ TI Anxiety-Related Behaviors in Mice SO METHODS OF BEHAVIOR ANALYSIS IN NEUROSCIENCE, SECOND EDITION SE Frontiers in Neuroscience LA English DT Article; Book Chapter ID ELEVATED PLUS-MAZE; FEAR-POTENTIATED STARTLE; INBRED MOUSE STRAINS; OPEN-FIELD ACTIVITY; ANIMAL-MODELS; SOCIAL-INTERACTION; KNOCKOUT MICE; ANXIOLYTIC-LIKE; TEST BATTERIES; LOCOMOTOR-ACTIVITY C1 [Bailey, Kathleen R.] Susquehanna Univ, Dept Psychol, Selinsgrove, PA 17870 USA. [Crawley, Jacqueline N.] NIMH, Lab Behav Neurosci, NIH, Bethesda, MD 20892 USA. RP Bailey, KR (reprint author), Susquehanna Univ, Dept Psychol, Selinsgrove, PA 17870 USA. NR 122 TC 64 Z9 64 U1 0 U2 2 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA J9 FRONT NEUROSCI JI Front. Neurosci. PY 2009 SI 2nd BP 77 EP 101 PG 25 WC Neurosciences SC Neurosciences & Neurology GA BKW98 UT WOS:000269503500005 ER PT J AU Deserno, TM Antani, S Long, LR AF Deserno, T. M. Antani, S. Long, L. Rodney TI Content-based Image Retrieval for Scientific Literature Access SO METHODS OF INFORMATION IN MEDICINE LA English DT Article DE Content-based image retrieval (CBIR); scientific literature; information system integration; radiology; data mining; information retrieval ID MEDICAL IMAGES; CLASSIFICATION; CATEGORIZATION; DATABASES; FRAMEWORK; SYSTEMS; FUTURE AB Objectives: An increasing number of articles are published electronically in the scientific literature, but access is limited to alphanumerical search on title, author, or abstract, and may disregard numerous figures. In this paper, we estimate the benefits of using content-based image retrieval (CBIR) on article figures to augment traditional access to articles. Methods: We selected four high-impact (JCR) 2005. Figures were automatically extracted from the PDF article files, and manually classified on their content and number of sub-figure panels. We make a quantitative estimate by projecting from data from the Cross-Language Evaluation Forum (Image-CLEF) campaigns, and qualitatively validate it through experiments using the Image Retrieval in Medical Applications (IRMA) project. Results: Based on 2077 articles with 11,753 pages, 4493 figures, and 11,238 individual images, the predicted accuracy for article retrieval may reach 97.08%. Conclusions: Therefore, CBIR potentially has a high impact in medical literature search and retrieval. C1 [Deserno, T. M.] Aachen Univ Technol RWTH, Dept Med Informat, D-52057 Aachen, Germany. [Deserno, T. M.; Antani, S.; Long, L. Rodney] US Natl Inst Hlth, US Natl Lib Med, Bethesda, MD USA. RP Deserno, TM (reprint author), Aachen Univ Technol RWTH, Dept Med Informat, Pauwelsstr 30, D-52057 Aachen, Germany. EM deserno@ieee.org OI Antani, Sameer/0000-0002-0040-1387 FU Intramural NIH HHS NR 33 TC 10 Z9 10 U1 0 U2 2 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0026-1270 J9 METHOD INFORM MED JI Methods Inf. Med. PY 2009 VL 48 IS 4 BP 371 EP 380 DI 10.3414/ME0561 PG 10 WC Computer Science, Information Systems; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA 489QH UT WOS:000269435700011 PM 19621115 ER PT S AU Ubaldi, M Sommer, W Soverchia, L Lourdusamy, A Ruggeri, B Ciccocioppo, R Hardiman, G AF Ubaldi, Massimo Sommer, Wolfgang Soverchia, Laura Lourdusamy, Anbarasu Ruggeri, Barbara Ciccocioppo, Roberto Hardiman, Gary BE Hardiman, G TI Microarrays in Neuroscience SO MICROARRAY INNOVATIONS: TECHNOLOGY AND EXPERIMENTATION SE Drug Discovery Series LA English DT Article; Book Chapter ID PARAFFIN-EMBEDDED TISSUE; GENE-EXPRESSION ANALYSIS; LASER CAPTURE MICRODISSECTION; POLYMERASE CHAIN-REACTION; MESSENGER-RNA EXPRESSION; TYRAMIDE SIGNAL AMPLIFICATION; ALZHEIMERS-DISEASE; FRONTAL-CORTEX; BRAIN-TISSUE; PREFRONTAL CORTEX C1 [Ubaldi, Massimo; Soverchia, Laura; Lourdusamy, Anbarasu; Ruggeri, Barbara; Ciccocioppo, Roberto] Univ Camerino, Dept Pharmacol Sci & Expt Med, I-62032 Camerino, Italy. [Sommer, Wolfgang] NIH, Bethesda, MD 20892 USA. [Hardiman, Gary] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. RP Ubaldi, M (reprint author), Univ Camerino, Dept Pharmacol Sci & Expt Med, I-62032 Camerino, Italy. RI Lourdusamy, Anbarasu/G-3387-2011; Lourdusamy, Anbarasu/P-6606-2014; OI Lourdusamy, Anbarasu/0000-0002-1978-6301 NR 135 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA SN 2154-5200 BN 978-1-4200-9448-0 J9 DRUG DISCOV SER JI Drug Discov. Ser. PY 2009 VL 11 BP 271 EP 288 D2 10.1201/9781420094510 PG 18 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BKH88 UT WOS:000268160100018 ER PT B AU Liu, RH Grodzinski, P AF Liu, Robin H. Grodzinski, Piotr BE Dill, K Liu, RH Grodzinski, P TI Fully Integrated Microfluidic Device for Direct Sample-to-Answer Genetic Analysis SO MICROARRAYS: PREPARATION, MICROFLUIDICS, DETECTION METHODS, AND BIOLOGICAL APPLICATIONS SE Integrated Analytical Systems LA English DT Article; Book Chapter ID POLYMERASE-CHAIN-REACTION; DNA ANALYSIS DEVICE; CAPILLARY-ELECTROPHORESIS; PCR AMPLIFICATION; MICROARRAY HYBRIDIZATION; ANALYSIS SYSTEM; NUCLEIC-ACIDS; CHAOTIC MIXER; FLOW-CONTROL; WHOLE-BLOOD AB Integration of microfluidics technology with DNA microarrays enables building complete sample-to-answer systems that are useful in many applications such as clinic diagnostics. In this chapter, a fully integrated microfluidic device [1] that consists of microfluidic mixers, valves, pumps, channels, chambers, heaters, and a DNA microarray sensor to perform DNA analysis of complex biological sample solutions is present. This device can perform on-chip sample preparation (including magnetic bead-based cell capture, cell preconcentration and purification, and cell lysis) of complex biological sample solutions (such as whole blood), polymerase chain reaction, DNA hybridization, and electrochemical detection. A few novel microfluidic techniques were developed and employed. A micromixing technique based on a cavitation microstreaming principle was implemented to enhance target cell capture from whole blood samples using immunomagnetic beads. This technique was also employed to accelerate DNA hybridization reaction. Thermally actuated paraffin-based microvalves were developed to regulate flows. Electrochemical pumps and thermopneumatic pumps were integrated on the chip to provide pumping of liquid solutions. The device is completely self-contained: no external pressure sources, fluid storage, mechanical pumps, or valves are necessary for fluid manipulation, thus eliminating possible sample contamination and simplifying device operation. Pathogenic bacteria detection from similar to mL whole blood samples and single-nucleotide polymorphism analysis directly from diluted blood were demonstrated. The device provides a cost-effective solution to direct sample-to-answer genetic analysis, and thus has a potential impact in the fields of point-of-care genetic analysis, environmental testing, and biological warfare agent detection. C1 [Liu, Robin H.] Osmetech Mol Diagnost, Pasadena, CA 91105 USA. [Grodzinski, Piotr] NCI, NIH, Bethesda, MD 20892 USA. RP Liu, RH (reprint author), Osmetech Mol Diagnost, 757 S Raymond Ave, Pasadena, CA 91105 USA. EM Robin.Liu@osmetech.com; grodzinp@mail.nih.gov; Robin.Liu@osmetech.com; grodzinp@mail.nih.gov NR 84 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-72716-5 J9 INTEGR ANAL SYST PY 2009 BP 37 EP 65 DI 10.1007/978-0-387-72719-6_3 D2 10.1007/978-0-387-72719-6 PG 29 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA BJY42 UT WOS:000267419200003 ER PT J AU Reale, M Greig, NH Kamal, MA AF Reale, M. Greig, N. H. Kamal, M. A. TI Peripheral Chemo-Cytokine Profiles in Alzheimer's and Parkinson's Diseases SO MINI-REVIEWS IN MEDICINAL CHEMISTRY LA English DT Review DE Alzheimer's Disease; Parkinson's Disease; neuroinflammation; neurodegeneration; cytokines; chemokines ID MILD COGNITIVE IMPAIRMENT; CENTRAL-NERVOUS-SYSTEM; AMYLOID PRECURSOR PROTEIN; GROWTH-FACTOR-BETA; MONOCYTE CHEMOATTRACTANT PROTEIN-1; BLOOD MONONUCLEAR-CELLS; NECROSIS-FACTOR-ALPHA; CEREBROSPINAL-FLUID; TNF-ALPHA; INFLAMMATORY MARKERS AB The identification of peripheral biomarkers for neurodegenerative diseases is required to improve the accuracy of clinical diagnosis and monitor both disease progression and response to treatments. The data reviewed in this paper suggest that, in neurodegenerative disease, cytokines are links between peripheral immune system and nervous system dysfunction. C1 [Reale, M.] Univ G DAnnunzio, Dept Oncol & Neurosci, Chieti, Italy. [Greig, N. H.] NIA, Drug Design & Dev Sect, Neurosci Lab, Intramural Res Program,NIH,Biomed Res Ctr, Baltimore, MD 21224 USA. [Kamal, M. A.] Enzymoics, Hebersham, NSW 2770, Australia. RP Reale, M (reprint author), Univ G DAnnunzio, Dept Oncol & Neurosci, Chieti, Italy. EM mreale@unich.it RI Kamal, Mohammad/H-9643-2012; Kamal, Mohammad/J-4622-2013; OI Kamal, Mohammad/0000-0003-1862-173X; Kamal, Mohammad Amjad/0000-0003-0088-0565 FU University "Gabriele D'Annunzio", Chieti-Pescara, Italy; National Institute on Aging, NIH, Baltimore, USA FX The authors thank members of their respective laboratories for advice and encouragement. This work was supported in part by the University "Gabriele D'Annunzio", Chieti-Pescara, Italy, and the Intramural Research Program of the National Institute on Aging, NIH, Baltimore, USA. NR 135 TC 34 Z9 35 U1 0 U2 12 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-5575 J9 MINI-REV MED CHEM JI Mini-Rev. Med. Chem. PY 2009 VL 9 IS 10 BP 1229 EP 1241 PG 13 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 517MW UT WOS:000271619500008 PM 19817713 ER PT S AU Chan, SSL Copeland, WC AF Chan, Sherine S. L. Copeland, William C. BE Stuart, JA TI Functional Analysis of Mutant Mitochondrial DNA Polymerase Proteins Involved in Human Disease SO MITOCHONDRIAL DNA: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE DNA polymerase gamma; mitochondrial DNA polymerase; DNA replication; DNA repair; mitochondrial disease; enzyme assays; POLG; POLG2 ID PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA; ACCESSORY SUBUNIT; GAMMA; MUTATION; IDENTIFICATION; TOXICITY; DEFECTS AB DNA polymerase gamma (pol gamma) is the only DNA polymerase within the mitochondrion and is thus essential for replication and repair of mtDNA. POLG, the gene encoding the catalytic subunit of pol gamma, is a major locus for a wide spectrum of mitochondrial diseases with more than 100 known disease mutations. Thus, we need to understand how and why pol gamma defects lead to disease. By using an extensive array of methods, we are developing a clearer understanding of how defects in pol gamma contribute to disease. Furthermore, crucial knowledge concerning the role of pol gamma in mtDNA replication and repair can be acquired. Here we present the protocols to characterize mutant DNA pol gamma proteins, namely, assays for processivc DNA synthesis, exonuclease activity, DNA binding, subunit interaction, and protein stability. C1 [Chan, Sherine S. L.; Copeland, William C.] Natl Inst Environm Hlth Sci, Mol Genet Lab, Mitochondrial DNA Replicat Grp, NIH, Res Triangle Pk, NC 27709 USA. RP Chan, SSL (reprint author), Natl Inst Environm Hlth Sci, Mol Genet Lab, Mitochondrial DNA Replicat Grp, NIH, Res Triangle Pk, NC 27709 USA. FU Intramural NIH HHS [Z01 ES065078-14]; NIEHS NIH HHS [1K99-ES015555-01, R00 ES015555, K99 ES015555-01, K99 ES015555] NR 18 TC 4 Z9 4 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-934115-60-2 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2009 VL 554 BP 59 EP 72 DI 10.1007/978-1-59745-521-3_4 D2 10.1007/978-1-59745-521-3 PG 14 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA BKY51 UT WOS:000269615700004 PM 19513667 ER PT S AU Longley, MJ Smith, LA Copeland, WC AF Longley, Matthew J. Smith, Leslie A. Copeland, William C. BE Stuart, JA TI Preparation of Human Mitochondrial Single-Stranded DNA-Binding Protein SO MITOCHONDRIAL DNA: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Mitochondria; single-stranded DNA-binding protein; DNA replication; EMSA; tetramer; mtDNA; protein purification ID ESCHERICHIA-COLI-SSB; POLYMERASE-GAMMA; IN-VITRO; EXPRESSION; PURIFICATION; REPLICATION; SEQUENCE; COMPLEX AB Defects in mtDNA replication arc the principle cause of severe, heritable metabolic disorders classified as mitochondrial diseases. In vitro analysis of the biochemical mechanisms of mtDNA replication has proven to be a powerful tool for understanding the origins of mitochondrial disease. Mitochondrial single-stranded DNA-binding protein (mtSSB) is an essential component of the mtDNA replication machinery. To facilitate ongoing biochemical studies, a recombinant source of mtSSB is needed to avoid the time and expense of human tissue culture. This chapter focuses oil the subcloning, purification, and initial functional validation of the recombinant human mitochondrial single-stranded DNA-binding protein. The cDNA encoding the mature form of the human mtSSB protein was amplified from a HeLa cDNA library, and recombinant human mtSSB was overproduced in Escherichia coli. A procedure was developed to rapidly purify milligram quantities of homogenous, nuclease-free mtSSB that avoids DNA-cellulose chromatography. We show that, similar to E. coli SSB, human mtSSB assembles into a tetramer and binds single-stranded oligonucleotides in a 4-to-1 protein:oligonucleotide molar ratio. C1 [Longley, Matthew J.; Smith, Leslie A.; Copeland, William C.] Natl Inst Environm Hlth Sci, Mitochondrial DNA Replicat Grp, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Longley, MJ (reprint author), Natl Inst Environm Hlth Sci, Mitochondrial DNA Replicat Grp, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. FU Intramural NIH HHS [Z01 ES065078-15] NR 20 TC 5 Z9 5 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-934115-60-2 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2009 VL 554 BP 73 EP 85 DI 10.1007/978-1-59745-521-3_5 D2 10.1007/978-1-59745-521-3 PG 13 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA BKY51 UT WOS:000269615700005 PM 19513668 ER PT J AU Alberti, N Val, D Vicens, J Garijo, MF Val-Bernal, JF de Agustin, P Merino, MJ AF Alberti, N. Val, D. Vicens, J. Garijo, M. F. Val-Bernal, J. F. de Agustin, P. Merino, M. J. TI Molecular Profile of Breast Cancer Metastases to the Central Nervous System SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 NCI, Bethesda, MD 20892 USA. Marques de Valdecilla Univ Hosp, Santander, Spain. 12 Octubre Univ Hosp, Madrid, Spain. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 105 BP 26A EP 26A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371500106 ER PT J AU Sherman, ME Gaudet, MM Campan, M Yang, XR Figueroa, JD Lissowska, J Peplonska, B Brinton, LA Garcia-Closas, M Laird, PW AF Sherman, M. E. Gaudet, M. M. Campan, M. Yang, X. R. Figueroa, J. D. Lissowska, J. Peplonska, B. Brinton, L. A. Garcia-Closas, M. Laird, P. W. TI DNA Methylation of ESR1 and PGR in Breast Cancer: Relationship to Pathologic and Epidemiologic Features SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 NCI, Rockville, MD USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ So Calif, Los Angeles, CA USA. Canc Ctr & M Sklodowska Curie Inst Oncol, Warsaw, Poland. Nofer Inst Occupat Med, Lodz, Poland. RI Peplonska, Beata/F-6004-2010; Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 0 TC 0 Z9 0 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 292 BP 67A EP 68A PG 2 WC Pathology SC Pathology GA 393KF UT WOS:000262371500293 ER PT J AU Liu, Q Wrathall, L Galli, S Vicens, J Linehan, WM Tsokos, M Merino, MJ AF Liu, Q. Wrathall, L. Galli, S. Vicens, J. Linehan, W. M. Tsokos, M. Merino, M. J. TI Renal Medullary Carcinoma: Molecular, IHC, and Pathologic Correlation SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 [Liu, Q.; Wrathall, L.; Galli, S.; Vicens, J.; Linehan, W. M.; Tsokos, M.; Merino, M. J.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 809 BP 179A EP 179A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371500810 ER PT J AU Chowdhuri, SR Vicens, J Teller, L Linehan, WM Merino, MJ AF Chowdhuri, S. Roy Vicens, J. Teller, L. Linehan, W. M. Merino, M. J. TI Renal Cancer in Tuberous Sclerosis: An Underdiagnosed Disease? Molecular, IHC and Pathologic Correlation SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 [Chowdhuri, S. Roy; Vicens, J.; Teller, L.; Linehan, W. M.; Merino, M. J.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 866 BP 191A EP 191A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371500867 ER PT J AU Vicens, J Pinto, P Linehan, WM Merino, MJ AF Vicens, J. Pinto, P. Linehan, W. M. Merino, M. J. TI Percutaneous Core Needle Biopsy; a Helpful Tool in the Diagnosis of Hereditary Kidney Tumors SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 [Vicens, J.; Pinto, P.; Linehan, W. M.; Merino, M. J.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 907 BP 200A EP 200A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371500908 ER PT J AU Bechert, CJ Shively, SB Yuldasheva, N Glasker, S Vortmeyer, A AF Bechert, C. J. Shively, S. B. Yuldasheva, N. Glasker, S. Vortmeyer, A. TI VHL Deficiency in the Female Genital Tract SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Univ Texas Med Branch, Galveston, TX USA. NINDS, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. Univ Freiburg, Freiburg, Germany. Yale Univ, Sch Med, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 SU 1 MA 941 BP 207A EP 207A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371500942 ER PT J AU Castellar, ERP Merino, MJ Diaz-Montes, TP AF Castellar, E. R. Parrilla Merino, M. J. Diaz-Montes, T. P. TI Cross-Sectional Study of Ovarian Tumors among Hispanic Women Living in the United States SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 [Castellar, E. R. Parrilla; Merino, M. J.; Diaz-Montes, T. P.] NIH, Bethesda, MD 20892 USA. [Castellar, E. R. Parrilla; Merino, M. J.; Diaz-Montes, T. P.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 1052 BP 231A EP 231A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371501053 ER PT J AU Garcia, A Villamor, N Gaulard, P Jaffe, E Campo, E Martinez, A AF Garcia, A. Villamor, N. Gaulard, P. Jaffe, E. Campo, E. Martinez, A. TI Characterization of TCR delta Expression in Paraffin Embedded Tissue Sections: A New Diagnostic Tool for gamma delta T-Cell Lymphomas SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Hosp Clin Barcelona, Barcelona, Spain. Hosp Henri Mondor, Creteil, France. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 1195 BP 263A EP 263A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371501196 ER PT J AU Kovach, AE Humsi, MK Jaffe, ES Calvo, KR AF Kovach, A. E. Humsi, M. K. Jaffe, E. S. Calvo, K. R. TI Basal Activation of NFkB Protein Signaling Pathway in Follicular Lymphoma In Vivo SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 [Kovach, A. E.; Humsi, M. K.; Jaffe, E. S.; Calvo, K. R.] NCI, NIH, Bethesda, MD 20892 USA. RI Calvo, Katherine/A-8109-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 BP 273A EP 273A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371501239 ER PT J AU Maric, I Giri, N Arthur, D Noel, P Alter, BP AF Maric, I. Giri, N. Arthur, D. Noel, P. Alter, B. P. TI Distinct Patterns of Marrow Fibrosis in Patients with Inherited Bone Marrow Failure Syndromes SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 CC NIH, Bethesda, MD USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 1254 BP 276A EP 276A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371501254 ER PT J AU Meyer, PN Weisenburger, DD Choi, WL Smith, LM Greiner, TC Aoun, P Delabie, J Braziel, RM Vose, JM Lenz, G Staudt, LM Chan, WC Fu, K AF Meyer, P. N. Weisenburger, D. D. Choi, W. L. Smith, L. M. Greiner, T. C. Aoun, P. Delabie, J. Braziel, R. M. Vose, J. M. Lenz, G. Staudt, L. M. Chan, W. C. Fu, K. TI LMO2 Expression and the Hans Algorithm in Predicting Germinal Center Phenotype and Survival in Diffuse Large B-Cell Lymphoma Treated with Rituximab SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Univ Nebraska Med Ctr, Omaha, NE USA. Univ Hong Kong, Fac Med, Hong Kong, Hong Kong, Peoples R China. Univ Oslo, Med Ctr, Oslo, Norway. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 1258 BP 277A EP 277A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371501258 ER PT J AU Schrager, JA Pittaluga, S Raffeld, M Jaffe, ES AF Schrager, J. A. Pittaluga, S. Raffeld, M. Jaffe, E. S. TI EBV Reactivation Syndromes in Adults without Known Immunodeficiency SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 [Schrager, J. A.; Pittaluga, S.; Raffeld, M.; Jaffe, E. S.] NCI, Bethesda, MD 20892 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 1291 BP 285A EP 285A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371501291 ER PT J AU Slotta-Huspenina, J Koch, I De Leval, L Keller, G Bink, K Kremer, M Raffeld, M Fend, F Quintanilla-Martinez, L AF Slotta-Huspenina, J. Koch, I. De Leval, L. Keller, G. Bink, K. Kremer, M. Raffeld, M. Fend, F. Quintanilla-Martinez, L. TI High Proliferation Rate in Mantle Cell Lymphoma Is Associated with p53 Mutations and Blastoid Morphology, but Not with 3 ' UTR Deficient Cyclin D1 mRNA or High Total Cyclin D1 mRNA Levels SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Tech Univ Munich, Inst Pathol, Munich, Germany. Helmholtz Ctr Munich, Inst Pathol, Munich, Germany. Univ Tubingen, Inst Pathol 3, Tubingen, Germany. Univ Liege, Liege, Belgium. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 1298 BP 287A EP 287A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371501298 ER PT J AU Taylor, J Huang, W Facchetti, F Jaffe, E Chang, C AF Taylor, J. Huang, W. Facchetti, F. Jaffe, E. Chang, C. TI Genomic Profiling of Plasmablastic Lymphoma Using BAC Array CGH - Revealing Significant Overlapping Genomic Lesions with DLBCL SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 Methodist Hosp TMHRI, Houston, TX USA. Chang Gung Mem Hosp, Kaohsiung, Taiwan. Univ Brescia, Brescia, Italy. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 1303 BP 288A EP 288A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371501303 ER PT J AU Mani, H Saxena, R Hoofnagle, JH Kleiner, DE AF Mani, H. Saxena, R. Hoofnagle, J. H. Kleiner, D. E. TI Temporal Evolution of Amoxicillin-Clavulanate Induced Liver Injury SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 NCI, NIH, Bethesda, MD 20892 USA. Indiana Univ, Indianapolis, IN 46204 USA. NIDDK, NIH, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 1430 BP 316A EP 316A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371501429 ER PT J AU Galli, S Li, G Ren, Y Tsokos, M AF Galli, S. Li, G. Ren, Y. Tsokos, M. TI Expression of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) Receptor DR5 in Ewing Sarcoma Family Tumors (ESFT) SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 [Galli, S.; Li, G.; Ren, Y.; Tsokos, M.] NIH, NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 SU 1 MA 1569 BP 346A EP 346A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371501568 ER PT J AU Galli, S Perlman, E Tsokos, M AF Galli, S. Perlman, E. Tsokos, M. TI Survivin, Bcl-2 and Caspase 8 Expression in Wilms Tumors with Favorable Histology Does Not Correlate with Clinical Stage SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 NIH, NCI, Bethesda, MD 20892 USA. Childrens Mem Med Ctr, Chicago, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 SU 1 MA 1568 BP 346A EP 346A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371501567 ER PT J AU Valera, VA Walter, BA Linehan, WM Sobel, ME Merino, MJ AF Valera, V. A. Walter, B. A. Linehan, W. M. Sobel, M. E. Merino, M. J. TI microRNA Regulation of VHL Gene in Clear Cell Renal Cell Carcinomas SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 NCI, Bethesda, MD 20892 USA. Amer Soc Invest Pathol, Bethesda, MD USA. 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 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 1709 BP 377A EP 377A PG 1 WC Pathology SC Pathology GA 393KF UT WOS:000262371501707 ER PT J AU Osman, JM Fliedner, SL Abu-Asah, M Pacak, K Tsokos, M AF Osman, J. M. Fliedner, S. L. Abu-Asah, M. Pacak, K. Tsokos, M. TI Unique Ultrastructural Features in Pheochromocytoma from Patients with Mutations in the Succinate Dehydrogenase B and D Genes SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol C1 [Osman, J. M.; Fliedner, S. L.; Abu-Asah, M.; Pacak, K.; Tsokos, M.] NIH, Bethesda, MD 20892 USA. RI Fliedner, Stephanie/D-3406-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2009 VL 22 MA 1779 BP 392A EP 393A PG 2 WC Pathology SC Pathology GA 393KF UT WOS:000262371501777 ER PT J AU Solier, S Sordet, O Kohn, KW Pommier, Y AF Solier, Stephanie Sordet, Olivier Kohn, Kurt W. Pommier, Yves TI Death Receptor-Induced Activation of the Chk2-and Histone H2AX-Associated DNA Damage Response Pathways SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DEPENDENT PROTEIN-KINASE; DOUBLE-STRAND BREAKS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; INDUCED APOPTOSIS; GENOMIC INSTABILITY; CANCER-CELLS; H2AX PHOSPHORYLATION; APO2 LIGAND/TRAIL; INHIBITOR NU7441; TUMOR-SUPPRESSOR AB TRAIL is an endogenous death receptor ligand also used therapeutically because of its selective proapoptotic activity in cancer cells. In the present study, we examined chromatin alterations induced by TRAIL and show that TRAIL induces a rapid activation of DNA damage response (DDR) pathways with histone H2AX, Chk2, ATM, and DNA-PK phosphorylations. Within 1 h of TRAIL exposure, immunofluorescence confocal microscopy revealed gamma-H2AX peripheral nuclear staining (gamma-H2AX ring) colocalizing with phosphorylated/activated Chk2, ATM, and DNA-PK inside heterochromatin regions. The marginal distribution of DDR proteins in early apoptotic cells is remarkably different from the focal staining seen after DNA damage. TRAIL-induced DDR was suppressed upon caspase inhibition or Bax inactivation, demonstrating that the DDR activated by TRAIL is downstream from the mitochondrial death pathway. H2AX phosphorylation was dependent on DNA-PK, while Chk2 phosphorylation was dependent on both ATM and DNA-PK. Downregulation of Chk2 decreased TRAIL-induced cell detachment; delayed the activation of caspases 2, 3, 8, and 9; and reduced TRAIL-induced cell killing. Together, our findings suggest that nuclear activation of Chk2 by TRAIL acts as a positive feedback loop involving the mitochondrion-dependent activation of caspases, independently of p53. C1 [Solier, Stephanie; Sordet, Olivier; Kohn, Kurt W.; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Pommier, Y (reprint author), NIH, Bldg 37,Room 5068, Bethesda, MD 20892 USA. EM pommier@nih.gov RI Sordet, Olivier/M-3271-2014 FU NIH; National Cancer Institute; Center for Cancer Research FX This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 67 TC 53 Z9 58 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN 1 PY 2009 VL 29 IS 1 BP 68 EP 82 DI 10.1128/MCB.00581-08 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 383TW UT WOS:000261697500005 PM 18955500 ER PT J AU Ramsden, C Holmes, EC Charleston, MA AF Ramsden, Cadhla Holmes, Edward C. Charleston, Michael A. TI Hantavirus Evolution in Relation to Its Rodent and Insectivore Hosts: No Evidence for Codivergence SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article ID ENVELOPE GLYCOPROTEINS G1; TO-PERSON TRANSMISSION; SIN-NOMBRE-VIRUS; PULMONARY SYNDROME; GENETIC DIVERSITY; MOLECULAR EVOLUTION; PARASITE PHYLOGENIES; NUCLEOCAPSID PROTEIN; THOTTAPALAYAM VIRUS; BORNE HANTAVIRUSES AB Hantaviruses are considered one of the best examples of a long-term association between RNA viruses and their hosts. Based on the appearance of strong host specificity, it has been suggested that hantaviruses cospeciated with the rodents and insectivores they infect since these mammals last shared a common ancestor, approximately 100 million years ago. We tested this hypothesis of host-virus codivergence in two ways: 1) we used cophylogenetic reconciliation analysis to assess the fit of the virus tree onto that of the host and 2) we estimated the evolutionary rates and divergence times for the Hantavirus genus using a Bayesian Markov Chain Monte Carlo method and similarly compared these with those of their hosts. Our reconciliation analysis provided no evidence for a history of codivergence between hantaviruses and their hosts. Further, the divergence times for the Hantavirus genus were many orders of magnitude too recent to correspond with the timescale of their hosts' speciation. We therefore propose that apparent similarities between the phylogenies of hantaviruses and their mammalian hosts are the result of a more recent history of preferential host switching and local adaptation. Based on the presence of clade-defining amino acids in all genomic segments, we propose that the patterns of amino acid replacement in these viruses are also compatible with a history of host-specific adaptation. C1 [Ramsden, Cadhla; Holmes, Edward C.] Penn State Univ, Ctr Infect Dis Dynam, Dept Biol, Mueller Lab, University Pk, PA 16802 USA. [Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Charleston, Michael A.] Univ Sydney, Sch Informat Technol, Sydney, NSW 2006, Australia. [Charleston, Michael A.] Univ Sydney, Ctr Math Biol, Sydney, NSW 2006, Australia. RP Ramsden, C (reprint author), Penn State Univ, Ctr Infect Dis Dynam, Dept Biol, Mueller Lab, University Pk, PA 16802 USA. EM cbr134@psu.edu OI Holmes, Edward/0000-0001-9596-3552 FU Natural Sciences and Engineering Research Council (Canada) FX Natural Sciences and Engineering Research Council (Canada) to C. R. NR 74 TC 111 Z9 111 U1 1 U2 26 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 JAN PY 2009 VL 26 IS 1 BP 143 EP 153 DI 10.1093/molbev/msn234 PG 11 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 383OC UT WOS:000261681900014 PM 18922760 ER PT S AU Cho, H Kehrl, JH AF Cho, Hyeseon Kehrl, John H. BE Fisher, RA TI Regulation of Immune Function by G Protein-Coupled Receptors, Trimeric G Proteins, and RGS Proteins SO MOLECULAR BIOLOGY OF RGS PROTEINS SE Progress in Molecular Biology and Translational Science LA English DT Review; Book Chapter ID G-BETA-GAMMA; NUCLEOTIDE EXCHANGE FACTOR; HETEROTRIMERIC G-PROTEINS; BRUTONS TYROSINE KINASE; T-CELL-ACTIVATION; LEUCINE-ZIPPER PROTEIN; N-TERMINAL KINASE; FAMILY G-PROTEINS; ZONE B-CELLS; DENDRITIC CELLS AB Receptors for chemokines and a variety of ligands such as histamine, nucleosides, and bioactive lipids signal through heterotrimeric G proteins and play critical roles in immune function. Heterotrimeric G protein signaling pathways are subjected to many layers of regulation including regulators of G protein signaling (RGS) proteins that mainly function to attenuate these signaling pathways. This review focuses on the overall importance of G protein-coupled receptor-heterotrimeric G protein-RGS protein signaling in immune function with emphasis on lymphocyte trafficking and motility. Considerable portion is devoted to discussing mechanisms by which chemoattractant receptors activate downstream signaling pathways that function during leukocyte migration. Studies using intravital imaging techniques to monitor lymphocyte trafficking and motility as well as ones probing intracellular spatiotemporal dynamics of trimeric signaling components are also discussed as they increasingly provide mechanistic insights into trimeric G protein signaling networks. C1 [Cho, Hyeseon; Kehrl, John H.] NIAID, B Cell Mol Immunol Sect, Immunoregulat Lab, Bethesda, MD 20892 USA. RP Cho, H (reprint author), NIAID, B Cell Mol Immunol Sect, Immunoregulat Lab, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 273 TC 22 Z9 22 U1 1 U2 6 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1877-1173 BN 978-0-12-374759-4 J9 PROG MOL BIOL TRANSL JI Prog. Molec. Biol. Transl. Sci. PY 2009 VL 86 BP 249 EP 298 PG 50 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BBJ04 UT WOS:000307008500010 PM 20374719 ER PT J AU Lee, HS Mood, K Battu, G Ji, YJ Singh, A Daar, IO AF Lee, Hyun-Shik Mood, Kathleen Battu, Gopala Ji, Yon Ju Singh, Arvinder Daar, Ira O. TI Fibroblast Growth Factor Receptor-induced Phosphorylation of EphrinB1 Modulates Its Interaction with Dishevelled SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID XENOPUS EMBRYOS; EPH RECEPTORS; TYROSINE PHOSPHORYLATION; TRANSMEMBRANE LIGANDS; MOUSE GASTRULATION; FORMATION REQUIRE; CELL-MIGRATION; RETINAL FATE; EYE FIELD; FGF AB The Eph family of receptor tyrosine kinases and their membrane-bound ligands, the ephrins, have been implicated in regulating cell adhesion and migration during development by mediating cell-to-cell signaling events. The transmembrane ephrinB1 protein is a bidirectional signaling molecule that signals through its cytoplasmic domain to promote cellular movements into the eye field, whereas activation of the fibroblast growth factor receptor (FGFR) represses these movements and retinal fate. In Xenopus embryos, ephrinB1 plays a role in retinal progenitor cell movement into the eye field through an interaction with the scaffold protein Dishevelled (Dsh). However, the mechanism by which the FGFR may regulate this cell movement is unknown. Here, we present evidence that FGFR-induced repression of retinal fate is dependent upon phosphorylation within the intracellular domain of ephrinB1. We demonstrate that phosphorylation of tyrosines 324 and 325 disrupts the ephrinB1/Dsh interaction, thus modulating retinal progenitor movement that is dependent on the planar cell polarity pathway. These results provide mechanistic insight into how fibroblast growth factor signaling modulates ephrinB1 control of retinal progenitor movement within the eye field. C1 [Lee, Hyun-Shik; Mood, Kathleen; Battu, Gopala; Ji, Yon Ju; Singh, Arvinder; Daar, Ira O.] Natl Canc Inst, Lab Cell & Dev Signaling, Ft Detrick, MD 21702 USA. RP Daar, IO (reprint author), Natl Canc Inst, Lab Cell & Dev Signaling, Ft Detrick, MD 21702 USA. EM daar@ncifcrf.gov RI Lee, Hyun-Shik/G-3555-2011 FU National Institutes of Health; National Cancer Institute FX We thank J. Miller for the GFP-Dsh construct. We also thank Sally Moody, J. Acharya, and S. Sharan for helpful discussions. This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. NR 46 TC 29 Z9 30 U1 0 U2 0 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 JAN PY 2009 VL 20 IS 1 BP 124 EP 133 DI 10.1091/mbc.E08-06-0662 PG 10 WC Cell Biology SC Cell Biology GA 389ZT UT WOS:000262134800012 PM 19005214 ER PT J AU Taguchi, Y Shi, ZD Ruddy, B Dorward, DW Greene, L Baron, GS AF Taguchi, Yuzuru Shi, Zhen-Dan Ruddy, Brian Dorward, David W. Greene, Lois Baron, Gerald S. TI Specific Biarsenical Labeling of Cell Surface Proteins Allows Fluorescent- and Biotin-tagging of Amyloid Precursor Protein and Prion Proteins SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID TETRACYSTEINE-TAGGED PROTEINS; SCRAPIE-ASSOCIATED FORM; LIVING CELLS; TRANSGENIC MICE; FULL-LENGTH; LIVE CELLS; IN-VITRO; PRP; PROPAGATION; STRAINS AB Fluorescent tagging is a powerful tool for imaging proteins in living cells. However, the steric effects imposed by fluorescent tags impair the behavior of many proteins. Here, we report a novel technique, Instant with DTT, EDT, And Low temperature (IDEAL)-labeling, for rapid and specific FlAsH-labeling of tetracysteine-tagged cell surface proteins by using prion protein (PrP) and amyloid precursor protein (APP) as models. In prion-infected cells, FlAsH-labeled tetracysteine-tagged PrP converted from the normal isoform (PrPsen) to the disease-associated isoform (PrPres), suggesting minimal steric effects of the tag. Pulse-chase analysis of PrP and APP by fluorescent gel imaging demonstrated the utility of IDEAL labeling in investigating protein metabolism by identifying an as-yet-unrecognized C-terminal fragment (C3) of PrPsen and by characterizing the kinetics of PrPres and APP metabolism. C3 generation and N-terminal truncation of PrPres were inhibited by the anti-prion compound E64, a cysteine protease inhibitor. Surprisingly, E64 did not inhibit the synthesis of new PrPres, providing insight into the mechanism by which E64 reduces steady-state PrPres levels in prion-infected cells. To expand the versatility of tetracysteine tagging, we created new Alexa Fluor- and biotin-conjugated tetracysteine-binding molecules that were applied to imaging PrP endocytosis and ultrastructural localization. IDEAL-labeling extends the use of biarsenical derivatives to extracellular proteins and beyond microscopic imaging. C1 [Taguchi, Yuzuru; Baron, Gerald S.] NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. [Shi, Zhen-Dan; Ruddy, Brian] NIAID, Rocky Mt Labs, Res Technol Branch, NIH, Hamilton, MT 59840 USA. [Shi, Zhen-Dan; Ruddy, Brian] NHLBI, Imaging Probe Dev Ctr, NIH, Bethesda, MD 20892 USA. [Greene, Lois] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Baron, GS (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. EM gbaron@niaid.nih.gov FU National Institutes of Health FX We thank Lynne and Greg Raymond, Danielle Offerdahl, and Lindsay Hohsfield for technical support. We thank Ted Hackstadt for access to the Typhoon instrument, Dennis Burton and Anthony Williamson for providing R1 antibody, and Gary Griffiths for overseeing the synthesis of the new biarsenical molecules. We are grateful to Evan Eisenberg, Byron Caughey, Bruce Chesebro, Suzette A. Priola, John Portis, and Valerie Sim for critical reading and helpful advice. This research was supported by the Intramural Research Program of the National Institutes of Health (National Institute of Allergy and Infectious Diseases and the Imaging Probe Development Center, National Heart Lung and Blood Institute). NR 48 TC 33 Z9 33 U1 1 U2 8 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 JAN PY 2009 VL 20 IS 1 BP 233 EP 244 DI 10.1091/mbc.E08-06-0635 PG 12 WC Cell Biology SC Cell Biology GA 389ZT UT WOS:000262134800022 PM 18987338 ER PT J AU Sason, H Milgrom, M Weiss, AM Melamed-Book, N Balla, T Grinstein, S Backert, S Rosenshine, I Aroeti, B AF Sason, Hagit Milgrom, Michal Weiss, Aryeh M. Melamed-Book, Naomi Balla, Tamas Grinstein, Sergio Backert, Steffen Rosenshine, Ilan Aroeti, Benjamin TI Enteropathogenic Escherichia coli Subverts Phosphatidylinositol 4,5-Bisphosphate and Phosphatidylinositol 3,4,5-Trisphosphate upon Epithelial Cell Infection SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID ACTIN PEDESTAL FORMATION; TRANSLOCATED INTIMIN RECEPTOR; PLECKSTRIN HOMOLOGY DOMAINS; BUNDLE-FORMING PILI; PLASMA-MEMBRANE; ALPHA-ACTININ; N-WASP; BACTERIAL PATHOGENS; SIGNAL-TRANSDUCTION; LIPID RAFTS AB Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P(2)] and phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P(3)] are phosphoinositides (PIs) present in small amounts in the inner leaflet of the plasma membrane (PM) lipid bilayer of host target cells. They are thought to modulate the activity of proteins involved in enteropathogenic Escherichia coli (EPEC) infection. However, the role of PI(4,5)P(2) and PI(3,4,5)P(3) in EPEC pathogenesis remains obscure. Here we show that EPEC induces a transient PI(4,5)P(2) accumulation at bacterial infection sites. Simultaneous actin accumulation, likely involved in the construction of the actin-rich pedestal, is also observed at these sites. Acute PI(4,5)P(2) depletion partially diminishes EPEC adherence to the cell surface and actin pedestal formation. These findings are consistent with a bimodal role, whereby PI(4,5)P(2) contributes to EPEC association with the cell surface and to the maximal induction of actin pedestals. Finally, we show that EPEC induces PI(3,4,5)P(3) clustering at bacterial infection sites, in a translocated intimin receptor (Tir)dependent manner. Tir phosphorylated on tyrosine 454, but not on tyrosine 474, forms complexes with an active phosphatidylinositol 3-kinase (PI3K), suggesting that PI3K recruited by Tir prompts the production of PI(3,4,5)P(3) beneath EPEC attachment sites. The functional significance of this event may be related to the ability of EPEC to modulate cell death and innate immunity. C1 [Sason, Hagit; Milgrom, Michal; Aroeti, Benjamin] Hebrew Univ Jerusalem, Dept Cell & Anim Biol, IL-91904 Jerusalem, Israel. [Weiss, Aryeh M.; Melamed-Book, Naomi] Hebrew Univ Jerusalem, Confocal Unit, Inst Life Sci, IL-91904 Jerusalem, Israel. [Weiss, Aryeh M.] Bar Ilan Univ, Sch Engn, IL-52900 Ramat Gan, Israel. [Balla, Tamas] NICHHD, Sect Mol Signal Transduct, NIH, Bethesda, MD 20892 USA. [Grinstein, Sergio] Hosp Sick Children, Cell Biol Program, Toronto, ON M5G 1X8, Canada. [Backert, Steffen] Univ Coll Dublin, Sch Biomol & Biomed Sci, Dublin 4, Ireland. [Rosenshine, Ilan] Hebrew Univ Jerusalem, Fac Med, Dept Mol Genet & Biotechnol, IL-91120 Jerusalem, Israel. RP Aroeti, B (reprint author), Hebrew Univ Jerusalem, Dept Cell & Anim Biol, IL-91904 Jerusalem, Israel. EM aroeti@cc.huji.ac.il OI Balla, Tamas/0000-0002-9077-3335 FU Israel Science Foundation [626/04, 1167/08]; Ministry of Health FX We are especially indebted to Dr. Julieta Leyt and Shulamit Cohen for consultation and advise. We also thank Dr. Sharon Eden ( Hebrew University, Medical School) for contributing the GFP-actin construct. This work was supported by grants from the Israel Science Foundation ( I. R.), and by the Israel Science Foundation Grants 626/04 and 1167/08 and a grant from the Ministry of Health ( B. A.); I. R. is the Etta Rosensohn Professor of Bacteriology. NR 96 TC 34 Z9 34 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 JAN PY 2009 VL 20 IS 1 BP 544 EP 555 DI 10.1091/mbc.E08-05-0516 PG 12 WC Cell Biology SC Cell Biology GA 389ZT UT WOS:000262134800049 PM 18987340 ER PT J AU Tsai, CJ Del Sol, A Nussinov, R AF Tsai, Chung-Jung Del Sol, Antonio Nussinov, Ruth TI Protein allostery, signal transmission and dynamics: a classification scheme of allosteric mechanisms SO MOLECULAR BIOSYSTEMS LA English DT Editorial Material ID PDZ DOMAIN PROTEIN; STRUCTURAL DETERMINANTS; PLAUSIBLE MODEL; BINDING; NETWORKS; COOPERATIVITY; ACTIVATION; PATHWAYS; SITE; COMMUNICATION AB Allostery has come of age; the number, breadth and functional roles of documented protein allostery cases are rising quickly. Since all dynamic proteins are potentially allosteric and allostery plays crucial roles in all cellular pathways, sorting and classifying allosteric mechanisms in proteins should be extremely useful in understanding and predicting how the signals are regulated and transmitted through the dynamic multi-molecular cellular organizations. Classification organizes the complex information thereby unraveling relationships and patterns in molecular activation and repression. In signaling, current classification schemes consider classes of molecules according to their functions; for example, epinephrine and norepinephrine secreted by the central nervous system are classified as neurotransmitters. Other schemes would account for epinephrine when secreted by the adrenal medulla to be hormone-like. Yet, such classifications account for the global function of the molecule; not for the molecular mechanism of how the signal transmission initiates and how it is transmitted. Here we provide a unified view of allostery and the first classification framework. We expect that a classification scheme would assist in comprehension of allosteric mechanisms, in prediction of signaling on the molecular level, in better comprehension of pathways and regulation of the complex signals, in translating them to the cascading events, and in allosteric drug design. We further provide a range of examples illustrating mechanisms in protein allostery and their classification from the cellular functional standpoint. C1 [Tsai, Chung-Jung; Nussinov, Ruth] NCI, Basic Res Program, SAIC Frederick, Ctr Canc Res,Neurobiol Program, Frederick, MD 21702 USA. [Del Sol, Antonio] Fujirebio Inc, Div Res & Dev, Bioinformat Res Unit, Hachioji, Tokyo 1920031, Japan. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Del Sol, A (reprint author), Almendro 8, Madrid 28005, Spain. EM antdelsol@gmail.com; ruthn@ncifcrf.gov FU NCI NIH HHS [N01CO12400] NR 51 TC 195 Z9 197 U1 0 U2 32 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1742-206X J9 MOL BIOSYST JI Mol. Biosyst. PY 2009 VL 5 IS 3 BP 207 EP 216 DI 10.1039/b819720b PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 408WW UT WOS:000263467300001 PM 19225609 ER PT J AU Balaji, S Iyer, LM Aravind, L AF Balaji, S. Iyer, Lakshminarayan M. Aravind, L. TI HPC2 and ubinuclein define a novel family of histone chaperones conserved throughout eukaryotes SO MOLECULAR BIOSYSTEMS LA English DT Article ID ASSEMBLY FACTOR-I; MYOCYTE ENHANCER FACTOR-2; SYNDROME CRITICAL REGION; SACCHAROMYCES-CEREVISIAE; HIR PROTEINS; TRANSCRIPTIONAL REPRESSORS; FUNCTIONAL DISSECTION; STRUCTURE PREDICTION; CHROMATIN-STRUCTURE; COMPLEX AB While histone chaperones have been intensely studied, the roles of components of the Hir-Asfl histone chaperone complex such as Hir3p and Hpc2p are poorly understood. Using sensitive protein sequence profile analyses we investigated the evolution of these proteins and showed that Hir3p and Hpc2p have a much wider phyletic pattern than was previously known. We established the animal histone-deacetylase-complex-interacting proteins, CAIN/CABIN, to be orthologs of Hir3p. They contain a conserved core of around 30 TPR-like bi-helical repeats that are likely to form a super-helical scaffold. We identified a conserved domain, the HUN domain, in all Hpc2p homologs, including animal ubinuclein/yemanuclein and the recently discovered vertebrate cell-cycle regulator FLJ25778. The HUN domain has a characteristic pattern of conserved acidic residues based on which we predict that it is a previously unrecognized histone-tail-binding chaperone. By analyzing various high-throughput data sets, such as RNAi knock-downs, genetic and protein interaction maps and cell-cycle-specific gene expression data, we present evidence that Hpc2p homologs might be deployed in specific processes of chromatin dynamics relating to cell-cycle progression in vertebrates and schizogony in Plasmodium. Beyond the conserved HUN domain these proteins show extensive divergence patterns in different eukaryotic lineages. Hence, we propose that Hpc2p homologs are probably involved in recruitment of the ancient conserved histone-loading Hir-Asfl complex to different lineage-specific chromatin reorganization processes. C1 [Balaji, S.; Iyer, Lakshminarayan M.; Aravind, L.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Balaji, S (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM sbalaji@mail.nih.gov FU Intramural research program of National Institutes of Health, USA FX SB, LMI and LA acknowledge the Intramural research program of National Institutes of Health, USA for funding their research. NR 66 TC 35 Z9 35 U1 1 U2 2 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1742-206X J9 MOL BIOSYST JI Mol. Biosyst. PY 2009 VL 5 IS 3 BP 269 EP 275 DI 10.1039/b816424j PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 408WW UT WOS:000263467300010 PM 19225618 ER PT J AU Johnson, RL Huang, RL Jadhav, A Southall, N Wichterman, J MacArthur, R Xia, MH Bi, K Printen, J Austin, CP Inglese, J AF Johnson, Ronald L. Huang, Ruili Jadhav, Ajit Southall, Noel Wichterman, Jennifer MacArthur, Ryan Xia, Menghang Bi, Kun Printen, John Austin, Christopher P. Inglese, James TI A quantitative high-throughput screen for modulators of IL-6 signaling: a model for interrogating biological networks using chemical libraries SO MOLECULAR BIOSYSTEMS LA English DT Article ID BETA-LACTAMASE; CANCER CELLS; RECEPTOR EXPRESSION; CARCINOMA CELLS; IN-VITRO; JAK-STAT; INTERLEUKIN-6; ASSAYS; REPORTER; IDENTIFICATION AB Small molecule modulators are critical for dissecting and understanding signaling pathways at the molecular level. Interleukin 6 (IL-6) is a cytokine that signals via the JAK-STAT pathway and is implicated in cancer and inflammation. To identify modulators of this pathway, we screened a chemical collection against an IL-6 responsive cell line stably expressing a beta-lactamase reporter gene fused to a sis-inducible element (SIE-bla cells). This assay was optimized for a 1536-well microplate format and screened against 11 693 small molecules using quantitative high-throughput screening (qHTS), a method that assays a chemical library at multiple concentrations to generate titration-response profiles for each compound. The qHTS recovered 564 actives with well-fit curves that clustered into 32 distinct chemical series of 13 activators and 19 inhibitors. A retrospective analysis of the qHTS data indicated that single concentration data at 1.5 and 7.7 mu M scored 35 and 71% of qHTS actives, respectively, as inactive and were therefore false negatives. Following counter screens to identify fluorescent and non-selective series, we found four activator and one inhibitor series that modulated SIE-bla cells but did not show similar activity in reporter gene assays induced by EGF and hypoxia. Small molecules within these series will make useful tool compounds to investigate IL-6 signaling mediated by JAK-STAT activation. C1 [Johnson, Ronald L.; Huang, Ruili; Jadhav, Ajit; Southall, Noel; Wichterman, Jennifer; MacArthur, Ryan; Xia, Menghang; Austin, Christopher P.; Inglese, James] NIH, Chem Genom Ctr, Bethesda, MD 20892 USA. [Bi, Kun; Printen, John] Invitrogen Discovery Sci Madison, Madison, WI 53719 USA. RP Johnson, RL (reprint author), NIH, Chem Genom Ctr, Bldg 10, Bethesda, MD 20892 USA. EM rjohnso2@mail.nih.gov RI Southall, Noel/H-8991-2012 OI Southall, Noel/0000-0003-4500-880X FU National Human Genome Research Institute, National Institutes of Health FX We gratefully acknowledge Sam Michael and Carleen Klumpp for automation assistance, Paul Shinn and Adam Yasgar for compound management, Anton Simeonov for critical reading of the manuscript and Dr Craig Thomas for helpful discussions. This research was supported by the NIH Roadmap for Medical Research and the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. NR 48 TC 10 Z9 10 U1 0 U2 1 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1742-206X EI 1742-2051 J9 MOL BIOSYST JI Mol. Biosyst. PY 2009 VL 5 IS 9 BP 1039 EP 1050 DI 10.1039/b902021g PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 482KE UT WOS:000268886000022 PM 19668870 ER PT J AU Kamrava, M Bernstein, MB Camphausen, K Hodge, JW AF Kamrava, Mitchell Bernstein, Michael B. Camphausen, Kevin Hodge, James W. TI Combining radiation, immunotherapy, and antiangiogenesis agents in the management of cancer: the Three Musketeers or just another quixotic combination? SO MOLECULAR BIOSYSTEMS LA English DT Review ID ENDOTHELIAL GROWTH-FACTOR; RENAL-CELL CARCINOMA; TYROSINE KINASE INHIBITOR; TUMOR-SUPPRESSOR GENE; PHASE-II TRIAL; METASTATIC COLORECTAL-CANCER; FACTOR RECEPTOR-2 BLOCKADE; ANTI-VEGF THERAPY; DENDRITIC CELLS; IMMUNE-SYSTEM AB With the advent of new cancer therapies in the last few years, the goals of reducing disease burden and improving quality of life are frequently achieved. Yet despite the advances seen with numerous monotherapies, a multimodality approach that targets different aspects of tumor biology may yield the greatest clinical benefit for patients with late-stage disease. Many such strategies have been employed with varying degrees of success. The addition of immunotherapy to standard-of-care radiation therapy has shown evidence of efficacy in some preclinical models and in the clinical setting. However, exploiting these two modalities safely and effectively remains an ongoing challenge. It is feasible that the addition of another therapeutic modality could further enhance the antitumor effects of these treatments. The recent addition of angiogenesis inhibitors to the cancer treatment armamentarium represents an attractive option, especially since these agents have been shown to be most effective when combined with other therapies. This review examines preclinical and clinical data on the interaction between immunotherapy and radiation, and discusses the potential synergy between these two modalities and angiogenesis inhibitors. C1 [Bernstein, Michael B.; Hodge, James W.] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Kamrava, Mitchell; Camphausen, Kevin] NCI, Dept Radiat Oncol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Hodge, JW (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, 10 Ctr Dr,Room 8B13, Bethesda, MD 20892 USA. EM hodgej@mail.nih.gov RI Hodge, James/D-5518-2015 OI Hodge, James/0000-0001-5282-3154 NR 95 TC 28 Z9 28 U1 0 U2 5 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1742-206X J9 MOL BIOSYST JI Mol. Biosyst. PY 2009 VL 5 IS 11 BP 1262 EP 1270 DI 10.1039/b911313b PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 506GC UT WOS:000270761400001 PM 19823740 ER PT J AU Alford, R Ogawa, M Choyke, PL Kobayashi, H AF Alford, Raphael Ogawa, Mikako Choyke, Peter L. Kobayashi, Hisataka TI Molecular probes for the in vivo imaging of cancer SO MOLECULAR BIOSYSTEMS LA English DT Review ID POSITRON-EMISSION-TOMOGRAPHY; CELL LUNG-CANCER; FLUORESCENCE LIFETIME SPECTROSCOPY; NON-HODGKINS-LYMPHOMA; MAGNETIC-RESONANCE; FDG-PET; BREAST-CANCER; ESOPHAGEAL CANCER; OVARIAN-CANCER; F-18-FLT PET AB Advancements in medical imaging have brought about unprecedented changes in the in vivo assessment of cancer. Positron emission tomography, single photon emission computed tomography, optical imaging, and magnetic resonance imaging are the primary tools being developed for oncologic imaging. These techniques may still be in their infancy, as recently developed chemical molecular probes for each modality have improved in vivo characterization of physiologic and molecular characteristics. Herein, we discuss advances in these imaging techniques, and focus on the major design strategies with which molecular probes are being developed. C1 [Alford, Raphael; Ogawa, Mikako; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Alford, Raphael] Case Western Reserve Sch Med, Cleveland, OH USA. RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bldg 10,Room 1B40,MSC1088, Bethesda, MD 20892 USA. EM kobayash@mail.nih.gov FU Intramural Research Program of the NIH; National Cancer Institute, Center for Cancer Research FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 136 TC 39 Z9 40 U1 0 U2 11 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1742-206X J9 MOL BIOSYST JI Mol. Biosyst. PY 2009 VL 5 IS 11 BP 1279 EP 1291 DI 10.1039/b911307j PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 506GC UT WOS:000270761400003 PM 19823742 ER PT J AU Iyer, LM Abhiman, S Burroughs, AM Aravind, L AF Iyer, Lakshminarayan M. Abhiman, Saraswathi Burroughs, A. Maxwell Aravind, L. TI Amidoligases with ATP-grasp, glutamine synthetase-like and acetyltransferase-like domains: synthesis of novel metabolites and peptide modifications of proteins SO MOLECULAR BIOSYSTEMS LA English DT Review ID PUTRESCINE UTILIZATION PATHWAY; BIOSYNTHETIC GENE-CLUSTER; UBIQUITIN-LIKE PROTEINS; ESCHERICHIA-COLI K-12; COMPARATIVE GENOMICS; STRUCTURE PREDICTION; CRYSTAL-STRUCTURE; SULFUR TRANSFER; POSTTRANSLATIONAL MODIFICATION; MYCOBACTERIUM-TUBERCULOSIS AB Recent studies have shown that the ubiquitin system had its origins in ancient cofactor/amino acid biosynthesis pathways. Preliminary studies also indicated that conjugation systems for other peptide tags on proteins, such as pupylation, have evolutionary links to cofactor/amino acid biosynthesis pathways. Following up on these observations, we systematically investigated the non-ribosomal amidoligases of the ATP-grasp, glutamine synthetase-like and acetyltransferase folds by classifying the known members and identifying novel versions. We then established their contextual connections using information from domain architectures and conserved gene neighborhoods. This showed remarkable, previously uncharacterized functional links between diverse peptide ligases, several peptidases of unrelated folds and enzymes involved in synthesis of modified amino acids. Using the network of contextual connections we were able to predict numerous novel pathways for peptide synthesis and modification, amine-utilization, secondary metabolite synthesis and potential peptide-tagging systems. One potential peptide-tagging system, which is widely distributed in bacteria, involves an ATP-grasp domain and a glutamine synthetase-like ligase, both of which are circularly permuted, an NTN-hydrolase fold peptidase and a novel alpha helical domain. Our analysis also elucidates key steps in the biosynthesis of antibiotics such as friulimicin, butirosin and bacilysin and cell surface structures such as capsular polymers and teichuronopeptides. We also report the discovery of several novel ribosomally synthesized bacterial peptide metabolites that are cyclized via amide and lactone linkages formed by ATP-grasp enzymes. We present an evolutionary scenario for the multiple convergent origins of peptide ligases in various folds and clarify the bacterial origin of eukaryotic peptide-tagging enzymes of the TTL family. C1 [Iyer, Lakshminarayan M.; Abhiman, Saraswathi; Aravind, L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [Burroughs, A. Maxwell] RIKEN Yokohama Inst, OSC, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan. RP Aravind, L (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM aravind@mail.nih.gov FU National Library of Medicine at the National Institutes of Health, USA FX L. M. I., S. A. and L. A. are supported by the intramural funds of the National Library of Medicine at the National Institutes of Health, USA. NR 111 TC 41 Z9 41 U1 1 U2 15 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1742-206X J9 MOL BIOSYST JI Mol. Biosyst. PY 2009 VL 5 IS 12 BP 1636 EP 1660 DI 10.1039/b917682a PG 25 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 518WX UT WOS:000271727600023 PM 20023723 ER PT J AU Tuncbag, N Kar, G Gursoy, A Keskin, O Nussinov, R AF Tuncbag, Nurcan Kar, Gozde Gursoy, Attila Keskin, Ozlem Nussinov, Ruth TI Towards inferring time dimensionality in protein-protein interaction networks by integrating structures: the p53 example SO MOLECULAR BIOSYSTEMS LA English DT Article ID TRANSACTIVATION DOMAIN; INTERACTION PREDICTION; TUMOR-SUPPRESSOR; MDM2 ONCOPROTEIN; SYSTEMS BIOLOGY; CELL CYCLE; C-ABL; INTERFACES; DATABASE; PHOSPHORYLATION AB Inspection of protein-protein interaction maps illustrates that a hub protein can interact with a very large number of proteins, reaching tens and even hundreds. Since a single protein cannot interact with such a large number of partners at the same time, this presents a challenge: can we figure out which interactions can occur simultaneously and which are mutually excluded? Addressing this question adds a fourth dimension into interaction maps: that of time. Including the time dimension in structural networks is an immense asset; time dimensionality transforms network node-and-edge maps into cellular processes, assisting in the comprehension of cellular pathways and their regulation. While the time dimensionality can be further enhanced by linking protein complexes to time series of mRNA expression data, current robust, network experimental data are lacking. Here we outline how, using structural data, efficient structural comparison algorithms and appropriate datasets and filters can assist in getting an insight into time dimensionality in interaction networks; in predicting which interactions can and cannot co-exist; and in obtaining concrete predictions consistent with experiment. As an example, we present p53-linked processes. C1 [Tuncbag, Nurcan; Kar, Gozde; Gursoy, Attila; Keskin, Ozlem] Koc Univ, Ctr Computat Biol & Bioinformat, TR-34450 Rumelifeneri Yolu, Sariyer Istanbu, Turkey. [Tuncbag, Nurcan; Kar, Gozde; Gursoy, Attila; Keskin, Ozlem] Koc Univ, Coll Engn, TR-34450 Rumelifeneri Yolu, Sariyer Istanbu, Turkey. [Nussinov, Ruth] NCI, Basic Res Program, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Gursoy, A (reprint author), Koc Univ, Ctr Computat Biol & Bioinformat, TR-34450 Rumelifeneri Yolu, Sariyer Istanbu, Turkey. EM agursoy@ku.edu.tr; okeskin@ku.edu.tr; ruthnu@helix.nih.gov RI Tuncbag, Nurcan/D-3383-2011; Gursoy, Attila/E-9565-2015 OI Gursoy, Attila/0000-0002-2297-2113 FU National Cancer Institute; National Institutes of Health [NO1-CO-12400]; Intramural Research Program of the NIH; Center for Cancer Research FX O.K. acknowledges a Turkish Academy of Sciences (TUBA) Distinguished Young Investigator Award. N.T. is supported by a TUBITAK fellowship. This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under contract number NO1-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U. S. Government. This research was supported (in part) by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 56 TC 52 Z9 52 U1 2 U2 8 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1742-206X J9 MOL BIOSYST JI Mol. Biosyst. PY 2009 VL 5 IS 12 BP 1770 EP 1778 DI 10.1039/b905661k PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 518WX UT WOS:000271727600035 PM 19585003 ER PT J AU Wang, JR Bowen, NJ Marino-Ramirez, L Jordan, IK AF Wang, Jianrong Bowen, Nathan J. Marino-Ramirez, Leonardo Jordan, I. King TI A c-Myc regulatory subnetwork from human transposable element sequences SO MOLECULAR BIOSYSTEMS LA English DT Article ID HUMAN B-CELLS; TRANSCRIPTION FACTOR; HUMAN GENOME; NONCODING SEQUENCES; MOBILE ELEMENTS; GENE-REGULATION; BINDING-SITES; EVOLUTION; DNA; NETWORKS AB Transposable elements (TEs) can donate regulatory sequences that help to control the expression of human genes. The oncogene c-Myc is a promiscuous transcription factor that is thought to regulate the expression of hundreds of genes. We evaluated the contribution of TEs to the c-Myc regulatory network by searching for c-Myc binding sites derived from TEs and by analyzing the expression and function of target genes with nearby TE-derived c-Myc binding sites. There are thousands of TE sequences in the human genome that are bound by c-Myc. A conservative analysis indicated that 816-4564 of these TEs contain canonical c-Myc binding site motifs. c-Myc binding sites are over-represented among sequences derived from the ancient TE families L2 and MIR, consistent with their preservation by purifying selection. Genes associated with TE-derived c-Myc binding sites are co-expressed with each other and with c-Myc. A number of these putative TE-derived c-Myc target genes are differentially expressed between Burkitt's lymphoma cells versus normal B cells and encode proteins with cancer-related functions. Despite several lines of evidence pointing to their regulation by c-Myc and relevance to cancer, the set of genes identified as TE-derived c-Myc targets does not significantly overlap with two previously characterized c-Myc target gene sets. These data point to a substantial contribution of TEs to the regulation of human genes by c-Myc. Genes that are regulated by TE-derived c-Myc binding sites appear to form a distinct c-Myc regulatory subnetwork. C1 [Wang, Jianrong; Bowen, Nathan J.; Jordan, I. King] Georgia Inst Technol, Sch Biol, Atlanta, GA 30332 USA. [Bowen, Nathan J.] Georgia Inst Technol, Ovarian Canc Inst, Atlanta, GA 30332 USA. [Marino-Ramirez, Leonardo] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [Marino-Ramirez, Leonardo] Corp Colombiana Invest Agropecuaria CORPOICA, Computat Biol & Bioinformat Unit, Bioind & Biotechnol Ctr, Bogota, Colombia. RP Jordan, IK (reprint author), Georgia Inst Technol, Sch Biol, Atlanta, GA 30332 USA. EM jwang64@gatech.edu; bowen@gatech.edu; lmarino@corpoica.org.co; king.jordan@biology.gatech.edu RI Marino-Ramirez, Leonardo/I-5759-2013; Bowen, Nathan/F-3132-2010 OI Marino-Ramirez, Leonardo/0000-0002-5716-8512; Bowen, Nathan/0000-0002-1609-6698 FU School of Biology, Georgia Institute of Technology; Alfred P. Sloan Research Fellowship in Computational and Evolutionary Molecular Biology [BR-4839]; Ovarian Cancer Institute Laboratory; School of Biology; Georgia Institute of Technology; NIH; NLM; NCBI; Corporacion Colombiana de Investigacion Agropecuaria-CORPOICA FX I. K. J. and J. W. were supported by the School of Biology, Georgia Institute of Technology. I. K. J. was supported by an Alfred P. Sloan Research Fellowship in Computational and Evolutionary Molecular Biology (BR-4839). N. J. B. was supported by the Ovarian Cancer Institute Laboratory, School of Biology, Georgia Institute of Technology. This research was supported in part by the Intramural Research Program of the NIH, NLM, NCBI. LMR was supported by Corporacion Colombiana de Investigacion Agropecuaria-CORPOICA. NR 41 TC 14 Z9 15 U1 0 U2 2 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1742-206X J9 MOL BIOSYST JI Mol. Biosyst. PY 2009 VL 5 IS 12 BP 1831 EP 1839 DI 10.1039/b908494k PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 518WX UT WOS:000271727600041 PM 19763338 ER PT J AU Koshimizu, H Kiyosue, K Hara, T Hazama, S Suzuki, S Uegaki, K Nagappan, G Zaitsev, E Hirokawa, T Tatsu, Y Ogura, A Lu, B Kojima, M AF Koshimizu, Hisatsugu Kiyosue, Kazuyuki Hara, Tomoko Hazama, Shunsuke Suzuki, Shingo Uegaki, Koichi Nagappan, Guhan Zaitsev, Eugene Hirokawa, Takatsugu Tatsu, Yoshiro Ogura, Akihiko Lu, Bai Kojima, Masami TI Multiple functions of precursor BDNF to CNS neurons: negative regulation of neurite growth, spine formation and cell survival SO MOLECULAR BRAIN LA English DT Article AB Background: Proneurotrophins and mature neurotrophins elicit opposite effects via the p75 neurotrophin receptor (p75(NTR)) and Trk tyrosine kinase receptors, respectively; however the molecular roles of proneurotrophins in the CNS are not fully understood. Results: Based on two rare single nucleotide polymorphisms (SNPs) of the human brain-derived neurotrophic factor (BDNF) gene, we generated R125M-, R127L- and R125M/R127L-BDNF, which have amino acid substitution(s) near the cleavage site between the pro-and mature-domain of BDNF. Western blot analyses demonstrated that these BDNF variants are poorly cleaved and result in the predominant secretion of proBDNF. Using these cleavage-resistant proBDNF (CR-proBDNF) variants, the molecular and cellular roles of proBDNF on the CNS neurons were examined. First, CR-proBDNF showed normal intracellular distribution and secretion in cultured hippocampal neurons, suggesting that inhibition of proBDNF cleavage does not affect intracellular transportation and secretion of BDNF. Second, we purified recombinant CR-proBDNF and tested its biological effects using cultured CNS neurons. Treatment with CR-proBDNF elicited apoptosis of cultured cerebellar granule neurons (CGNs), while treatment with mature BDNF (matBDNF) promoted cell survival. Third, we examined the effects of CR-proBDNF on neuronal morphology using more than 2-week cultures of basal forebrain cholinergic neurons (BFCNs) and hippocampal neurons. Interestingly, in marked contrast to the action of matBDNF, which increased the number of cholinergic fibers and hippocampal dendritic spines, CR-proBDNF dramatically reduced the number of cholinergic fibers and hippocampal dendritic spines, without affecting the survival of these neurons. Conclusion: These results suggest that proBDNF has distinct functions in different populations of CNS neurons and might be responsible for specific physiological cellular processes in the brain. C1 [Koshimizu, Hisatsugu; Kiyosue, Kazuyuki; Hara, Tomoko; Hazama, Shunsuke; Suzuki, Shingo; Uegaki, Koichi; Hirokawa, Takatsugu; Tatsu, Yoshiro; Kojima, Masami] Natl Inst Adv Ind Sci & Technol, Ikeda, Osaka 5638577, Japan. [Hara, Tomoko; Suzuki, Shingo; Uegaki, Koichi; Hirokawa, Takatsugu; Tatsu, Yoshiro; Kojima, Masami] Japan Sci & Technol Agcy JST, CREST, Kawaguchi, Saitama 3320012, Japan. [Hazama, Shunsuke; Ogura, Akihiko] Osaka Univ, Dept Neurosci, Grad Sch Frontier Biosci, Toyonaka, Osaka 5600043, Japan. [Nagappan, Guhan; Zaitsev, Eugene; Lu, Bai] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Neural Dev & Plast, NIH, Bethesda, MD 20892 USA. RP Kojima, M (reprint author), Natl Inst Adv Ind Sci & Technol, Ikeda, Osaka 5638577, Japan. EM koshimih@mail.nih.gov; kiyosue-k@aist.go.jp; tomo-hara@aist.go.jp; hazashun@fbs.osaka-u.ac.jp; s-suzuki@aist.go.jp; k-uegaki@aist.go.jp; nagappang@mail.nih.gov; zaitseve@mail.nih.gov; t-hirokawa@aist.go.jp; y-tatsu@aist.go.jp; oguraa@bio.sci.osaka-u.ac.jp; lub@mail.nih.gov; m-kojima@aist.go.jp RI kiyosue, Kazuyuki/L-2857-2016 OI kiyosue, Kazuyuki/0000-0001-9439-3295 FU Ministry of Education, Culture, Sports, Science and Technology of Japan [40344171]; Japan Society for the Promotion of Science (JSPS); Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST); National Institute of Mental Health (NIMH); NICHD FX We thank Dr. N.X. Cawley (NICHD, NIH) for critical reading of this manuscript. We thank Dr. H. Nawa (Brain Research Institute, Niigata University) for Sindbis vector (IRES-GFP vector). We thank Dr. S. Koizumi (Novartis Pharma K. K.) for proNGF plasmid. We thank Dr. T. Watanabe (Department of Urology, Asahikawa Medical College) for anti-SgII antibody. We thank Drs. B. Hempstead and K. Teng (Weill Medical College of Cornell University) for proNT-3 vector. We thank Drs. N. Takei (Brain Research Institute, Niigata University) for helpful discussion. We thank M. Kashihara and M. Ohtsuka (RICE, AIST) for technical assistance. This work was supported by Grant-in-Aid for Scientific Research on Priority Areas-Elucidation of neural network function in the brain-from the Ministry of Education, Culture, Sports, Science and Technology of Japan (40344171) (MK), Japan Society for the Promotion of Science (JSPS) (HK), Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST) (MK), and The National Institute of Mental Health (NIMH) and NICHD intramural research programs (BL). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 60 TC 64 Z9 64 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-6606 J9 MOL BRAIN JI Mol. Brain PY 2009 VL 2 AR 27 DI 10.1186/1756-6606-2-27 PG 19 WC Neurosciences SC Neurosciences & Neurology GA V25CW UT WOS:000208457100027 PM 19674479 ER PT J AU Lai, C Xie, CS Shim, H Chandran, J Howell, BW Cai, HB AF Lai, Chen Xie, Chengsong Shim, Hoon Chandran, Jayanth Howell, Brian W. Cai, Huaibin TI Regulation of endosomal motility and degradation by amyotrophic lateral sclerosis 2/alsin SO MOLECULAR BRAIN LA English DT Article AB Dysfunction of alsin, particularly its putative Rab5 guanine-nucleotide-exchange factor activity, has been linked to one form of juvenile onset recessive familial amyotrophic lateral sclerosis (ALS2). Multiple lines of alsin knockout (ALS2(-/-)) mice have been generated to model this disease. However, it remains elusive whether the Rab5-dependent endocytosis is altered in ALS2(-/-) neurons. To directly examine the Rab5-mediated endosomal trafficking in ALS2(-/-) neurons, we introduced green fluorescent protein (GFP)-tagged Rab5 into cultured hippocampal neurons to monitor the morphology and motility of Rab5-associated early endosomes. Here we report that Rab5-mediated endocytosis was severely altered in ALS2(-/-) neurons. Excessive accumulation of Rab5-positive vesicles was observed in ALS2(-/-) neurons, which correlated with a significant reduction in endosomal motility and augmentation in endosomal conversion to lysosomes. Consequently, a significant increase in endosome/lysosome-dependent degradation of internalized glutamate receptors was observed in ALS2(-/-) neurons. These phenotypes closely resembled the endosomal trafficking abnormalities induced by a constitutively active form of Rab5 in wild-type neurons. Therefore, our findings reveal a negatively regulatory mechanism of alsin in Rab5-mediated endosomal trafficking, suggesting that enhanced endosomal degradation in ALS2(-/-) neurons may underlie the pathogenesis of motor neuron degeneration in ALS2 and related motor neuron diseases. C1 [Lai, Chen; Xie, Chengsong; Shim, Hoon; Chandran, Jayanth; Cai, Huaibin] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Howell, Brian W.] NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. RP Lai, C (reprint author), NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. EM laichi@mail.nih.gov; xiech@mail.nih.gov; shimh@vcu.edu; jchandra@staffmail.ed.ac.uk; howellb@ninds.nih.gov; caih@mail.nih.gov RI Cai, Huaibin/H-3359-2013; OI Cai, Huaibin/0000-0002-8596-6108; Howell, Brian/0000-0002-0204-0773 FU National Institute on Aging; National Institute of Neurological Disorders and Stroke FX This project was supported by the Intramural Research Programs of the National Institute on Aging and National Institute of Neurological Disorders and Stroke. We thank Dr. Roberto Weigert of the National Heart, Lung, and Blood Institute for providing GFP-tagged Rab5 plasmids, Dr. Jian-Sheng Kang of National Institute of Neurological Disorders and Stroke for help with image analysis, Ms. Lihong Cui of National Institute of Mental Health for statistic analysis, all members of Dr. Cai's lab for their critical discussion and helpful suggestions, and the NIH Fellows Editorial Board for editing the manuscript. NR 45 TC 16 Z9 16 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-6606 J9 MOL BRAIN JI Mol. Brain PY 2009 VL 2 AR 23 DI 10.1186/1756-6606-2-23 PG 12 WC Neurosciences SC Neurosciences & Neurology GA V25CW UT WOS:000208457100023 PM 19630956 ER PT J AU Gartside, MG Chen, HB Ibrahimi, OA Byron, SA Curtis, AV Wellens, CL Bengston, A Yudt, LM Eliseenkova, AV Ma, JH Curtin, JA Hyder, P Harper, UL Riedesel, E Mann, GJ Trent, JM Bastian, BC Meltzer, PS Mohammadi, M Pollock, PM AF Gartside, Michael G. Chen, Huaibin Ibrahimi, Omar A. Byron, Sara A. Curtis, Amy V. Wellens, Candice L. Bengston, Ana Yudt, Laura M. Eliseenkova, Anna V. Ma, Jinghong Curtin, John A. Hyder, Pilar Harper, Ursula L. Riedesel, Erica Mann, Graham J. Trent, Jeffrey M. Bastian, Boris C. Meltzer, Paul S. Mohammadi, Moosa Pollock, Pamela M. TI Loss-of-Function Fibroblast Growth Factor Receptor-2 Mutations in Melanoma SO MOLECULAR CANCER RESEARCH LA English DT Article ID STRUCTURAL BASIS; MALIGNANT PROGRESSION; HUMAN MELANOCYTES; FGFR2 MUTATIONS; APERT-SYNDROME; HUMAN PROSTATE; LADD SYNDROME; TUMOR-GROWTH; CELLS; DIFFERENTIATION AB We report that 10% of melanoma tumors and cell lines harbor mutations in the fibroblast growth factor receptor 2 (FGFR2) gene. These novel mutations include three truncating mutations and 20 missense mutations occurring at evolutionary conserved residues In FGFR2 as well as among all four FGFRs. The mutation spectrum Is characteristic of those induced by UV radiation. Mapping of these mutations onto the known crystal structures of FGFR2 followed by In vitro and in vivo studies show that these mutations result in receptor loss of function through several distinct mechanisms, including loss of ligand binding affinity, impaired receptor dimerization, destabilization of the extracellular domains, and reduced kinase activity. To our knowledge, this is the first demonstration of loss-of-function mutations in a class IV receptor tyrosine kinase in cancer. Taken Into account with our recent discovery of activating FGFR2 mutations in endometrial cancer, we suggest that FGFR2 may join the list of genes that play context-dependent opposing roles In cancer. (Mol Cancer Res 2009;7(1):41-54) C1 [Gartside, Michael G.; Byron, Sara A.; Curtis, Amy V.; Wellens, Candice L.; Bengston, Ana; Hyder, Pilar; Pollock, Pamela M.] Translat Genom Res Inst, Div Canc & Cell Biol, Phoenix, AZ USA. [Trent, Jeffrey M.] Translat Genom Res Inst, Div Genet Basis Human Dis, Phoenix, AZ USA. [Chen, Huaibin; Ibrahimi, Omar A.; Eliseenkova, Anna V.; Ma, Jinghong; Mohammadi, Moosa] NYU, Sch Med, Dept Pharmacol, New York, NY USA. [Yudt, Laura M.; Harper, Ursula L.; Riedesel, Erica; Meltzer, Paul S.] NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Curtin, John A.; Bastian, Boris C.] Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. [Mann, Graham J.] Univ Sydney, Westmead Inst Canc Res, Westmead Millennium Inst, Westmead, NSW 2145, Australia. RP Pollock, PM (reprint author), TGen, 445 N 5th St, Phoenix, AZ 85004 USA. EM ppollock@tgen.org RI Mann, Graham/G-4758-2014; OI Mann, Graham/0000-0003-1301-405X; Curtin, John/0000-0001-6299-9110; Mohammadi, Moosa/0000-0003-2434-9437 FU Harry J. Lloyd Charitable Trust; Melanoma Research Foundation; Leslie Ann Ballard Foundation; NIH [2R01 DE 13686-08]; American Cancer Society Postdoctoral Fellowship grant [PF-07-215-01-TBE] FX Harry J. Lloyd Charitable Trust, Melanoma Research Foundation, and Leslie Ann Ballard Foundation (P.M. Pollock); NIH grant 2R01 DE 13686-08 (M. Mohammadi); and American Cancer Society Postdoctoral Fellowship grant PF-07-215-01-TBE. (S.A. Byron). NR 43 TC 66 Z9 66 U1 0 U2 3 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 JAN PY 2009 VL 7 IS 1 BP 41 EP 54 DI 10.1158/1541-7786.MCR-08-0021 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 400LQ UT WOS:000262869900005 PM 19147536 ER PT J AU Ogawa, M Regino, CAS Choyke, PL Kobayashi, H AF Ogawa, Mikako Regino, Celeste A. S. Choyke, Peter L. Kobayashi, Hisataka TI In vivo target-specific activatable near-infrared optical labeling of humanized monoclonal antibodies SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID QUANTUM DOTS; FLUORESCENT PROTEINS; CANCER; ANGIOGENESIS; EXPRESSION; CONJUGATE; PROBES; TUMORS; MICE AB Imaging with labeled monoclonal antibodies may be useful in detecting, staging, and monitoring tumors. Despite their high affinity and specificity, a critical limitation of antibody imaging is the high background signal due to prolonged clearance from the blood, which reduces the tumor-to-background ratio. To address this problem, we developed a molecular imaging probe consisting of multiple self-quenching fluorophores [Cy5.5 or Alexa Fluor 680 (Alexa680)] conjugated to a monoclonal antibody (trastuzumab) to synthesize Tra-Cy5.5(SQ) or Tra-Alexa680(SQ), respectively. This agent only becomes fluorescently "active" after cellular internalization but is quenched in the unbound state leading to high tumor-to-background ratios. The in vitro quenching capacity for both conjugates was similar to 9-fold. In vivo imaging experiments were done in mice bearing both 3T3/HER-2(+) and BALB/3T3/ZsGreen/HER-2(-) xenografts. Tra-Alexa680(SQ) produced specific enhancement in the 3T3/HER-2(+) tumors but not in the HER-2(-) control tumors. However, Tra-Cy5.5(SQ) produced nonspecific enhancement in both 3T3/HER-2(+) and control tumors. In conclusion, whereas Cy5.5-conjugates produced nonspecific results as well as rapid liver accumulation, conjugating multiple Alexa680 molecules to a single monoclonal antibody resulted in a near-infrared optical agent that activated within specific target tumors with high tumor-to-background ratio with considerable potential for clinical translation. [Mol Cancer Ther 2009;8(1):232-9] C1 [Ogawa, Mikako; Regino, Celeste A. S.; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bldg 10,Room 1B40,MSC1088, Bethesda, MD 20892 USA. EM kobayash@mail.nih.gov FU Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research FX Grant support: Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 24 TC 53 Z9 54 U1 0 U2 7 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 JAN PY 2009 VL 8 IS 1 BP 232 EP 239 DI 10.1158/1535-7163.MCT-08-0862 PG 8 WC Oncology SC Oncology GA 395BM UT WOS:000262497100027 PM 19139133 ER PT J AU Marchand, C Lea, WA Jadhav, A Dexheimer, TS Austin, CP Inglese, J Pommier, Y Simeonov, A AF Marchand, Christophe Lea, Wendy A. Jadhav, Ajit Dexheimer, Thomas S. Austin, Christopher P. Inglese, James Pommier, Yves Simeonov, Anton TI Identification of phosphotyrosine mimetic inhibitors of human tyrosyl-DNA phosphodiesterase I by a novel AlphaScreen high-throughput assay SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID TOPOISOMERASE-I; SPINOCEREBELLAR ATAXIA; COVALENT COMPLEXES; BIOLOGICAL-ACTIVITIES; AXONAL NEUROPATHY; SCREENING ASSAYS; HUMAN-CELLS; TDP1; REPAIR; DAMAGE AB Tyrosyl-DNA phosphodiesterase I (Tdp1) resolves topoisomerase I (Top1)-DNA adducts accumulated from natural DNA damage as well as from the action of certain anticancer drugs. Tdp1 catalyzes the hydrolysis of the phosphodiester bond between the catalytic tyrosine residue of topoisomerase I and the DNA 3'-phosphate. Only a limited number of weak inhibitors have been reported for Tdp1, and there is an unmet need to identify novel chemotypes through screening of chemical libraries. Herein, we present an easily configured, highly miniaturized, and robust Tdp1 assay using the AlphaScreen technology. Uninhibited enzyme reaction is associated with low signal, whereas inhibition leads to a gain of signal, making the present assay format especially attractive for automated large-collection high-throughput screening. We report the identification and initial characterization of four previously unreported inhibitors of Tdp1. Among them, suramin, NF449, and methyl-3,4-dephostatin are phosphotyrosine mimetics; that may act as Tdp1 substrate decoys. We also report a novel biochemical assay using the SCAM Tdp1 mutant to study the mechanism of action of methyl-3,4-dephostatin. [Mol Cancer Ther 2009;8(1):240-8] C1 [Lea, Wendy A.; Jadhav, Ajit; Austin, Christopher P.; Inglese, James; Simeonov, Anton] NHGRI, NIH, Chem Genom Ctr, Bethesda, MD 20892 USA. [Marchand, Christophe; Dexheimer, Thomas S.; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Simeonov, A (reprint author), NHGRI, NIH, Chem Genom Ctr, 9800 Med Ctr Dr, Rockville, MD 20850 USA. EM asimeono@mail.nih.gov RI Marchand, Christophe/D-8559-2016 FU National Human Genome Research Institute, NIH; Center for Cancer Research, National Cancer Institute, NIH FX Grant support: Molecular Libraries Initiative of the NIH Roadmap for Medical Research and Intramural Research Program of the National Human Genome Research Institute, NIH and Intramural Research Program of the Center for Cancer Research, National Cancer Institute, NIH. NR 47 TC 41 Z9 42 U1 0 U2 4 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 JAN PY 2009 VL 8 IS 1 BP 240 EP 248 DI 10.1158/1535-7163.MCT-08-0878 PG 9 WC Oncology SC Oncology GA 395BM UT WOS:000262497100028 PM 19139134 ER PT J AU John-Aryankalayil, M Palayoor, ST Cerna, D Falduto, MT Magnuson, SR Coleman, CN AF John-Aryankalayil, Molykutty Palayoor, Sanjeewani T. Cerna, David Falduto, Michael T. Magnuson, Scott R. Coleman, C. Norman TI NS-398, ibuprofen, and cyclooxygenase-2 RNA interference produce significantly different gene expression profiles in prostate cancer cells SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; ANGIOPOIETIN-LIKE PROTEIN-4; VIOXX INDUCES EXPRESSION; HUMAN PANCREATIC-CANCER; SLOWS TUMOR-GROWTH; CYCLE ARREST GENES; CARCINOMA-CELLS; SELECTIVE INHIBITOR; COLORECTAL-CANCER; SULINDAC SULFIDE AB Cyclooxygenase-2 (COX-2) plays a significant role in tumor development and progression. Nonsteroidal antiinflammatory drugs (NSAID) exhibit potent anticancer effects in vitro and in vivo by COX-2-dependent and COX-2-independent mechanisms. In this study, we used microarray analysis to identify the change of expression profile regulated by a COX-2-specific NSAID NS-398 (0.01 and 0.1 mmol/L), a nonspecific NSAID ibuprofen (0.1 and 1.5 mmol/L) and RNA interference (RNAi)mediated COX-2 inhibition in PC3 prostate cancer cells. A total of 3,362 differentially expressed genes with 2-fold change and P < 0.05 were identified. Low concentrations of NSAIDs and COX-2 RNAi altered very few genes (1-3%) compared with the higher concentration of NS-398 (17%) and ibuprofen (80%). Ingenuity Pathway Analysis was used for distributing the differentially expressed genes into biological networks and for evaluation of functional significance. The top 3 networks for both NSAIDs included functional categories of DNA replication, recombination and repair, and gastrointestinal disease. Immunoresponse function was specific to NS-398, and cell cycle and cellular movement were among the top functions for ibuprofen. Ingenuity Pathway Analysis also identified renal and urologic disease as a function specific for ibuprofen. This comprehensive study identified several COX-2-independent targets of NSAIDs, which may help explain the antitumor and radiosensitizing effects of NSAIDs. However, none of these categories were reflected in the identified networks in PC3 cells treated with clinically relevant low concentrations of NS-398 and ibuprofen or with COX-2 RNAi, suggesting the benefit to fingerprinting preclinical drug concentrations to improve their relevance to the clinical setting. [Mol Cancer Ther 2009;8(1):261 -73] C1 [John-Aryankalayil, Molykutty; Palayoor, Sanjeewani T.; Cerna, David; Coleman, C. Norman] NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Falduto, Michael T.; Magnuson, Scott R.] GenUs BioSyst Inc, Northbrook, IL USA. RP John-Aryankalayil, M (reprint author), NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, 9000 Rockville Pike,Room B3 B 406,Bldg 10, Bethesda, MD 20892 USA. EM Aryankalayilm@mail.nih.gov RI ayyadevara, rajaram/D-1572-2009 FU Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research FX Grant support: Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 60 TC 28 Z9 30 U1 0 U2 3 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 JAN PY 2009 VL 8 IS 1 BP 261 EP 273 DI 10.1158/1535-7163.MCT-08-0928 PG 13 WC Oncology SC Oncology GA 395BM UT WOS:000262497100030 PM 19139136 ER PT J AU Dhungana, S Merrick, BA Tomer, KB Fessler, MB AF Dhungana, Suraj Merrick, B. Alex Tomer, Kenneth B. Fessler, Michael B. TI Quantitative Proteomics Analysis of Macrophage Rafts Reveals Compartmentalized Activation of the Proteasome and of Proteasome-mediated ERK Activation in Response to Lipopolysaccharide SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID NF-KAPPA-B; RESONANCE ENERGY-TRANSFER; NITRIC-OXIDE SYNTHASE; RAW 264.7 MACROPHAGES; LIPID RAFTS; BACTERIAL LIPOPOLYSACCHARIDE; NF-KAPPA-B1 P105; CELL-MEMBRANES; PROTEIN-KINASE; DEPENDENT ENDOCYTOSIS AB Lipopolysaccharide (LPS), a glycolipid component of the outer membrane of Gram-negative bacteria, is a potent initiator of the innate immune response of the macrophage. LPS triggers downstream signaling by selectively recruiting and activating proteins in cholesterol-rich membrane microdomains called lipid rafts. We applied proteomics analysis to macrophage detergent-resistant membranes (DRMs) during an LPS exposure time course in an effort to identify and validate novel events occurring in macrophage rafts. Following metabolic incorporation in cell culture of heavy isotopes of amino acids arginine and lysine ([(13)C(6)]Arg and [(13)C(6)]Lys) or their light counterparts, a SILAC (stable isotope labeling with amino acids in cell culture)-based quantitative, liquid chromatography-tandem mass spectrometry proteomics approach was used to profile LPS-induced changes in the lipid raft proteome of RAW 264.7 macrophages. Unsupervised network analysis of the proteomics data set revealed a marked representation of the ubiquitin-proteasome system as well as changes in proteasome subunit composition following LPS challenge. Functional analysis of DRMs confirmed that LPS causes selective activation of the proteasome in macrophage rafts and proteasome inactivation outside of rafts. Given previous reports of an essential role for proteasomal degradation of I kappa B kinase-phosphorylated p105 in LPS activation of ERK mitogen-activated protein kinase, we tested for a role of rafts in compartmentalization of these events. Immunoblotting of DRMs revealed proteasome-dependent activation of MEK and ERK specifically occurring in lipid rafts as well as proteasomal activity upon raft-localized p105 that was enhanced by LPS. Cholesterol extraction from the intact macrophage with methyl-beta-cyclodextrin was sufficient to activate ERK, recapitulating the LPS-I kappa B kinase-p105-MEK-ERK cascade, whereas both it and the alternate raft-disrupting agent nystatin blocked subsequent LPS activation of the ERK cascade. Taken together, our findings indicate a critical, selective role for raft compartmentalization and regulation of proteasome activity in activation of the MEK-ERK pathway. Molecular & Cellular Proteomics 8:201-213, 2009. C1 [Dhungana, Suraj; Merrick, B. Alex; Fessler, Michael B.] NIEHS, Lab Resp Biol, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. [Tomer, Kenneth B.] NIEHS, Struct Biol Lab, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. RP Fessler, MB (reprint author), NIEHS, Lab Resp Biol, NIH, US Dept HHS, 111 TW Alexander Dr,POB 12233,Md D2-01, Res Triangle Pk, NC 27709 USA. EM fesslerm@niehs.nih.gov RI Tomer, Kenneth/E-8018-2013 FU National Institutes of Health; NIEHS FX This work was supported, in whole or in part, by the National Institutes of Health Intramural Research Program of the NIEHS. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. Section 1734 solely to indicate this fact. NR 66 TC 44 Z9 44 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD JAN PY 2009 VL 8 IS 1 BP 201 EP 213 DI 10.1074/mcp.M800286-MCP200 PG 13 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 394FJ UT WOS:000262431000017 PM 18815123 ER PT J AU Stroncek, DF Jin, P Wang, E Ren, JG Sabatino, M Marincola, FM AF Stroncek, David F. Jin, Ping Wang, Ena Ren, Jiagiang Sabatino, Marianna Marincola, Francesco M. TI Global Transcriptional Analysis for Biomarker Discovery and Validation in Cellular Therapies SO MOLECULAR DIAGNOSIS & THERAPY LA English DT Review ID HEMATOPOIETIC PROGENITOR CELLS; BLOOD MONONUCLEAR-CELLS; GENE-EXPRESSION PROFILES; MESENCHYMAL STEM-CELLS; COLONY-STIMULATING FACTOR; CXCR4 ANTAGONIST AMD3100; PERIPHERAL-BLOOD; G-CSF; MOLECULAR SIGNATURES; MICRORNA EXPRESSION AB Potency testing is an important part of the evaluation of cellular therapy products. Potency assays are quantitative measures of a product-specific biologic activity that is linked to a relevant biologic property and, ideally, a product's in vivo mechanism of action. Both in vivo and in vitro assays can be used for potency testing. Since there is often a limited period of time between the completion of production and the release from the laboratory for administration to the patient, in vitro assays such as flow cytometry, ELISA, and cytotoxicity are typically used. Better potency assays are needed to assess the complex and multiple functions of cellular therapy products, some of which are not well understood. Gene expression profiling using microarray technology has been widely and effectively used to assess changes of cells in response to stimuli and to classify cancers. Preliminary studies have shown that the expression of non-coding microRNA (miRNA), which plays an important role in cellular development, differentiation, metabolism, and signal transduction, can distinguish between different types of stem cells and leukocytes. Both gene and miRNA expression profiling have the potential to be important tools for testing the potency of cellular therapies. Potency testing, the complexities associated with potency testing of cellular therapies, and the potential role of gene and miRNA expression microarrays in potency testing of cellular therapies are discussed. C1 [Stroncek, David F.; Jin, Ping; Wang, Ena; Ren, Jiagiang; Sabatino, Marianna; Marincola, Francesco M.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. RP Stroncek, DF (reprint author), NIH, Dept Transfus Med, Ctr Clin, Bldg 10,Room 1C711,10 Ctr Dr MSC-1184, Bethesda, MD 20892 USA. EM dstroncek@cc.nih.gov FU Department of Transfusion Medicine; Clinical Center; National Institutes of Health FX The authors thank the Department of Transfusion Medicine, Clinical Center, National Institutes of Health for their support of this work. The authors have no conflicts of interest directly related to the content of this review. NR 60 TC 6 Z9 6 U1 0 U2 8 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1177-1062 J9 MOL DIAGN THER JI Mol. Diagn. Ther. PY 2009 VL 13 IS 3 BP 181 EP 193 PG 13 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 487QT UT WOS:000269290600003 PM 19650671 ER PT J AU Magklara, A Smith, CL AF Magklara, Angeliki Smith, Catharine L. TI A Composite Intronic Element Directs Dynamic Binding of the Progesterone Receptor and GATA-2 SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID BREAST-CANCER CELLS; TRANSCRIPTION FACTOR GATA-2; HORMONE RESPONSE ELEMENTS; ESTROGEN-RECEPTOR; GLUCOCORTICOID-RECEPTOR; GENE-EXPRESSION; NUCLEAR RECEPTORS; DISTAL ENHANCER; MAMMARY-GLAND; TARGET GENES AB The progesterone receptor (PR) plays a pivotal role in proper development and function of the mammary gland and has also been implicated in mammary tumorigenesis. PR is a ligand-activated transcription factor; however, relatively, little is known about its mechanisms of action at endogenous target promoters. The aim of our study was to identify a natural PR-responsive gene and investigate its transcriptional regulation in the mammary microenvironment. Our experiments revealed FKBP5 as a direct target of the PR, because it exhibited a rapid activation by progestin that was cycloheximide independent and correlated with recruitment of RNA polymerase II to the promoter. Site-directed mutagenesis and chromatin immunoprecipitation assays showed that progestin responsiveness is mediated through a composite element in the first intron, to which the PR binds concomitantly with GATA-2. Mutational analysis of the element revealed that the GATA-2 site is essential for progestin activation. Direct binding of PR to DNA contributes to the efficiency of activation but is not sufficient, suggesting that the receptor makes important protein-protein interactions as part of its mechanism of action at the FKBP5 promoter. Using chromatin immunoprecipitation assays we also determined that the intronic region is in communication with the promoter, probably via DNA looping. Time course analysis revealed a cyclical pattern of PR recruitment to the FKBP5 gene but a persistent recruitment to the mouse mammary tumor virus promoter, indicating that receptor cycling is a gene-specific phenomenon rather than a characteristic of the receptor itself. Our study offers new insight in the nature of PR-regulated transcription in mammary cancer cells. (Molecular Endocrinology 23: 61-73, 2009) C1 [Magklara, Angeliki; Smith, Catharine L.] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. [Smith, Catharine L.] Univ Arizona, Coll Pharm, Dept Pharmacol & Toxicol, Tucson, AZ 85721 USA. RP Smith, CL (reprint author), 1703 E Mabel St, Tucson, AZ 85721 USA. EM csmith@pharmacy.arizona.edu NR 61 TC 25 Z9 26 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 JAN PY 2009 VL 23 IS 1 BP 61 EP 73 DI 10.1210/me.2008-0028 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 390KI UT WOS:000262162300006 PM 19036901 ER PT S AU Charmandari, E Chrousos, GP Kino, T AF Charmandari, Evangelia Chrousos, George P. Kino, Tomoshige BE ParkSarge, O Curry, TE TI Identification of Natural Human Glucocorticoid Receptor (hGR) Mutations or Polymorphisms and Their Functional Consequences at the Hormone-Receptor Interaction Level SO MOLECULAR ENDOCRINOLOGY: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Cytoplasmic to nuclear translocation; dexamethasone binding assay; gene sequencing; fluorescent recovery after photobleaching; glucocorticoid receptor; glucocorticoid resistance; glucocorticoid hypersensitivity; green fluorescent protein; glutathione-S transferase pull-down assay; reporter assay; thymidine incorporation assay; transfection ID LIGAND-BINDING DOMAIN; NUCLEAR RECEPTOR; POINT MUTATION; MOLECULAR DETERMINANTS; ACTION NETWORKS; LIVING CELLS; RESISTANCE; GENE; MECHANISMS; MUTANTS AB Glucocorticoids regulate a broad spectrum of physiologic functions essential for life and play an important role in the maintenance of basal and stress-related homeostasis. At the cellular level, the actions of glucocorticoids arc mediated by the human glucocorticoid receptor alpha (hGF alpha), a ligand-dependent transcription factor ubiquitously expressed in almost all tissues and cells. The molecular mechanisms of hGR alpha action involve (a) binding to glucocorticoids, (b) cytoplasmic to nuclear translocation, (c) binding/association to DNA/chromatin, and (d) transcriptional activation or repression by interacting with cofactors and other transcription factors. Mutations or polymorphisms in the hGR gene may impair these molecular mechanisms of hGRa action, thereby altering tissue sensitivity to glucocorticoids. The latter may take the form of glucocorticoid resistance or glucocorticoid hypersensitivity and may be associated with significant morbidity. The identification of natural pathologic mutations in patients' hGR gene and the Subsequent examination of the functional defects of the natural mutant hGRa receptors would enhance our understanding of the molecular mechanisms of hGRa action and highlight the importance of integrated cellular and molecular signaling mechanisms for maintaining homeostasis and preserving normal physiology. C1 [Charmandari, Evangelia] Acad Athens, Biomed Res Fdn, Sect Pediat Endocrinol, Div Endocrinol & Metab, Athens, Greece. [Chrousos, George P.] Univ Athens, Sch Med, Dept Pediat, GR-11527 Athens, Greece. [Kino, Tomoshige] NICHHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA. RP Charmandari, E (reprint author), Acad Athens, Biomed Res Fdn, Sect Pediat Endocrinol, Div Endocrinol & Metab, Athens, Greece. FU Intramural NIH HHS [ZIA HD008732-08] NR 41 TC 5 Z9 6 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-377-0 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2009 VL 590 BP 33 EP 60 DI 10.1007/978-1-60327-378-7_3 PG 28 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BMR47 UT WOS:000273395300003 PM 19763496 ER PT S AU Horvath, A Stratakis, C AF Horvath, Anelia Stratakis, Constantine BE ParkSarge, O Curry, TE TI Basic Molecular Techniques for the Detection of Single Nucleotide Polymorphisms: Genome-Wide Applications in Search for Endocrine Tumor Related Genes SO MOLECULAR ENDOCRINOLOGY: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE SNP; variation; microarray; endocrinology; genome ID COMMON VARIANT; MICROARRAY TECHNOLOGY; PROSTATE-CANCER; RISK LOCI; ASSOCIATION; DNA; ASSAY; SNPS; CHILDHOOD; ARRAYS AB The necessity of genotyping high number of variations in extended sample sets has become apparent in the era of large genomic studies of common complex disorders, in cancer and in pharmacogenomics. The single nucleotide polymorphisms' (SNPs) apparent advantages over other genetic markers such as high frequency, relative stability, and statistically random distribution across the genome have made them a method of choice for most of these genome-wide oriented applications. The requirement for simultaneous genotyping of high number of SNPs, keeping at the same time reasonable price and reliable accuracy,. p triggered the rise of the genotyping throughput, and led to the development of the array-based technologies. The present chapter briefly reviews the methodological and historical aspect of the basic SNP detecting techniques that lie in the basis of the modern high-throughput technologies, providing at the same time detailed guide on the application of one of the most advanced SNP microarray platform on the market: the genome-wide SNP Array 6.0 recently developed by Affymetrix, which we have used to study families with Catney complex and Micronodular adrenocortical hyperplasia. In addition, we discuss practical clues and tips aiming at extending applications and improving performance. C1 [Horvath, Anelia; Stratakis, Constantine] Natl Inst Child Hlth & Human Dev NICHD, SEGEN, PDEGEN, NIH, Bethesda, MD 20892 USA. RP Horvath, A (reprint author), Natl Inst Child Hlth & Human Dev NICHD, SEGEN, PDEGEN, NIH, Bethesda, MD 20892 USA. NR 50 TC 1 Z9 1 U1 1 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-377-0 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2009 VL 590 BP 143 EP 163 DI 10.1007/978-1-60327-378-7_9 PG 21 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BMR47 UT WOS:000273395300009 PM 19763502 ER PT J AU Griggs, RC Batshaw, M Dunkle, M Gopal-Srivastava, R Kaye, E Krischer, J Nguyen, T Paulus, K Merkel, PA AF Griggs, Robert C. Batshaw, Mark Dunkle, Mary Gopal-Srivastava, Rashmi Kaye, Edward Krischer, Jeffrey Nguyen, Tan Paulus, Kathleen Merkel, Peter A. CA Rare Dis Clinical Res Network TI Clinical research for rare disease: Opportunities, challenges, and solutions SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE Rare diseases; Research training; Clinical trials; Patient advocacy groups (PAGs) ID RANDOMIZED-TRIALS; CONDUCT; DESIGN AB Over 7000 rare diseases, each <200,000 US residents, affect nearly 30 million people in the United States. Furthermore, for the 10% of people with a rare disease and for their families, these disorders no longer seem rare. Molecular genetics have characterized the cause of many rare diseases and provide unprecedented opportunities for identifying patients, determining phenotypes, and devising treatments to prevent, stabilize, or improve each disease. Rare disease research poses challenges to investigators requiring specific approaches to: (1) the design of clinical studies; (2) the funding of research programs; (3) the discovery, testing, and approval of new treatments, and (4) the training of clinical scientists. Rigorous, statistically-valid, natural history-controlled, cross-over, and n-of-1 trials can establish efficacy and support regulatory approval of new treatments for rare diseases. The U.S. Orphan Drug Act of the U.S. FDA has stimulated industry investment in clinical trials to develop treatments for rare diseases. For trainees interested in finding a treatment for a rare disease, a commitment to longitudinal care of patients provides a base for the characterization of phenotype and natural history, a stimulus for innovation, a target population for research and helps fund training and research. The scientific methodology, financial resources, and logistics of clinical research for rare diseases have changed dramatically in the past two decades resulting in increased understanding of the pathophysiology of these disorders and direct benefit to patients. (C) 2008 Elsevier Inc. All rights reserved. C1 [Griggs, Robert C.] Univ Rochester, Dept Neurol, Rochester, NY 14620 USA. [Batshaw, Mark] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Dunkle, Mary] NORD, Danbury, CT 06813 USA. [Gopal-Srivastava, Rashmi] NIH, Off Rare Dis, Bethesda, MD 20892 USA. [Kaye, Edward] Genzyme Corp, Cambridge, MA 02142 USA. [Krischer, Jeffrey; Paulus, Kathleen] Univ S Florida, Data Technol Coordinat Off, Tampa, FL 33612 USA. [Nguyen, Tan] US FDA, Off Vitro Diagnost, Rockville, MD 20857 USA. [Merkel, Peter A.] Boston Univ, Sch Med, Rheumatol Sect, Boston, MA 02118 USA. [Merkel, Peter A.] Boston Univ, Sch Med, Clin Epidemiol Unit, Vasculitis Ctr E5, Boston, MA 02118 USA. RP Griggs, RC (reprint author), Univ Rochester, Dept Neurol, 1351 Mt Hope Ave,Suite 203, Rochester, NY 14620 USA. EM Robert_griggs@urmc.rochester.edu FU NIH [R13 RR024337, U54 NS059065, U54 RR019497, U54-RR019453, U54-RR019478, U54-RR019480, U54-RR019397, U54-RR019484, U54-RR019498, U54-RR019259, U54-HL077878, U54-DK078377] FX R13 RR024337 Merkel, Peter A., Boston University, Boston, MA.; U54 NS059065 Griggs, Robert C., University of Rochester, Rochester, NY.; U54 RR019497 Merkel, Peter, Boston University, Boston, MA.; U54-RR019453 Batshaw, Mark, National Children's Hospital, Washington, DC.; U54-RR019478 Beaudet, Arthur, Baylor College of Medicine, Houston, TX.; U54-RR019480 Knowles, Michael, University of North Carolina, Chapel Hill, NC.; U54-RR019397 Maciejewski, Jaroslaw, Cleveland Clinic College of Medicine-CWRU, Cleveland, OH.; U54-RR019484 New, Maria, Mount Sinai School of Medicine, New York, NY.; U54-RR019498 Trapnell, Bruce, Children's Hospital, Cincinnati, OH.; U54-RR019259 Krischer, Jeff, University of South Florida,Tampa, FL.; U54-HL077878 Ortel, Thomas, Duke University Medical Center, Durham, NC.; U54-DK078377 Sokol, Ronald, Children's Hospital, Denver, CO.; The Rare Diseases Clinical Research Network (RDCRN) Steering Committee includes the following: Barbara Alving, MD, Mark L. Batshaw, MD, Elaine Collier, MD, Robert C. Griggs, MD, Stephen Groft, PharmD, Michael R. Knowles, MD, Peter A. Merkel, MD, MPH, Maria 1. New, MD, Thomas L. Ortel, MD, Ph.D., Alan K. Percy, MD, Ronald J. Sokol, MD, Bruce C. Trapnell, MD, PK Burnette, Ph.D. NR 20 TC 98 Z9 99 U1 0 U2 12 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD JAN PY 2009 VL 96 IS 1 BP 20 EP 26 DI 10.1016/j.ymgme.2008.10.003 PG 7 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 398KV UT WOS:000262731900004 PM 19013090 ER PT J AU Pan, CJ Chen, SY Lee, S Chou, JY AF Pan, Chi-Jiunn Chen, Shih-Yin Lee, Soojung Chou, Janice Y. TI Structure-function study of the glucose-6-phosphate transporter, an eukaryotic antiporter deficient in glycogen storage disease type Ib SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE Glycogen storage disease type I; Antiporter; Glycosylation scanning; G6P transport; Phosphate transport; Endoplasmic reticulum ID PHOSPHOHISTIDINE-ENZYME INTERMEDIATE; MAJOR FACILITATOR SUPERFAMILY; ESCHERICHIA-COLI; GLYCEROL-3-PHOSPHATE TRANSPORTER; PROTEIN; CATALYSIS; SYSTEMS; LIVER; UHPT AB Glycogen storage disease type Ib is caused by deficiencies in the glucose-6-phosphate transporter (GUT), a phosphate (P(i))-linked antiporter capable of homologous (P(i):P(i)) and heterologous (G6P:P(i)) exchanges similar to the bacterial hexose-6-phosphate transporter, UhpT. Protease protection and glycosylation scanning assays have suggested that G6PT is anchored to the endoplasmic reticulum by 10 transmembrane domains. However, recent homology modeling proposed that G6PT may contain 12 helices and that amino acids essential for the functions of UhpT also play important roles in GUT Site-directed mutagenesis and in vitro expression assays demonstrated that only one of the four residues critical for UhpT activity is essential in G6PT. Furthermore, glycosylation scanning and protease sensitivity assays showed that the 10-domain model of G6PT is more probable than the 12-domain UhpT-like model. (C) 2008 Elsevier Inc. All rights reserved. C1 [Pan, Chi-Jiunn; Chen, Shih-Yin; Lee, Soojung; Chou, Janice Y.] NICHHD, Sect Cellular Differentiat, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. RP Chou, JY (reprint author), NICHHD, Sect Cellular Differentiat, Program Dev Endocrinol & Genet, NIH, Bldg 10,Room 9D42,10 Ctr Dr, Bethesda, MD 20892 USA. EM chouja@mail.nih.gov FU NICHD, NIH FX This research was supported in part by the Intramural Research Programs of the NICHD, NIH. NR 30 TC 7 Z9 8 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD JAN PY 2009 VL 96 IS 1 BP 32 EP 37 DI 10.1016/j.ymgme.2008.10.005 PG 6 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 398KV UT WOS:000262731900006 PM 19008136 ER PT J AU Schou, M Zoghbi, SS Shetty, HU Shchukin, E Liow, JS Hong, J Andree, BA Gulyas, B Farde, L Innis, RB Pike, VW Halldin, C AF Schou, Magnus Zoghbi, Sami S. Shetty, H. Umesha Shchukin, Evgeny Liow, Jeih-San Hong, Jinsoo Andree, Bengt A. Gulyas, Balazs Farde, Lars Innis, Robert B. Pike, Victor W. Halldin, Christer TI Investigation of the Metabolites of (S,S)-[C-11] MeNER in Humans, Monkeys and Rats SO MOLECULAR IMAGING AND BIOLOGY LA English DT Article DE MeNER; Metabolism; PET ID NOREPINEPHRINE TRANSPORTER; HUMAN BRAIN; IN-VIVO; UPTAKE SITES; PET; RADIOLIGAND; BINDING; AUTORADIOGRAPHY; REBOXETINE AB Introduction: (S,S)-[C-11] MeNER ((S,S)- 2-(alpha-(2-[C-11] methoxyphenoxy) benzyl) morpholine) is a positron emission tomography (PET) radioligand recently applied in clinical studies of norepinephrine transporters (NETs) in the human brain in vivo. In view of further assessment of the suitability of (S,S)-[C-11] MeNER as a NET radioligand, its metabolism and the identity of the in vivo radiometabolites of (S,S)-[C-11] MeNER are of great interest. Materials and Methods: Thus, PET studies were used to measure brain dynamics of (S,S)-[C-11] MeNER, and plasma reverse-phase radiochromatographic analysis was performed to monitor and quantify its rate of metabolism. Eighteen healthy human volunteers, five cynomolgus monkeys, and five rats were studied. Results and Discussion: In human subjects, the plasma radioactivity representing (S,S)-[C-11] MeNER decreased from 88+/-5% at 4 min after injection to 82+/-7% at 40 min, while a polar radiometabolite increased from 3+/-3% to 16+/-7% at the same time-points, respectively. A more lipophilic radiometabolite than (S,S)-[C-11] MeNER decreased from 9+/-5% at 4 min to 1+/-2% at 40 min. In monkeys, plasma radioactivity representing (S,S)-[C-11] MeNER decreased from 97 +/- 2% at 4 min to 74+/-7% at 45 min, with a polar fraction as the major radiometabolite. A more lipophilic radiometabolite than (S,S)-[C-11] MeNER, constituted 3+/-2% of radioactivity at 4 min and was not detectable later on. In rats, 17+/-4% of plasma radioactivity was parent radioligand at 30 min with the remainder comprising mainly a polar radiometabolite. (S,S)-[C-11] MeNER in rat brain and urine at 30 min after injection were 90% and 4%, respectively. On a brain regional level, parent radioligand ranged from 87.5+/-3.9% (57.2+/-14.2% SUV [standard uptake values, % injected radioactivity per mL multiplied with animal weight (in g)]; cerebellum) to 92.9+/-1.8% (36.1+/-4.7% SUV; striatum), with differential distribution of the radiometabolite in the cerebellum (6.7+/-0.3% SUV) and the striatum (2.5+/-0.3% SUV). Liquid chromatography-mass spectrometry analysis of rat urine identified a hydroxylation product of the methoxyphenoxy ring of (S,S)-MeNER as the main metabolite. In the brain, the corresponding main metabolite was the product from O-de-methylation of (S,S)-MeNER. PET measurements were performed in rats as well as in wild-type and P-gp-knock-out mice. In rats, the brain peak level of radioactivity was found to be very low (65%SUV). In mice, there was only a small difference in peak brain accumulation between P-gp knock-out and wild-type mice (145 vs. 125% SUV) with the following rank order of regional brain radioactivity: cerebellum x thalamus > cortical regions > striatum. Conclusion: It can be concluded that radiometabolites of (S, S)-[C-11]MeNER are of minor importance in rat and monkey brain imaging. The presence of a transient lipophilic radiometabolite in peripheral human plasma may induce complications with brain imaging, but its kinetics appear favorable in relation to the slow kinetics of (S, S)-[C-11]MeNER in humans. C1 [Schou, Magnus; Shchukin, Evgeny; Andree, Bengt A.; Gulyas, Balazs; Farde, Lars; Halldin, Christer] Karolinska Hosp, Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, S-17176 Stockholm, Sweden. [Schou, Magnus; Zoghbi, Sami S.; Shetty, H. Umesha; Liow, Jeih-San; Hong, Jinsoo; Innis, Robert B.; Pike, Victor W.] NIMH, NIH, Mol Imaging Branch, Bethesda, MD 20892 USA. RP Schou, M (reprint author), Karolinska Hosp, Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, S-17176 Stockholm, Sweden. EM magnus.schou@astrazeneca.com RI Gulyas, Balazs/F-9508-2015 FU Intramural NIH HHS [Z01 MH002795-07] NR 19 TC 11 Z9 11 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1536-1632 J9 MOL IMAGING BIOL JI Mol. Imaging. Biol. PD JAN PY 2009 VL 11 IS 1 BP 23 EP 30 DI 10.1007/s11307-008-0175-y PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 403XV UT WOS:000263116200004 PM 18800204 ER PT J AU Park, SK Beaven, MA AF Park, Seung-Kiel Beaven, Michael A. TI Mechanism of upregulation of the inhibitory regulator, src-like adaptor protein (SLAP), by glucocorticoids in mast cells SO MOLECULAR IMMUNOLOGY LA English DT Article DE Mast cells; SLAP; Gene transcription; Glucocorticoids; Glucocorticoid response element ID CBL-DEPENDENT MANNER; C-CBL; GENE-EXPRESSION; NEGATIVE REGULATOR; RBL-2H3 CELLS; RECEPTOR; DEXAMETHASONE; ACTIVATION; KINASE; TRISTETRAPROLIN AB Glucocorticoids suppress mast cell activation by inhibiting signaling events as well as transcription of cytokine genes. The inhibition of signaling events has been attributed to Upregulation of inhibitory regulators Such as Si-c-like adaptor protein1 (SLAP), downstream of tyrosine kinase1 (Dok1), and dual specificity protein phospahatase1 (DUSP1). As reported here. the upregulation of SLAP and Dok1, but not DUSP1, in the RBL-2H3 mast cell line was inhibited by actinomycin D and was thus dependent on gene transcription. Examination of the gene sequences revealed a glucocorticoid response element (GRE) and a half GRE as potential regulators of the SLAP and Dok1, respectively. As indicated by luciferase reporter assays, SLAP GRE, but not the Dok1 half GRE, robustly activated gene transcription after treatment of cells with glucocorticoids. Binding of the glucocorticoid receptor to the SLAP GRE was verified by chromatin immunoprecipitation assay. These findings further support the notion that the immunosuppressive actions of glucocorticoids are exerted in part through upregulation of inhibitory regulators by various mechanisms. In the case of SLAP specifically, this requires activation of gene transcription through the interaction of the glucocorticoid receptor with GRE. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Park, Seung-Kiel; Beaven, Michael A.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. [Park, Seung-Kiel] Chungnam Natl Univ, Coll Med, Dept Biochem, Taejon 301130, South Korea. RP Beaven, MA (reprint author), NHLBI, Lab Mol Immunol, NIH, Room 8N109,Bldg 10, Bethesda, MD 20892 USA. EM beavenm@nhlbi.nih.gov FU National Heart, Lung, and Blood Institute FX The authors thank Drs Tae-Young Rho and Keji Zhao (NHLBI) for helpful advice on the ChIP assay. This work was supported by the Intramural research program of the National Heart, Lung, and Blood Institute. NR 37 TC 13 Z9 14 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD JAN PY 2009 VL 46 IS 3 BP 492 EP 497 DI 10.1016/j.molimm.2008.10.011 PG 6 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 399OY UT WOS:000262810400022 PM 19036452 ER PT J AU Drgon, T Montoya, I Johnson, C Liu, QR Walther, D Hamer, D Uhl, GR AF Drgon, Tomas Montoya, Ivan Johnson, Catherine Liu, Qing-Rong Walther, Donna Hamer, Dean Uhl, George R. TI Genome-Wide Association for Nicotine Dependence and Smoking Cessation Success in NIH Research Volunteers SO MOLECULAR MEDICINE LA English DT Article ID FAGERSTROM TOLERANCE QUESTIONNAIRE; SAMPLE-SIZE CALCULATIONS; MOLECULAR-GENETICS; POLYSUBSTANCE ABUSERS; SUBSTANCE USE; LUNG-CANCER; GENES; TWINS; SNPS; VULNERABILITY AB Phenotypes related to both nicotine dependence and ability to successfully quit smoking display substantial heritabilities in classical and molecular genetic studies. Twin studies suggest that some genetic components for dependence overlap with genetic components of ability to quit, but that many components do not overlap. Initial genome-wide association (GWA) studies have demonstrated haplotypes that distinguish nicotine-dependent from nondependent smokers. These haplotypes overlap partially with those that distinguish individuals who successfully quit smoking from those who were not able to quit smoking in clinical trials for smoking cessation. We now report novel genome-wide association results from National Institutes of Health research volunteers who reported smoking histories, symptoms of nicotine dependence, and ability to successfully quit smoking outside the context of a clinical trial. These results buttress data from several prior GWA studies. The data from these volunteers support the idea that previously reported studies of genes associated with smoking cessation success in clinical trial participants may also apply to smokers who are more or less able to initiate and sustain abstinence outside of clinical trial settings. (C) 2009 The Feinstein Institute for Medical Research, www.feinsteininstitute.org C1 [Drgon, Tomas; Montoya, Ivan; Johnson, Catherine; Liu, Qing-Rong; Walther, Donna; Uhl, George R.] Natl Inst Drug Abuse, Mol Neurobiol Branch, NIH, Intramural Res Program, Baltimore, MD USA. [Montoya, Ivan] Natl Inst Drug Abuse, Div Pharmacotherapies & Med Consequences Drug Ab, NIH, Rockville, MD USA. [Hamer, Dean] NCI, Gene Struct & Regulat Sect, Biochem Lab, NIH,Intramural Res Program, Bethesda, MD 20892 USA. RP Uhl, GR (reprint author), Box 5180, Baltimore, MD 21224 USA. EM guhl@intra.nida.nih.gov RI Liu, Qing-Rong/A-3059-2012 OI Liu, Qing-Rong/0000-0001-8477-6452 FU NIH Intramural Research Programs; National Institute on Drug Abuse; National Institute of Mental Health; National Cancer Institute, Department of Health and Social Services FX We are grateful for thoughtful advice and discussion from Dr. J Rose and for fruitful collaborations with Drs. Rose, Lerman, Niaura, and David. This research was supported financially by the NIH Intramural Research Programs, National Institute on Drug Abuse, National Institute of Mental Health, and National Cancer Institute, Department of Health and Social Services. NR 26 TC 39 Z9 40 U1 1 U2 4 PU FEINSTEIN INST MED RES PI MANHASSET PA 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1076-1551 J9 MOL MED JI Mol. Med. PD JAN-FEB PY 2009 VL 15 IS 1-2 BP 21 EP 27 DI 10.2119/molmed.2008.00096 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 604FI UT WOS:000278262300003 PM 19009022 ER PT J AU Curti, E McDonald, JP Mead, S Woodgate, R AF Curti, Elena McDonald, John P. Mead, Samantha Woodgate, Roger TI DNA polymerase switching: effects on spontaneous mutagenesis in Escherichia coli SO MOLECULAR MICROBIOLOGY LA English DT Article ID SPONTANEOUS MUTATION-RATES; POL-II; REPLICATION ERRORS; SOS MUTAGENESIS; BETA-CLAMP; DEOXYRIBONUCLEIC ACID; GENETIC REQUIREMENTS; MISMATCH CORRECTION; CYCLOBUTANE DIMER; ADAPTIVE MUTATION AB Escherichia coli possesses five known DNA polymerases (pols). Pol III holoenzyme is the cell's main replicase, while pol I is responsible for the maturation of Okazaki fragments and filling gaps generated during nucleotide excision repair. Pols II, IV and V are significantly upregulated as part of the cell's global SOS response to DNA damage and under these conditions, may alter the fidelity of DNA replication by potentially interfering with the ability of pols I and III to complete their cellular functions. To test this hypothesis, we determined the spectrum of rpoB mutations arising in an isogenic set of mutL strains differentially expressing the chromosomally encoded pols. Interestingly, mutagenic hot spots in rpoB were identified that are susceptible to the actions of pols I-V. For example, in a recA730 lexA(Def) mutL background most transversions were dependent upon pols IV and V. In contrast, transitions were largely dependent upon pol I and to a lesser extent, pol III. Furthermore, the extent of pol I-dependent mutagenesis at one particular site was modulated by pols II and IV. Our observations suggest that there is considerable interplay among all five E. coli polymerases that either reduces or enhances the mutagenic load on the E. coli chromosome. C1 [Curti, Elena; McDonald, John P.; Mead, Samantha; Woodgate, Roger] NICHHD, Lab Genom Integr, NIH, Bethesda, MD 20892 USA. RP Woodgate, R (reprint author), NICHHD, Lab Genom Integr, NIH, Bethesda, MD 20892 USA. EM woodgate@nih.gov FU NICHD/NIH Intramural Research Program FX This study was supported by funds from the NICHD/NIH Intramural Research Program. We thank Patricia Foster for her expert advice on statistical analysis of mutation rates and Iwona Fijalkowska, Piotr Jonczyk and members of the Laboratory of Genomic Integrity for their comments on the manuscript. NR 93 TC 24 Z9 25 U1 1 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD JAN PY 2009 VL 71 IS 2 BP 315 EP 331 DI 10.1111/j.1365-2958.2008.06526.x PG 17 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 392LO UT WOS:000262304400004 PM 19019142 ER PT B AU Kane, AB AF Kane, Agnes B. BE Coleman, WB Tsongalis, GJ TI Molecular Pathology The Molecular Basis of Human Disease Foreword SO MOLECULAR PATHOLOGY: THE MOLECULAR BASIS OF HUMAN DISEASE LA English DT Editorial Material; Book Chapter C1 [Kane, Agnes B.] Brown Univ, Dept Pathol & Lab Med, Warren Alpert Med Sch, Providence, RI 02912 USA. [Kane, Agnes B.] Brown Univ, NIEHS Training Program Environm Pathol, Warren Alpert Med Sch, Providence, RI 02912 USA. RP Kane, AB (reprint author), Brown Univ, Dept Pathol & Lab Med, Warren Alpert Med Sch, Providence, RI 02912 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-092219-5; 978-0-12-374419-7 PY 2009 BP XVII EP XVII PG 1 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology GA BIE36 UT WOS:000327879900002 ER PT B AU Pang, ALY Martin, MM Martin, ALA Chan, WY AF Pang, Alan Lap-Yin Martin, Malcolm M. Martin, Arline L. A. Chan, Wai-Yee BE Coleman, WB Tsongalis, GJ TI Molecular Basis of Diseases of the Endocrine System SO MOLECULAR PATHOLOGY: THE MOLECULAR BASIS OF HUMAN DISEASE LA English DT Article; Book Chapter ID PITUITARY-HORMONE DEFICIENCY; THYROID PEROXIDASE GENE; FAMILIAL GLUCOCORTICOID DEFICIENCY; CONGENITAL ADRENAL-HYPERPLASIA; IODIDE ORGANIFICATION DEFECT; THYROTROPIN RECEPTOR GENE; CENTRAL PRECOCIOUS PUBERTY; CALCIUM-SENSING RECEPTOR; OF-THE-LITERATURE; GROWTH-HORMONE C1 [Pang, Alan Lap-Yin; Chan, Wai-Yee] NICHHD, Lab Clin Genom, NIH, Bethesda, MD 20892 USA. [Martin, Arline L. A.; Chan, Wai-Yee] Georgetown Univ, Sch Med, Dept Pediat, Washington, DC 20007 USA. [Chan, Wai-Yee] Georgetown Univ, Med Ctr, Dept Biochem & Mol Biol, Washington, DC 20007 USA. RP Pang, ALY (reprint author), NICHHD, Lab Clin Genom, NIH, Bethesda, MD 20892 USA. NR 153 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-092219-5; 978-0-12-374419-7 PY 2009 BP 435 EP 463 PG 29 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology GA BIE36 UT WOS:000327879900024 ER PT J AU Pan, XG Chen, L Liu, SJ Yang, XJ Gao, JX Lee, RJ AF Pan, Xiaogang Chen, Li Liu, Shujun Yang, Xiaojuan Gao, Jian-Xin Lee, Robert J. TI Antitumor Activity of G3139 Lipid Nanoparticles (LNPs) SO MOLECULAR PHARMACEUTICS LA English DT Article DE CpG motif; G3139; oligodeoxyribonucleotide; lipid nanoparticles; immunotherapy; cancer ID BCL-2 ANTISENSE OLIGONUCLEOTIDE; RECEPTOR-TARGETED LIPOSOMES; CPG OLIGODEOXYNUCLEOTIDES; BACTERIAL-DNA; EFFICIENT DELIVERY; DENDRITIC CELLS; INNATE IMMUNITY; TYPE-1 INNATE; T-CELLS; MOTIFS AB G3139, an antisense oligodeoxyribonucleotide (ODN) against Bcl-2, contains two CpG dinucleotides and has shown immunostimulatory activities in preclinical studies. It has been suggested that immunoactivation, rather than antisense activity, is primarily responsible for the therapeutic efficacy of G3139. Nanoparticle formulations naturally target phagocytic antigen presenting cells and therefore might enhance the immunological effects of G3139. In this study, a novel formulation of lipid nanoparticles (LNPs) encapsulating 63139 was synthesized and evaluated in mice bearing L1210 subcutaneous tumors. Intravenous injection of G3139-LNPs into mice led to increased serum levels of IL-6 and IFN-gamma, promoted proliferation of natural killer (NK) cells and dendritic cells (DCs), and triggered a strong antitumor immune response in mice. The observed effects were much greater than those induced by free G3139. Correspondingly, the G3139-LNPs more effectively inhibited tumor, growth and induced complete tumor regression in some mice. In contrast, free 63139 was ineffective in tumor growth inhibition and did not prolong survival of the tumor-bearing mice. These results suggest that G3139-LNPs are a potential immunomodulatory agent and may have applications in cancer therapy. C1 [Pan, Xiaogang; Yang, Xiaojuan; Lee, Robert J.] Ohio State Univ, Coll Pharm, Div Pharmaceut, Columbus, OH 43210 USA. [Pan, Xiaogang; Yang, Xiaojuan; Lee, Robert J.] Ohio State Univ, NSF NSEC, Affordable Nanoengn Polymer Biomed Devices CANPBD, Columbus, OH 43210 USA. [Chen, Li; Gao, Jian-Xin] Ohio State Univ, Dept Pathol, Columbus, OH 43210 USA. [Liu, Shujun] Ohio State Univ, Dept Internal Med, Coll Med & Publ Hlth, Columbus, OH 43210 USA. [Gao, Jian-Xin; 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 Jian-Xin.Gao@osutnc.edu; lee.1339@osu.edu FU NSF [EEC-0425626]; OSU Comprehensive Cancer Center seed; American Cancer Society [IRG-112367] FX This work was supported in part by NSF Grant EEC-0425626 (R.J.L.), an OSU Comprehensive Cancer Center seed grant (J.-X.G.), and American Cancer Society Grant IRG-112367 (J.-X.G.). NR 33 TC 25 Z9 26 U1 0 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 JAN-FEB PY 2009 VL 6 IS 1 BP 211 EP 220 DI 10.1021/mp800146j PG 10 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 402TC UT WOS:000263035000022 PM 19072654 ER PT J AU Yang, XJ Koh, CG Liu, SJ Pan, XG Santhanam, R Yu, B Peng, Y Pang, JX Golan, S Talmon, Y Jin, Y Muthusamy, N Byrd, JC Chan, KK Lee, LJ Marcucci, G Lee, RJ AF Yang, Xiaojuan Koh, Chee Guan Liu, Shujun Pan, Xiaogang Santhanam, Ramasamy Yu, Bo Peng, Yong Pang, Jiuxia Golan, Sharon Talmon, Yeshayahu Jin, Yan Muthusamy, Natarajan Byrd, John C. Chan, Kenneth K. Lee, L. James Marcucci, Guido Lee, Robert J. TI Transferrin Receptor-Targeted Lipid Nanoparticles for Delivery of an Antisense Oligodeoxyribonucleotide against Bcl-2 SO MOLECULAR PHARMACEUTICS LA English DT Article DE Transferrin receptor; lipid nanoparticles; protamine; antisense oligonucleotide; G3139 ID ACUTE MYELOID-LEUKEMIA; IN-VIVO; SERUM TRANSFERRIN; GENE-TRANSFER; PLASMID DNA; LIPOSOMES; ENCAPSULATION; TRANSCRIPTION; PARTICLES; COMPLEXES AB Antisense oligonucleotide G3139-mediated down-regulation of Bcl-2 is a potential strategy for overcoming chemoresistance in leukemia. However, the limited efficacy shown in recent clinical trials calls attention to the need for further development of novel and more efficient delivery systems. In order to address this issue, transferrin receptor (TfR)-targeted, protamine-containing lipid nanoparticles (Tf-LNs) were synthesized as delivery vehicles for G3139. The LNs were produced by an ethanol dilution method, and lipid-conjugated Tf ligand was then incorporated by a postinsertion method. The resulting Tf-LNs had a mean particle diameter of similar to 90 nm and 63139 loading efficiency of 90.4%. Antisense delivery efficiency of Tf-LNs was evaluated in K562, MV4-11, and Raji leukemia cell lines. The results showed that Tf-LNs were more effective than nontargeted LNs and free 63139 (p < 0.05) in decreasing Bcl-2 expression (by up to 62% at the mRNA level in K562 cells) and in inducing caspase-dependent apoptosis. In addition, Bcl-2 down-regulation and apoptosis induced by Tf-LN 63139 were shown to be blocked by excess free Tf and thus were TfR-dependent. Cell lines with higher TfR expression also showed greater Bcl-2 down-regulation. Furthermore, up-regulation of TfR expression in leukemia cells by iron chelator deferoxamine resulted in a further increase in antisense effect (up to 79% Bcl-2 reduction in K562 at the mRNA level) and in caspase-dependent apoptosis (by similar to 3-fold) by Tf-LN. Tf-LN-mediated delivery combined with TfR up-regulation by deferoxamine appears to be a potentially promising strategy for enhancing the delivery efficiency and therapeutic efficacy of antisense oligonucleotides. C1 [Yang, Xiaojuan; Pan, Xiaogang; Chan, Kenneth K.; Lee, Robert J.] Ohio State Univ, Coll Pharm, Div Pharmaceut, Columbus, OH 43210 USA. [Yang, Xiaojuan; Koh, Chee Guan; Pan, Xiaogang; Yu, Bo; Jin, Yan; Chan, Kenneth K.; Lee, L. James; Lee, Robert J.] Ohio State Univ, NSF NSEC, Affordable Nanoengn Polymer Biomed Devices CANPBD, Columbus, OH 43210 USA. [Koh, Chee Guan; Yu, Bo; Lee, L. James] Ohio State Univ, Dept Chem & Biomol Engn, Columbus, OH 43210 USA. [Liu, Shujun; Santhanam, Ramasamy; Pang, Jiuxia; Byrd, John C.; Chan, Kenneth K.; Marcucci, Guido; Lee, Robert J.] Ohio State Univ, NCI, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Peng, Yong] Ohio State Univ, Dept Mol & Cellular Biochem, Columbus, OH 43210 USA. [Muthusamy, Natarajan; Byrd, John C.; Marcucci, Guido] Ohio State Univ, Div Hematol & Oncol, Columbus, OH 43210 USA. [Golan, Sharon; Talmon, Yeshayahu] Technion Israel Inst Technol, Dept Chem Engn, IL-32000 Haifa, Israel. RP Lee, RJ (reprint author), Ohio State Univ, Coll Pharm, Div Pharmaceut, 500 W 12th Ave, Columbus, OH 43210 USA. EM guido.marcucci@osumc.edu; lee.1339@osu.edu RI Muthusamy, Natarajan/A-6915-2009 FU NSF [EEC-0425626]; NIH [R01 CA135243] FX This work was support in part by NSF Grant EEC-0425626 and NIH Grant R01 CA135243. We wish to thank Dr. Robert Brown at Genta for providing us with oligonucleotides 63139 and 64243 (FITC-63139). NR 31 TC 52 Z9 53 U1 2 U2 9 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 JAN-FEB PY 2009 VL 6 IS 1 BP 221 EP 230 DI 10.1021/mp800149s PG 10 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 402TC UT WOS:000263035000023 PM 19183107 ER PT J AU Woo, AYH Wang, TB Zeng, XK Zhu, WZ Abernethy, DR Wainer, IW Xiao, RP AF Woo, Anthony Yiu-Ho Wang, Tian-Bing Zeng, Xiaokun Zhu, Weizhong Abernethy, Darrell R. Wainer, Irving W. Xiao, Rui-Ping TI Stereochemistry of an Agonist Determines Coupling Preference of beta(2)-Adrenoceptor to Different G Proteins in Cardiomyocytes SO MOLECULAR PHARMACOLOGY LA English DT Article ID DILATED ISCHEMIC CARDIOMYOPATHY; BETA(2) ADRENERGIC-RECEPTOR; FAILING HUMAN-HEART; CARDIAC MYOCYTES; FUNCTIONAL SELECTIVITY; CONFORMATIONAL-CHANGES; SUBTYPE; FAILURE; KINASE; STIMULATION AB A fundamental question regarding receptor-G protein interaction is whether different agonists can lead a receptor to different intracellular signaling pathways. Our previous studies have demonstrated that although most beta(2)-adrenoceptor agonists activate both G(s) and G(i) proteins, fenoterol, a full agonist of beta(2)adrenoceptor, selectively activates G(s) protein. Fenoterol contains two chiral centers and may exist as four stereoisomers. We have synthesized a series of stereoisomers of fenoterol and its derivatives and characterized their receptor binding and pharmacological properties. We tested the hypothesis that the stereochemistry of an agonist determines selectivity of receptor coupling to different G protein(s). We found that the R, R isomers of fenoterol and methoxyfenoterol exhibited more potent effects to increase cardiomyocyte contraction than their S, R isomers. It is noteworthy that although (R,R)-fenoterol and (R,R)-methoxyfenoterol preferentially activate G(s) signaling, their S, R isomers were able to activate both G(s) and G(i) proteins as evidenced by the robust pertussis toxin sensitivities of their effects on cardiomyocyte contraction and on phosphorylation of extracellular signal-regulated kinase 1/2. The differential G protein selectivities of the fenoterol stereoisomers were further confirmed by photoaffinity labeling studies on G(s), G(i2), and G(i3) proteins. The inefficient G(i) signaling with the R, R isomers is not caused by the inability of the R, R isomers to trigger the protein kinase A (PKA)-mediated phosphorylation of the beta(2)-adrenoceptor, because the R, R isomers also markedly increased phosphorylation of the receptor at serine 262 by PKA. We conclude that in addition to receptor subtype and phosphorylation status, the stereochemistry of a given agonist plays an important role in determining receptor-G protein selectivity and downstream signaling events. C1 [Woo, Anthony Yiu-Ho] NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. [Abernethy, Darrell R.; Wainer, Irving W.] NIA, Clin Invest Lab, NIH, Baltimore, MD 21224 USA. [Wang, Tian-Bing] Peking Univ, Peoples Hosp, Dept Orthopaed & Trauma, Beijing 100871, Peoples R China. RP Woo, AYH (reprint author), NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM wooa@mail.nih.gov RI Woo, Anthony/D-4305-2014 OI Woo, Anthony/0000-0003-0662-698X FU National Institutes of Health; National Institute on Aging FX This work was supported by the intramural research program of the National Institutes of Health, National Institute on Aging (to A.Y.H.W., D.R.A., I.W.W., R.P.X., T.B.W., W.Z., X.Z.) NR 40 TC 60 Z9 63 U1 0 U2 4 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 JAN PY 2009 VL 75 IS 1 BP 158 EP 165 DI 10.1124/mol.108.051078 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 386AK UT WOS:000261854500017 PM 18838481 ER PT J AU Bai, R Edler, MC Bonate, PL Copeland, TD Pettit, GR Luduena, RF Hamel, E AF Bai, Ruoli Edler, Michael C. Bonate, Peter L. Copeland, Terry D. Pettit, George R. Luduena, Richard F. Hamel, Ernest TI Intracellular Activation and Deactivation of Tasidotin, an Analog of Dolastatin 15: Correlation with Cytotoxicity SO MOLECULAR PHARMACOLOGY LA English DT Article ID ANTINEOPLASTIC AGENTS; PHASE-I; ANTIMITOTIC AGENTS; CELL-LINES; TUBULIN; LU103793; PEPTIDE; CANCER; INHIBITION; GROWTH AB Tasidotin, an oncolytic drug in phase II clinical trials, is a peptide analog of the antimitotic depsipeptide dolastatin 15. In tasidotin, the carboxyl-terminal ester group of dolastatin 15 has been replaced by a carboxy-terminal tert-butyl amide. As expected from studies with cemadotin, [(3)H]tasidotin, with the radiolabel in the second proline residue, was hydrolyzed intra-cellularly, with formation of N,N-dimethylvalyl-valyl-N-methyl-valyl-prolyl-proline (P5), a pentapeptide also present in dolastatin 15 and cemadotin. P5 was more active as an inhibitor of tubulin polymerization and less active as a cytotoxic agent than tasidotin, cemadotin, and dolastatin 15. [3H] P5 was not the end product of tasidotin metabolism. Large amounts of [3H] proline were formed in every cell line studied, with proline ultimately becoming the major radiolabeled product. The putative second product of the hydrolysis of P5, N, N-dimethylvalyl-valyl-N-methyl-valyl-proline (P4), had little activity as either an antitubulin or cytotoxic agent. In seven suspension cell lines, the cytotoxicity of tasidotin correlated with total cell uptake of the compound and was probably affected negatively by the extent of degradation of P5 to proline and, presumably, P4. The intracellular enzyme prolyl oligopeptidase probably degrades tasidotin to P5. When CCRF-CEM human leukemia cells were treated with N-benzyl-oxycarbonylprolylprolinal (BCPP), an inhibitor of prolyl oligopeptidase, there was a 30-fold increase in the IC(50) of tasidotin and a marked increase in intracellular [(3)H] tasidotin. BCPP also caused a 4-fold increase in the IC(50) of P5, so the enzyme probably does not convert P5 to P4. Inhibiting degradation of P5 should have led to a decrease in the IC(50) obtained for P5 in the presence of BCPP. C1 [Bai, Ruoli; Edler, Michael C.; Hamel, Ernest] NCI, Toxicol & Pharmacol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Ft Detrick, MD 21702 USA. [Bonate, Peter L.] Genzyme Corp, San Antonio, TX USA. [Copeland, Terry D.] NCI, Lab Prot Dynam & Signalling, Ctr Canc Res, NIH, Ft Detrick, MD 21702 USA. [Pettit, George R.] Arizona State Univ, Dept Chem & Biochem, Tempe, AZ USA. [Luduena, Richard F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. RP Hamel, E (reprint author), NCI, Toxicol & Pharmacol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Bldg 469,Room 104, Ft Detrick, MD 21702 USA. EM hamele@mail.nih.gov NR 25 TC 18 Z9 19 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD JAN PY 2009 VL 75 IS 1 BP 218 EP 226 DI 10.1124/mol.108.051110 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 386AK UT WOS:000261854500023 PM 18927208 ER PT J AU Zuchner, S Wendland, JR Ashley-Koch, AE Collins, AL Tran-Viet, KN Quinn, K Timpano, KC Cuccaro, ML Pericak-Vance, MA Steffens, DC Krishnan, KR Feng, G Murphy, DL AF Zuchner, S. Wendland, J. R. Ashley-Koch, A. E. Collins, A. L. Tran-Viet, K. N. Quinn, K. Timpano, K. C. Cuccaro, M. L. Pericak-Vance, M. A. Steffens, D. C. Krishnan, K. R. Feng, G. Murphy, D. L. TI Multiple rare SAPAP3 missense variants in trichotillomania and OCD SO MOLECULAR PSYCHIATRY LA English DT Letter ID OBSESSIVE-COMPULSIVE DISORDER; ASSOCIATION C1 [Zuchner, S.; Cuccaro, M. L.; Pericak-Vance, M. A.] Univ Miami, Miller Sch Med, Miami Inst Human Genom, Miami, FL 33136 USA. [Wendland, J. R.; Timpano, K. C.; Murphy, D. L.] NIMH, NIH, Intramural Res Program, Clin Sci Lab, Bethesda, MD 20892 USA. [Ashley-Koch, A. E.; Collins, A. L.; Tran-Viet, K. N.; Quinn, K.] Duke Univ, Med Ctr, Ctr Human Genet, Durham, NC USA. [Steffens, D. C.; Krishnan, K. R.] Duke Univ, Med Ctr, Dept Psychiat, Durham, NC 27710 USA. [Feng, G.] Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC 27710 USA. RP Zuchner, S (reprint author), Univ Miami, Miller Sch Med, Miami Inst Human Genom, Miami, FL 33136 USA. EM szuchner@med.miami.edu RI Wendland, Jens/A-1809-2012; Timpano, Kiara/C-8760-2012; OI Timpano, Kiara/0000-0002-0665-8722; Ashley-Koch, Allison/0000-0001-5409-9155 FU Intramural NIH HHS [ZIA MH000336-30]; NINDS NIH HHS [P01 NS026630, P01 NS026630-19] NR 9 TC 67 Z9 69 U1 0 U2 5 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 JAN PY 2009 VL 14 IS 1 BP 6 EP 9 DI 10.1038/mp.2008.83 PG 5 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 386EY UT WOS:000261866300003 PM 19096451 ER PT J AU Cichon, S Craddock, N Daly, M Faraone, SV Gejman, PV Kelsoe, J Lehner, T Levinson, DF Moran, A Sklar, P Sullivan, PF AF Cichon, Sven Craddock, Nick Daly, Mark Faraone, Stephen V. Gejman, Pablo V. Kelsoe, John Lehner, Thomas Levinson, Douglas F. Moran, Audra Sklar, Pamela Sullivan, Patrick F. CA Psychiatric GWAS Consortium Steeri TI A framework for interpreting genome-wide association studies of psychiatric disorders The Psychiatric GWAS Consortium Steering Committee SO MOLECULAR PSYCHIATRY LA English DT Article DE genome-wide association; attention-deficit hyperactivity disorder; autism; bipolar disorder; major depressive disorder; schizophrenia ID COMMON DISEASE; HAPLOTYPE MAP; SCHIZOPHRENIA; PSYCHOSIS; VARIANTS; OBESITY; RISK; GENE AB Genome-wide association studies (GWAS) have yielded a plethora of new findings in the past 3 years. By early 2009, GWAS on 47 samples of subjects with attention-deficit hyperactivity disorder, autism, bipolar disorder, major depressive disorder and schizophrenia will be completed. Taken together, these GWAS constitute the largest biological experiment ever conducted in psychiatry ( 59 000 independent cases and controls, 7700 family trios and > 40 billion genotypes). We know that GWAS can work, and the question now is whether it will work for psychiatric disorders. In this review, we describe these studies, the Psychiatric GWAS Consortium for meta-analyses of these data, and provide a logical framework for interpretation of some of the conceivable outcomes. C1 [Sklar, Pamela] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. [Cichon, Sven] Univ Bonn, D-5300 Bonn, Germany. [Craddock, Nick] Cardiff Univ, Cardiff, S Glam, Wales. [Daly, Mark] Harvard Univ, Sch Med, Broad Inst, Cambridge, MA 02138 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, New York, NY USA. [Gejman, Pablo V.] Northwestern Univ, Evanston NW Healthcare & Feinberg Sch Med, Evanston, IL 60208 USA. [Kelsoe, John] Univ Calif San Diego, San Diego, CA 92103 USA. [Lehner, Thomas] NIMH, Bethesda, MD 20892 USA. [Levinson, Douglas F.] Stanford Univ, Stanford, CA 94305 USA. [Sklar, Pamela] Massachusetts Gen Hosp, Broad Inst, Boston, MA 02114 USA. RP Sullivan, PF (reprint author), Univ N Carolina, Dept Genet, CB 7264,4109D Neurosci Res Bldg, Chapel Hill, NC 27599 USA. EM pfsulliv@med.unc.edu RI turton, miranda/F-4682-2011; Franke, Barbara/D-4836-2009; Cichon, Sven/H-8803-2013; Cichon, Sven/B-9618-2014 OI Franke, Barbara/0000-0003-4375-6572; Cichon, Sven/0000-0002-9475-086X; Cichon, Sven/0000-0002-9475-086X FU NIMH [MH085520]; Netherlands Scientific Organization [NWO 480-05-003]; Dutch Brain Foundation; NARSAD FX This article was written early in the history of the PGC by its coordinating committee who takes responsibility for its content. We wish to acknowledge our enduring debt to our PGC colleagues for their many contributions to this work. The members of the PGC Coordinating Committee are: Sven Cichon (University of Bonn), Nick Craddock (Cardiff University), Mark Daly (Harvard Medical School, Broad Institute), Stephen V Faraone (SUNY Upstate Medical University), Pablo V Gejman (Evanston Northwestern Healthcare and Feinberg School of Medicine, Northwestern University), John Kelsoe (University of California, San Diego), Thomas Lehner (NIMH), Douglas F Levinson (Stanford University), Audra Moran (NARSAD, ex officio), Pamela Sklar (Massachusetts General Hospital, Broad Institute) and Patrick F Sullivan (University of North Carolina at Chapel Hill). The PGC is supported by NIMH MH085520 (http://www.nimh.gov). Statistical analyses are conducted on the Genetic Cluster Computer, which is supported by the Netherlands Scientific Organization (NWO 480-05-003, PI Danielle Posthuma) along with a supplement from the Dutch Brain Foundation (http://www.hersenstichting.nl, PI Roel Ophoff). We are indebted to NARSAD for infrastructure support. NR 28 TC 103 Z9 104 U1 0 U2 12 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 JAN PY 2009 VL 14 IS 1 BP 10 EP 17 DI 10.1038/mp.2008.126 PG 8 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 386EY UT WOS:000261866300004 ER PT J AU O'Donovan, MC Norton, N Williams, H Peirce, T Moskvina, V Nikolov, I Hamshere, M Carroll, L Georgieva, L Dwyer, S Holmans, P Marchini, JL Spencer, CCA Howie, B Leung, HT Giegling, I Hartmann, AM Moller, HJ Morris, DW Shi, Y Feng, G Hoffmann, P Propping, P Vasilescu, C Maier, W Rietschel, M Zammit, S Schumacher, J Quinn, EM Schulze, TG Iwata, N Ikeda, M Darvasi, A Shifman, S He, L Duan, J Sanders, AR Levinson, DF Adolfsson, R Osby, U Terenius, L Jonsson, EG Cichon, S Nothen, MM Gill, M Corvin, AP Rujescu, D Gejman, PV Kirov, G Craddock, N Williams, NM Owen, MJ AF O'Donovan, M. C. Norton, N. Williams, H. Peirce, T. Moskvina, V. Nikolov, I. Hamshere, M. Carroll, L. Georgieva, L. Dwyer, S. Holmans, P. Marchini, J. L. Spencer, C. C. A. Howie, B. Leung, H-T Giegling, I. Hartmann, A. M. Moeller, H.-J. Morris, D. W. Shi, Y. Feng, G. Hoffmann, P. Propping, P. Vasilescu, C. Maier, W. Rietschel, M. Zammit, S. Schumacher, J. Quinn, E. M. Schulze, T. G. Iwata, N. Ikeda, M. Darvasi, A. Shifman, S. He, L. Duan, J. Sanders, A. R. Levinson, D. F. Adolfsson, R. Osby, U. Terenius, L. Jonsson, E. G. Cichon, S. Noethen, M. M. Gill, M. Corvin, A. P. Rujescu, D. Gejman, P. V. Kirov, G. Craddock, N. Williams, N. M. Owen, M. J. CA Mol Genetics Schizophrenia Collabo TI Analysis of 10 independent samples provides evidence for association between schizophrenia and a SNP flanking fibroblast growth factor receptor 2 SO MOLECULAR PSYCHIATRY LA English DT Article DE FGFR2; schizophrenia; genome-wide association study ID GENOME-WIDE ASSOCIATION; POSSIBLE SUSCEPTIBILITY LOCUS; BIPOLAR AFFECTIVE-DISORDER; PSYCHIATRIC-DISORDERS; GENE-EXPRESSION; SCAN; LINKAGE; POPULATION; VARIANTS; FAMILIES AB We and others have previously reported linkage to schizophrenia on chromosome 10q25-q26 but, to date, a susceptibility gene in the region has not been identified. We examined data from 3606 single-nucleotide polymorphisms (SNPs) mapping to 10q25-q26 that had been typed in a genome-wide association study (GWAS) of schizophrenia (479 UK cases/2937 controls). SNPs with P < 0.01 (n = 40) were genotyped in an additional 163 UK cases and those markers that remained nominally significant at P < 0.01 (n = 22) were genotyped in replication samples from Ireland, Germany and Bulgaria consisting of a total of 1664 cases with schizophrenia and 3541 controls. Only one SNP, rs17101921, was nominally significant after meta-analyses across the replication samples and this was genotyped in an additional six samples from the United States/Australia, Germany, China, Japan, Israel and Sweden (n = 5142 cases/6561 controls). Across all replication samples, the allele at rs17101921 that was associated in the GWAS showed evidence for association independent of the original data (OR 1.17 (95% CI 1.06-1.29), P = 0.0009). The SNP maps 85 kb from the nearest gene encoding fibroblast growth factor receptor 2 (FGFR2) making this a potential susceptibility gene for schizophrenia. C1 [O'Donovan, M. C.; Norton, N.; Williams, H.; Peirce, T.; Moskvina, V.; Nikolov, I.; Hamshere, M.; Carroll, L.; Georgieva, L.; Dwyer, S.; Holmans, P.; Zammit, S.; Kirov, G.; Craddock, N.; Williams, N. M.; Owen, M. J.] Cardiff Univ, Sch Med, Dept Psychol Med, Cardiff, S Glam, Wales. [Marchini, J. L.; Spencer, C. C. A.; Howie, B.] Univ Oxford, Dept Stat, Oxford OX1 3TG, England. [Leung, H-T] Univ Cambridge, Dept Med Genet, Juvenile Diabet Res Fdn, Wellcome Trust Diabet & Inflammat Lab, Cambridge, England. [Giegling, I.; Hartmann, A. M.; Rujescu, D.] Univ Munich, Div Mol & Clin Neurobiol, Munich, Germany. [Moeller, H.-J.] Univ Munich, Dept Psychiat, D-8000 Munich, Germany. [Morris, D. W.; Quinn, E. M.; Gill, M.; Corvin, A. P.] Trinity Coll Dublin, Sch Med, Neuropsychiat Genet Res Grp, Dublin, Ireland. [Shi, Y.; He, L.] Shanghai Jiao Tong Univ, Bio X Ctr, Shanghai 200030, Peoples R China. [Feng, G.] Shanghai Inst Mental Hlth, Shanghai, Peoples R China. [Hoffmann, P.; Vasilescu, C.; Cichon, S.; Noethen, M. M.] Univ Bonn, Dept Genom, Life & Brain Ctr, D-5300 Bonn, Germany. [Propping, P.; Cichon, S.; Noethen, M. M.] Univ Bonn, Inst Human Genet, D-5300 Bonn, Germany. [Maier, W.] Univ Bonn, Dept Psychiat, D-5300 Bonn, Germany. [Rietschel, M.] Cent Inst Mental Hlth, Div Genet Epidemiol Psychiat, D-6800 Mannheim, Germany. [Schumacher, J.; Schulze, T. G.] NIMH, NIH, Bethesda, MD 20892 USA. [Iwata, N.; Ikeda, M.] Fujita Hlth Univ, Sch Med, Dept Psychiat, Aichi, Japan. [Iwata, N.; Ikeda, M.] Japan Sci & Technol Agcy, CREST, Saitama, Japan. [Darvasi, A.; Shifman, S.] Hebrew Univ Jerusalem, Inst Life Sci, Dept Genet, IL-91904 Jerusalem, Israel. [He, L.] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Shanghai, Peoples R China. [Duan, J.; Sanders, A. R.; Gejman, P. V.] Northwestern Univ, Evanston NW Healthcare, Ctr Psychiat Genet, Evanston, IL USA. [Duan, J.; Sanders, A. R.; Gejman, P. V.] Northwestern Univ, Feinberg Sch Med, Evanston, IL USA. [Levinson, D. F.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Adolfsson, R.] Umea Univ, Dept Clin Sci, Div Psychiat, Umea, Sweden. [Osby, U.; Terenius, L.; Jonsson, E. G.] Karolinska Inst, Dept Clin Neurosci, HUBIN Project, Stockholm, Sweden. RP O'Donovan, MC (reprint author), Cardiff Univ, Sch Med, Dept Psychol Med, Cardiff, S Glam, Wales. EM odonovanmc@cf.ac.uk; owenmj@cf.ac.uk RI Schulze, Thomas/H-2157-2013; Cichon, Sven/H-8803-2013; Cichon, Sven/B-9618-2014; Holmans, Peter/F-4518-2015; Schumacher, Johannes/F-4970-2015; Shifman, Sagiv/D-8749-2017; OI Morris, Derek/0000-0002-3413-570X; Gill, Michael/0000-0003-0206-5337; Cichon, Sven/0000-0002-9475-086X; Cichon, Sven/0000-0002-9475-086X; Holmans, Peter/0000-0003-0870-9412; Schumacher, Johannes/0000-0001-9217-6457; Shifman, Sagiv/0000-0003-4071-5361; Zammit, Stanley/0000-0002-2647-9211; Corvin, Aiden/0000-0001-6717-4089; O'Donovan, Michael/0000-0001-7073-2379; Buccola, Nancy/0000-0003-1378-4636; Escott-Price, Valentina/0000-0003-1784-5483; Adolfsson, Rolf/0000-0001-9785-8473; Jonsson, Erik/0000-0001-8368-6332; Nothen, Markus/0000-0002-8770-2464; Hoffmann, Per/0000-0002-6573-983X FU Wellcome Trust [076113]; MRC; NIMH (USA) CONTE [2 P50 MH066392-05A1]; Science Foundation Ireland; Health Research Board (Ireland); National Genomic Network of the 'Bundesministerium fur Bildung und Forschung' (BMBF); GlaxoSmithKline; Swedish Research Council [K2007-62X-15078-04-3, K2008-62P-20597-01-3]; Wallenberg Foundation; HUBIN FX This study makes use of data generated by the Wellcome Trust Case Control Consortium. A full list of the investigators who contributed to the generation of the data is available from www.wtccc.org.uk. Funding for the project was provided by the Wellcome Trust under award 076113. The UK research was supported by grants from the MRC, the Wellcome Trust and by a NIMH (USA) CONTE: 2 P50 MH066392-05A1. In Dublin, the research was supported by Science Foundation Ireland, the Health Research Board (Ireland), and the Wellcome Trust. We are grateful to Professor John Waddington for sample recruitment. Irish controls were supplied by Dr Joe McPartlin and the Trinity College Biobank. In Bonn and Mannheim, the work was supported by the National Genomic Network of the 'Bundesministerium fur Bildung und Forschung' (BMBF), the Alfried Krupp von Bohlen und Halbach-Stiftung and in Bethesda the work was supported in part by the Intramural Program of the NIMH. We also thank the Department of Psychiatry, LMU Munich for clinical characterization of the Munich subjects and the processing of the samples. Recruitment in Munich was partially supported by GlaxoSmithKline. The Ashkenazi samples are part of the Hebrew University Genetic Resource, HUGR (www.hugr.org). In Sweden support was obtained from the Swedish Research Council (K2007-62X-15078-04-3, K2008-62P-20597-01-3), the Wallenberg Foundation and the HUBIN project. The following authors are included under the Molecular Genetics of Schizophrenia Collaboration: PV Gejman, AR Sanders, J Duan (Evanston Healthcare and Northwestern University, IL, USA), DF Levinson (Stanford University, CA, USA), NG Buccola (Louisiana State University, LA, USA), BJ Mowry (University of Queensland, Brisbane, Australia), R Freedman (University of Colorado Health Science Centre, Denver, USA), F Amin (Emory University, Atlanta, USA), DW Black (University of Iowa College of Medicine, IA, USA), JM Silverman (Mount Sinai School of Medicine, New York, USA), WJ Byerley (University of California, San Francisco, USA), CR Cloninger (Washington University). NR 38 TC 42 Z9 42 U1 2 U2 6 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 JAN PY 2009 VL 14 IS 1 BP 30 EP 36 DI 10.1038/mp.2008.108 PG 7 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 386EY UT WOS:000261866300006 PM 18813210 ER PT J AU Yasuda, S Liang, MH Marinova, Z Yahyavi, A Chuang, DM AF Yasuda, S. Liang, M-H Marinova, Z. Yahyavi, A. Chuang, D-M TI The mood stabilizers lithium and valproate selectively activate the promoter IV of brain-derived neurotrophic factor in neurons SO MOLECULAR PSYCHIATRY LA English DT Article DE BDNF promoter IV; lithium; VPA; GSK-3; HDAC; cortical culture ID GLYCOGEN-SYNTHASE KINASE-3; RAT BDNF-GENE; HISTONE DEACETYLASE; GLUTAMATE EXCITOTOXICITY; TRANSCRIPTION FACTOR; CALCIUM REGULATION; MESSENGER-RNA; EXPRESSION; PHOSPHORYLATION; ACID AB Brain-derived neurotrophic factor (BDNF) has been strongly implicated in the synaptic plasticity, neuronal survival and pathophysiology of depression. Lithium and valproic acid (VPA) are two primary mood-stabilizing drugs used to treat bipolar disorder. Treatment of cultured rat cortical neurons with therapeutic concentrations of LiCl or VPA selectively increased the levels of exon IV (formerly rat exon III)-containing BDNF mRNA, and the activity of BDNF promoter IV. Surprisingly, lithium- or VPA-responsive element(s) in promoter IV resides in a region upstream from the calcium-responsive elements (CaREs) responsible for depolarization-induced BDNF induction. Moreover, activation of BDNF promoter IV by lithium or VPA occurred in cortical neurons depolarized with KCl, and deletion of these three CaREs did not abolish lithium- or VPA-induced activation. Lithium and VPA are direct inhibitors of glycogen synthase kinase-3 (GSK-3) and histone deacetylase (HDAC), respectively. We showed that lithium-induced activation of promoter IV was mimicked by pharmacological inhibition of GSK-3 or short interfering RNA (siRNA)-mediated gene silencing of GSK-3 alpha or GSK-3 beta isoforms. Furthermore, treatment with other HDAC inhibitors, sodium butyrate and trichostatin A, or transfection with an HDAC1-specific siRNA also activated BDNF promoter IV. Our study demonstrates for the first time that GSK-3 and HDAC are respective initial targets for lithium and VPA to activate BDNF promoter IV, and that this BDNF induction involves a novel responsive region in promoter IV of the BDNF gene. Our results have strong implications for the therapeutic actions of these two mood stabilizers. C1 [Yasuda, S.; Liang, M-H; Marinova, Z.; Yahyavi, A.; Chuang, D-M] NIMH, NIH, Mol Neurobiol Sect, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RP Chuang, DM (reprint author), NIMH, NIH, Mol Neurobiol Sect, Mood & Anxiety Disorders Program, Bldg 10,Rm 3D38,10 Ctr Dr,MSC 1363, Bethesda, MD 20892 USA. EM chuang@mail.nih.gov FU NIMH; NIH; NARSAD FX This work was supported by the intramural research fund of NIMH, NIH and the NARSAD Distinguished Investigator Award. We thank Dr Hirotoshi Fuda in NICHD, NIH for advice in the real-time PCR experiments. We are also grateful to Dr Yan Leng and Peter Leeds in the Molecular Neurobiology Section, NIMH for discussions and the NIH Fellows Editorial Board for editorial assistance. NR 48 TC 164 Z9 170 U1 1 U2 12 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 JAN PY 2009 VL 14 IS 1 BP 51 EP 59 DI 10.1038/sj.mp.4002099 PG 9 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 386EY UT WOS:000261866300008 PM 17925795 ER PT B AU McElhinny, SAN Pursell, ZF Kunkel, TA AF McElhinny, Stephanie A. Nick Pursell, Zachary F. Kunkel, Thomas A. BE Cox, LS TI Mechanisms for High Fidelity DNA Replication SO MOLECULAR THEMES IN DNA REPLICATION LA English DT Article; Book Chapter ID THYMINE-THYMINE DIMER; CEREVISIAE CDC2 GENE; HUMAN GINS COMPLEX; SACCHAROMYCES-CEREVISIAE; POLYMERASE-DELTA; TRANSLESION SYNTHESIS; CRYSTAL-STRUCTURE; SOMATIC HYPERMUTATION; MISMATCH REPAIR; ERROR-PRONE C1 [McElhinny, Stephanie A. Nick; Pursell, Zachary F.; Kunkel, Thomas A.] NIEHS, Labs Mol Genet & Struct Biol, DHHS, NIH, Res Triangle Pk, NC 27709 USA. RP McElhinny, SAN (reprint author), NIEHS, Labs Mol Genet & Struct Biol, DHHS, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 96 TC 2 Z9 2 U1 0 U2 2 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, CAMBRIDGE CB4 4WF, CAMBS, ENGLAND BN 978-0-85404-164-0 PY 2009 BP 86 EP 111 D2 10.1039/9781847559852 PG 26 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BLV56 UT WOS:000271175600004 ER PT J AU Lee, H Larson, RG AF Lee, Hwankyu Larson, Ronald G. TI Multiscale Modeling of Dendrimers and Their Interactions with Bilayers and Polyelectrolytes SO MOLECULES LA English DT Review DE Simulation of dendrimer; Dendrimer-bilayer interaction; Dendrimer-induced pore formation; Dendrimer-DNA interaction ID SUPPORTED LIPID-BILAYERS; COARSE-GRAINED MODEL; MOLECULAR-DYNAMICS SIMULATIONS; POLY(AMIDOAMINE) DENDRIMERS; PAMAM DENDRIMER; PORE FORMATION; LINEAR POLYELECTROLYTES; POLYCATIONIC POLYMERS; STARBURST DENDRIMERS; HOLE FORMATION AB Recent advances in molecular dynamics simulation methodologies and computational power have allowed accurate predictions of dendrimer size, shape, and interactions with bilayers and polyelectrolytes with modest computational effort. Atomistic and coarse-grained (CG) models show strong interactions of cationic dendrimers with lipid bilayers. The CG simulations with explicit lipid and water capture bilayer penetration and pore formation, showing that pore formation is enhanced at high dendrimer concentration, but suppressed at low temperature and high salt concentration, in agreement with experiments. Cationic linear polymers have also been simulated, but do not perforate membranes, evidently because by deforming into a pancake, the charges on a linear polymer achieve intimate contact with a single bilayer leaflet. The relatively rigid dendrimers, on the other hand, penetrate the bilayer, because only by interacting with both leaflets can they achieve a similar degree of contact between charged groups. Also, a "dendrimer-filled vesicle" structure for the dendrimer-membrane interaction is predicted by mesoscale thermodynamic simulations, in agreement with a picture derived from experimental observations. In simulations of complexes of dendrimer and polyelectrolyte, anionic linear chains wrap around the cationic dendrimer and penetrate inside it. Overall, these new results indicate that simulations can now provide predictions in excellent agreement with experimental observations, and provide atomic-scale insights into dendrimer structure and dynamics. C1 [Lee, Hwankyu] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. [Larson, Ronald G.] Univ Michigan, Dept Chem Engn, Ann Arbor, MI 48109 USA. [Larson, Ronald G.] Univ Michigan, Dept Biomed Engn, Ann Arbor, MI 48109 USA. [Larson, Ronald G.] Univ Michigan, Dept Mech Engn, Ann Arbor, MI 48109 USA. [Larson, Ronald G.] Univ Michigan, Dept Macromol Sci, Ann Arbor, MI 48109 USA. [Larson, Ronald G.] Univ Michigan, Engn Program, Ann Arbor, MI 48109 USA. RP Lee, H (reprint author), NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. EM leeh3@nhlbi.nih.gov; rlarson@umich.edu FU NIH; National Heart, Lung and Blood Institute FX This work was supported by the Intramural Research Program of the NIH, National Heart, Lung and Blood Institute. NR 42 TC 68 Z9 68 U1 5 U2 47 PU MOLECULAR DIVERSITY PRESERVATION INTERNATIONAL-MDPI PI BASEL PA KANDERERSTRASSE 25, CH-4057 BASEL, SWITZERLAND SN 1420-3049 J9 MOLECULES JI Molecules PD JAN PY 2009 VL 14 IS 1 BP 423 EP 438 DI 10.3390/molecules14010423 PG 16 WC Chemistry, Organic SC Chemistry GA 399HO UT WOS:000262791200035 PM 19158654 ER PT S AU Winslow, JT AF Winslow, James T. BE Gould, TD TI Ultrasonic Vocalizations by Infant Mice: An Ethological Expression of Separation Anxiety SO MOOD AND ANXIETY RELATED PHENOTYPES IN MICE: CHARACTERIZATION USING BEHAVIORAL TESTS SE Neuromethods LA English DT Article; Book Chapter DE Ultrasonic vocalization; isolation calling; mice; rats; rodents; crying; infant; separation anxiety; emotion; maternal separation; depression; mood ID RAT PUPS; LARYNGEAL BRAKING; ANIMAL-MODELS; MOUSE MODELS; BEHAVIOR; RESPONSES; CALLS; POTENTIATION; EXPERIENCE; NORVEGICUS AB The ultrasonic vocalization, or isolation calling, of infant rats and mice has been studied as a measure of anxious affective state and as an early communicative behavior between a pup and mother. The protocol described herein is the typical separation testing procedure. Also included arc procedures used to modulate crying by providing contact with littermates and/or dam and increased isolation calling response by a prior brief maternal interaction. These procedures provide the basis for experimental research on the early development of emotion and communication in a critically important experimental model species - the mouse. C1 NIMH IRP Neurobiol, NIH, Bethesda, MD 20892 USA. RP Winslow, JT (reprint author), NIMH IRP Neurobiol, NIH, Bethesda, MD 20892 USA. NR 56 TC 1 Z9 1 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 0893-2336 BN 978-1-60761-302-2 J9 NEUROMETHODS JI Neuromethods PY 2009 VL 42 BP 67 EP 84 DI 10.1007/978-1-60761-303-9_5 D2 10.1007/978-1-60761-303-9 PG 18 WC Neurosciences; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA BMR46 UT WOS:000273395200005 ER PT B AU Blair, J AF Blair, James BE Verplaetse, J DeSchrijver, J Vanneste, S Braeckman, J TI Neuro-Cognitive Systems Involved in Moral Reasoning SO MORAL BRAIN: ESSAYS ON THE EVOLUTIONARY AND NEUROSCIENTIFIC ASPECTS OF MORALITY LA English DT Article; Book Chapter ID FUNCTIONAL MRI C1 NIMH, US Dept HHS, Mood & Anxiety Program, NIH, Bethesda, MD 20892 USA. RP Blair, J (reprint author), NIMH, US Dept HHS, Mood & Anxiety Program, NIH, Bethesda, MD 20892 USA. EM JamesBlair@mail.nih.gov NR 8 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 978-1-4020-6286-5 PY 2009 BP 87 EP 107 DI 10.1007/978-1-4020-6287-2_4 D2 10.1007/978-1-4020-6287-2 PG 21 WC Psychology, Biological; Behavioral Sciences; Evolutionary Biology; Neurosciences; Philosophy; Psychology, Social SC Psychology; Behavioral Sciences; Evolutionary Biology; Neurosciences & Neurology; Philosophy GA BLD60 UT WOS:000269971800004 ER PT B AU Qiang, YW Rudikoff, S AF Qiang, Ya-Wei Rudikoff, Stuart BE Georgiev, M Bachev, E TI Wnt Signaling Pathways in Multiple Myeloma SO MULTIPLE MYELOMA: SYMPTOMS, DIAGNOSIS AND TREATMENT SE Cancer Etiology Diagnosis and Treatments LA English DT Article; Book Chapter ID BONE-MARROW MICROENVIRONMENT; MESENCHYMAL STEM-CELLS; SOLUBLE RECEPTOR ACTIVATOR; RHO-ASSOCIATED KINASE; KAPPA-B LIGAND; BETA-CATENIN; IN-VIVO; PLASMA-CELLS; OSTEOCLAST DIFFERENTIATION; PROMOTES PROLIFERATION AB Multiple myeloma is a malignancy of terminally differentiated, antibody-secreting plasma cells frequently associated with osteolytic bone lesions. Wnt signaling is critical in normal bone development and homeostasis, and defects in Wnt signaling pathways have been associated with skeletal diseases. Recent identification of activated Wnt signaling and production of Wnt antagonists (e.g. Dkk1) in multiple myeloma (MM) has attracted attention to the importance of this signaling pathway in myeloma pathogenesis and osteolytic bone disease. Functional signaling through two distinct Wnt pathways (Wnt/beta-catenin and Wnt/RhoA) has been characterized in MM plasma cells. Additionally, Wnt/beta-catenin signaling plays a significant role in directly regulating osteoblast function responsible for bone formation and indirectly controlling osteoclast function leading to bone resorption. The disruption of this pathway by myeloma plasma cell-derived Dkk1 in the bone marrow microenvironment results in suppression of osteoblast differentiation and enhanced osteoclast function via inhibition of production of regulatory molecules, such as osteoprotegerin, normally produced by osteoblasts. Activation of Wnt/RhoA signaling is also associated with myeloma cell adhesion and drug resistance. Increase in Wnt/beta-catenin signaling by Wnt ligands or blockage of Dkkl via specific antibody prevents MM-induced bone disease and inhibits myeloma cell growth in vivo. Herein, we review the current understanding of Wnt signaling in myeloma pathogenesis and bone disease and discuss potential therapeutic implications of modulating this pathway in the treatment of MM. C1 [Qiang, Ya-Wei] Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA. [Rudikoff, Stuart] NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Qiang, YW (reprint author), Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, 4301 W Markham St,Slot 776, Little Rock, AR 72205 USA. EM yqiang@uams.edu NR 144 TC 1 Z9 1 U1 0 U2 0 PU NOVA SCIENCE PUBLISHERS, INC PI HAUPPAUGE PA 400 OSER AVE, STE 1600, HAUPPAUGE, NY 11788-3635 USA BN 978-1-60876-108-1 J9 CANCER ETIOL DIAGN T PY 2009 BP 51 EP 75 PG 25 WC Biochemistry & Molecular Biology; Oncology; Hematology SC Biochemistry & Molecular Biology; Oncology; Hematology GA BNU91 UT WOS:000275618900002 ER PT J AU Iacobaeus, E Ryschkewitsch, C Gravell, M Khademi, M Wallstrom, E Olsson, T Brundin, L Major, EO AF Iacobaeus, E. Ryschkewitsch, C. Gravell, M. Khademi, M. Wallstrom, E. Olsson, T. Brundin, L. Major, E. O. TI Analysis of cerebrospinal fluid and cerebrospinal fluid cells from patients with multiple sclerosis for detection of JC virus DNA SO MULTIPLE SCLEROSIS LA English DT Article DE cerebrospinal fluid; JC virus DNA; multiple sclerosis; progressive multifocal; leukoencephalopathy ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; NUCLEOTIDE-SEQUENCES; HUMAN POLYOMAVIRUSES; NATALIZUMAB; BK; LYMPHOCYTES; ANTIBODY; HEALTHY; DISEASE; SAMPLES AB Objective 1) To determine whether JC virus (JCV) DNA was present in the cerebrospinal fluid (CSF) and blood from patients with multiple sclerosis (MS) in comparison with controls and 2) to find out if our clinical material, based on presence of JCV DNA, included any patient at risk for progressive multifocal leukoencephalopathy (PML). Methods The prevalence of JCV DNA was analyzed in CSF and plasma from 217 patients with MS, 86 patients with clinically isolated syndrome (CIS), and 212 patients with other neurological diseases (OND). In addition, we analyzed CSF cells, the first report of JCV DNA in CSF cells in a single sample, and peripheral blood cells in a subgroup of MS (n = 49), CIS (n = 14) and OND ( n = 53). Results A low copy number of JCV DNA was detected in one MS cell free CSF sample and in one MS CSF cell samples. None of these had any signs of PML or developed this disease during follow-up. In addition, two OND plasma samples were JCV DNA positive, whereas all the other samples had no detectable virus. Results A low copy number of JCV DNA was detected in one MS cell free CSF sample and in one MS CSF cell samples. None of these had any signs of PML or developed this disease during follow-up. In addition, two OND plasma samples were JCV DNA positive, whereas all the other samples had no detectable virus. Conclusion A low copy number of JCV DNA may occasionally be observed both in MS and other diseases and may occur as part of the normal biology of JC virus in humans. This study does not support the hypothesis that patients with MS would be at increased risk to develop PML, and consequently screening of CSF as a measurable risk for PML is not useful. Multiple Sclerosis 2009; 15: 28-35. http://msj.sagepub.com C1 [Iacobaeus, E.] Karolinska Univ Hosp, Karolinska Inst, CMM, Neuroimmunol Unit,Dept Clin Neurosci, SE-17176 Stockholm, Sweden. [Ryschkewitsch, C.; Gravell, M.; Major, E. O.] NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. RP Iacobaeus, E (reprint author), Karolinska Univ Hosp, Karolinska Inst, CMM, Neuroimmunol Unit,Dept Clin Neurosci, L8 04, SE-17176 Stockholm, Sweden. EM Ellen.lacobaeus@karolinska.se OI Khademi, Mohsen/0000-0003-0801-1444 FU Torsten and Ragnar Soderberg Foundation, the Swedish research council; NeuroProMise [(LSHM-CT-2005-018637] FX This study was supported through the NINDS Division of Intramural Research, by Torsten and Ragnar Soderberg Foundation, the Swedish research council, and NeuroProMise (LSHM-CT-2005-018637). NR 34 TC 29 Z9 30 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 J9 MULT SCLER JI Mult. Scler. PD JAN PY 2009 VL 15 IS 1 BP 28 EP 35 DI 10.1177/1352458508096870 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 387IY UT WOS:000261947100004 PM 18805840 ER PT J AU Goel, P Sherman, A Friedman, A AF Goel, Pranay Sherman, Arthur Friedman, Avner TI MULTISCALE MODELING OF ELECTRICAL AND INTRACELLULAR ACTIVITY IN THE PANCREAS: THE ISLET TRIDOMAIN EQUATIONS SO MULTISCALE MODELING & SIMULATION LA English DT Article DE homogenization; islet multiscale modeling; formal asymptotic expansion ID SYNCYTIAL TISSUES; CELL; HOMOGENIZATION; OSCILLATIONS; LANGERHANS; DIFFUSION; BURSTERS; BOUNDARY AB We derive continuum models of the electrical syncytia of the pancreatic islet of Langerhans using homogenization. Beta-cells in the islets are coupled in their intra-and extracellular potential fields via membrane currents and can exchange calcium (and metabolite) via direct intracellular communication through gap junctional connections. In earlier work, Goel, Sneyd, and Friedman [Multiscale Model. Simul., 5 (2006), pp. 1045-1062] have derived homogenized models of cytosolic calcium and endoplasmic reticulum (ER) calcium in cells. The islet tridomain presented here extends that scheme to three domains: the extracellular space, the cytosol, and the intracellular ER (or sarcoplasmic reticulum (SR)) are each represented at every point in space. We also consider three different models of gap junctions: as pores, as semipermeable membranes, and as thin conductors. We derive the macroscopic equations for all three cases. The islet tridomain equations are different depending on the gap junction model. In addition, we study the consequences of beta-cell heterogeneity, and the arrangement of heterogeneous cells in the islet, for the macroscopic equations. C1 [Goel, Pranay; Sherman, Arthur] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA. [Friedman, Avner] Ohio State Univ, Math Biosci Inst, Columbus, OH 43210 USA. RP Goel, P (reprint author), Indian Inst Sci Educ & Res, Pune 411021, Maharashtra, India. EM goelpra@mail.nih.gov; asherman@nih.gov; afriedman@mbi.osu.edu RI Goel, Pranay/D-1081-2013; OI Goel, Pranay/0000-0002-2249-0288 FU National Science Foundation [0112050] FX This work was performed by an employee of the U.S. Government or under U. S. Government contract. The U. S. Government retains a nonexclusive, royalty-free license to publish or reproduce the published form of this contribution, or allow others to do so, for U.S. Government purposes. Copyright is owned by SIAM to the extent not limited by these rights. The first author (partially) and the third author were supported by the National Science Foundation under agreement 0112050. NR 24 TC 1 Z9 1 U1 0 U2 3 PU SIAM PUBLICATIONS PI PHILADELPHIA PA 3600 UNIV CITY SCIENCE CENTER, PHILADELPHIA, PA 19104-2688 USA SN 1540-3459 J9 MULTISCALE MODEL SIM JI Multiscale Model. Simul. PY 2009 VL 7 IS 4 BP 1609 EP 1642 DI 10.1137/080736053 PG 34 WC Mathematics, Interdisciplinary Applications; Physics, Mathematical SC Mathematics; Physics GA 499BY UT WOS:000270192800005 ER PT J AU Groll, AH Mickiene, D Petraitiene, R Petraitis, V Piscitelli, S Walsh, TJ AF Groll, A. H. Mickiene, D. Petraitiene, R. Petraitis, V. Piscitelli, S. Walsh, T. J. TI Pharmacodynamics of posaconazole in a neutropenic animal model of invasive pulmonary Aspergillosis SO MYCOSES LA English DT Meeting Abstract C1 [Groll, A. H.] Childrens Univ Hosp, Munster, Germany. [Mickiene, D.; Petraitiene, R.; Petraitis, V.; Walsh, T. J.] NCI, Bethesda, MD 20892 USA. [Piscitelli, S.] NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0933-7407 J9 MYCOSES JI Mycoses PY 2009 VL 52 BP 24 EP 25 PG 2 WC Dermatology; Mycology SC Dermatology; Mycology GA 514UU UT WOS:000271422000068 ER PT J AU Walsh, TJ Pyrgos, V Kasai, M Harrington, SM Hope, WW Wubneh, R Petraitiene, R Petraitis, V Greene, L Aghamolla, T Suffredini, AF Wayne, AS Gea-Banacloche, J Holland, SM Malech, HL Childs, R Fahle, G Kemp, M Shea, Y Murray, PR AF Walsh, T. J. Pyrgos, V. Kasai, M. Harrington, S. M. Hope, W. W. Wubneh, R. Petraitiene, R. Petraitis, V. Greene, L. Aghamolla, T. Suffredini, A. F. Wayne, A. S. Gea-Banacloche, J. Holland, S. M. Malech, H. L. Childs, R. Fahle, G. Kemp, M. Shea, Y. Murray, P. R. TI Bench to bedside: development and implementation of a clinical protocol for the early molecular detection for the improved diagnosis of invasive pulmonary aspergillosis and zygomycosis SO MYCOSES LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0933-7407 J9 MYCOSES JI Mycoses PY 2009 VL 52 BP 51 EP 52 PG 2 WC Dermatology; Mycology SC Dermatology; Mycology GA 514UU UT WOS:000271422000134 ER PT J AU Simitsopoulou, M Georgiadou, E Walsh, TJ Roilides, E AF Simitsopoulou, M. Georgiadou, E. Walsh, T. J. Roilides, E. TI Comparison of the effects of deoxycholate amphotericin B and amphotericin B lipid complex on the gene exression of inflammatory cytokines and receptors in human monocytes exposed to Candida albicans SO MYCOSES LA English DT Meeting Abstract C1 [Simitsopoulou, M.; Georgiadou, E.; Roilides, E.] Aristotle Univ Thessaloniki, GR-54006 Thessaloniki, Greece. [Walsh, T. J.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0933-7407 J9 MYCOSES JI Mycoses PY 2009 VL 52 BP 98 EP 98 PG 1 WC Dermatology; Mycology SC Dermatology; Mycology GA 514UU UT WOS:000271422000251 ER PT J AU Simitsopoulou, M Georgiadou, E Walsh, TJ Roilides, E AF Simitsopoulou, M. Georgiadou, E. Walsh, T. J. Roilides, E. TI Expression of inflammatory cytokines and receptors in human monocytes exposed to Aspergillus fumigatus hyphae, amphotericin B and amphotericin B lipid complex SO MYCOSES LA English DT Meeting Abstract C1 [Simitsopoulou, M.; Georgiadou, E.; Roilides, E.] Aristotle Univ Thessaloniki, GR-54006 Thessaloniki, Greece. [Walsh, T. J.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0933-7407 J9 MYCOSES JI Mycoses PY 2009 VL 52 BP 98 EP 98 PG 1 WC Dermatology; Mycology SC Dermatology; Mycology GA 514UU UT WOS:000271422000250 ER PT J AU Stergiopoulou, T Meletiadis, J Walsh, TJ Roilides, E AF Stergiopoulou, T. Meletiadis, J. Walsh, T. J. Roilides, E. TI In vitro interactions of antifungal agents with fluoroquinolones in the presence of cyclosporine or neutrophils against Candida albicans and Aspergillus fumigatus SO MYCOSES LA English DT Meeting Abstract C1 [Stergiopoulou, T.; Roilides, E.] Aristotle Univ Thessaloniki, GR-54006 Thessaloniki, Greece. [Meletiadis, J.] Univ Athens, Athens, Greece. [Walsh, T. J.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0933-7407 J9 MYCOSES JI Mycoses PY 2009 VL 52 BP 112 EP 113 PG 2 WC Dermatology; Mycology SC Dermatology; Mycology GA 514UU UT WOS:000271422000290 ER PT B AU Devalapally, H Clogston, JD Amiji, MM McNeil, S Stern, ST AF Devalapally, Harikrishna Clogston, Jeffrey D. Amiji, Mansoor M. McNeil, Scott Stern, Stephan T. BE Laudon, M Romanowicz, B TI Use of PBMC Partitioning to Predict RES-Uptake of a Nanoemulsion in a Colon Cancer Xenograft SO NANOTECH CONFERENCE & EXPO 2009, VOL 2, TECHNICAL PROCEEDINGS LA English DT Proceedings Paper CT Nanotech 2009 Conference CY MAY 03-07, 2009 CL Houston, TX SP Acctron AG, Adv Energy Consortium, Alliance NanoHealth, Appl Mat, Bayer MaterialScience, Buchanan Ingersoll & Rooney PC, Buhler PARTEC GmbH, Ctr Appl Nanotechnol GmbH, Ctr Biol & Environm Nanotechnol, Clean Technol & Sustainable Ind Org, CMP, CTC Nanotechnol GmbH, DREEBIT GmbH, ETH Zurich, ETH Transfer, ETH Zurich, MNSP, Folcy & Lardner LLP, FDA, Goodwin Procter LLC, HiNanoAnalytics, Houston Technol Ctr, Inno X GmbH, Innovat Alliance Carbon Nanotubes, Italian Tradde Commiss, Jackson Walket LLP, JENOPTIK, Lockheed Martin, Nano Sci & Technol Inst, nano tech 2009 Japan, NanoEurope Fair & Conf, Nanograde Llc, NanoInk, NANOSENSORS, NanoSPRINT, NanoWorld AG, NCI, NIH, Opportun Houston, OSEC, Pearland Econ Dev Corp, Res Germany Land Ideas, Richard Smalley Inst Nanoscale Sci & Technol, Taylor & Francis Grp LLC, CRC Press, TechConnect, Texas Nanotechnol Initiat, IEEE Stand Assoc, Russian Corp Nanotechnologies, TurboBeads Llc, Weidmann Plast Technol AG C1 [Devalapally, Harikrishna; Clogston, Jeffrey D.; McNeil, Scott; Stern, Stephan T.] NCI, Adv Technol Program, Nanotechnol Characterizat Lab, SAIC Frederick, Ft Detrick, MD 21702 USA. RP Devalapally, H (reprint author), NCI, Adv Technol Program, Nanotechnol Characterizat Lab, SAIC Frederick, Ft Detrick, MD 21702 USA. EM devalapallyh@mail.nih.gov RI Amiji, Mansoor/A-4365-2014 OI Amiji, Mansoor/0000-0001-6170-881X NR 0 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4398-1783-4 PY 2009 BP 56 EP 57 PG 2 WC Biotechnology & Applied Microbiology; Engineering, Biomedical; Nanoscience & Nanotechnology SC Biotechnology & Applied Microbiology; Engineering; Science & Technology - Other Topics GA BMQ02 UT WOS:000273330500016 ER PT B AU Georgiev, VS AF Georgiev, Vassil St. BA StGeorgiev, V BF StGeorgiev, V TI National Institute of Allergy and Infectious Diseases, NIH Volume 2 Impact on Global Health Introduction SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 2: IMPACT ON GLOBAL HEALTH SE Infectious Disease LA English DT Editorial Material; Book Chapter C1 NIAID, Off Global Res, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Georgiev, VS (reprint author), NIAID, Off Global Res, Dept Hlth & Human Serv, NIH, 6610 Rockledge Dr, Bethesda, MD 20892 USA. EM vgeorgiev@niaid.nih.gov NR 0 TC 1 Z9 1 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-296-4 J9 INFECT DIS PY 2009 BP 3 EP 7 DI 10.1007/978-1-60327-297-1_1 D2 10.1007/978-1-60327-297-1 PG 5 WC Infectious Diseases SC Infectious Diseases GA BKI41 UT WOS:000268206400001 ER PT S AU Koonin, EV AF Koonin, Eugene V. BE Witzany, G TI On the Origin of Cells and Viruses Primordial Virus World Scenario SO NATURAL GENETIC ENGINEERING AND NATURAL GENOME EDITING SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on Natural Genetic Engineering and Natural Genome Editing CY JUL 03-06, 2008 CL Salzburg, AUSTRIA DE comparative genomics; evolution of cells; evolution of viruses; origin of membranes; viral hallmark genes ID UNIVERSAL COMMON ANCESTOR; DNA-REPLICATION PROTEINS; TRANSFER-RNA SYNTHETASES; HORIZONTAL GENE-TRANSFER; COMPARATIVE GENOMICS; EVOLUTIONARY TRANSITIONS; PHYLOGENETIC TREES; CELLULAR EVOLUTION; BIG-BANG; LIFE AB It is proposed that the precellular stage of biological evolution unraveled within networks of inorganic compartments that harbored a diverse mix of virus-like genetic elements. This stage of evolution might makes up the Last Universal Cellular Ancestor (LUCA) that more appropriately could be denoted Last Universal Cellular Ancestral State (LUCAS). Such a scenario recapitulates the ideas of J. B. S. Haldane sketched in his classic 1928 essay. However, unlike in Haldane's day, considerable support for this scenario exits today: lack of homology between core DNA replication system components in archaea and bacteria, distinct membrane chemistries and enzymes of lipid biosynthesis in archaea and bacteria, spread of several viral hallmark genes among diverse groups of viruses, and the extant archaeal and bacterial chromosomes appear to be shaped by accretion of diverse, smaller replicons. Under the viral model of precellular evolution, the key components of cells originated as components of virus-like entities. The two surviving types of cellular life forms, archaea and bacteria, might have emerged from the LUCAS independently, along with, probably, numerous forms now extinct. C1 NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. RP Koonin, EV (reprint author), NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bldg 10, Bethesda, MD 20892 USA. EM koonin@nebi.nlm.nih.gov FU National Institutes of Health, National Library of Medicine FX Valerian Dolja, Bill Martin, Tania Senkevich, and Yuri Wolf contributed to the development of various aspects of this model. I also thank the participants of the meeting on the LUCA at Fondacion Les Treilles (France), in September, 2007, and specifically, the organizers of the meeting, Patrick Forterre, Celine Brochier-Armanet, and Simonetta Gribaldo, for most helpful discussions during which the acronym LUCAS was coined collectively This work was supported by the Intramural Research Program of the National Institutes of Health, National Library of Medicine. NR 107 TC 43 Z9 46 U1 3 U2 13 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-765-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2009 VL 1178 BP 47 EP 64 DI 10.1111/j.1749-6632.2009.04992.x PG 18 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Science & Technology - Other Topics GA BOV05 UT WOS:000277729600004 PM 19845627 ER PT J AU Kim, YC Gerlitz, G Furusawa, T Catez, F Nussenzweig, A Oh, KS Kraemer, KH Shiloh, Y Bustin, M AF Kim, Yong-Chul Gerlitz, Gabi Furusawa, Takashi Catez, Frederic Nussenzweig, Andre Oh, Kyu-Seon Kraemer, Kenneth H. Shiloh, Yosef Bustin, Michael TI Activation of ATM depends on chromatin interactions occurring before induction of DNA damage SO NATURE CELL BIOLOGY LA English DT Article ID DOUBLE-STRAND BREAKS; CHROMOSOMAL-PROTEIN HMGN1; HIGH-MOBILITY; CHECKPOINT; ACETYLATION; REPAIR; MDC1; AUTOPHOSPHORYLATION; PHOSPHORYLATION; MEDIATOR AB Efficient and correct responses to double-stranded breaks (DSB) in chromosomal DNA are crucial for maintaining genomic stability and preventing chromosomal alterations that lead to cancer(1,2). The generation of DSB is associated with structural changes in chromatin and the activation of the protein kinase ataxia-telangiectasia mutated (ATM), a key regulator of the signalling network of the cellular response to DSB(3,4). The interrelationship between DSB-induced changes in chromatin architecture and the activation of ATM is unclear(4). Here we show that the nucleosome-binding protein HMGN1 modulates the interaction of ATM with chromatin both before and after DSB formation, thereby optimizing its activation. Loss of HMGN1 or ablation of its ability to bind to chromatin reduces the levels of ionizing radiation (IR)-induced ATM autophosphorylation and the activation of several ATM targets. IR treatments lead to a global increase in the acetylation of Lys 14 of histone H3 (H3K14) in an HMGN1-dependent manner and treatment of cells with histone deacetylase inhibitors bypasses the HMGN1 requirement for efficient ATM activation. Thus, by regulating the levels of histone modifications, HMGN1 affects ATM activation. Our studies identify a new mediator of ATM activation and demonstrate a direct link between the steady-state intranuclear organization of ATM and the kinetics of its activation after DNA damage. C1 [Kim, Yong-Chul; Gerlitz, Gabi; Furusawa, Takashi; Catez, Frederic; Bustin, Michael] NCI, Lab Metab, CCR, NIH, Bethesda, MD 20892 USA. [Nussenzweig, Andre] NCI, Expt Immunol Branch, CCR, NIH, Bethesda, MD 20892 USA. [Oh, Kyu-Seon; Kraemer, Kenneth H.] NCI, Basic Res Lab, CCR, NIH, Bethesda, MD 20892 USA. [Shiloh, Yosef] Tel Aviv Univ, Sackler Sch Med, Dept Human Mol Genet & Biochem, IL-69978 Tel Aviv, Israel. RP Bustin, M (reprint author), NCI, Lab Metab, CCR, NIH, Bethesda, MD 20892 USA. EM bustin@helix.nih.gov RI Bustin, Michael/G-6155-2015 FU NCI; A-T Medical Research Foundation; A-T Children's Project; The Israel Science Foundation; A-T Medical Research Trust; Israel-Germany Joint Program on Cancer Research; A-T Ease Foundation FX We thank A. Celeste (NCI) for advice and help, and S. Garfield (Confocal Core Facility of the LEC, NCI), for help with imaging. The research was supported by the intramural program of the NCI. Work in the laboratory of Y. S. is supported by the A-T Medical Research Foundation, the A-T Children's Project, The Israel Science Foundation, the A-T Medical Research Trust, the Israel-Germany Joint Program on Cancer Research, and the A-T Ease Foundation. NR 32 TC 80 Z9 81 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD JAN PY 2009 VL 11 IS 1 BP 92 EP U192 DI 10.1038/ncb1817 PG 12 WC Cell Biology SC Cell Biology GA 390IH UT WOS:000262157000016 PM 19079244 ER PT J AU Cohen, SD Kimmel, PL AF Cohen, Scott D. Kimmel, Paul L. TI Renal biopsy is necessary for the diagnosis of HIV-associated renal diseases SO NATURE CLINICAL PRACTICE NEPHROLOGY LA English DT Editorial Material ID INFECTED PATIENTS; KIDNEY-DISEASE; NEPHROPATHY; RECOMMENDATIONS C1 [Kimmel, Paul L.] George Washington Univ, Med Ctr, Dept Med, Div Renal Dis & Hypertens, Washington, DC 20037 USA. [Cohen, Scott D.] Columbia Univ, Div Nephrol, Dept Med, Coll Phys & Surg, New York, NY USA. [Kimmel, Paul L.] NIDDK, HIV Kidney Program, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD USA. RP Kimmel, PL (reprint author), George Washington Univ, Med Ctr, Dept Med, Div Renal Dis & Hypertens, 2150 Penn Ave NW, Washington, DC 20037 USA. EM pkimmel@mfa.gwu.edu NR 13 TC 14 Z9 14 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1745-8323 J9 NAT CLIN PRACT NEPHR JI Nat. Clin. Pract. Nephrol. PD JAN PY 2009 VL 5 IS 1 BP 22 EP 23 DI 10.1038/ncpneph0990 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 385ED UT WOS:000261795200010 PM 19015655 ER PT J AU Manolio, TA AF Manolio, Teri A. TI Cohort studies and the genetics of complex disease SO NATURE GENETICS LA English DT Editorial Material AB Three new studies identify nearly 20 new loci for serum lipid levels using predominantly a prospective cohort study design which also permits extensive and unbiased characterization of environmental exposures. Given the known, strong environmental influences on these traits, investigation of gene-environment interactions should be emphasized in attempts to understand the complete epidemiologic and genetic architecture of these complex traits. C1 NHGRI, NIH, Bethesda, MD 20892 USA. RP Manolio, TA (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA. EM manolio@nih.gov NR 10 TC 76 Z9 76 U1 0 U2 8 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 JAN PY 2009 VL 41 IS 1 BP 5 EP 6 DI 10.1038/ng0109-5 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 389IE UT WOS:000262085300002 PM 19112455 ER PT J AU Whitby, D AF Whitby, Denise TI Searching for targets of viral microRNAs SO NATURE GENETICS LA English DT Editorial Material ID SARCOMA-ASSOCIATED HERPESVIRUS; ENCODED MICRORNAS; IDENTIFICATION; EXPRESSION; MIR-155; CELLS AB The identification of targets of virally encoded microRNAs is essential to understanding their role in the viral life cycle. a new study reports the successful use of a microarray-based approach to identify a key target of a microRNA encoded by Kaposi's sarcoma-associated herpesvirus, with implications for microRNA target identification in other contexts as well. C1 NCI, Viral Oncol Sect, AIDS & Canc Virus Program, SAIC Frederick, Frederick, MD 21701 USA. RP Whitby, D (reprint author), NCI, Viral Oncol Sect, AIDS & Canc Virus Program, SAIC Frederick, POB B, Frederick, MD 21701 USA. EM whitbyd@ncifcrf.gov NR 15 TC 5 Z9 5 U1 1 U2 1 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 JAN PY 2009 VL 41 IS 1 BP 7 EP 8 DI 10.1038/ng0109-7 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 389IE UT WOS:000262085300003 PM 19112456 ER PT J AU Willer, CJ Speliotes, EK Loos, RJF Li, SX Lindgren, CM Heid, IM Berndt, SI Elliott, AL Jackson, AU Lamina, C Lettre, G Lim, N Lyon, HN McCarroll, SA Papadakis, K Qi, L Randall, JC Roccasecca, RM Sanna, S Scheet, P Weedon, MN Wheeler, E Zhao, JH Jacobs, LC Prokopenko, I Soranzo, N Tanaka, T Timpson, NJ Almgren, P Bennett, A Bergman, RN Bingham, SA Bonnycastle, LL Brown, M Burtt, NLP Chines, P Coin, L Collins, FS Connell, JM Cooper, C Smith, GD Dennison, EM Deodhar, P Elliott, P Erdos, MR Estrada, K Evans, DM Gianniny, L Gieger, C Gillson, CJ Guiducci, C Hackett, R Hadley, D Hall, AS Havulinna, AS Hebebrand, J Hofman, A Isomaa, B Jacobs, KB Johnson, T Jousilahti, P Jovanovic, Z Khaw, KT Kraft, P Kuokkanen, M Kuusisto, J Laitinen, J Lakatta, EG Luan, J Luben, RN Mangino, M McArdle, WL Meitinger, T Mulas, A Munroe, PB Narisu, N Ness, AR Northstone, K O'Rahilly, S Purmann, C Rees, MG Ridderstraale, M Ring, SM Rivadeneira, F Ruokonen, A Sandhu, MS Saramies, J Scott, LJ Scuteri, A Silander, K Sims, MA Song, K Stephens, J Stevens, S Stringham, HM Tung, YCL Valle, TT Van Duijn, CM Vimaleswaran, KS Vollenweider, P Waeber, G Wallace, C Watanabe, RM Waterworth, DM Watkins, N Witteman, JCM Zeggini, E Zhai, GJ Zillikens, MC Altshuler, D Caulfield, MJ Chanock, SJ Farooqi, IS Ferrucci, L Guralnik, JM Hattersley, AT Hu, FB Jarvelin, MR Laakso, M Mooser, V Ong, KK Ouwehand, WH Salomaa, V Samani, NJ Spector, TD Tuomi, T Tuomilehto, J Uda, M Uitterlinden, AG Wareham, NJ Deloukas, P Frayling, TM Groop, LC Hayes, RB Hunter, DJ Mohlke, KL Peltonen, L Schlessinger, D Strachan, DP Wichmann, HE McCarthy, MI Boehnke, M Barroso, I Abecasis, GR Hirschhorn, JN AF Willer, Cristen J. Speliotes, Elizabeth K. Loos, Ruth J. F. Li, Shengxu Lindgren, Cecilia M. Heid, Iris M. Berndt, Sonja I. Elliott, Amanda L. Jackson, Anne U. Lamina, Claudia Lettre, Guillaume Lim, Noha Lyon, Helen N. McCarroll, Steven A. Papadakis, Konstantinos Qi, Lu Randall, Joshua C. Roccasecca, Rosa Maria Sanna, Serena Scheet, Paul Weedon, Michael N. Wheeler, Eleanor Zhao, Jing Hua Jacobs, Leonie C. Prokopenko, Inga Soranzo, Nicole Tanaka, Toshiko Timpson, Nicholas J. Almgren, Peter Bennett, Amanda Bergman, Richard N. Bingham, Sheila A. Bonnycastle, Lori L. Brown, Morris Burtt, Noel L. P. Chines, Peter Coin, Lachlan Collins, Francis S. Connell, John M. Cooper, Cyrus Smith, George Davey Dennison, Elaine M. Deodhar, Parimal Elliott, Paul Erdos, Michael R. Estrada, Karol Evans, David M. Gianniny, Lauren Gieger, Christian Gillson, Christopher J. Guiducci, Candace Hackett, Rachel Hadley, David Hall, Alistair S. Havulinna, Aki S. Hebebrand, Johannes Hofman, Albert Isomaa, Bo Jacobs, Kevin B. Johnson, Toby Jousilahti, Pekka Jovanovic, Zorica Khaw, Kay-Tee Kraft, Peter Kuokkanen, Mikko Kuusisto, Johanna Laitinen, Jaana Lakatta, Edward G. Luan, Jian'an Luben, Robert N. Mangino, Massimo McArdle, Wendy L. Meitinger, Thomas Mulas, Antonella Munroe, Patricia B. Narisu, Narisu Ness, Andrew R. Northstone, Kate O'Rahilly, Stephen Purmann, Carolin Rees, Matthew G. Ridderstrale, Martin Ring, Susan M. Rivadeneira, Fernando Ruokonen, Aimo Sandhu, Manjinder S. Saramies, Jouko Scott, Laura J. Scuteri, Angelo Silander, Kaisa Sims, Matthew A. Song, Kijoung Stephens, Jonathan Stevens, Suzanne Stringham, Heather M. Tung, Y. C. Loraine Valle, Timo T. Van Duijn, Cornelia M. Vimaleswaran, Karani S. Vollenweider, Peter Waeber, Gerard Wallace, Chris Watanabe, Richard M. Waterworth, Dawn M. Watkins, Nicholas Witteman, Jacqueline C. M. Zeggini, Eleftheria Zhai, Guangju Zillikens, M. Carola Altshuler, David Caulfield, Mark J. Chanock, Stephen J. Farooqi, I. Sadaf Ferrucci, Luigi Guralnik, Jack M. Hattersley, Andrew T. Hu, Frank B. Jarvelin, Marjo-Riitta Laakso, Markku Mooser, Vincent Ong, Ken K. Ouwehand, Willem H. Salomaa, Veikko Samani, Nilesh J. Spector, Timothy D. Tuomi, Tiinamaija Tuomilehto, Jaakko Uda, Manuela Uitterlinden, Andre G. Wareham, Nicholas J. Deloukas, Panagiotis Frayling, Timothy M. Groop, Leif C. Hayes, Richard B. Hunter, David J. Mohlke, Karen L. Peltonen, Leena Schlessinger, David Strachan, David P. Wichmann, H-Erich McCarthy, Mark I. Boehnke, Michael Barroso, Ines Abecasis, Goncalo R. Hirschhorn, Joel N. CA Wellcome Trust Case Control Giant Consortium TI Six new loci associated with body mass index highlight a neuronal influence on body weight regulation SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; CORONARY-ARTERY-DISEASE; FTO GENE; ALCOHOL DEPENDENCE; COMMON VARIANTS; NEURITE OUTGROWTH; CHILDHOOD OBESITY; ADULT OBESITY; EXPRESSION; MICE AB Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 x 10(-8)): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity. C1 [Speliotes, Elizabeth K.; Lyon, Helen N.; Hirschhorn, Joel N.] Harvard & Massachusetts Inst Technol, Broad Inst, Metabol Initiat, Cambridge, MA 02142 USA. [Speliotes, Elizabeth K.; Lyon, Helen N.; Hirschhorn, Joel N.] Harvard & Massachusetts Inst Technol, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Speliotes, Elizabeth K.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Willer, Cristen J.; Jackson, Anne U.; Scott, Laura J.; Stringham, Heather M.; Boehnke, Michael] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA. [Loos, Ruth J. F.; Li, Shengxu; Zhao, Jing Hua; Gillson, Christopher J.; Luan, Jian'an; Sandhu, Manjinder S.; Sims, Matthew A.; Vimaleswaran, Karani S.; Wareham, Nicholas J.] Addenbrookes Hosp, MRC, Epidemiol Unit, Cambridge CB2 0QQ, England. [Loos, Ruth J. F.; Li, Shengxu; Zhao, Jing Hua; Gillson, Christopher J.; Jovanovic, Zorica; Luan, Jian'an; Purmann, Carolin; Sims, Matthew A.; Farooqi, I. Sadaf; Ong, Ken K.; Wareham, Nicholas J.] Addenbrookes Hosp, Inst Metab Sci, Cambridge CB2 0QQ, England. [Lindgren, Cecilia M.; Randall, Joshua C.; Prokopenko, Inga; Zeggini, Eleftheria; McCarthy, Mark I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. [Heid, Iris M.; Gieger, Christian; Wichmann, H-Erich] Helmholtz Zentrum Munchen, Inst Epidemiol, D-85764 Neuherberg, Germany. [Berndt, Sonja I.; Chanock, Stephen J.; Hayes, Richard B.] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Lettre, Guillaume; McCarroll, Steven A.; Bennett, Amanda; Burtt, Noel L. P.; Kuokkanen, Mikko; Hunter, David J.; Peltonen, Leena] MIT & Harvard, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Elliott, Amanda L.; McCarroll, Steven A.; Altshuler, David] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Lettre, Guillaume; Lyon, Helen N.; Hirschhorn, Joel N.] Childrens Hosp, Program Genom, Boston, MA 02115 USA. [Lettre, Guillaume; Lyon, Helen N.; Hirschhorn, Joel N.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Lettre, Guillaume; Lyon, Helen N.; Hirschhorn, Joel N.] Childrens Hosp, Div Genet, Boston, MA 02115 USA. [Papadakis, Konstantinos; Hadley, David; Strachan, David P.] Univ London, Div Commun Hlth Sci, London SW17 0RE, England. [Qi, Lu; Hu, Frank B.; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Qi, Lu; Hu, Frank B.; Hunter, David J.] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. [Roccasecca, Rosa Maria; Wheeler, Eleanor; Ouwehand, Willem H.; Deloukas, Panagiotis; Peltonen, Leena; Barroso, Ines] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. [Sanna, Serena; Uda, Manuela] CNR, Inst Neurogenet & Neurofarmacol, I-09042 Cagaliai, Italy. [Scheet, Paul; Abecasis, Goncalo R.] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Weedon, Michael N.; Frayling, Timothy M.] Peninsula Med Sch, Exeter EX1 2LU, Devon, England. [Jacobs, Leonie C.; Zillikens, M. Carola; Uitterlinden, Andre G.] Eramus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands. [Prokopenko, Inga; McCarthy, Mark I.] Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7LJ, England. [Soranzo, Nicole; Zhai, Guangju; Spector, Timothy D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England. [Tanaka, Toshiko; Ferrucci, Luigi] NIA, Clin Res Branch, Longitudinal Studies Sect, Baltimore, MD 21225 USA. [Timpson, Nicholas J.; Smith, George Davey; Evans, David M.] Univ Bristol, Dept Social Med, Ctr Causal Analyses Translat Epidemiol, MRC, Bristol BS8 2PR, Avon, England. [Almgren, Peter; Groop, Leif C.] Lund Univ, Dept Clin Sci, Ctr Diabet, Malmo 20502, Sweden. [Bennett, Amanda] Churchill Hosp, OCDEM, DRL, Oxford OX3 7LJ, England. [Bergman, Richard N.] Univ So Calif, Sch Med, Los Angeles, CA 90033 USA. [Bingham, Sheila A.] MRC, Dunn Human Nutr Unit, Cambridge CB2 0XY, England. [Bingham, Sheila A.] MRC, Ctr Nutr Epidemiol Canc Prevent & Survival, Cambridge CB1 8RN, England. [Bonnycastle, Lori L.; Chines, Peter; Collins, Francis S.; Deodhar, Parimal; Erdos, Michael R.; Rees, Matthew G.] NHGRI, Bethesda, MD 20892 USA. [Brown, Morris] Univ Cambridge, Addenbrookes Hosp, Clin Pharmacol Unit, Cambridge CB2 0QQ, England. [Coin, Lachlan; Elliott, Paul; Jarvelin, Marjo-Riitta] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Publ Hlth, London W2 1PG, England. [Connell, John M.] Univ Glasgow, Fac Med, Glasgow Cardiovasc Res Ctr, British Heart Fdn, Glasgow G12 8TA, Lanark, Scotland. [Cooper, Cyrus; Dennison, Elaine M.] Univ Southampton, Southampton Gen Hosp, Epidemiol Resource Ctr, MRC, Southampton SO16 6YD, Hants, England. [Hall, Alistair S.] Leeds Gen Infirm, Yorkshire Heart Ctr, Leeds LS1 3EX, W Yorkshire, England. [Havulinna, Aki S.; Jousilahti, Pekka; Salomaa, Veikko] Natl Publ Hlth Inst, KTL, FI-00300 Helsinki, Finland. [Hebebrand, Johannes] Univ Duisburg Essen, Dept Child & Adolescent Psychiat, D-45147 Essen, Germany. [Hofman, Albert; Van Duijn, Cornelia M.; Uitterlinden, Andre G.] Erasmus MC, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands. [Isomaa, Bo] Malmska Municipal Hlth Ctr & Hosp, Folkhalsan Res Ctr, FIN-00014 Helsinki, Finland. [Jacobs, Kevin B.] Bioinformed Consulting Serv, Gaithersburg, MD 20877 USA. [Johnson, Toby] Univ Lausanne, Dept Med Genet, CH-1005 Lausanne, Switzerland. [Johnson, Toby] CHU Vaudois, Univ Inst Social & Preventat Med, CH-1005 Lausanne, Switzerland. [Johnson, Toby] Swiss Inst Bioinformat, CH-1005 Lausanne, Switzerland. [Jovanovic, Zorica; O'Rahilly, Stephen; Purmann, Carolin; Tung, Y. C. Loraine] Univ Cambridge, Addenbrookes Hosp, Metab Res Labs, Cambridge CB2 0QQ, England. [Khaw, Kay-Tee; Luben, Robert N.; Sandhu, Manjinder S.; Farooqi, I. Sadaf] Univ Cambridge, Inst Publ Hlth, Dept Publ Hlth & Primary Care, Cambridge CB2 0SR, England. [Kraft, Peter; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. [Silander, Kaisa] Natl Publ Hlth Inst, Dept Mol Med, FIN-00300 Helsinki, Finland. [Kuusisto, Johanna; Laakso, Markku] Univ Kuopio, Dept Med, SF-70210 Kuopio, Finland. [Laitinen, Jaana] Finnish Inst Occupat Hlth, FIN-90220 Oulu, Finland. [Lakatta, Edward G.] NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. [Mangino, Massimo; Stevens, Suzanne; Samani, Nilesh J.] Univ Leicester, Glenfield Gen Hosp, Dept Cardiovasc Sci, Leicester LE3 9QP, Leics, England. [McArdle, Wendy L.; Northstone, Kate; Ring, Susan M.] Univ Bristol, Dept Social Med, ALSPAC, Bristol BS8 1TQ, Avon, England. [Meitinger, Thomas] Helmholtz Zentrum Munchen, Inst Human Genet, D-85764 Neuherberg, Germany. [Meitinger, Thomas] Tech Univ Munich, Inst Human Genet, D-81765 Munich, Germany. [Munroe, Patricia B.; Wallace, Chris; Caulfield, Mark J.; McCarthy, Mark I.] Barts & London Queen Marys Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England. [Ness, Andrew R.] Univ Bristol, Dept Oral & Dent Sci, Bristol BS1 2LY, Avon, England. [Ruokonen, Aimo] Univ Oulu, Dept Clin Chem, FIN-90220 Oulu, Finland. [Saramies, Jouko] Savitaipale Hlth Ctr, FIN-54800 Savitaipale, Finland. [Scuteri, Angelo] Ist Nazl Ricovero & Cura Anziani, Unita Operat Geriatria, I-00189 Rome, Italy. [Stephens, Jonathan; Watkins, Nicholas] Univ Cambridge, Dept Haematol, NHS Blood & Transplant, Cambridge CB2 2PR, England. [Valle, Timo T.] Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, FIN-00300 Helsinki, Finland. [Vollenweider, Peter] BH 10 Ctr Hosp Univ Vaudois, Dept Internal Med, CH-1011 Lausanne, Switzerland. [Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Div Biostat, Dept Prevent Med, Los Angeles, CA 90089 USA. [Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Gerontol Res Ctr, Bethesda, MD 20892 USA. [Hattersley, Andrew T.] Peninsula Med Sch, Exeter EX5 2DW, Devon, England. [Groop, Leif C.] Univ Helsinki, Cent Hosp, Dept Med, FIN-00290 Helsinki, Finland. [Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. [Peltonen, Leena] Univ Helsinki, Inst Mol Med, FIN-00014 Helsinki, Finland. [Schlessinger, David] NIA, US Natl Inst Hlth Biomed Res Ctr, Genet Lab, Baltimore, MD 21224 USA. [Wichmann, H-Erich] Univ Munich, Inst Med Informat Proc Biometry & Epidemiol, D-81377 Munich, Germany. [McCarthy, Mark I.] Univ Oxford, Oxford Biomed Res Ctr, Natl Inst Hlth Res, Oxford OX3 7LJ, England. [Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Hirschhorn, JN (reprint author), Harvard & Massachusetts Inst Technol, Broad Inst, Metabol Initiat, Cambridge, MA 02142 USA. EM mark.mccarthy@drl.ox.ac.uk; boehnke@umich.edu; ib1@sanger.ac.uk; goncalo@umich.edu; joelh@broad.mit.edu RI Evans, David/H-6325-2013; Colaus, PsyColaus/K-6607-2013; Ness, Andy/M-7612-2013; Meitinger, Thomas/O-1318-2015; Rivadeneira, Fernando/O-5385-2015; Prokopenko, Inga/H-3241-2014; mangino, massimo/F-5134-2011; Kuokkanen, Mikko/M-8247-2016; Coin, Lachlan/A-9001-2014; Davey Smith, George/A-7407-2013; McCarroll, Steven/A-8433-2009; Deloukas, Panos/B-2922-2013; Abecasis, Goncalo/B-7840-2010; Altshuler, David/A-4476-2009; Northstone, Kate/A-8165-2011; Li, Shengxu/D-8915-2012; Spector, Tim/F-6533-2012; Ridderstrale, Martin/F-7678-2012; Elliott, Amanda/G-5120-2012; Lamina, Claudia/F-7608-2010; Hadley, David/I-6902-2012 OI Timpson, Nicholas/0000-0002-7141-9189; Luben, Robert/0000-0002-5088-6343; Gieger, Christian/0000-0001-6986-9554; Hayes, Richard/0000-0002-0918-661X; Jarvelin, Marjo-Riitta/0000-0002-2149-0630; Farooqi, Sadaf/0000-0001-7609-3504; Tuomi, Tiinamaija/0000-0002-8306-6202; Wallace, Chris/0000-0001-9755-1703; Evans, David/0000-0003-0663-4621; Zeggini, Eleftheria/0000-0003-4238-659X; Soranzo, Nicole/0000-0003-1095-3852; Willer, Cristen/0000-0001-5645-4966; sanna, serena/0000-0002-3768-1749; Johnson, Toby/0000-0002-5998-3270; Monsalve, Beatriz Elena/0000-0002-5994-866X; Brown, Matthew A/0000-0003-0538-8211; Abecasis, Goncalo/0000-0003-1509-1825; Ness, Andy/0000-0003-3548-9523; Rivadeneira, Fernando/0000-0001-9435-9441; Prokopenko, Inga/0000-0003-1624-7457; mangino, massimo/0000-0002-2167-7470; Kuokkanen, Mikko/0000-0003-4375-9327; Coin, Lachlan/0000-0002-4300-455X; Davey Smith, George/0000-0002-1407-8314; Mulas, Antonella/0000-0002-6856-1483; Karani, Vimal/0000-0002-8485-8930; Deloukas, Panos/0000-0001-9251-070X; Altshuler, David/0000-0002-7250-4107; Northstone, Kate/0000-0002-0602-1983; FU British Heart Foundation [FS/05/061/19501]; Intramural NIH HHS; Medical Research Council [G0000649, G0000934, G0400874, G0401527, G0600705, G0601261, G0701863, G0800582, G9521010, G9815508, G9824984, MC_U105630924, MC_U106179471, MC_U106179472, MC_U106188470, MC_U147585819, MC_UP_A620_1014, U.1475.00.003.00010.02 (85819)]; NCI NIH HHS [P01 CA087969, 5UO1CA098233, CA49449, CA50385, CA65725, CA67262, CA87969, R01 CA049449, R01 CA050385, R01 CA065725, R01 CA067262, U01 CA049449, U01 CA067262, U01 CA098233]; NHGRI NIH HHS [01-HG-65403, 1Z01 HG000024, HG02651, N01HG65403, R01 HG002651, Z01 HG000024]; NHLBI NIH HHS [HL084729, HL087679, R01 HL087679, U01 HL084729]; NIA NIH HHS [N01-AG-1-2109]; NIDDK NIH HHS [DK062370, DK072193, DK075787, F32 DK079466, F32 DK079466-01, K23 DK067288, K23 DK080145, K23 DK080145-01, R01 DK029867, R01 DK062370, R01 DK072193, R01 DK075787, R56 DK062370, T32 DK007191, T32DK07191, U01 DK062370]; NIMH NIH HHS [1RL1MH083268, RL1 MH083268]; Wellcome Trust [068545/Z/02, 076113, 076467/Z/05/Z, 077011, 077016, 079557, 082390, 089061, 090532] NR 49 TC 936 Z9 964 U1 15 U2 137 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 JAN PY 2009 VL 41 IS 1 BP 25 EP 34 DI 10.1038/ng.287 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 389IE UT WOS:000262085300013 PM 19079261 ER PT J AU Kathiresan, S Willer, CJ Peloso, GM Demissie, S Musunuru, K Schadt, EE Kaplan, L Bennett, D Li, Y Tanaka, T Voight, BF Bonnycastle, LL Jackson, AU Crawford, G Surti, A Guiducci, C Burtt, NP Parish, S Clarke, R Zelenika, D Kubalanza, KA Morken, MA Scott, LJ Stringham, HM Galan, P Swift, AJ Kuusisto, J Bergman, RN Sundvall, J Laakso, M Ferrucci, L Scheet, P Sanna, S Uda, M Yang, Q Lunetta, KL Dupuis, J de Bakker, PIW O'Donnell, CJ Chambers, JC Kooner, JS Hercberg, S Meneton, P Lakatta, EG Scuteri, A Schlessinger, D Tuomilehto, J Collins, FS Groop, L Altshuler, D Collins, R Lathrop, GM Melander, O Salomaa, V Peltonen, L Orho-Melander, M Ordovas, JM Boehnke, M Abecasis, GR Mohlke, KL Cupples, LA AF Kathiresan, Sekar Willer, Cristen J. Peloso, Gina M. Demissie, Serkalem Musunuru, Kiran Schadt, Eric E. Kaplan, Lee Bennett, Derrick Li, Yun Tanaka, Toshiko Voight, Benjamin F. Bonnycastle, Lori L. Jackson, Anne U. Crawford, Gabriel Surti, Aarti Guiducci, Candace Burtt, Noel P. Parish, Sarah Clarke, Robert Zelenika, Diana Kubalanza, Kari A. Morken, Mario A. Scott, Laura J. Stringham, Heather M. Galan, Pilar Swift, Amy J. Kuusisto, Johanna Bergman, Richard N. Sundvall, Jouko Laakso, Markku Ferrucci, Luigi Scheet, Paul Sanna, Serena Uda, Manuela Yang, Qiong Lunetta, Kathryn L. Dupuis, Josee de Bakker, Paul I. W. O'Donnell, Christopher J. Chambers, John C. Kooner, Jaspal S. Hercberg, Serge Meneton, Pierre Lakatta, Edward G. Scuteri, Angelo Schlessinger, David Tuomilehto, Jaakko Collins, Francis S. Groop, Leif Altshuler, David Collins, Rory Lathrop, G. Mark Melander, Olle Salomaa, Veikko Peltonen, Leena Orho-Melander, Marju Ordovas, Jose M. Boehnke, Michael Abecasis, Goncalo R. Mohlke, Karen L. Cupples, L. Adrienne TI Common variants at 30 loci contribute to polygenic dyslipidemia SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; HIGH-DENSITY-LIPOPROTEIN; CORONARY-ARTERY-DISEASE; HEPATOCYTE NUCLEAR FACTOR-1-ALPHA; PHOSPHOLIPID TRANSFER PROTEIN; HEART-DISEASE; LDL-CHOLESTEROL; GENE-EXPRESSION; PLASMA-LIPIDS; RECEPTOR AB Blood low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglyceride levels are risk factors for cardiovascular disease. To dissect the polygenic basis of these traits, we conducted genome-wide association screens in 19,840 individuals and replication in up to 20,623 individuals. We identified 30 distinct loci associated with lipoprotein concentrations (each with P < 5 x 10(-8)), including 11 loci that reached genome-wide significance for the first time. The 11 newly defined loci include common variants associated with LDL cholesterol near ABCG8, MAFB, HNF1A and TIMD4; with HDL cholesterol near ANGPTL4, FADS1-FADS2-FADS3, HNF4A, LCAT, PLTP and TTC39B; and with triglycerides near AMAC1L2, FADS1-FADS2-FADS3 and PLTP. The proportion of individuals exceeding clinical cut points for high LDL cholesterol, low HDL cholesterol and high triglycerides varied according to an allelic dosage score (P < 10(-15) for each trend). These results suggest that the cumulative effect of multiple common variants contributes to polygenic dyslipidemia. C1 [Kathiresan, Sekar; Musunuru, Kiran] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Kathiresan, Sekar; Musunuru, Kiran] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Kathiresan, Sekar; Musunuru, Kiran; Voight, Benjamin F.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Kathiresan, Sekar; Voight, Benjamin F.; Crawford, Gabriel; Surti, Aarti; Guiducci, Candace; Burtt, Noel P.; Altshuler, David; Peltonen, Leena] Harvard & Massachusetts Inst, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Kathiresan, Sekar; Peloso, Gina M.; Demissie, Serkalem; Yang, Qiong; Lunetta, Kathryn L.; Dupuis, Josee; O'Donnell, Christopher J.; Cupples, L. Adrienne] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Kathiresan, Sekar; Peloso, Gina M.; Demissie, Serkalem; Yang, Qiong; Lunetta, Kathryn L.; Dupuis, Josee; O'Donnell, Christopher J.; Cupples, L. Adrienne] Boston Univ, Framingham, MA 01702 USA. [Kathiresan, Sekar; Altshuler, David] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Willer, Cristen J.; Li, Yun; Jackson, Anne U.; Scott, Laura J.; Stringham, Heather M.; Scheet, Paul; Peltonen, Leena; Boehnke, Michael; Abecasis, Goncalo R.] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Bonnycastle, Lori L.; Kubalanza, Kari A.; Morken, Mario A.; Swift, Amy J.; Collins, Francis S.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Schadt, Eric E.] Merck & Co Inc, Rosetta Inpharmat LLC, Seattle, WA 98109 USA. [Kaplan, Lee] Massachusetts Gen Hosp, Weight Ctr, Boston, MA 02114 USA. [Bennett, Derrick; Parish, Sarah; Clarke, Robert; Collins, Rory] Univ Oxford, Clin Trial Serv Unit, Oxford OX3 7LF, England. [Tanaka, Toshiko; Ferrucci, Luigi] NIA, Clin Res Branch, NIH, Baltimore, MD 21225 USA. [Voight, Benjamin F.; Altshuler, David] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Kubalanza, Kari A.; Morken, Mario A.; Swift, Amy J.; Collins, Francis S.] NHGRI, NIH, Bethesda, MD 20892 USA. [Zelenika, Diana; Lathrop, G. Mark] Inst Genom Commissariat Energie Atom, Ctr Natl Genotypage, F-91057 Evry, France. [Galan, Pilar; Hercberg, Serge] Paris 13 SMBH, CNAM, INRA, INSERM,U557,U1125, Bobigny, France. [Kuusisto, Johanna; Laakso, Markku] Univ Kuopio, Dept Med, SF-70210 Kuopio, Finland. [Bergman, Richard N.] Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA. [Sundvall, Jouko; Tuomilehto, Jaakko] Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Diabet Unit, SF-00300 Helsinki, Finland. [Sanna, Serena; Uda, Manuela] CNR, Ist Neurogenet & Neurofarmacol, I-08045 Cagliari, Italy. [de Bakker, Paul I. W.] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [O'Donnell, Christopher J.] Natl Lung & Blood Inst, NIH, Framingham, MA 01702 USA. [Chambers, John C.] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Publ Hlth, London W2 1PG, England. [Kooner, Jaspal S.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Hammersmith Hosp, London W12 0NN, England. [Meneton, Pierre] Ctr Rech Cordeliers, INSERM, U872, F-75270 Paris 06, France. [Lakatta, Edward G.] NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. [Scuteri, Angelo] Ist Nazl Ricovero & Cura Anziani, Unita Operat Geriatria, I-00189 Rome, Italy. [Schlessinger, David] NIA, Genet Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. [Groop, Leif; Orho-Melander, Marju] Lund Univ, Malmo Univ Hosp, Dept Clin Sci Diabet & Endocrinol, S-20502 Malmo, Sweden. [Groop, Leif] Helsinki Univ Hosp, Dept Med, Helsinki 00029, Finland. [Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Melander, Olle] Lund Univ, Malmo Univ Hosp, Dept Clin Sci Hypertens & Cardiovasc Dis, S-20502 Malmo, Sweden. [Peltonen, Leena] Univ Helsinki, Inst Mol Med, Helsinki 00029, Finland. [Salomaa, Veikko] Natl Publ Hlth Inst, Chron Dis Epidemiol Unit, Dept Hlth Promot & Chron Dis Prevent, SF-00300 Helsinki, Finland. [Peltonen, Leena] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. [Ordovas, Jose M.] Tufts Univ, Human Nutr Res Ctr Aging, Jean Mayer US Dept Agr, Nutr & Genom Lab, Boston, MA 02111 USA. [Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. RP Kathiresan, S (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. EM skathiresan@partners.org; goncalo@umich.edu; mohlke@med.unc.edu; adrienne@bu.edu RI Abecasis, Goncalo/B-7840-2010; Altshuler, David/A-4476-2009; Voight, Benjamin/F-1775-2011; de Bakker, Paul/B-8730-2009; Yang, Qiong/G-5438-2014; OI Willer, Cristen/0000-0001-5645-4966; sanna, serena/0000-0002-3768-1749; Cupples, L. Adrienne/0000-0003-0273-7965; Abecasis, Goncalo/0000-0003-1509-1825; Dupuis, Josee/0000-0003-2871-3603; Ordovas, Jose/0000-0002-7581-5680; Altshuler, David/0000-0002-7250-4107; de Bakker, Paul/0000-0001-7735-7858; Lunetta, Kathryn/0000-0002-9268-810X FU British Heart Foundation; Cancer Research UK; Department of Health; Intramural NIH HHS; Medical Research Council [, MC_U137686857]; NHGRI NIH HHS [HG02651, N01HG65403, R01 HG002651, Z01 HG000024]; NHLBI NIH HHS [HL-54776, HL084729, K23 HL083102, K23 HL083102-03, N01-HC-25195, N01HC25195, R01 HL054776, U01 HL084729]; NIDDK NIH HHS [DK062370, DK072193, P30 DK040561, P30 DK040561-13, R01 DK029867, R01 DK062370, R01 DK072193, R01 DK075030, R56 DK062370, U01 DK062370]; PHS HHS [53-K06-5-10]; Wellcome Trust [089061] NR 50 TC 748 Z9 762 U1 4 U2 54 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 JAN PY 2009 VL 41 IS 1 BP 56 EP 65 DI 10.1038/ng.291 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 389IE UT WOS:000262085300016 PM 19060906 ER PT J AU Keinan, A Mullikin, JC Patterson, N Reich, D AF Keinan, Alon Mullikin, James C. Patterson, Nick Reich, David TI Accelerated genetic drift on chromosome X during the human dispersal out of Africa SO NATURE GENETICS LA English DT Article ID DROSOPHILA-MELANOGASTER; Y-CHROMOSOME; PATTERNS; DIVERSITY; SELECTION; DNA; VARIABILITY; POPULATIONS; MITOCHONDRIAL; EVOLUTION AB Comparisons of chromosome X and the autosomes can illuminate differences in the histories of males and females as well as shed light on the forces of natural selection. We compared the patterns of variation in these parts of the genome using two datasets that we assembled for this study that are both genomic in scale. Three independent analyses show that around the time of the dispersal of modern humans out of Africa, chromosome X experienced much more genetic drift than is expected from the pattern on the autosomes. This is not predicted by known episodes of demographic history, and we found no similar patterns associated with the dispersals into East Asia and Europe. We conclude that a sex-biased process that reduced the female effective population size, or an episode of natural selection unusually affecting chromosome X, was associated with the founding of non-African populations. C1 [Keinan, Alon; Reich, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Keinan, Alon; Patterson, Nick; Reich, David] Harvard & Massachusetts Inst Technol, Broad Inst, Cambridge, MA 02142 USA. [Mullikin, James C.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. RP Keinan, A (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. EM akeinan@genetics.med.harvard.edu; reich@genetics.med.harvard.edu FU US National Human Genome Research Institutes (NHGRI); US National Institutes of Health (NIH); Wellcome Career Development Award in the Biomedical Sciences; NIH [U01 HG004168] FX We thank C. Aquadro, O. Bar-Yosef, M. Bernstein, B. Charlesworth, A. Helgason, E. Lander, D. Lieberman, K. Lohmueller, S. Myers, S. Paabo, A. Price, S. Schaffner and C. Stringer for comments, and J. Neubauer and A. Waliszewska for genotyping SNPs discovered in two West African X chromosomes. The orangutan sequence reads were generated by the Washington University genome sequencing center (ftp.ncbi.nih.gov/pub/TraceDB/pongo_pygmaeus_abelii); we thank R. Wilson for permission to use these data. J. C. M. was supported by the Intramural Research Program of the US National Human Genome Research Institutes (NHGRI), N. P. by a K-01 career transition award from the US National Institutes of Health (NIH) and D. R. by a Burroughs Wellcome Career Development Award in the Biomedical Sciences. A. K., N. P. and D. R. were also supported by NIH grant U01 HG004168. NR 30 TC 67 Z9 68 U1 2 U2 19 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 JAN PY 2009 VL 41 IS 1 BP 66 EP 70 DI 10.1038/ng.303 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 389IE UT WOS:000262085300017 PM 19098910 ER PT J AU Prokopenko, I Langenberg, C Florez, JC Saxena, R Soranzo, N Thorleifsson, G Loos, RJF Manning, AK Jackson, AU Aulchenko, Y Potter, SC Erdos, MR Sanna, S Hottenga, JJ Wheeler, E Kaakinen, M Lyssenko, V Chen, WM Ahmadi, K Beckmann, JS Bergman, RN Bochud, M Bonnycastle, LL Buchanan, TA Cao, A Cervino, A Coin, L Collins, FS Crisponi, L De Geus, EJC Dehghan, A Deloukas, P Doney, ASF Elliott, P Freimer, N Gateva, V Herder, C Hofman, A Hughes, TE Hunt, S Illig, T Inouye, M Isomaa, B Johnson, T Kong, A Krestyaninova, M Kuusisto, J Laakso, M Lim, N Lindblad, U Lindgren, CM McCann, OT Mohlke, KL Morris, AD Naitza, S Orru, M Palmer, CNA Pouta, A Randall, J Rathmann, W Saramies, J Scheet, P Scott, LJ Scuteri, A Sharp, S Sijbrands, E Smit, JH Song, K Steinthorsdottir, V Stringham, HM Tuomi, T Tuomilehto, J Uitterlinden, AG Voight, BF Waterworth, D Wichmann, HE Willemsen, G Witteman, JCM Yuan, X Zhao, JH Zeggini, E Schlessinger, D Sandhu, M Boomsma, DI Uda, M Spector, TD Penninx, BWJH Altshuler, D Vollenweider, P Jarvelin, MR Lakatta, E Waeber, G Fox, CS Peltonen, L Groop, LC Mooser, V Cupples, LA Thorsteinsdottir, U Boehnke, M Barroso, IS Van Duijn, C Dupuis, J Watanabe, RM Stefansson, K McCarthy, MI Wareham, NJ Meigs, JB Abecasis, GR AF Prokopenko, Inga Langenberg, Claudia Florez, Jose C. Saxena, Richa Soranzo, Nicole Thorleifsson, Gudmar Loos, Ruth J. F. Manning, Alisa K. Jackson, Anne U. Aulchenko, Yurii Potter, Simon C. Erdos, Michael R. Sanna, Serena Hottenga, Jouke-Jan Wheeler, Eleanor Kaakinen, Marika Lyssenko, Valeriya Chen, Wei-Min Ahmadi, Kourosh Beckmann, Jacques S. Bergman, Richard N. Bochud, Murielle Bonnycastle, Lori L. Buchanan, Thomas A. Cao, Antonio Cervino, Alessandra Coin, Lachlan Collins, Francis S. Crisponi, Laura De Geus, Eco J. C. Dehghan, Abbas Deloukas, Panos Doney, Alex S. F. Elliott, Paul Freimer, Nelson Gateva, Vesela Herder, Christian Hofman, Albert Hughes, Thomas E. Hunt, Sarah Illig, Thomas Inouye, Michael Isomaa, Bo Johnson, Toby Kong, Augustine Krestyaninova, Maria Kuusisto, Johanna Laakso, Markku Lim, Noha Lindblad, Ulf Lindgren, Cecilia M. McCann, Owen T. Mohlke, Karen L. Morris, Andrew D. Naitza, Silvia Orru, Marco Palmer, Colin N. A. Pouta, Anneli Randall, Joshua Rathmann, Wolfgang Saramies, Jouko Scheet, Paul Scott, Laura J. Scuteri, Angelo Sharp, Stephen Sijbrands, Eric Smit, Jan H. Song, Kijoung Steinthorsdottir, Valgerdur Stringham, Heather M. Tuomi, Tiinamaija Tuomilehto, Jaakko Uitterlinden, Andre G. Voight, Benjamin F. Waterworth, Dawn Wichmann, H-Erich Willemsen, Gonneke Witteman, Jacqueline C. M. Yuan, Xin Zhao, Jing Hua Zeggini, Eleftheria Schlessinger, David Sandhu, Manjinder Boomsma, Dorret I. Uda, Manuela Spector, Tim D. Penninx, Brenda W. J. H. Altshuler, David Vollenweider, Peter Jarvelin, Marjo Riitta Lakatta, Edward Waeber, Gerard Fox, Caroline S. Peltonen, Leena Groop, Leif C. Mooser, Vincent Cupples, L. Adrienne Thorsteinsdottir, Unnur Boehnke, Michael Barroso, Ines Van Duijn, Cornelia Dupuis, Josee Watanabe, Richard M. Stefansson, Kari McCarthy, Mark I. Wareham, Nicholas J. Meigs, James B. Abecasis, Goncalo R. TI Variants in MTNR1B influence fasting glucose levels SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; BETA-CELL FUNCTION; GENE-EXPRESSION; PLASMA-GLUCOSE; RISK LOCI; MELATONIN; TRIGLYCERIDE; REPLICATION; HAPLOTYPE; IMPACT AB To identify previously unknown genetic loci associated with fasting glucose concentrations, we examined the leading association signals in ten genome-wide association scans involving a total of 36,610 individuals of European descent. Variants in the gene encoding melatonin receptor 1B (MTNR1B) were consistently associated with fasting glucose across all ten studies. The strongest signal was observed at rs10830963, where each G allele (frequency 0.30 in HapMap CEU) was associated with an increase of 0.07 (95% CI = 0.06-0.08) mmol/l in fasting glucose levels (P = 3.2 x 10(-50)) and reduced beta-cell function as measured by homeostasis model assessment (HOMA-B, P = 1.1 x 10(-15)). The same allele was associated with an increased risk of type 2 diabetes (odds ratio = 1.09 (1.05-1.12), per G allele P = 3.3 x 10(-7)) in a meta-analysis of 13 case-control studies totaling 18,236 cases and 64,453 controls. Our analyses also confirm previous associations of fasting glucose with variants at the G6PC2 (rs560887, P = 1.1 x 10(-57)) and GCK (rs4607517, P = 1.0 x 10(-25)) loci. C1 [Jackson, Anne U.; Gateva, Vesela; Scheet, Paul; Scott, Laura J.; Stringham, Heather M.; Boehnke, Michael; Abecasis, Goncalo R.] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Prokopenko, Inga; McCarthy, Mark I.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7LJ, England. [Prokopenko, Inga; Lindgren, Cecilia M.; Randall, Joshua; Zeggini, Eleftheria; McCarthy, Mark I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. [Langenberg, Claudia; Loos, Ruth J. F.; Sharp, Stephen; Waterworth, Dawn; Zhao, Jing Hua; Sandhu, Manjinder; Wareham, Nicholas J.] Addenbrookes Hosp, Epidemiol Unit, MRC, Cambridge CB2 0QQ, England. [Florez, Jose C.; Saxena, Richa; Voight, Benjamin F.; Altshuler, David] Harvard & MIT, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Florez, Jose C.; Altshuler, David; Meigs, James B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Florez, Jose C.; Waterworth, Dawn; Altshuler, David] Massachusetts Gen Hosp, Dept Med, Ctr Human Genet Res, Boston, MA 02114 USA. [Florez, Jose C.; Waterworth, Dawn; Altshuler, David] Massachusetts Gen Hosp, Dept Med, Diabet Unit, Boston, MA 02114 USA. [Saxena, Richa; Voight, Benjamin F.; Altshuler, David] Massachusetts Gen Hosp, Dept Mol Biol, Ctr Human Genet Res, Boston, MA 02114 USA. [Soranzo, Nicole; Potter, Simon C.; Wheeler, Eleanor; Deloukas, Panos; Hunt, Sarah; Inouye, Michael; McCann, Owen T.; Peltonen, Leena; Barroso, Ines] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. [Soranzo, Nicole; Ahmadi, Kourosh; Cervino, Alessandra; Spector, Tim D.] Kings Coll London, Twin Res & Genet Epidemiol Dept, London SE1 7EH, England. [Thorleifsson, Gudmar; Kong, Augustine; Steinthorsdottir, Valgerdur; Stefansson, Kari] deCODE Genet, IS-101 Reykjavik, Iceland. [Manning, Alisa K.; Cupples, L. Adrienne; Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Aulchenko, Yurii; Dehghan, Abbas; Hofman, Albert; Witteman, Jacqueline C. M.; Van Duijn, Cornelia] Erasmus MC, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands. [Erdos, Michael R.; Bonnycastle, Lori L.; Collins, Francis S.] NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA. [Sanna, Serena; Cao, Antonio; Crisponi, Laura; Naitza, Silvia; Orru, Marco; Uda, Manuela] Cittadella Univ Monserrato, CNR, INN, I-09042 Cagliari, Italy. [Hottenga, Jouke-Jan; De Geus, Eco J. C.; Willemsen, Gonneke; Boomsma, Dorret I.] Vrije Univ Amsterdam, Dept Biol Psychol, NL-1081 BT Amsterdam, Netherlands. [Kaakinen, Marika; Jarvelin, Marjo Riitta] Univ Oulu, Inst Hlth Sci & Biocenter Oulu, Oulu 90014, Finland. [Lyssenko, Valeriya; Groop, Leif C.] Lund Univ, Malmo Univ Hosp, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden. [Chen, Wei-Min] Univ Virginia, Ctr Publ Hlth Gen, Charlottesville, VA 22908 USA. [Chen, Wei-Min] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA 22908 USA. [Beckmann, Jacques S.; Johnson, Toby] Univ Lausanne, Dept Med Genet, CH-1005 Lausanne, Switzerland. [Beckmann, Jacques S.] CHU Vaudois, Serv Med Genet, CH-1011 Lausanne, Switzerland. [Bergman, Richard N.; Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA. [Bochud, Murielle] CHU Vaudois, Univ Inst Social & Prevent Med, CH-1011 Lausanne, Switzerland. [Buchanan, Thomas A.] Univ So Calif, Keck Sch Med, Div Endocrinol, Dept Med, Los Angeles, CA 90033 USA. [Coin, Lachlan; Elliott, Paul; Jarvelin, Marjo Riitta] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Publ Hlth, London, England. [Doney, Alex S. F.; Morris, Andrew D.] Univ Dundee, Ninewells Hosp & Med Sch, Div Med & Therapeut, Diabet Res Grp, Dundee DD1 9SY, Scotland. [Freimer, Nelson] Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA 90095 USA. [Herder, Christian; Johnson, Toby] Univ Dusseldorf, Leibniz Inst, German Diabet Ctr, Inst Clin Diabetol, Dusseldorf, Germany. [Hughes, Thomas E.] Novartis Inst BioMed Res, Diabet & Metab Dis Area, Cambridge, MA 02139 USA. [Illig, Thomas; Wichmann, H-Erich] Helmholtz Zentrum Muenchen, Natl Res Ctr Environm Hlth, Inst Epidemiol, Neuherberg, Germany. [Isomaa, Bo] Malmska Municipal Hlth Ctr & Hosp, Pietarsaari, Finland. [Krestyaninova, Maria; Yuan, Xin] European Bioinformat Inst, EMBL, Hinxton, England. [Kuusisto, Johanna; Laakso, Markku] Univ Kuopio, Dept Med, SF-70210 Kuopio, Finland. [Kuusisto, Johanna; Laakso, Markku] Kuopio Univ Hosp, SF-70210 Kuopio, Finland. [Lim, Noha; Song, Kijoung; Mooser, Vincent] Glaxo SmithKline, Med Genet Clin Pharmacol & Discovery Med, King Of Prussia, PA 19406 USA. [Lindblad, Ulf] Skaraborg Inst, Skovde, Sweden. [Lindblad, Ulf] Lund Univ, Malmo Univ Hosp, Dept Clin Sci, Malmo, Sweden. [Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. [Palmer, Colin N. A.] Univ Dundee, Ninewells Hosp & Med Sch, Biomed Res Ctr, Populat Pharmacogenet Grp, Dundee DD1 9SY, Scotland. [Pouta, Anneli] Oulu Univ Hosp, Dept Obstet & Gynaecol, Oulu, Finland. [Jarvelin, Marjo Riitta] Natl Publ Hlth Inst KLT, Dept Child & Adolescent Hlth, Oulu 90101, Finland. [Rathmann, Wolfgang] Univ Dusseldorf, Leibniz Inst, German Diabet Ctr, Inst Biometr & Epidemiol, Dusseldorf, Germany. [Saramies, Jouko] Savitaipale Hlth Ctr, Savitaipale 54800, Finland. [Scuteri, Angelo] Ist Patol Endocrina & Metabol, Unita Operat Geriatria, Rome, Italy. [Sijbrands, Eric; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands. [Smit, Jan H.] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, NL-9713 GZ Groningen, Netherlands. [Tuomi, Tiinamaija] Univ Helsinki, Helsinki Univ Hosp, Dept Med, FIN-00014 Helsinki, Finland. [Tuomilehto, Jaakko] Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Diabet Unit, SF-00300 Helsinki, Finland. [Tuomilehto, Jaakko] S Ostrobothnia Cent Hosp, Senajoki 60220, Finland. [Wichmann, H-Erich] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany. [Schlessinger, David; Lakatta, Edward] NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. [Sandhu, Manjinder; Penninx, Brenda W. J. H.] Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Cambridge, England. [Penninx, Brenda W. J. H.] Leiden Univ, Med Ctr, Dept Psychiat, NL-2300 RC Leiden, Netherlands. [Penninx, Brenda W. J. H.] Vrije Univ Amsterdam Med Ctr, Inst Neurosci, EMGO Inst, Dept Psychiat, NL-1081 AL Amsterdam, Netherlands. [Vollenweider, Peter; Waeber, Gerard] CHU Vaudois, Dept Internal Med, CH-1011 Lausanne, Switzerland. [Fox, Caroline S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. [Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Peltonen, Leena] Inst Mol Med, Biomedicum, Helsinki 00290, Finland. [Peltonen, Leena] MIT, Broad Inst, Cambridge, MA 02141 USA. [Thorsteinsdottir, Unnur; Stefansson, Kari] Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland. [Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90089 USA. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. RP Abecasis, GR (reprint author), Univ Michigan, Sch Publ Hlth, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA. EM mark.mccarthy@drl.ox.ac.uk; nick.wareham@mrc-epid.cam.ac.uk; jmeigs@partners.org; goncalo@umich.edu RI de Geus, Eco/M-9318-2015; Prokopenko, Inga/H-3241-2014; Study, GoDARTS/K-9448-2016; Coin, Lachlan/A-9001-2014; Naitza, Silvia/D-5620-2017; Palmer, Colin/C-7053-2008; Altshuler, David/A-4476-2009; Voight, Benjamin/F-1775-2011; Beckmann, Jacques S /A-9772-2008; Spector, Tim/F-6533-2012; Deloukas, Panos/B-2922-2013; Colaus, PsyColaus/K-6607-2013; Aulchenko, Yurii/M-8270-2013; Chen, Wei-Min/A-8469-2009; Morris, Andrew/C-2837-2009; Abecasis, Goncalo/B-7840-2010; Bochud, Murielle/A-3981-2010; OI de Geus, Eco/0000-0001-6022-2666; Prokopenko, Inga/0000-0003-1624-7457; Coin, Lachlan/0000-0002-4300-455X; Krestyaninova, Maria/0000-0002-8705-8111; Kaakinen, Marika/0000-0002-9228-0462; Sijbrands, Eric/0000-0001-8857-7389; sanna, serena/0000-0002-3768-1749; Johnson, Toby/0000-0002-5998-3270; Palmer, Colin/0000-0002-6415-6560; Altshuler, David/0000-0002-7250-4107; Beckmann, Jacques S /0000-0002-9741-1900; Deloukas, Panos/0000-0001-9251-070X; Aulchenko, Yurii/0000-0002-7899-1575; Bochud, Murielle/0000-0002-5727-0218; Hunt, Sarah/0000-0002-8350-1235; Cupples, L. Adrienne/0000-0003-0273-7965; Abecasis, Goncalo/0000-0003-1509-1825; Zeggini, Eleftheria/0000-0003-4238-659X; Dupuis, Josee/0000-0003-2871-3603; Soranzo, Nicole/0000-0003-1095-3852; Jarvelin, Marjo-Riitta/0000-0002-2149-0630; Tuomi, Tiinamaija/0000-0002-8306-6202; Dehghan, Abbas/0000-0001-6403-016X FU Intramural NIH HHS; Medical Research Council [G0000649, G016121, G0500539, G0601261, G0701863, MC_U106179471, MC_U106188470]; NCRR NIH HHS [RR-163736]; NHGRI NIH HHS [HG-02651, R01 HG002651, R01 HG002651-05, Z01 HG000024]; NHLBI NIH HHS [HL-087679, HC-25195, HL-084729, N01 HC025195, N01HC25195, N02-HL-6-4278, R01 HL087679, R01 HL087679-02, U01 HL084729, U01 HL084729-03]; NIDA NIH HHS [DA-021519, U54 DA021519, U54 DA021519-04]; NIDDK NIH HHS [DK-062370, DK-065978, DK-072193, DK-078616, DK-080140, DK069922, K23 DK065978, K23 DK065978-05, K24 DK080140, K24 DK080140-01, K24 DK080140-02, R01 DK029867, R01 DK062370, R01 DK062370-05, R01 DK069922, R01 DK069922-02, R01 DK072193, R01 DK072193-04, R01 DK078616, R01 DK078616-01A1, R56 DK062370, U01 DK062370, U01 DK078616]; NIMH NIH HHS [MH059160, R01 MH059160, R01 MH059160-04]; Wellcome Trust [076113, 077011, 077016, 079557, 083948, 089061, 090532, GR069224, GR072960] NR 30 TC 377 Z9 386 U1 2 U2 30 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 JAN PY 2009 VL 41 IS 1 BP 77 EP 81 DI 10.1038/ng.290 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 389IE UT WOS:000262085300019 PM 19060907 ER PT J AU Lyssenko, V Nagorny, CLF Erdos, MR Wierup, N Jonsson, A Spegel, P Bugliani, M Saxena, R Fex, M Pulizzi, N Isomaa, B Tuomi, T Nilsson, P Kuusisto, J Tuomilehto, J Boehnke, M Altshuler, D Sundler, F Eriksson, JG Jackson, AU Laakso, M Marchetti, P Watanabe, RM Mulder, H Groop, L AF Lyssenko, Valeriya Nagorny, Cecilia L. F. Erdos, Michael R. Wierup, Nils Jonsson, Anna Spegel, Peter Bugliani, Marco Saxena, Richa Fex, Malin Pulizzi, Nicolo Isomaa, Bo Tuomi, Tiinamaija Nilsson, Peter Kuusisto, Johanna Tuomilehto, Jaakko Boehnke, Michael Altshuler, David Sundler, Frank Eriksson, Johan G. Jackson, Anne U. Laakso, Markku Marchetti, Piero Watanabe, Richard M. Mulder, Hindrik Groop, Leif TI Common variant in MTNR1B associated with increased risk of type 2 diabetes and impaired early insulin secretion SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; BETA-CELL; MELATONIN RECEPTORS; PANCREATIC-ISLETS; MINIMAL MODEL; SENSITIVITY; LOCI; EXPRESSION; REPLICATION; PATHWAYS AB Genome-wide association studies have shown that variation in MTNR1B (melatonin receptor 1B) is associated with insulin and glucose concentrations. Here we show that the risk genotype of this SNP predicts future type 2 diabetes (T2D) in two large prospective studies. Specifically, the risk genotype was associated with impairment of early insulin response to both oral and intravenous glucose and with faster deterioration of insulin secretion over time. We also show that the MTNR1B mRNA is expressed in human islets, and immunocytochemistry confirms that it is primarily localized in beta cells in islets. Nondiabetic individuals carrying the risk allele and individuals with T2D showed increased expression of the receptor in islets. Insulin release from clonal beta cells in response to glucose was inhibited in the presence of melatonin. These data suggest that the circulating hormone melatonin, which is predominantly released from the pineal gland in the brain, is involved in the pathogenesis of T2D. Given the increased expression of MTNR1B in individuals at risk of T2D, the pathogenic effects are likely exerted via a direct inhibitory effect on beta cells. In view of these results, blocking the melatonin ligand-receptor system could be a therapeutic avenue in T2D. C1 [Lyssenko, Valeriya; Jonsson, Anna; Groop, Leif] Lund Univ, Univ Hosp, Dept Clin Sci Malmoe, Unit Diabet & Endocrinol,Diabet Ctr, S-20520 Malmo, Sweden. [Nagorny, Cecilia L. F.; Spegel, Peter; Mulder, Hindrik] Lund Univ, Ctr Diabet, Dept Clin Sci Malmoe, Unit Mol Metab, S-20502 Malmo, Sweden. [Erdos, Michael R.] NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA. [Wierup, Nils; Sundler, Frank] Lund Univ, Dept Expt Med Sci, Unit Neuroendocrine Cell Biol, S-22184 Lund, Sweden. [Bugliani, Marco; Pulizzi, Nicolo; Marchetti, Piero] Univ Pisa, Dept Endocrinol & Metab, I-56124 Pisa, Italy. [Saxena, Richa; Altshuler, David] Harvard & Massachusetts Inst Technol, Program Med & Populat Genet, Broad Inst, Cambridge, MA 02142 USA. [Saxena, Richa; Altshuler, David] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fex, Malin] Lund Univ, Ctr Diabet, Dept Clin Sci Malmoe, Unit Diabet & Celiac Dis, S-20502 Malmo, Sweden. [Isomaa, Bo; Tuomi, Tiinamaija] Folkhalsan Res Ctr, Helsinki 00251, Finland. [Tuomi, Tiinamaija; Groop, Leif] Univ Helsinki, Cent Hosp, Dept Med, Helsinki 00140, Finland. [Tuomi, Tiinamaija; Groop, Leif] Univ Helsinki, Res Program Mol Med, Helsinki 00140, Finland. [Nilsson, Peter] Lund Univ, Dept Clin Sci, S-20502 Malmo, Sweden. [Kuusisto, Johanna; Laakso, Markku] Univ Kuopio, Dept Med, SF-70210 Kuopio, Finland. [Kuusisto, Johanna; Laakso, Markku] Kuopio Univ Hosp, SF-70210 Kuopio, Finland. [Tuomilehto, Jaakko] Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Diabet Unit, SF-00300 Helsinki, Finland. [Tuomilehto, Jaakko] Univ Helsinki, Dept Publ Hlth, Helsinki 00014, Finland. [Tuomilehto, Jaakko] S Ostrobothnia Cent Hosp, Senajoki 60220, Finland. [Boehnke, Michael; Jackson, Anne U.] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Eriksson, Johan G.] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, FIN-00014 Helsinki, Finland. [Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA. RP Groop, L (reprint author), Lund Univ, Univ Hosp, Dept Clin Sci Malmoe, Unit Diabet & Endocrinol,Diabet Ctr, S-20520 Malmo, Sweden. EM Leif.Groop@med.lu.se RI Altshuler, David/A-4476-2009; Mulder, Hindrik/E-1045-2012; Marchetti, Piero/J-7439-2013; OI Altshuler, David/0000-0002-7250-4107; Tuomi, Tiinamaija/0000-0002-8306-6202; Eriksson, Johan/0000-0002-2516-2060; Marchetti, Piero/0000-0003-4907-0635; Fex, Malin/0000-0003-0675-7576 FU Novartis; Swedish Research Council [31475113580]; Lund University; Pahlsson Foundation; Heart and Lung Foundation; Wallenberg Foundation; Swedish Diabetes Research Society; Crafoord Foundation; Swedish Medical Society; Swedish Royal Physiographic Society; Nordic Centre of Excellence Grant in Disease Genetics; Finnish Diabetes Research Society; Sigrid Juselius Foundation; Folkhalsan Research Foundation; Novo Nordisk Foundation; European Network of Genomic and Genetic Epidemiology (ENGAGE); Italian Ministry of University and Research [PRIN 2007-2008]; European Community [LSHM-CT-2006-518153]; NIH [DK062370]; American Diabetes Association [1-05-RA-140, DK072193]; Academy of Finland [124243] FX The DGI study was supported by a grant from Novartis. Studies in Malmoe were supported by grants from the Swedish Research Council, including a Linne grant (No. 31475113580), the Diabetes Programme at Lund University, the Pahlsson Foundation, the Heart and Lung Foundation, the Wallenberg Foundation, the Swedish Diabetes Research Society, the Crafoord Foundation, Swedish Medical Society, Swedish Royal Physiographic Society, a Nordic Centre of Excellence Grant in Disease Genetics, the Finnish Diabetes Research Society, the Sigrid Juselius Foundation, Folkhalsan Research Foundation, Novo Nordisk Foundation, the European Network of Genomic and Genetic Epidemiology (ENGAGE), the Wallenberg Foundation, the European Foundation for the Study of Diabetes (EFSD) and the Human Tissue facility at the Lund University Diabetes Center. Studies in human islets were supported in part by the Italian Ministry of University and Research (PRIN 2007-2008) and the European Community (LSHM-CT-2006-518153). Pancreatic islets at US National Institutes of Health were obtained through the ICR Basic Science Islet Distribution Program (City of Hope Hospital, Joslin Diabetes Center, Northwestern University, Southern California Islet Consortium, University of Alabama Birmingham, University of Illinois, University of Miami, University of Minnesota, University of Pennsylvania, University of Wisconsin and Washington University), the Juvenile Diabetes Research Foundation Islet Resources (Washington University) and the National Disease Resource Interchange (NDRI). The FUSION study would like to thank the many research volunteers who generously participated in the various studies represented in FUSION. We also thank A. J. Swift, M. Morken, P. S. Chines and N. Narisu for genotying and informatics support. Support for FUSION was provided by the following: NIH grant DK062370 (M. Boehnke), American Diabetes Association research grant 1-05-RA-140 ( R. M. W.), DK072193 ( K. L. Mohlke) and National Human Genome Research Institute intramural project number 1 Z01 HG000024 ( F. S. Collins). The METSIM study was supported by Academy of Finland grant 124243 ( M. L.). NR 30 TC 324 Z9 333 U1 1 U2 19 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 JAN PY 2009 VL 41 IS 1 BP 82 EP 88 DI 10.1038/ng.288 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 389IE UT WOS:000262085300020 PM 19060908 ER PT J AU Lagresle-Peyrou, C Six, EM Picard, C Rieux-Laucat, F Michel, V Ditadi, A Demerens-de Chappedelaine, C Morillon, E Valensi, F Simon-Stoos, KL Mullikin, JC Noroski, LM Besse, C Wulffraat, NM Ferster, A Abecasis, MM Calvo, F Petit, C Candotti, F Abel, L Fischer, A Cavazzana-Calvo, M AF Lagresle-Peyrou, Chantal Six, Emmanuelle M. Picard, Capucine Rieux-Laucat, Frederic Michel, Vincent Ditadi, Andrea Demerens-de Chappedelaine, Corinne Morillon, Estelle Valensi, Francoise Simon-Stoos, Karen L. Mullikin, James C. Noroski, Lenora M. Besse, Celine Wulffraat, Nicolas M. Ferster, Alina Abecasis, Manuel M. Calvo, Fabien Petit, Christine Candotti, Fabio Abel, Laurent Fischer, Alain Cavazzana-Calvo, Marina TI Human adenylate kinase 2 deficiency causes a profound hematopoietic defect associated with sensorineural deafness SO NATURE GENETICS LA English DT Article ID MITOCHONDRIAL-INTERMEMBRANE SPACE; BONE-MARROW-TRANSPLANTATION; RETICULAR DYSGENESIS; CYTOCHROME-C; APOPTOTIC PATHWAY; EXPRESSION; KOSTMANN; SURVIVAL; CELLS; DNA AB Reticular dysgenesis is an autosomal recessive form of human severe combined immunodeficiency characterized by an early differentiation arrest in the myeloid lineage and impaired lymphoid maturation. In addition, affected newborns have bilateral sensorineural deafness. Here we identify biallelic mutations in AK2 (adenylate kinase 2) in seven individuals affected with reticular dysgenesis. These mutations result in absent or strongly decreased protein expression. We then demonstrate that restoration of AK2 expression in the bone marrow cells of individuals with reticular dysgenesis overcomes the neutrophil differentiation arrest, underlining its specific requirement in the development of a restricted set of hematopoietic lineages. Last, we establish that AK2 is specifically expressed in the stria vascularis region of the inner ear, which provides an explanation of the sensorineural deafness in these individuals. These results identify a previously unknown mechanism involved in regulation of hematopoietic cell differentiation and in one of the most severe human immunodeficiency syndromes. C1 [Lagresle-Peyrou, Chantal; Six, Emmanuelle M.; Picard, Capucine; Rieux-Laucat, Frederic; Ditadi, Andrea; Demerens-de Chappedelaine, Corinne; Morillon, Estelle; Valensi, Francoise; Fischer, Alain; Cavazzana-Calvo, Marina] INSERM, U768, Res Lab Normal & Pathol Dev Immune Syst, F-75015 Paris, France. [Lagresle-Peyrou, Chantal; Six, Emmanuelle M.; Picard, Capucine; Rieux-Laucat, Frederic; Ditadi, Andrea; Demerens-de Chappedelaine, Corinne; Morillon, Estelle; Abel, Laurent; Fischer, Alain; Cavazzana-Calvo, Marina] Univ Paris 05, Fac Med, IFR94, F-75015 Paris, France. [Lagresle-Peyrou, Chantal] Ecole Prat Hautes Etud, Lab Immunol Cellulaire & Immunopathol, F-75015 Paris, France. [Lagresle-Peyrou, Chantal] Univ Paris 07, CNRS, UMR 7151, F-75015 Paris, France. [Picard, Capucine] Hop Necker Enfants Malad, AP HP, Ctr Etud Deficits Immunitaires, F-75015 Paris, France. [Picard, Capucine; Abel, Laurent] INSERM, U550, Lab Human Genet Infect Dis, F-75015 Paris, France. [Michel, Vincent; Petit, Christine] Univ Paris 06, Inst Pasteur, INSERM, Unite Genet & Physiol Audit,UMRS587, F-75015 Paris, France. [Simon-Stoos, Karen L.] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. [Mullikin, James C.; Candotti, Fabio] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. [Noroski, Lenora M.] Baylor Coll Med, Dept Pediat, Div Allergy & Immunol, Houston, TX 77030 USA. [Besse, Celine] Commissariat Energie Atom, Inst Genom, Ctr Natl Genotypage, F-91000 Evry, France. [Wulffraat, Nicolas M.] Wilhelmina Childrens Hosp, Utrecht Med Ctr, Dept Immunol BMT, NL-3584 CX Utrecht, Netherlands. [Ferster, Alina] Childrens Univ Hosp Reine Fabiola, Pediat Hematooncol Unit, B-1020 Brussels, Belgium. [Abecasis, Manuel M.] Portuguese Inst Oncol Francisco Gentil, Bone Marrow Transplantat Unit, P-1099023 Lisbon, Portugal. [Calvo, Fabien] Univ Paris 07, Hop St Louis, AP HP, INSERM,U716,Clin Invest Ctr, F-75015 Paris, France. [Petit, Christine] Coll France, F-75015 Paris, France. [Fischer, Alain] Hop Necker Enfants Malad, AP HP, Serv Immunol & Hematol Pediat, F-75015 Paris, France. [Cavazzana-Calvo, Marina] Hop Necker Enfants Malad, AP HP, Dept Biotherapie, F-75015 Paris, France. RP Cavazzana-Calvo, M (reprint author), INSERM, U768, Res Lab Normal & Pathol Dev Immune Syst, F-75015 Paris, France. EM m.cavazzana@nck.aphp.fr RI Ditadi, Andrea/K-3461-2016; Rieux-Laucat, Frederic/A-7916-2017; OI Ditadi, Andrea/0000-0003-3283-8943; Rieux-Laucat, Frederic/0000-0001-7858-7866; Picard, Capucine/0000-0001-8788-5056 FU Intramural NIH HHS [Z01 HG000122-10, Z99 HG999999] NR 26 TC 85 Z9 88 U1 1 U2 3 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 JAN PY 2009 VL 41 IS 1 BP 106 EP 111 DI 10.1038/ng.278 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 389IE UT WOS:000262085300024 PM 19043416 ER PT J AU Nemeth, K Leelahavanichkul, A Yuen, PST Mayer, B Parmelee, A Doi, K Robey, PG Leelahavanichkul, K Koller, BH Brown, JM Hu, XZ Jelinek, I Star, RA Mezey, E AF Nemeth, Krisztian Leelahavanichkul, Asada Yuen, Peter S. T. Mayer, Balazs Parmelee, Alissa Doi, Kent Robey, Pamela G. Leelahavanichkul, Kantima Koller, Beverly H. Brown, Jared M. Hu, Xuzhen Jelinek, Ivett Star, Robert A. Mezey, Eva TI Bone marrow stromal cells attenuate sepsis via prostaglandin E-2-dependent reprogramming of host macrophages to increase their interleukin-10 production SO NATURE MEDICINE LA English DT Article ID MESENCHYMAL STEM-CELLS; ACUTE-RENAL-FAILURE; ACUTE KIDNEY INJURY; ANTI-ASIALO GM1; ISCHEMIA-REPERFUSION; IMMUNE MODULATION; ORGAN DAMAGE; MICE; INFLAMMATION; NEUTROPHIL AB Sepsis causes over 200,000 deaths yearly in the US; better treatments are urgently needed. Administering bone marrow stromal cells (BMSCs-also known as mesenchymal stem cells) to mice before or shortly after inducing sepsis by cecal ligation and puncture reduced mortality and improved organ function. The beneficial effect of BMSCs was eliminated by macrophage depletion or pretreatment with antibodies specific for interleukin-10 (IL-10) or IL-10 receptor. Monocytes and/or macrophages from septic lungs made more IL-10 when prepared from mice treated with BMSCs versus untreated mice. Lipopolysaccharide (LPS)-stimulated macrophages produced more IL-10 when cultured with BMSCs, but this effect was eliminated if the BMSCs lacked the genes encoding Toll-like receptor 4, myeloid differentiation primary response gene-88, tumor necrosis factor (TNF) receptor-1a or cyclooxygenase-2. Our results suggest that BMSCs ( activated by LPS or TNF-alpha) reprogram macrophages by releasing prostaglandin E-2 that acts on the macrophages through the prostaglandin EP2 and EP4 receptors. Because BMSCs have been successfully given to humans and can easily be cultured and might be used without human leukocyte antigen matching, we suggest that cultured, banked human BMSCs may be effective in treating sepsis in high-risk patient groups. C1 [Nemeth, Krisztian; Mayer, Balazs; Parmelee, Alissa; Robey, Pamela G.; Leelahavanichkul, Kantima; Mezey, Eva] NIDCR, Craniofacial & Skeletal Dis Branch, Bethesda, MD 20892 USA. [Leelahavanichkul, Asada; Yuen, Peter S. T.; Doi, Kent; Hu, Xuzhen; Star, Robert A.] NIDDK, Renal Diagnost & Therapeut Unit, Bethesda, MD 20892 USA. [Jelinek, Ivett] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. [Koller, Beverly H.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. [Brown, Jared M.] E Carolina Univ, Dept Pharmacol & Toxicol, Greenville, NC 27858 USA. RP Mezey, E (reprint author), NIDCR, Craniofacial & Skeletal Dis Branch, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM mezeye@mail.nih.gov RI Mayer, Balazs/B-7864-2013; Robey, Pamela/H-1429-2011; Yuen, Peter/B-1954-2008 OI Mayer, Balazs/0000-0003-3577-3823; Robey, Pamela/0000-0002-5316-5576; Yuen, Peter/0000-0001-9557-3909 FU Intramural NIH HHS [Z01 DE000714-03] NR 47 TC 801 Z9 861 U1 18 U2 82 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 JAN PY 2009 VL 15 IS 1 BP 42 EP 49 DI 10.1038/nm.1905 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 394DF UT WOS:000262425100017 PM 19098906 ER PT J AU Urano, Y Asanuma, D Hama, Y Koyama, Y Barrett, T Kamiya, M Nagano, T Watanabe, T Hasegawa, A Choyke, PL Kobayashi, H AF Urano, Yasuteru Asanuma, Daisuke Hama, Yukihiro Koyama, Yoshinori Barrett, Tristan Kamiya, Mako Nagano, Tetsuo Watanabe, Toshiaki Hasegawa, Akira Choyke, Peter L. Kobayashi, Hisataka TI Selective molecular imaging of viable cancer cells with pH-activatable fluorescence probes SO NATURE MEDICINE LA English DT Article ID PRIMARY BREAST-CANCER; IN-VIVO; RATIONAL DESIGN; ANTITUMOR-ACTIVITY; METASTATIC SITES; LIVE CELLS; RHODAMINE; ANTIBODY; HER2/NEU; MICE AB A long-term goal of cancer diagnosis is to develop tumor-imaging techniques that have sufficient specificity and sensitivity. To achieve this goal, minimizing the background signal originating from nontarget tissues is crucial. Here we achieve highly specific in vivo cancer visualization by using a newly designed targeted 'activatable' fluorescent imaging probe. This agent is activated after cellular internalization by sensing the pH change in the lysosome. Novel acidic pH-activatable probes based on the boron-dipyrromethene fluorophore were synthesized and then conjugated to a cancer-targeting monoclonal antibody. As proof of concept, ex vivo and in vivo imaging of human epidermal growth factor receptor type 2-positive lung cancer cells in mice was performed. The probe was highly specific for tumors with minimal background signal. Furthermore, because the acidic pH in lysosomes is maintained by the energy-consuming proton pump, only viable cancer cells were successfully visualized. The design concept can be widely adapted to cancer-specific, cell surface-targeting molecules that result in cellular internalization. C1 [Urano, Yasuteru; Asanuma, Daisuke; Kamiya, Mako; Nagano, Tetsuo] Univ Tokyo, Grad Sch Pharmaceut Sci, Bunkyo Ku, Tokyo 1130033, Japan. [Urano, Yasuteru] Japan Sci & Technol Agcy, PRESTO, Chiyoda Ku, Tokyo 1020075, Japan. [Hama, Yukihiro; Koyama, Yoshinori; Barrett, Tristan; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Watanabe, Toshiaki; Hasegawa, Akira] Olympus Corp, Div Res & Dev, Adv Core Technol Dept, Mol Diagnost Technol Grp, Tokyo 1928512, Japan. RP Urano, Y (reprint author), Univ Tokyo, Grad Sch Pharmaceut Sci, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan. EM urano@mol.f.u-tokyo.ac.jp; kobayash@mail.nih.gov RI Urano, Yasuteru/H-1380-2012 FU Precursory Research for Embryonic Sciences and Technology from the Japan Science and Technology Agency [19021010, 19205021]; Intramural Research Program of the US National Institutes of Health; National Cancer Institute, Center for Cancer Research FX This study was supported in part by the Precursory Research for Embryonic Sciences and Technology from the Japan Science and Technology Agency, by research grants 19021010 and 19205021 to Y. U. and by the Intramural Research Program of the US National Institutes of Health, National Cancer Institute, Center for Cancer Research to Y. H., Y. K., T. B., P. L. C. and H. K. NR 32 TC 367 Z9 373 U1 34 U2 241 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 JAN PY 2009 VL 15 IS 1 BP 104 EP 109 DI 10.1038/nm.1854 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 394DF UT WOS:000262425100025 PM 19029979 ER PT J AU Lippincott-Schwartz, J Manley, S AF Lippincott-Schwartz, Jennifer Manley, Suliana TI Putting super-resolution fluorescence microscopy to work SO NATURE METHODS LA English DT Article ID PHOTOACTIVATED LOCALIZATION MICROSCOPY; STRUCTURED-ILLUMINATION MICROSCOPY; OPTICAL RECONSTRUCTION MICROSCOPY; RESOLUTION; BREAKING; LIMIT AB Super-resolution microscopy is poised to revolutionize our understanding of the workings of the cell. But the technology still has some limitations, and these must be taken into consideration if widespread application is to yield biological insight. C1 [Lippincott-Schwartz, Jennifer; Manley, Suliana] NICHHD, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA. RP Lippincott-Schwartz, J (reprint author), NICHHD, Cell Biol & Metab Program, NIH, Bldg 18T,Room 101,18 Lib Dr, Bethesda, MD 20892 USA. EM lippincj@mail.nih.gov; manleysu@mail.nih.gov RI Manley, Suliana/D-3818-2012 OI Manley, Suliana/0000-0002-4755-4778 FU Intramural NIH HHS [Z01 HD008850-01] NR 15 TC 112 Z9 115 U1 5 U2 51 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 J9 NAT METHODS JI Nat. Methods PD JAN PY 2009 VL 6 IS 1 BP 21 EP 23 DI 10.1038/NMETH.F.233 PG 3 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 393JS UT WOS:000262370200011 PM 19116610 ER PT J AU Matsumoto, M Hikosaka, O AF Matsumoto, Masayuki Hikosaka, Okihide TI Representation of negative motivational value in the primate lateral habenula SO NATURE NEUROSCIENCE LA English DT Article ID MIDBRAIN DOPAMINE NEURONS; DORSAL RAPHE NUCLEUS; ORBITOFRONTAL CORTEX; MATCHING BEHAVIOR; PREFRONTAL CORTEX; AVERSIVE STIMULI; NEURAL RESPONSES; REWARD; RAT; PREDICTION AB An action may lead to either a reward or a punishment. Therefore, an appropriate action needs to be chosen on the basis of the values of both expected rewards and expected punishments. To understand the underlying neural mechanisms, we conditioned monkeys using a Pavlovian procedure with two distinct contexts: one in which rewards were available and another in which punishments were feared. We found that the population of lateral habenula neurons was most strongly excited by a conditioned stimulus associated with the most unpleasant event in each context: the absence of the reward or the presence of the punishment. The population of lateral habenula neurons was also excited by the punishment itself and inhibited by the reward itself, especially when they were less predictable. These results suggest that the lateral habenula has the potential to adaptively control both reward-seeking and punishment-avoidance behaviors, presumably through its projections to dopaminergic and serotonergic systems. C1 [Matsumoto, Masayuki; Hikosaka, Okihide] NEI, Sensorimotor Res Lab, US Natl Inst Hlth, Bethesda, MD 20892 USA. RP Matsumoto, M (reprint author), NEI, Sensorimotor Res Lab, US Natl Inst Hlth, 49 Convent Dr, Bethesda, MD 20892 USA. EM matsumotom@nei.nih.gov FU National Institutes of Health, National Eye Institute FX We thank S. Hong, M. Yasuda and E. Bromberg-Martin for valuable discussion, and M. K. Smith, J. W. McClurkin, A. M. Nichols, T. W. Ruffner, A. V. Hays and L. P. Jensen for technical assistance. This research was supported by the Intramural Research Program at the National Institutes of Health, National Eye Institute. NR 40 TC 200 Z9 203 U1 2 U2 17 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 JAN PY 2009 VL 12 IS 1 BP 77 EP 84 DI 10.1038/nn.2233 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 388HL UT WOS:000262010800018 PM 19043410 ER PT J AU Huang, DW Sherman, BT Lempicki, RA AF Huang, Da Wei Sherman, Brad T. Lempicki, Richard A. TI Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources SO NATURE PROTOCOLS LA English DT Article ID FUNCTIONAL-ANALYSIS; ONTOLOGY; TOOL AB DAVID bioinformatics resources consists of an integrated biological knowledgebase and analytic tools aimed at systematically extracting biological meaning from large gene/protein lists. This protocol explains how to use DAVID, a high-throughput and integrated data-mining environment, to analyze gene lists derived from high-throughput genomic experiments. The procedure first requires uploading a gene list containing any number of common gene identifiers followed by analysis using one or more text and pathway-mining tools such as gene functional classification, functional annotation chart or clustering and functional annotation table. By following this protocol, investigators are able to gain an in-depth understanding of the biological themes in lists of genes that are enriched in genome-scale studies. C1 [Huang, Da Wei; Sherman, Brad T.; Lempicki, Richard A.] NCI, Lab Immunopathogenesis & Bioinformat, Clin Serv Program, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Huang, DW (reprint author), NCI, Lab Immunopathogenesis & Bioinformat, Clin Serv Program, SAIC Frederick Inc, Frederick, MD 21702 USA. EM huangdawei@mail.nih.gov; rlempicki@mail.nih.gov RI Lempicki, Richard/E-1844-2012 OI Lempicki, Richard/0000-0002-7059-409X FU National Institute of Allergy and Infectious Diseases (NIAID); National Institutes of Health (NIH) [N01-C0-56000] FX We are grateful to the referees for their constructive comments and thank Robert Stephens, David Bryant and David Liu in the ABCC group for Web server support. Thanks also go to Xin Zheng and Jun Yang in the Laboratory of Immunopathogenesis and Bioinformatics ( LIB) group for discussion. We also thank Bill Wilton and Mike Tartakovsky for information technology and network support. The project has been funded with federal funds from the National Institute of Allergy and Infectious Diseases (NIAID) and National Institutes of Health (NIH), under Contract no. N01-C0-56000. The annotation of this tool and 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 United States Government. NR 16 TC 8754 Z9 8858 U1 114 U2 791 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PY 2009 VL 4 IS 1 BP 44 EP 57 DI 10.1038/nprot.2008.211 PG 14 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 441PS UT WOS:000265781800006 ER PT J AU Moaddel, R Wainer, IW AF Moaddel, Ruin Wainer, Irving W. TI The preparation and development of cellular membrane affinity chromatography columns SO NATURE PROTOCOLS LA English DT Article ID IMMOBILIZED P-GLYCOPROTEIN; NICOTINIC ACETYLCHOLINE-RECEPTORS; PROTEIN-COUPLED RECEPTOR; COATED MAGNETIC BEADS; HUMAN SERUM-ALBUMIN; STATIONARY-PHASE; CONFORMATIONAL MOBILITY; GLUCOSE-TRANSPORTER; CYTOCHALASIN-B; LIGAND AB Cellular membrane affinity chromatography is a technique that is based on the immobilization of a target trans-membrane protein onto a stationary phase. The target protein is isolated by homogenization and solubilization of a source (e. g., cell line) followed by immobilization on either the immobilized artificial membrane-phosphatidyl choline (IAM-PC) stationary phase or the surface of an open tubular capillary during a dialysis step. The procedure typically takes 3-4 d for the IAM-PC stationary phase, whereas the open-tubular method takes an extra week for the preparation of the capillary. The resulting columns can then be used to characterize binding sites on the target protein through frontal chromatographic and/or nonlinear chromatographic studies using a wide variety of ligands including small molecules and polypeptides. The columns have been used in drug discovery as well as in the screening of tobacco smoke condensates. C1 [Moaddel, Ruin; Wainer, Irving W.] NIA, Clin Invest Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Moaddel, R (reprint author), NIA, Clin Invest Lab, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM moaddelru@mail.nih.gov FU Intramural Research Program of the National Institute on Aging/NIH FX This work was funded by the Intramural Research Program of the National Institute on Aging/NIH. NR 34 TC 49 Z9 50 U1 4 U2 28 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PY 2009 VL 4 IS 2 BP 197 EP 205 DI 10.1038/nprot.2008.225 PG 9 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 441PT UT WOS:000265781900007 PM 19180089 ER PT J AU Sharan, SK Thomason, LC Kuznetsov, SG Court, DL AF Sharan, Shyam K. Thomason, Lynn C. Kuznetsov, Sergey G. Court, Donald L. TI Recombineering: a homologous recombination-based method of genetic engineering SO NATURE PROTOCOLS LA English DT Article ID GRAM-NEGATIVE BACTERIA; ESCHERICHIA-COLI; BETA-PROTEIN; PHAGE-LAMBDA; DNA FRAGMENTS; BAC; EFFICIENT; SYSTEM; EXONUCLEASE; CHROMOSOME AB Recombineering is an efficient method of in vivo genetic engineering applicable to chromosomal as well as episomal replicons in Escherichia coli. This method circumvents the need for most standard in vitro cloning techniques. Recombineering allows construction of DNA molecules with precise junctions without constraints being imposed by restriction enzyme site location. Bacteriophage homologous recombination proteins catalyze these recombineering reactions using double- and single-stranded linear DNA substrates, so-called targeting constructs, introduced by electroporation. Gene knockouts, deletions and point mutations are readily made, gene tags can be inserted and regions of bacterial artificial chromosomes or the E. coli genome can be subcloned by gene retrieval using recombineering. Most of these constructs can be made within about 1 week's time. C1 [Sharan, Shyam K.; Kuznetsov, Sergey G.] Natl Canc Inst, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA. [Court, Donald L.] Natl Canc Inst, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res, Frederick, MD 21702 USA. [Thomason, Lynn C.] SAIC Frederick Inc, Gene Regulat & Chromosome Biol Lab, Basic Res Program, Frederick, MD 21702 USA. RP Sharan, SK (reprint author), Natl Canc Inst, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA. EM sharans@mail.nih.gov; court@mail.ncifcrf.gov OI Kuznetsov, Sergey/0000-0002-5662-9700 FU National Cancer Institute, National Institutes of Health [N01-C0-12400] FX We thank Nina Costantino and James Sawitzke for helpful comments. This research was supported by the Intramural Research Program of NIH, National Cancer Institute, Center for Cancer Research. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract N01-C0-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. NR 57 TC 235 Z9 250 U1 15 U2 122 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PY 2009 VL 4 IS 2 BP 206 EP 223 DI 10.1038/nprot.2008.227 PG 18 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 441PT UT WOS:000265781900008 PM 19180090 ER PT J AU Grivel, JC Margolis, L AF Grivel, Jean-Charles Margolis, Leonid TI Use of human tissue explants to study human infectious agents SO NATURE PROTOCOLS LA English DT Article ID HUMAN LYMPHOID-TISSUE; IMMUNODEFICIENCY-VIRUS TYPE-1; T-CELL DEPLETION; HUMAN CERVICAL TISSUE; EX-VIVO; HIV-INFECTION; IN-VITRO; CXCR4-TROPIC HIV-1; HUMAN-CYTOMEGALOVIRUS; TOPICAL MICROBICIDES AB The study of human cell-cell and cell-pathogen interactions that occur in the context of complex tissue cytoarchitecture is critical for deciphering the mechanisms of many normal and pathogenic processes. This protocol describes methods for culturing and infecting explants of human tissues to study the pathogenesis of human infectious agents and their local interactions. The protocol relies on the use of fresh human tissues dissected into small blocks or biopsies that are cultured at the liquid-air interface on collagen rafts. These tissue blocks retain their cytoarchitecture and support productive infection of various pathogens without exogenous stimulation. Experimental details for setting up cultures of human tonsils, lymph nodes and cervicovaginal and rectosigmoid tissues, including protocols for their infection with HIV-1 and other pathogens, are described here. Using this protocol, culture and infections can be set up in 3-6 h and be maintained for 2-3 weeks, depending on the tissue used. C1 [Grivel, Jean-Charles; Margolis, Leonid] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Intercellular Interact, Program Phys Biol, Bethesda, MD 20892 USA. RP Margolis, L (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Intercellular Interact, Program Phys Biol, 10 Ctr Dr,Room 9D58, Bethesda, MD 20892 USA. EM margolil@mail.nih.gov FU Eunice Kennedy Shriver National Institute of Child Health and Human Development FX We are grateful to the past and present members of the laboratory who contributed to the development of these techniques. These are (in alphabetical order) Massimo Alfano, Naomi Amichay, Boris Baibakov, Angelique Biancotto, Beda Brichacek, Silvia Chen, Cristian Condak, Wendy Fitzgerald, Svetlana Glushakova, Ingrid Karlsson, Rosangela Lima da Gomez, Andrea Lisco, Nina Malkevitch, Lucia Pinto da Silva, Atfa Sassi, Andrew Sylwester, Christophe Vanpouille and Joshua Zimmerberg. This work was supported by the intramural program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 54 TC 49 Z9 52 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PY 2009 VL 4 IS 2 BP 256 EP 269 DI 10.1038/nprot.2008.245 PG 14 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 441PT UT WOS:000265781900012 PM 19197269 ER PT J AU Erickson, HS Albert, PS Gillespie, JW Rodriguez-Canales, J Linehan, WM Pinto, PA Chuaqui, RF Emmert-Buck, MR AF Erickson, Heidi S. Albert, Paul S. Gillespie, John W. Rodriguez-Canales, Jaime Linehan, W. Marston Pinto, Peter A. Chuaqui, Rodrigo F. Emmert-Buck, Michael R. TI Quantitative RT-PCR gene expression analysis of laser microdissected tissue samples SO NATURE PROTOCOLS LA English DT Article ID POLYMERASE-CHAIN-REACTION; CANCER-CELL-LINES; REAL-TIME PCR; PROSTATE-CANCER; CAPTURE MICRODISSECTION; MESSENGER-RNA; HOUSEKEEPING GENES; MICROARRAY ANALYSIS; ENDOGENOUS CONTROLS; RENAL BIOPSIES AB Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) is a valuable tool for measuring gene expression in biological samples. However, unique challenges are encountered when studies are performed on cells microdissected from tissues derived from animal models or the clinic, including specimen-related issues, variability of RNA template quality and quantity, and normalization. qRT-PCR using small amounts of mRNA derived from dissected cell populations requires adaptation of standard methods to allow meaningful comparisons across sample sets. The protocol described here presents the rationale, technical steps, normalization strategy and data analysis necessary to generate reliable gene expression measurements of transcripts from dissected samples. The entire protocol from tissue microdissection through qRT-PCR analysis requires similar to 16 h. C1 [Erickson, Heidi S.; Rodriguez-Canales, Jaime; Chuaqui, Rodrigo F.; Emmert-Buck, Michael R.] NCI, Pathogenet Unit, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Erickson, Heidi S.; Rodriguez-Canales, Jaime; Linehan, W. Marston; Pinto, Peter A.; Chuaqui, Rodrigo F.; Emmert-Buck, Michael R.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. [Albert, Paul S.] NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. [Gillespie, John W.] NCI, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Emmert-Buck, MR (reprint author), NCI, Pathogenet Unit, Pathol Lab, NIH, Bethesda, MD 20892 USA. EM mbuck@helix.nih.gov OI Rodriguez-Canales, Jaime/0000-0002-0885-2377 FU NIH, National Cancer Institute, Center for Cancer Research FX The authors appreciatively thank S. Gonzalez and A. Velasco (The Catholic University, Santiago, Chile) for their collaboration in providing the frozen prostate whole-mount tissue blocks used to assess normalization strategies. R. F. C. and M. R. E.-B. are Federal employee inventors on NIH patents covering LCM and xMD technologies and are entitled to receive royalty payments through the NIH Technology Transfer program. This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 91 TC 47 Z9 47 U1 1 U2 15 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PY 2009 VL 4 IS 6 BP 902 EP 922 DI 10.1038/nprot.2009.61 PG 21 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 452NE UT WOS:000266546200010 PM 19478806 ER PT J AU Klauschen, F Qi, H Egen, JG Germain, RN Meier-Schellersheim, M AF Klauschen, Frederick Qi, Hai Egen, Jackson G. Germain, Ronald N. Meier-Schellersheim, Martin TI Computational reconstruction of cell and tissue surfaces for modeling and data analysis SO NATURE PROTOCOLS LA English DT Article ID REVEALS; SYSTEMS AB We present a method for the computational reconstruction of the 3-D morphology of biological objects, such as cells, cell conjugates or 3-D arrangements of tissue structures, using data from high-resolution microscopy modalities. The method is based on the iterative optimization of Voronoi representations of the spatial structures. The reconstructions of biological surfaces automatically adapt to morphological features of varying complexity with flexible degrees of resolution. We show how 3-D confocal images of single cells can be used to generate numerical representations of cellular membranes that may serve as the basis for realistic, spatially resolved computational models of membrane processes or intracellular signaling. Another example shows how the protocol can be used to reconstruct tissue boundaries from segmented two-photon image data that facilitate the quantitative analysis of lymphocyte migration behavior in relation to microanatomical structures. Processing time is of the order of minutes depending on data features and reconstruction parameters. C1 [Klauschen, Frederick; Germain, Ronald N.; Meier-Schellersheim, Martin] NIAID, Program Syst Immunol & Infect Dis Modeling, NIH, Bethesda, MD 20892 USA. [Qi, Hai; Egen, Jackson G.; Germain, Ronald N.] NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Klauschen, F (reprint author), NIAID, Program Syst Immunol & Infect Dis Modeling, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM fklauschen@niaid.nih.gov RI Klauschen, Frederick/C-5637-2015; OI Egen, Jackson/0000-0003-2053-0837 FU NIAID, NIH FX This research was supported by the Intramural Research Program of NIAID, NIH. NR 22 TC 8 Z9 8 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PY 2009 VL 4 IS 7 BP 1006 EP 1012 DI 10.1038/nprot.2009.94 PG 7 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 482BN UT WOS:000268858700001 PM 19536268 ER PT J AU Klauschen, F Ishii, M Qi, H Bajenoff, M Egen, JG Germain, RN Meier-Schellersheim, M AF Klauschen, Frederick Ishii, Masaru Qi, Hai Bajenoff, Marc Egen, Jackson G. Germain, Ronald N. Meier-Schellersheim, Martin TI Quantifying cellular interaction dynamics in 3D fluorescence microscopy data SO NATURE PROTOCOLS LA English DT Article ID BONE; OSTEOCLAST; COMPONENT; RECEPTOR; CELLS AB The wealth of information available from advanced fluorescence imaging techniques used to analyze biological processes with high spatial and temporal resolution calls for high-throughput image analysis methods. Here, we describe a fully automated approach to analyzing cellular interaction behavior in 3D fluorescence microscopy images. As example application, we present the analysis of drug-induced and S1P(1)-knockout-related changes in bone-osteoclast interactions. Moreover, we apply our approach to images showing the spatial association of dendritic cells with the fibroblastic reticular cell network within lymph nodes and to microscopy data regarding T-B lymphocyte synapse formation. Such analyses that yield important information about the molecular mechanisms determining cellular interaction behavior would be very difficult to perform with approaches that rely on manual/semi-automated analyses. This protocol integrates adaptive threshold segmentation, object detection, adaptive color channel merging, and neighborhood analysis and permits rapid, standardized, quantitative analysis and comparison of the relevant features in large data sets. C1 [Klauschen, Frederick; Germain, Ronald N.; Meier-Schellersheim, Martin] NIAID, Program Syst Immunol & Infect Dis Modeling, NIH, Bethesda, MD 20892 USA. [Klauschen, Frederick] Univ Med Berlin, Inst Pathol, Berlin, Germany. [Ishii, Masaru; Qi, Hai; Bajenoff, Marc; Egen, Jackson G.; Germain, Ronald N.] NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Klauschen, F (reprint author), NIAID, Program Syst Immunol & Infect Dis Modeling, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM fklauschen@mail.nih.gov; mms@niaid.nih.gov RI Klauschen, Frederick/C-5637-2015; OI Egen, Jackson/0000-0003-2053-0837 FU NIAID; NIH; International Human Frontier Science Program FX This research was supported by the Intramural Research Program of NIAID, NIH. M. I. was supported by a fellowship grant from the International Human Frontier Science Program. NR 19 TC 27 Z9 28 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PY 2009 VL 4 IS 9 BP 1305 EP 1312 DI 10.1038/nprot.2009.129 PG 8 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 504FQ UT WOS:000270601700008 PM 19696749 ER PT J AU Xu, XM Yoo, MH Carlson, BA Gladyshev, VN Hatfield, DL AF Xu, Xue-Ming Yoo, Min-Hyuk Carlson, Bradley A. Gladyshev, Vadim N. Hatfield, Dolph L. TI Simultaneous knockdown of the expression of two genes using multiple shRNAs and subsequent knock-in of their expression SO NATURE PROTOCOLS LA English DT Article ID SHORT HAIRPIN RNA; POLYMERASE-III PROMOTERS; HUMAN-CELLS; DOWN-REGULATION; INTERFERENCE; REPLACEMENT; VECTORS; PROTEIN; SELENOCYSTEINE; IDENTIFICATION AB Small hairpin RNA (shRNA) is a powerful tool for inhibiting gene expression. One limitation has been that this technique has been used primarily to target a single gene. This protocol expands upon previous methods by describing a knockdown vector that facilitates cloning of multiple shRNAs; this allows targeted knockdown of more than one gene or of a single gene that may otherwise be difficult to knockdown using a single shRNA. The targeted gene(s) can be readily re-expressed by transfecting knockdown cells with a knock-in vector, containing an shRNA-refractive cDNA that will express the protein-of-interest even in the presence of shRNAs. The constructed knockdown and knock-in vectors can be easily used concurrently to assess possible interrelationships between genes, the effects of gene loss on cell function and/or their restoration by replacing targeted genes one at a time. The entire knockdown or knock-in procedure can be completed in similar to 3-4 months. C1 [Xu, Xue-Ming; Yoo, Min-Hyuk; Carlson, Bradley A.; Hatfield, Dolph L.] NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Gladyshev, Vadim N.] Univ Nebraska, Dept Biochem, Lincoln, NE 68583 USA. [Gladyshev, Vadim N.] Redox Biol Ctr, Lincoln, NE USA. RP Hatfield, DL (reprint author), NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. EM hatfield@mail.nih.gov RI Gladyshev, Vadim/A-9894-2013 FU National Institutes of Health (NIH); NCI; Center for Cancer Research FX This research was supported by the Intramural Research Programof the National Institutes of Health (NIH), NCI, Center for Cancer Research to D. L. H. and NIH grants to V. N. G. NR 46 TC 18 Z9 18 U1 0 U2 13 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PY 2009 VL 4 IS 9 BP 1338 EP 1349 DI 10.1038/nprot.2009.145 PG 12 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 504FQ UT WOS:000270601700011 PM 19713955 ER PT J AU Macbeth, AH Edds, JS Young, WS AF Macbeth, Abbe H. Edds, Jennifer Stepp Young, W. Scott, III TI Housing conditions and stimulus females: a robust social discrimination task for studying male rodent social recognition SO NATURE PROTOCOLS LA English DT Article ID ESTROGEN-RECEPTOR-ALPHA; INBRED MOUSE STRAINS; BETA KNOCKOUT MICE; OXYTOCIN RECEPTOR; MALE-RATS; INDIVIDUAL-RECOGNITION; BEHAVIORAL PROFILES; LABORATORY MICE; GENETIC-BASIS; ODORS AB Social recognition (SRSR) enables rodents to distinguish between familiar and novel conspecifics, largely through individual odor cues. SRSR tasks utilize the tendency for a male to sniff and interact with a novel individual more than a familiar individual. Many paradigms have been used to study the roles of the neuropeptides oxytocin and vasopressin in SRSR. However, inconsistencies in results have arisen within similar mouse strains, and across different paradigms and laboratories, making reliable testing of SRSR difficult. The current protocol details a novel approach that is replicable across investigators and in different strains of mice. We created a protocol that uses gonadally intact, singly housed females presented within corrals to group-housed males. Housing females singly before testing is particularly important for reliable discrimination. This methodology will be useful for studying short-term social memory in rodents, and may also be applicable for longer term studies. C1 [Macbeth, Abbe H.; Edds, Jennifer Stepp; Young, W. Scott, III] NIMH, Sect Neural Gene Express, NIH, DHHS, Bethesda, MD 20892 USA. RP Young, WS (reprint author), NIMH, Sect Neural Gene Express, NIH, DHHS, Bethesda, MD 20892 USA. EM wsy@mail.nih.gov RI Young, W Scott/A-9333-2009 OI Young, W Scott/0000-0001-6614-5112 FU NIMH Intramural Research Program [Z01-MH-002498-20] FX We thank Dr. Scott Wersinger for his helpful review of an early version of this paper. The authors appreciate the excellent technical support provided by Emily Shepard, James Heath, Anna Brownstein and the Building 49 animal facility. This research was supported by the NIMH Intramural Research Program (Z01-MH-002498-20). NR 59 TC 23 Z9 23 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PY 2009 VL 4 IS 11 BP 1574 EP 1581 DI 10.1038/nprot.2009.141 PG 8 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 551RD UT WOS:000274225800002 PM 19816420 ER PT J AU Schwartzberg, PL Mueller, KL Qi, H Cannons, JL AF Schwartzberg, Pamela L. Mueller, Kristen L. Qi, Hai Cannons, Jennifer L. TI SLAM receptors and SAP influence lymphocyte interactions, development and function SO NATURE REVIEWS IMMUNOLOGY LA English DT Review ID LINKED LYMPHOPROLIFERATIVE-DISEASE; T-CELL DEVELOPMENT; FOLLICULAR-HELPER-CELLS; BONE-MARROW-TRANSPLANTATION; B-CELLS; HUMORAL IMMUNITY; GENE-PRODUCT; MICE DEFICIENT; CUTTING EDGE; THYMOCYTE INTERACTION AB Mutations that affect the adaptor molecule SLAM-associated protein (SAP) underlie the primary immunodeficiency disease X-linked lymphoproliferative syndrome. SAP is required for mediating signals from members of the signalling lymphocytic activation molecule (SLAM) family of immunomodulatory receptors. Recent data have highlighted a role for SAP in the development of innate-like T-cell lineages, including natural killer T cells, and in the regulation of the interactions between B cells and T cells that are required for germinal-centre formation and long-term humoral immunity. These data have revealed that SLAM family members and SAP have crucial roles in regulating lymphocyte interactions and adhesion, which are required for the normal development, homeostasis and function of the immune system. C1 [Schwartzberg, Pamela L.; Mueller, Kristen L.; Cannons, Jennifer L.] NHGRI, Bethesda, MD 20892 USA. [Qi, Hai] NIAID, NIH, Bethesda, MD 20892 USA. RP Schwartzberg, PL (reprint author), NHGRI, Bethesda, MD 20892 USA. EM pams@mail.nih.gov RI Qi, Hai/A-3955-2009 NR 67 TC 114 Z9 125 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD JAN PY 2009 VL 9 IS 1 BP 39 EP 46 DI 10.1038/nri2456 PG 8 WC Immunology SC Immunology GA 387JY UT WOS:000261949700013 PM 19079134 ER PT J AU Rothenburg, S Seo, EJ Gibbs, JS Dever, TE Dittmar, K AF Rothenburg, Stefan Seo, Eun Joo Gibbs, James S. Dever, Thomas E. Dittmar, Katharina TI Rapid evolution of protein kinase PKR alters sensitivity to viral inhibitors SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID STRANDED-RNA BINDING; INITIATION FACTOR-2-ALPHA; SUBSTRATE RECOGNITION; PHYLOGENETIC ANALYSIS; CRYSTAL-STRUCTURE; GENE-PRODUCT; SACCHAROMYCES-CEREVISIAE; TRANSLATIONAL CONTROL; MAXIMUM-LIKELIHOOD; ALPHA-SUBUNIT AB Protein kinase PKR (also known as EIF2AK2) is activated during viral infection and phosphorylates the a subunit of eukaryotic translation initiation factor 2 (eIF2), leading to inhibition of translation and viral replication. We report fast evolution of the PKR kinase domain in vertebrates, coupled with positive selection of specific sites. Substitution of positively selected residues in human PKR with residues found in related species altered sensitivity to PKR inhibitors from different poxviruses. Species-specific differences in sensitivity to poxviral pseudosubstrate inhibitors were identified between human and mouse PKR, and these differences were traced to positively selected residues near the eIF2 alpha binding site. Our findings indicate how an antiviral protein evolved to evade viral inhibition while maintaining its primary function. Moreover, the identified species-specific differences in the susceptibility to viral inhibitors have important implications for studying human infections in nonhuman model systems. C1 [Rothenburg, Stefan; Seo, Eun Joo; Dever, Thomas E.] Eunice Kennedy Shriver Natl Inst Chil Hlth & Huma, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. [Gibbs, James S.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. [Dittmar, Katharina] SUNY Buffalo, Dept Biol Sci, Buffalo, NY 14260 USA. RP Rothenburg, S (reprint author), Eunice Kennedy Shriver Natl Inst Chil Hlth & Huma, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. EM rothenst@mail.nih.gov RI Rothenburg, Stefan/A-8340-2008; OI Dever, Thomas/0000-0001-7120-9678 FU US National Institutes of Health, NICHD FX We are grateful to A. Hinnebusch, M. Yu and L. Tazi for helpful discussion and for careful reading of the manuscript; F. Sicheri, M. Dey, D. McClellan, A. Furano and C. Tellgren-Roth for helpful discussion; C. Samuel (University of California, Santa Barbara) for providing the PKR knockdown cells; and M. Kawagishi-Kobayashi and M. Dey (US National Institute of Child Health and Human Development (NICHD)) for yeast strains. This work was supported by funding from the Intramural Research Program of the US National Institutes of Health, NICHD, to T. E. D. NR 45 TC 47 Z9 48 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD JAN PY 2009 VL 16 IS 1 BP 63 EP U76 DI 10.1038/nsmb.1529 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 391XN UT WOS:000262267600014 PM 19043413 ER PT J AU Rodrigues, LG Ferraz, MJ Rodrigues, D Pais-Vieira, M Lima, D Brady, RO Sousa, MM Sa-Miranda, MC AF Rodrigues, L. G. Ferraz, M. J. Rodrigues, D. Pais-Vieira, M. Lima, D. Brady, R. O. Sousa, M. M. Sa-Miranda, M. C. TI Neurophysiological, behavioral and morphological abnormalities in the Fabry knockout mice SO NEUROBIOLOGY OF DISEASE LA English DT Article DE Fabry disease; Mouse model; SHIRPA; Sciatic nerve; Motor nerve conduction velocity; Hot-plate; Histology; Thin-layer chromatography ID SMALL FIBER DYSFUNCTION; ALPHA-GALACTOSIDASE; ENZYME REPLACEMENT; PERIPHERAL-NERVE; DEFICIENT MICE; DISEASE; NEUROPATHY; PHENOTYPE; MOUSE; GLOBOTRIAOSYLCERAMIDE AB Fabry disease (OMIM 301500) is a rare X-linked recessive disorder caused by mutations in the alpha-galactosidase gene (GLA). Loss of a-galactosidase (a-Gal) activity leads to the abnormal accumulation of glycosphingolipids in lysosomes predominantly of vascular endothelial cells. Clinically the disorder presents with angiokeratomas, clouding of the cornea, and renal, cardiac, and cerebrovascular complications. In addition, there is an increased incidence of neuropathic pain in Fabry patients. In this study, we investigated the implications of loss of a-galactosidase A activity on sensorimotor function and peripheral nervous system. Similar to the described in Fabry disease patients, the sensorimotor assessment of Fabry mice revealed diminished locomotor activity and warm hypoalgesia as assessed in the hot-plate. Moreover Fabry mice displayed alterations both in balance and co-ordination. By histological analysis, the cyto-architecture of Fabry mice sciatic nerves showed an increase in mean cross-sectional area accompanied by a decrease in the density of non-myelinated fibers as well as a trend for a decreased number of small myelinated fibers, a well established feature of Fabry disease. A relative preservation of large myelinated fibers and nerve conduction velocity measurements was observed. Our findings demonstrate for the first time that Fabry knockout mice have Gb3 accumulation in the peripheral nervous system, alterations in sensorimotor function, hypoalgesia and no impairment of motor nerve conduction. (c) 2008 Elsevier Inc. All rights reserved. C1 [Rodrigues, L. G.; Ferraz, M. J.; Rodrigues, D.; Sa-Miranda, M. C.] Inst Biol Mol & Celular, Lysosome & Peroxisome Biol Unit, P-4150180 Oporto, Portugal. [Brady, R. O.] NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Rodrigues, LG (reprint author), Inst Biol Mol & Celular, Lysosome & Peroxisome Biol Unit, Rua Campo Alegre 823, P-4150180 Oporto, Portugal. EM lorena@ibmc.up.pt; mcsamir@ibmc.up.pt RI sa Miranda, Maria Clara/K-3920-2013; Sousa, Monica/K-4367-2013; Rodrigues, Lorena/A-2127-2017; OI sa Miranda, Maria Clara/0000-0003-0123-5525; Sousa, Monica/0000-0002-4524-2260; Rodrigues, Lorena/0000-0003-3416-5412; Lima, Deolinda/0000-0002-5723-0777; Pais-Vieira, Miguel/0000-0002-1398-9060 FU Funda ao para a Ciencia a Tecnologia (FCT) [1TDC/SAL-NEU/66740/2006]; FCT [SFRH/BPD/25333/2005, SFRH/BD/24383/2005] FX The authors would like to acknowledge Dr. Antonio Guimaraes (Neuropathology Unit, Hospital Geral de Santo Antonio, Porto) for his invaluable help with the electron microscopy analysis, Maria Jose Ferreira and Rui Fernandes for their technical support in electron microscopy, and Dr. Isabel Carvalho, Fatima Martins and Isabel Duarte for their helpful assistance in colony maintenance. This work was supported by Funda ao para a Ciencia a Tecnologia (FCT) of Portugal (1TDC/SAL-NEU/66740/2006) and co-funded by FEDER. Lorena G. Rodrigues and Miguel Pais Vieira were supported by personal grants from FCT (SFRH/BPD/25333/2005 and SFRH/BD/24383/2005, respectively). NR 37 TC 20 Z9 20 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD JAN PY 2009 VL 33 IS 1 BP 48 EP 56 DI 10.1016/j.nbd.2008.09.001 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 394PB UT WOS:000262457900006 PM 18848893 ER PT J AU Brandt, KR Gardiner, JM Vargha-Khadem, F Baddeley, AD Mishkin, M AF Brandt, Karen R. Gardiner, John M. Vargha-Khadem, Faraneh Baddeley, Alan D. Mishkin, Mortimer TI Impairment of recollection but not familiarity in a case of developmental amnesia SO NEUROCASE LA English DT Article DE Developmental amnesia; Exclusion; Inclusion; Recollection; Familiarity ID RECOGNITION MEMORY; HIPPOCAMPAL DAMAGE; SEMANTIC MEMORY; TEMPORAL-LOBE; PATIENT; RECALL; DISSOCIATION; PATHOLOGY; TASK AB In a re-examination of the recognition memory of Jon, a young adult with developmental amnesia due to perinatal hippocampal damage, we used a test procedure that provides estimates of the separate contributions to recognition of recollection and familiarity. Comparison between Jon and his controls revealed that, whereas he was unimpaired in the familiarity process, he showed abnormally low levels of recollection, supporting the view that the hippocampus mediates the latter process selectively. C1 [Brandt, Karen R.] Univ Keele, Sch Psychol, Keele ST5 5BG, Staffs, England. [Gardiner, John M.] Univ Sussex, Dept Psychol, Brighton BN1 9RH, E Sussex, England. [Vargha-Khadem, Faraneh] UCL, Inst Child Hlth, London, England. [Vargha-Khadem, Faraneh] Great Ormond St Hosp Sick Children, Dev Neurosci Unit, London WC1N 3JH, England. [Baddeley, Alan D.] Univ York, Dept Psychol, York YO10 5DD, N Yorkshire, England. [Mishkin, Mortimer] NIMH, NIH DHHS, Bethesda, MD 20892 USA. RP Brandt, KR (reprint author), Univ Keele, Sch Psychol, Dorothy Hodgkin Bldg, Keele ST5 5BG, Staffs, England. EM k.r.brandt@psy.keele.ac.uk RI Vargha-Khadem, Faraneh/C-2558-2008 FU Economic and Social Research Council [R000223887]; MRC [65439]; Intramural Program of the NIMH/ NIH/DHHS FX This research was supported by the Economic and Social Research Council (ESRC Grant R000223887) and by a programme grant from the MRC (Grant ID: 65439) and the Intramural Program of the NIMH/ NIH/DHHS for which we thank both of them for their support. The research was carried out at the Department of Psychology, University of Sussex, Falmer, BN1 9QH. We are grateful to Jon and to his parents for their very willing cooperation. NR 28 TC 25 Z9 25 U1 0 U2 3 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1355-4794 J9 NEUROCASE JI Neurocase PY 2009 VL 15 IS 1 BP 60 EP 65 AR PII 906894450 DI 10.1080/13554790802613025 PG 6 WC Clinical Neurology; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 411LP UT WOS:000263651400008 PM 19090415 ER PT J AU Quarles, RH AF Quarles, Richard H. TI A Hypothesis About the Relationship of Myelin-Associated Glycoprotein's Function in Myelinated Axons to its Capacity to Inhibit Neurite Outgrowth SO NEUROCHEMICAL RESEARCH LA English DT Article DE Axon-glia interactions; Gangliosides; Myelin-associated glycoprotein; Myelinated axons; Neurite outgrowth inhibition; Nogo receptor; Sialic acid ID PERIPHERAL NERVOUS-SYSTEM; ACID BINDING-SITE; SIALIC-ACID; NOGO-66 RECEPTOR; MICE DEFICIENT; MUTANT MICE; LIPID RAFTS; GANGLIOSIDES; MAG; REGENERATION AB The myelin-associated glycoprotein (MAG) is selectively localized in periaxonal Schwann cell and oligodendroglial membranes of myelin sheaths suggesting that it functions in glia-axon interactions in the PNS and CNS, and this is supported by much experimental evidence. In addition, MAG is now well known as one of several white matter inhibitors of neurite outgrowth in vitro and axonal regeneration in vivo, and this latter area of research has provided a substantial amount of information about neuronal receptors or receptor complexes for MAG. This article makes the hypothesis that the capacity of MAG to inhibit outgrowth of immature developing or regenerating neurites is an aberration of its normal physiological function to promote the maturation, maintenance, and survival of myelinated axons. The overview summarizes the literature on the function of MAG in PNS and CNS myelin sheaths and its role as an inhibitor of neurite outgrowth to put this hypothesis into perspective. Additional research is needed to determine if receptors and signaling systems similar to those responsible for MAG inhibition of neurite outgrowth also promote the maturation, maintenance, and survival of myelinated axons as hypothesized here, or if substantially different MAG-mediated signaling mechanisms are operative at the glia-axon junction. C1 NINDS, NIH, Bethesda, MD 20892 USA. RP Quarles, RH (reprint author), NINDS, NIH, 5625 Fishers Lane,Rm 4S-30,MSC 9407, Bethesda, MD 20892 USA. EM quarlesr@ninds.nih.gov FU Intramural NIH HHS NR 57 TC 19 Z9 21 U1 0 U2 2 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 JAN PY 2009 VL 34 IS 1 BP 79 EP 86 DI 10.1007/s11064-008-9668-y PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 393VS UT WOS:000262403000011 PM 18408997 ER PT J AU Davis, LM Michaelides, M Cheskin, LJ Moran, TH Aja, S Watkins, PA Pei, Z Contoreggi, C McCullough, K Hope, B Wang, GJ Volkow, ND Thanos, PK AF Davis, Lisa M. Michaelides, Michael Cheskin, Lawrence J. Moran, Timothy H. Aja, Susan Watkins, Paul A. Pei, Zhengtong Contoreggi, Carlo McCullough, Karen Hope, Bruce Wang, Gene Jack Volkow, Nora D. Thanos, Panayotis K. TI Bromocriptine Administration Reduces Hyperphagia and Adiposity and Differentially Affects Dopamine D2 Receptor and Transporter Binding in Leptin-Receptor-Deficient Zucker Rats and Rats with Diet-Induced Obesity SO NEUROENDOCRINOLOGY LA English DT Article DE Bromocriptine; Dopamine; Dopamine D(2) receptor; Dopamine transporter; Leptin ID DECREASES EXTRACELLULAR DOPAMINE; BODY-FAT STORES; OB/OB MICE; NUCLEUS-ACCUMBENS; LOCOMOTOR-ACTIVITY; GLUCOSE-TOLERANCE; BRAIN DOPAMINE; D-2 RECEPTORS; FOOD-INTAKE; WEIGHT-LOSS AB Background: The dopamine (DA) D 2 receptor (D2R) agonist bromocriptine (BC) decreases body fat in animal and human models and increases lean muscle mass, improves glucose intolerance and insulin resistance, and reduces triglycerides and free fatty acids. We have previously shown a negative correlation between D2R and body weight in obese individuals and in rodents, and that chronic food restriction increases D2R binding in genetically obese rats. The purpose of this study was to assess whether the antiobesity and metabolic effects of BC are related to changes in midbrain DA and D2R activity by measuring D2R and DA transporter (DAT) binding in a genetic (leptin-receptor-deficient) and environmental (diet-induced) rodent obesity model. Methods: Obese (fa/fa) (leptin-receptor-deficient), lean (FA/FA) Zucker rats and rats with diet-induced obesity (DIO) were treated with 10 mg/kg BC for 4 weeks. Body weight, food intake, locomotor activity and blood glucose levels were measured along with D2R- and DAT-binding levels using in vitro receptor autoradiography. Results: BC decreased food intake and body fat and increased locomotor activity in both the (fa/fa) and DIO rats. Furthermore, BC increased D2R binding in (fa/fa) but not in DIO rats. Finally, BC increased DAT binding in DIO rats but not in the (fa/fa) rats. Conclusion: These observations are all consistent with the existence of unique leptin-DA interactions and the hypothesis that there is hyposensitivity of the DA system in obesity. Copyright (c) 2008 S. Karger AG, Basel C1 [Michaelides, Michael; Wang, Gene Jack; Volkow, Nora D.; Thanos, Panayotis K.] Brookhaven Natl Lab, Behav Neuropharmacol & Neuroimaging Lab, Dept Med, Baltimore, MD USA. [Davis, Lisa M.; Cheskin, Lawrence J.] Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Human Nutr, Dept Int Hlth, Baltimore, MD USA. [Moran, Timothy H.; Aja, Susan] Johns Hopkins Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD USA. [Watkins, Paul A.; Pei, Zhengtong] Johns Hopkins Univ, Sch Med, Kennedy Krieger Inst, Baltimore, MD USA. [Contoreggi, Carlo; McCullough, Karen; Hope, Bruce] Natl Inst Drug Abuse, Intramural Res Program, NIH, Baltimore, MD USA. [Thanos, Panayotis K.] SUNY Stony Brook, Neurosci Program, Stony Brook, NY 11794 USA. [Michaelides, Michael; Volkow, Nora D.; Thanos, Panayotis K.] NIAAA, Lab Neuroimaging, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. 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 Hope, Bruce/A-9223-2010; Michaelides, Michael/K-4736-2013; Biguzzi, Felipe/E-4724-2015 OI Hope, Bruce/0000-0001-5804-7061; Michaelides, Michael/0000-0003-0398-4917; FU National Institute on Drug Abuse (NIDA) Intramural Research Program; Center for Human Nutrition at the Johns Hopkins Bloomberg School of Public Health [DK19302] FX The work was supported by the National Institute on Drug Abuse ( NIDA) Intramural Research Program, the Center for Human Nutrition at the Johns Hopkins Bloomberg School of Public Health, and grant DK19302. A special thanks to Tomas Guilarte, PhD, and Jennifer Dziedzic in the Department of Environmental Health, and Marie Diener- West, PhD, and Kathryn Ziegler, PhD, in the Department of Biostatistics at Johns Hopkins Bloomberg School of Public Health. NR 64 TC 26 Z9 28 U1 1 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PY 2009 VL 89 IS 2 BP 152 EP 162 DI 10.1159/000170586 PG 11 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 412TQ UT WOS:000263747500004 PM 18984941 ER PT J AU Traynor, BJ AF Traynor, Bryan J. TI The Era of Genomic Epidemiology SO NEUROEPIDEMIOLOGY LA English DT Review DE Genetics; Genomics; Epidemiology ID AMYOTROPHIC-LATERAL-SCLEROSIS; WIDE ASSOCIATION; PARKINSONS-DISEASE; PROSTATE-CANCER; CORONAVIRUS; MUTATIONS; SEQUENCE; AGE AB The recent revolution in genomics is already having a profound impact on the practice of epidemiology. The purpose of this commentary is to demonstrate how genomics and epidemiology will continue to rely heavily on each other, now and in the future, by illustrating a number of interaction points between these 2 disciplines: (1) the use of genomics to estimate disease heritability; (2) the impact of genomics on analytical study design; (3) how genome-wide data can be employed to effectively overcome residual population stratification arising from selection bias; (4) the importance of genomics as a tool in epidemiological investigation; (5) the importance of epidemiology in the collection of adequately phenotyped samples for genomics studies, and (6) for unraveling the clinical and therapeutic relevance of genetic variants once they are discovered. Copyright (c) 2009 S. Karger AG, Basel C1 [Traynor, Bryan J.] NIA, Neurogenet Lab, NIH, Neuromuscular Dis Res Grp, Bethesda, MD 20892 USA. [Traynor, Bryan J.] NINDS, Neurogenet Branch, Bethesda, MD 20892 USA. RP Traynor, BJ (reprint author), NIA, Neurogenet Lab, NIH, Neuromuscular Dis Res Grp, Bldg 35,Room 1A-1000,35 Convent Dr, Bethesda, MD 20892 USA. EM traynorb@mail.nih.gov RI Traynor, Bryan/G-5690-2010 FU Intramural Research Program of the NIH; National Institute on Aging [Z01 AG000949-02]; National Institute of Neurological Disorders and Stroke FX This work was supported entirely by the Intramural Research Program of the NIH, the National Institute on Aging ( project Z01 AG000949-02) and the National Institute of Neurological Disorders and Stroke. NR 20 TC 4 Z9 4 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0251-5350 J9 NEUROEPIDEMIOLOGY JI Neuroepidemiology PY 2009 VL 33 IS 3 BP 276 EP 279 DI 10.1159/000235639 PG 4 WC Public, Environmental & Occupational Health; Clinical Neurology SC Public, Environmental & Occupational Health; Neurosciences & Neurology GA 503QH UT WOS:000270553300009 PM 19696518 ER PT J AU Lin, AL Fox, PT Yang, YH Lu, HZ Tan, LH Gao, JH AF Lin, Ai-Ling Fox, Peter T. Yang, Yihong Lu, Hanzhang Tan, Li-Hai Gao, Jia-Hong TI Time-dependent correlation of cerebral blood flow with oxygen metabolism in activated human visual cortex as measured by fMRI SO NEUROIMAGE LA English DT Article DE MRI; Cerebral blood flow; Oxygen metabolism; PET ID POSITRON-EMISSION-TOMOGRAPHY; CALIBRATED FUNCTIONAL MRI; VASCULAR-SPACE-OCCUPANCY; OXIDATIVE-METABOLISM; BRAIN ACTIVATION; GLUCOSE CONSUMPTION; STRIATE CORTEX; STIMULATION; VOLUME; PERFUSION AB The aim of this study was to investigate the relationship between relative cerebral blood flow (delta CBF) and relative cerebral metabolic rate of oxygen (delta CMRO(2)) during continuous visual stimulation (21 min at 8 Hz) with fMRI biophysical models by simultaneously measuring of BOLD, CBF and CBV fMRI signals. The delta CMRO(2) was determined by both a newly calibrated single-compartment model (SCM) and a multi-compartment model (MCM) and was in agreement between these two models (P>0.5). The duration-varying delta CBF and dCMRO(2) showed a negative correlation with time (r=-0.97, P<0.001); i.e., delta CBF declines while delta CMRO(2) increases during continuous stimulation. This study also illustrated that without properly calibrating the critical parameters employed in the SCM, an incorrect and even an opposite appearance of the flow-metabolism relationship during prolonged visual stimulation (positively linear coupling) can result. The time- dependent negative correlation between. ow and metabolism demonstrated in this fMRI study is consistent with a previous PET observation and further supports the view that the increase in CBF is driven by factors other than oxygen demand and the energy demands will eventually require increased aerobic metabolism as stimulation continues. (C) 2008 Elsevier Inc. All rights reserved. C1 [Gao, Jia-Hong] Univ Chicago, Dept Radiol, Chicago, IL 60637 USA. [Gao, Jia-Hong] Univ Chicago, Brain Res Imaging Ctr, Chicago, IL 60637 USA. [Tan, Li-Hai] Univ Hong Kong, State Key Lab Brain & Cognit Sci, Hong Kong, Hong Kong, Peoples R China. [Lu, Hanzhang] Univ Texas SW Med Ctr, Adv Imaging Res Ctr, Dallas, TX USA. [Yang, Yihong] NIDA, Neuroimaging Res Branch, NIH, Bethesda, MD 20892 USA. [Lin, Ai-Ling; Fox, Peter T.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Ctr, San Antonio, TX 78229 USA. RP Gao, JH (reprint author), Univ Chicago, Dept Radiol, 5841 S Maryland,Q-301B,MC 2026, Chicago, IL 60637 USA. EM lina3@uthscsa.edu; jgao@uchicago.edu RI Lin, Ai-Ling/F-3972-2010; Fox, Peter/B-4725-2010 OI Fox, Peter/0000-0002-0465-2028 NR 50 TC 27 Z9 29 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JAN 1 PY 2009 VL 44 IS 1 BP 16 EP 22 DI 10.1016/j.neuroimage.2008.08.029 PG 7 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 392KF UT WOS:000262300900003 PM 18804541 ER PT J AU Schwartzman, A Dougherty, RF Lee, J Ghahremani, D Taylor, JE AF Schwartzman, Armin Dougherty, Robert F. Lee, Jongho Ghahremani, Dara Taylor, Jonathan E. TI Empirical null and false discovery rate analysis in neuroimaging SO NEUROIMAGE LA English DT Article ID DIFFUSION DIRECTION MAPS; FMRI DATA; ACTIVATION; HYPOTHESIS; IMAGES AB Current strategies for thresholding statistical parametric maps in neuroimaging include control of the family-wise error rate, control of the false discovery rate (FDR) and thresholding of the posterior probability of a voxel being active given the data, the latter derived from a mixture model of active and inactive voxels. Correct inference using any of these criteria depends crucially on the specification of the null distribution of the test statistics. In this article we show examples from fMRI and DTI data where the theoretical null distribution does not match well the observed distribution of the test statistics. As a solution, we introduce the use of an empirical null, a null distribution empirically estimated from the data itself, allowing for global corrections of theoretical null assumptions. The theoretical null distributions considered are normal, t, chi(2) and F, all commonly encountered in neuroimaging. The empirical null estimate is accompanied by an estimate of the proportion of non-active voxels in the data. Based on the two-class mixture model, we present the equivalence between the strategies of controlling FDR and thresholding posterior probabilities in the context of neuroimaging and show that the FDR estimates derived from the empirical null can be seen as empirical Bayes estimates. (C) 2008 Elsevier Inc. All rights reserved. C1 [Schwartzman, Armin] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. [Dougherty, Robert F.] Stanford Univ, Dept Psychol, Stanford, CA 94305 USA. [Lee, Jongho] NINDS, Adv MRI Sect, LFMI, NIH, Bethesda, MD 20824 USA. [Ghahremani, Dara] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. [Taylor, Jonathan E.] Stanford Univ, Dept Stat, Stanford, CA 94305 USA. RP Schwartzman, A (reprint author), Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat, CLS-11007,44 Binney St, Boston, MA 02115 USA. EM armins@hsph.harvard.edu OI Schwartzman, Armin/0000-0001-5335-1611 FU NEI NIH HHS [EY-015000, R01 EY015000]; NIMH NIH HHS [MH15157-20] NR 31 TC 28 Z9 28 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JAN 1 PY 2009 VL 44 IS 1 BP 71 EP 82 DI 10.1016/j.neuroimage.2008.04.182 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 392KF UT WOS:000262300900009 PM 18547821 ER PT J AU Manji, HK AF Manji, Husseini K. BE Rumsey, JM Ernst, M TI Neuroimaging in Developmental Clinical Neuroscience Foreword SO NEUROIMAGING IN DEVELOPMENTAL CLINICAL NEUROSCIENCE LA English DT Editorial Material; Book Chapter C1 [Manji, Husseini K.] NIMH, Mol Pathophysiol Lab, Bethesda, MD 20892 USA. [Manji, Husseini K.] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RP Manji, HK (reprint author), NIMH, Mol Pathophysiol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-88357-3 PY 2009 BP XIII EP XV DI 10.1017/CBO9780511757402.001 D2 10.1017/CBO9780511757402 PG 3 WC Psychology, Biological; Neurosciences; Neuroimaging SC Psychology; Neurosciences & Neurology GA BDK13 UT WOS:000313574600001 ER PT J AU Ernst, M Hardin, MG AF Ernst, Monique Hardin, Michael G. BE Rumsey, JM Ernst, M TI Goal-directed behavior: evolution and ontogeny SO NEUROIMAGING IN DEVELOPMENTAL CLINICAL NEUROSCIENCE LA English DT Article; Book Chapter ID NUCLEUS-ACCUMBENS SHELL; ORBITOFRONTAL CORTEX; PREFRONTAL CORTEX; WILLIAMS-SYNDROME; DECISION-MAKING; DEVELOPMENTAL DIFFERENCES; AFFECTIVE NEUROSCIENCE; NEURAL MECHANISMS; VENTRAL STRIATUM; ADOLESCENT BRAIN C1 [Ernst, Monique] NIMH, Emot Dev & Affect Neurosci Branch, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. [Hardin, Michael G.] NIMH, Emot Dev & Affect Neurosci Branch, Mood & Anxiety Program, Bethesda, MD 20892 USA. RP Ernst, M (reprint author), NIMH, Emot Dev & Affect Neurosci Branch, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. NR 68 TC 1 Z9 1 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-88357-3 PY 2009 BP 53 EP 72 DI 10.1017/CBO9780511757402.007 D2 10.1017/CBO9780511757402 PG 20 WC Psychology, Biological; Neurosciences; Neuroimaging SC Psychology; Neurosciences & Neurology GA BDK13 UT WOS:000313574600006 ER PT J AU Pine, DS AF Pine, Daniel S. BE Rumsey, JM Ernst, M TI Anxiety and depressive disorders SO NEUROIMAGING IN DEVELOPMENTAL CLINICAL NEUROSCIENCE LA English DT Article; Book Chapter ID PEDIATRIC MAJOR DEPRESSION; GENERALIZED SOCIAL PHOBIA; POSTTRAUMATIC-STRESS-DISORDER; MAGNETIC-RESONANCE-SPECTROSCOPY; ANTERIOR CINGULATE CORTEX; CEREBRAL BLOOD-FLOW; INCREASED AMYGDALA; PREFRONTAL CORTEX; BEHAVIORAL-INHIBITION; HIPPOCAMPAL VOLUME C1 NIMH, Emot Dev & Affect Neurosci Branch, Bethesda, MD 20892 USA. RP Pine, DS (reprint author), NIMH, Emot Dev & Affect Neurosci Branch, Bethesda, MD 20892 USA. NR 84 TC 0 Z9 0 U1 1 U2 1 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-88357-3 PY 2009 BP 183 EP 198 DI 10.1017/CBO9780511757402.015 D2 10.1017/CBO9780511757402 PG 16 WC Psychology, Biological; Neurosciences; Neuroimaging SC Psychology; Neurosciences & Neurology GA BDK13 UT WOS:000313574600013 ER PT J AU Bjork, JM AF Bjork, James M. BE Rumsey, JM Ernst, M TI Alcohol exposure and the developing human brain SO NEUROIMAGING IN DEVELOPMENTAL CLINICAL NEUROSCIENCE LA English DT Article; Book Chapter ID SUBSTANCE USE DISORDERS; SPATIAL WORKING-MEMORY; DSM-IV ALCOHOL; PRENATAL COCAINE EXPOSURE; LEVEL-DEPENDENT RESPONSE; CORTICAL GRAY-MATTER; DRUG-USE; YOUNG-ADULTS; HIPPOCAMPAL VOLUME; EARLY-ONSET C1 NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD USA. RP Bjork, JM (reprint author), NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD USA. NR 104 TC 0 Z9 0 U1 2 U2 2 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-88357-3 PY 2009 BP 229 EP 244 DI 10.1017/CBO9780511757402.018 D2 10.1017/CBO9780511757402 PG 16 WC Psychology, Biological; Neurosciences; Neuroimaging SC Psychology; Neurosciences & Neurology GA BDK13 UT WOS:000313574600016 ER PT J AU Goldman, D Buzas, B Xu, K AF Goldman, David Buzas, Beata Xu, Ke BE Rumsey, JM Ernst, M TI Functional alleles, neuroimaging and intermediate phenotypes in the deconstruction of complex behavioral variation SO NEUROIMAGING IN DEVELOPMENTAL CLINICAL NEUROSCIENCE LA English DT Article; Book Chapter ID SEROTONIN TRANSPORTER BINDING; OBSESSIVE-COMPULSIVE DISORDER; POSITRON-EMISSION-TOMOGRAPHY; METHYLTRANSFERASE VAL(158)MET GENOTYPE; VAL(108/158) MET GENOTYPE; 22Q11.2 DELETION SYNDROME; WORKING-MEMORY; HUMAN BRAIN; GENETIC-VARIATION; COMT POLYMORPHISM C1 [Goldman, David] NIAAA, Neurogenet Lab, Bethesda, MD USA. [Buzas, Beata] NIAAA, Rockville, MD 20852 USA. [Xu, Ke] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. RP Goldman, D (reprint author), NIAAA, Neurogenet Lab, Bethesda, MD USA. NR 82 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-88357-3 PY 2009 BP 365 EP 382 DI 10.1017/CBO9780511757402.028 D2 10.1017/CBO9780511757402 PG 18 WC Psychology, Biological; Neurosciences; Neuroimaging SC Psychology; Neurosciences & Neurology GA BDK13 UT WOS:000313574600024 ER PT J AU Rumsey, JM Ernst, M AF Rumsey, Judith M. Ernst, Monique BE Rumsey, JM Ernst, M TI Neuroimaging in developmental clinical neuroscience today SO NEUROIMAGING IN DEVELOPMENTAL CLINICAL NEUROSCIENCE LA English DT Article; Book Chapter ID NORMAL BRAIN-DEVELOPMENT; CORTICAL ACTIVITY; MULTICENTER FMRI; NIH MRI; RELIABILITY; DISORDER; AUTISM; SCHIZOPHRENIA; SPECTROSCOPY; NEUROETHICS C1 [Rumsey, Judith M.] NIMH, Neurodev & Neuroimaging Program, Neurodev Disorders Branch, Div Dev Translat Res, Bethesda, MD 20892 USA. [Rumsey, Judith M.] NIMH, Execut Funct & Attent Deficit Hyperact Disorder P, Neurodev Disorders Branch, Div Dev Translat Res, Bethesda, MD 20892 USA. [Ernst, Monique] NIMH, Emot Dev & Affect Neurosci Branch, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RP Rumsey, JM (reprint author), NIMH, Neurodev & Neuroimaging Program, Neurodev Disorders Branch, Div Dev Translat Res, Bethesda, MD 20892 USA. NR 57 TC 4 Z9 4 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-88357-3 PY 2009 BP 387 EP 400 DI 10.1017/CBO9780511757402.030 D2 10.1017/CBO9780511757402 PG 14 WC Psychology, Biological; Neurosciences; Neuroimaging SC Psychology; Neurosciences & Neurology GA BDK13 UT WOS:000313574600025 ER PT J AU Chrousos, GP Kino, T Charmandari, E AF Chrousos, George P. Kino, Tomoshige Charmandari, Evangelia TI Evaluation of the Hypothalamic-Pituitary-Adrenal Axis Function in Childhood and Adolescence SO NEUROIMMUNOMODULATION LA English DT Article DE Hypothalamic-pituitary-adrenal axis; Glucocorticoids; Synacthen test; Dexamethasone suppression test; CRH test ID CORTICOTROPIN-RELEASING HORMONE; MIDNIGHT SERUM CORTISOL; DEXAMETHASONE-SUPPRESSION TEST; NIGHTTIME SALIVARY CORTISOL; URINARY FREE CORTISOL; CUSHINGS-SYNDROME; GLUCOCORTICOID-RECEPTOR; DIFFERENTIAL-DIAGNOSIS; CLINICAL-PRACTICE; STIMULATION TEST AB The hypothalamic-pituitary-adrenal (HPA) axis plays an important role in the maintenance of basal and stress-related homeostasis. The hypothalamus controls the secretion of adrenocorticotropic hormone (ACTH) from the anterior pituitary, which in turn stimulates the secretion of glucocorticoids from the adrenal cortex. Glucocorticoids, the final effectors of the HPA axis, regulate a broad spectrum of physiologic functions essential for life and exert their effects through their ubiquitously distributed intracellular receptors. Alterations in the activity of the HPA axis may present with symptoms and signs of glucocorticoid deficiency or excess. Detailed endocrinologic evaluation is of primary importance in determining the diagnosis and/or etiology of the underlying condition. We review the most common endocrinologic investigations used in the evaluation of the HPA axis integrity and function. Copyright (C) 2009 S. Karger AG, Basel C1 [Chrousos, George P.; Charmandari, Evangelia] Acad Athens, Biomed Res Fdn, Clin Res Ctr, Div Endocrinol & Metab, GR-11527 Athens, Greece. [Chrousos, George P.; Kino, Tomoshige; Charmandari, Evangelia] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Pediat Endocrinol, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA. RP Charmandari, E (reprint author), Acad Athens, Biomed Res Fdn, Clin Res Ctr, Div Endocrinol & Metab, 4 Soranou Tou Efessiou St, GR-11527 Athens, Greece. EM evangelia.charmandari@googlemail.com RI Charmandari, Evangelia/B-6701-2011 FU Intramural NIH HHS [ZIA HD008732-08] NR 66 TC 25 Z9 27 U1 0 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7401 EI 1423-0216 J9 NEUROIMMUNOMODULAT JI Neuroimmunomodulation PY 2009 VL 16 IS 5 BP 272 EP 283 DI 10.1159/000216185 PG 12 WC Endocrinology & Metabolism; Immunology; Neurosciences SC Endocrinology & Metabolism; Immunology; Neurosciences & Neurology GA 466GD UT WOS:000267648300003 PM 19571588 ER PT J AU Pancrazio, JJ AF Pancrazio, Joseph J. BE Krames, ES Peckham, PH Rezai, AR TI NEUROMODULATION Foreword SO NEUROMODULATION, VOLS 1 AND 2 LA English DT Editorial Material; Book Chapter C1 Natl Inst Neurol Disorders & Stroke, Neural Engn Program, Bethesda, MD USA. RP Pancrazio, JJ (reprint author), Natl Inst Neurol Disorders & Stroke, Neural Engn Program, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-092139-6 PY 2009 BP XXI EP XXI DI 10.1016/B978-0-12-374248-3.00093-8 PG 1 WC Anesthesiology; Clinical Neurology; Rehabilitation SC Anesthesiology; Neurosciences & Neurology; Rehabilitation GA BGD74 UT WOS:000322479800001 ER PT J AU Pancrazio, JJ Peckham, PH AF Pancrazio, Joseph J. Peckham, P. Hunter BE Krames, ES Peckham, PH Rezai, AR TI BIOMEDICAL ENGINEERING CONSIDERATIONS Introduction SO NEUROMODULATION, VOLS 1 AND 2 LA English DT Editorial Material; Book Chapter C1 [Pancrazio, Joseph J.] Natl Inst Neurol Disorders & Stroke, Neural Engn Program, Bethesda, MD USA. [Peckham, P. Hunter] Case Western Reserve Univ, Dept Biomed Engn, Donnell Inst, Cleveland, OH 44106 USA. [Peckham, P. Hunter] Louis Stokes Cleveland VA Med Ctr, Funct Elect Stimulat Ctr, Cleveland, OH USA. [Peckham, P. Hunter] Metrohlth Med Ctr, Cleveland, OH USA. RP Pancrazio, JJ (reprint author), Natl Inst Neurol Disorders & Stroke, Neural Engn Program, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-092139-6 PY 2009 BP 179 EP 179 PG 1 WC Anesthesiology; Clinical Neurology; Rehabilitation SC Anesthesiology; Neurosciences & Neurology; Rehabilitation GA BGD74 UT WOS:000322479800020 ER PT J AU Neumann, J Parkkinen, L Bras, J O'sullivan, SS Deas, E Lachmann, H Li, A Holton, L Guerreiro, R Paudel, R Segarane, B Singleton, A Lees, A Hardy, J Houlden, H Revesz, T Wood, NW AF Neumann, J. Parkkinen, L. Bras, J. O'sullivan, S. S. Deas, E. Lachmann, H. Li, A. Holton, L. Guerreiro, R. Paudel, R. Segarane, B. Singleton, A. Lees, A. Hardy, J. Houlden, H. Revesz, T. Wood, N. W. TI Glucocerebrosidase mutations in clinical and pathologically proven Parkinson's disease SO NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY LA English DT Meeting Abstract CT 110th Annual Meeting of the British-Neuropathological-Society CY JAN 07-09, 2009 CL Inst Child Hlth, London, ENGLAND SP British Neuropathol Soc HO Inst Child Hlth C1 [Neumann, J.; Parkkinen, L.; O'sullivan, S. S.; Deas, E.; Lachmann, H.; Li, A.; Holton, L.; Paudel, R.; Segarane, B.; Lees, A.; Hardy, J.; Houlden, H.; Revesz, T.; Wood, N. W.] UCL, Inst Neurol, Dept Mol Neurosci, London, England. [Neumann, J.; Parkkinen, L.; O'sullivan, S. S.; Deas, E.; Lachmann, H.; Li, A.; Holton, L.; Paudel, R.; Segarane, B.; Lees, A.; Hardy, J.; Houlden, H.; Revesz, T.; Wood, N. W.] UCL, Inst Neurol, Reta Lila Weston Inst, London, England. [Bras, J.; Guerreiro, R.; Singleton, A.] NIA, Mol Genet Unit, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Bras, J.; Guerreiro, R.] Univ Coimbra, Ctr Neurosci & Cell Biol, Coimbra, Portugal. [Neumann, J.] Charite Univ Med Berlin, Int Grad Program Med Neurosci, Berlin, Germany. EM l.parkkinen@ion.ucl.ac.uk RI Singleton, Andrew/C-3010-2009; Bras, Jose/D-3366-2009; Deas, Emma/A-6755-2010; O'Sullivan, Sean/C-9333-2012; Lees, Andrew/A-6605-2009; Bras, Jose/A-1428-2011; Houlden, Henry/C-1532-2008 OI O'Sullivan, Sean/0000-0002-0583-7956; Houlden, Henry/0000-0002-2866-7777 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0305-1846 J9 NEUROPATH APPL NEURO JI Neuropathol. Appl. Neurobiol. PD JAN PY 2009 VL 35 BP 3 EP 3 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 394YI UT WOS:000262488700007 ER PT J AU Shurtleff, D Liu, R Sasek, C AF Shurtleff, David Liu, Rita Sasek, Cathrine TI Frontiers in Addiction Research: Celebrating the 35th Anniversary of the National Institute on Drug Abuse Sponsor's foreword SO NEUROPHARMACOLOGY LA English DT Editorial Material ID NICOTINE DEPENDENCE C1 [Shurtleff, David] Natl Inst Drug Abuse, Div Basic Neurosci & Behav Res, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Shurtleff, D (reprint author), Natl Inst Drug Abuse, Div Basic Neurosci & Behav Res, NIH, US Dept Hlth & Human Serv, 6001 Execut Blvd Room 4282,MSC 9555, Bethesda, MD 20892 USA. EM dshurtle@mail.nih.gov NR 8 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PY 2009 VL 56 BP 1 EP 2 DI 10.1016/j.neuropharm.2008.08.009 PG 2 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 396XO UT WOS:000262625600001 PM 18789343 ER PT J AU Volkow, ND Fowler, JS Wang, GJ Baler, R Telang, F AF Volkow, N. D. Fowler, J. S. Wang, G. J. Baler, R. Telang, F. TI Imaging dopamine's role in drug abuse and addiction SO NEUROPHARMACOLOGY LA English DT Review DE Positron emission tomography; Orbitofrontal cortex; Cingulate gyrus; Dorsolateral prefrontal cortex; Dapamine D2 receptors; Reward; Predisposition; Salience; Raclopride; Fluoro-deoxyglucose ID POSITRON-EMISSION-TOMOGRAPHY; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; D-2 RECEPTOR AVAILABILITY; OPIATE-DEPENDENT SUBJECTS; VENTRAL STRIATUM; HUMAN BRAIN; ORBITOFRONTAL CORTEX; COCAINE ABUSERS; D2 RECEPTORS; SYNAPTIC PLASTICITY AB Dopamine is involved in drug reinforcement but its role in addiction is less clear. Here we describe PET imaging Studies that investigate dopamine's involvement in drug abuse in the human brain. In humans the reinforcing effects of drugs are associated with large and fast increases in extracellular dopamine. which mimic those induced by physiological dopamine cell firing but are more intense and protracted. Since dopamine cells fire in response to salient stimuli, supraphysiological activation by drugs is experienced as highly salient (driving attention, arousal, conditioned learning and motivation) and with repeated drug use may raise the thresholds required for dopamine cell activation and signaling. Indeed, imaging Studies show that drug abusers have marked decreases in dopamine D2 receptors and in dopamine release. This decrease in dopamine function is associated with reduced regional activity in orbitofrontal cortex (involved in salience attribution: its disruption results in compulsive behaviors), cingulate gyrus (involved in inhibitory control; its disruption results in impulsivity) and dorsolateral prefrontal cortex (involved in executive function: its disruption results in impaired regulation of intentional actions). In parallel, conditioning triggered by drugs leads to enhanced dopamine signaling when exposed to conditioned cues, which then drives the motivation to procure the drug in part by activation of prefrontal and striatal regions. These findings implicate deficits in dopamine activity-inked with prefrontal and striatal deregulation-in the loss of control and compulsive drug intake that results when the addicted person takes the drugs Or is exposed to conditioned Cues. The decreased dopamine function in addicted individuals also reduces their sensitivity to natural reinforcers. Therapeutic interventions aimed at restoring brain dopaminergic tone and activity of cortical projection regions Could improve prefrontal function, enhance inhibitory control and interfere with impulsivity and compulsive drug administration while helping to motivate the addicted person to engage in non-drug related behaviors. Published by Elsevier Ltd. C1 [Volkow, N. D.; Fowler, J. S.; Wang, G. J.; Baler, R.; Telang, F.] Natl Inst Drug Abuse, NIH, Bethesda, MD 20892 USA. RP Volkow, ND (reprint author), Natl Inst Drug Abuse, NIH, Bethesda, MD 20892 USA. EM nvolkow@nida.nih.gov FU Intramural NIH HHS [Z99 DA999999] NR 92 TC 327 Z9 339 U1 14 U2 77 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PY 2009 VL 56 BP 3 EP 8 DI 10.1016/j.neuropharm.2008.05.022 PG 6 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 396XO UT WOS:000262625600002 PM 18617195 ER PT J AU Szabo, ST Machado-Vieira, R Yuan, PX Wang, Y Wei, YL Falke, C Cirelli, C Tononi, GL Manji, HK Du, J AF Szabo, Steven T. Machado-Vieira, Rodrigo Yuan, Peixiong Wang, Yun Wei, Yanling Falke, Cynthia Cirelli, Chiara Tononi, Giulio Manji, Husseini K. Du, Jing TI Glutamate receptors as targets of protein kinase C in the pathophysiology and treatment of animal models of Mania SO NEUROPHARMACOLOGY LA English DT Article DE Protein kinase C (PKC); Mania; Lithium; Neurogranin; GluN1; GluA1 ID BIPOLAR AFFECTIVE-DISORDER; CELLULAR PLASTICITY CASCADES; TEENAGE SUICIDE VICTIMS; GLUR1 AMPA RECEPTOR; CNS IN-VIVO; SYNAPTIC PLASTICITY; MOOD DISORDERS; PHOSPHORYLATION SITE; PREFRONTAL CORTEX; SUBSTRATE MARCKS AB Considerable biochemical evidence suggests that the protein kinase C (PKC) signaling cascade may be a convergent point for the actions of anti-manic agents, and that excessive PKC activation can disrupt prefrontal cortical regulation of thinking and behavior. To date, however, brain protein targets of PKC's anti-manic effects have not been fully identified. Here we showed that PKC activity was enhanced in the prefrontal cortex of animals treated with the psychostimulant amphetamine. Phosphorylation of MARCKS, a marker of PKC activity, was increased in the prefrontal cortex of animals treated with the psychostimulant amphetamine, as well as in sleep-deprived animals (another animal model of mania), but decreased in lithium-treated animals. The antidepressant imipramine, which shows pro-manic properties in patients with bipolar disorder (BPD), also enhanced phospho-MARCKS in prefrontal cortex in vivo. We further explored the functional targets of PKC in mania-associated behaviors. Neurogranin is a brain-specific, postsynaptically located PKC substrate. PKC phosphorylation of neurogranin was robustly increased by pro-manic manipulations and decreased by anti-manic agents. PKC phosphorylation of the NMDA receptor site GluN1S896 and the AMPA receptor site GluA1T840 was also enhanced in the prefrontal cortex of animals treated with the antidepressant imipramine, as well as in behaviorally sleep-deprived animals, in striking contrast to the reduced activity seen in lithium-treated animals. These results suggest that PKC may play an important role in regulating NMDA and AMPA receptor functions. The biochemical profile of the PKC pathway thus encompasses both pro- and anti-manic effects on behavior. These results suggest that PKC modulators or their intracellular targets may ultimately represent novel avenues for the development of new therapeutics for mood disorders. Published by Elsevier Ltd. C1 [Szabo, Steven T.; Machado-Vieira, Rodrigo; Yuan, Peixiong; Wang, Yun; Wei, Yanling; Falke, Cynthia; Manji, Husseini K.; Du, Jing] NIMH, Mol Pathophysiol Lab, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. [Cirelli, Chiara; Tononi, Giulio] Univ Wisconsin, Dept Psychiat, Madison, WI 53719 USA. RP Du, J (reprint author), NIMH, Mol Pathophysiol Lab, Mood & Anxiety Disorders Program, NIH, Bldg 35,1C912, Bethesda, MD 20892 USA. EM duj@mail.nih.gov RI Du, Jing/A-9023-2012; MACHADO-VIEIRA, RODRIGO/D-8293-2012 OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190 FU National Institute of Mental Health [P20 MH077967]; National Institutes of Health; National Alliance on Research on Schizophrenia and Depression (NARSAD) FX This work was supported by the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health, and by NIMH (P20 MH077967 to CC), NIH Director's Pioneer award (to GT), and National Alliance on Research on Schizophrenia and Depression (NARSAD) award (to STS). We thank loline Henter for outstanding editorial. NR 89 TC 53 Z9 54 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD JAN PY 2009 VL 56 IS 1 BP 47 EP 55 DI 10.1016/j.neuropharm.2008.08.015 PG 9 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 396XN UT WOS:000262625500007 PM 18789340 ER PT J AU Plested, AJR Mayer, ML AF Plested, Andrew J. R. Mayer, Mark L. TI Engineering a high-affinity allosteric binding site for divalent cations in kainate receptors SO NEUROPHARMACOLOGY LA English DT Article DE Glutamate receptor; Cation binding site; Calcium; Magnesium ID GLUTAMATE-RECEPTOR; AMPA RECEPTORS; CHANNELS; BLOCK; DESENSITIZATION; MECHANISM; CALCIUM; CORE; RECTIFICATION; MODULATION AB Kainate receptors are allosterically regulated by sodium ions. Removal of Na(+) from the extracellular solution, or replacement of Na(+) by larger monovalent cations, inhibits kainate receptor activity. Sodium binds at a negatively charged cavity in the extracellular neurotransmitter binding domain that is capped by a small hydrophobic residue. Prior work revealed that introduction of aspartic acid at this site strongly reduces GluK2 sensitivity to monovalent cations of different size. We found that the GluK2 M739D mutant is also insensitive to substitution of Na(+) by the large organic cations Tris and NMDG. Because these are excluded from the Na(+) binding site by steric hindrance, we investigated the possibility that divalent cations can substitute for Na(+). We show that in Na(+) free solutions with low concentrations of Ca(2+) and Mg(2+) the GluK2 M739D mutant is inhibited by EDTA; that divalent ions in the micromolar concentration range act as positive allosteric modulators: and that the chemistry of the mutant cation binding site is typical of Ca(2+) and Mg(2+) binding sites found in protein crystal structures. Hence, the apparent insensitivity of the M739D mutant to monovalent cations is due to the adventitious allosteric effects of divalent ions at physiological concentrations and below. Published by Elsevier Ltd. C1 [Plested, Andrew J. R.; Mayer, Mark L.] NICHD, Lab Cellular & Mol Neurophysiol, Porter Neurosci Res Ctr, NIH,DHHS, Bethesda, MD 20892 USA. RP Mayer, ML (reprint author), NICHD, Lab Cellular & Mol Neurophysiol, Porter Neurosci Res Ctr, NIH,DHHS, Bldg 35,Room 3B 1002,35 Lincoln Dr, Bethesda, MD 20892 USA. EM mlm@helix.nih.gov RI Mayer, Mark/H-5500-2013; OI Plested, Andrew/0000-0001-6062-0832 FU NICHD; NIH; DHHS FX We thank Carla Glasser for preparing cDNAs-, the NINDS DNA sequencing facility for support and Drs. S. Heinemann and R Seeburg for the gift of wild-type cDNAs. This work was supported by the intramural research program of NICHD, NIH, DHHS. NR 38 TC 4 Z9 4 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD JAN PY 2009 VL 56 IS 1 BP 114 EP 120 DI 10.1016/j.neuropharm.2008.07.013 PG 7 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 396XN UT WOS:000262625500013 PM 18687343 ER PT J AU Dargan, SL Clarke, VRJ Alushin, GM Sherwood, JL Nistico, R Bortolotto, ZA Ogden, AM Bleakman, D Doherty, AJ Lodge, D Mayer, ML Fitzjohn, SM Jane, DE Collingridge, GL AF Dargan, Sheila L. Clarke, Vernon R. J. Alushin, Gregory M. Sherwood, John L. Nistico, Robert Bortolotto, Zuner A. Ogden, Ann M. Bleakman, David Doherty, Andrew J. Lodge, David Mayer, Mark L. Fitzjohn, Stephen M. Jane, David E. Collingridge, Graham L. TI ACET is a highly potent and specific kainate receptor antagonist: Characterisation and effects on hippocampal mossy fibre function SO NEUROPHARMACOLOGY LA English DT Article DE Hippocampus; Mossy fibre LTP; Calcium; Kainate; ACET; GluR5; GluK1; X-ray crystallography; 2-Photon ID N-3-SUBSTITUTED WILLARDIINE DERIVATIVES; EXCITATORY SYNAPTIC-TRANSMISSION; LONG-TERM POTENTIATION; GLUTAMATE RECEPTORS; CRYSTAL-STRUCTURES; RAT HIPPOCAMPUS; SYNAPSES; PLASTICITY; GLU(K5); GLUR5 AB Kainate receptors (KARs) are involved in both NMDA receptor-independent long-term potentiation (LTP) and synaptic facilitation at mossy fibre synapses in the CA3 region of the hippocampus. However, the identity of the KAR subtypes involved remains controversial. Here we used a highly potent and selective GluK1 (formerly G1uR5) antagonist (ACET) to elucidate roles of GluK1-containing KARs in these synaptic processes. We confirmed that ACET is an extremely potent GluK1 antagonist, with a K(b) value of 1.4 +/- 0.2 nM. In contrast, ACET was ineffective at GluK2 (formerly GluR6) receptors at all concentrations tested (up to 100 mu M) and had no effect at GluK3 (formerly GluR7) when tested at 1 mu M. The X-ray crystal structure of ACET bound to the ligand binding core of GluK1 was similar to the UBP310-GluK1 complex. In the CA1 region of hippocampal slices, ACET was effective at blocking the depression of both fEPSPs and monosynaptically evoked GABAergic transmission induced by ATPA, a GluK1 selective agonist. In the CA3 region of the hippocampus, ACET blocked the induction of NMDA receptor-independent mossy fibre LTP. To directly investigate the role of pre-synaptic GluK1-containing KARs we combined patch-clamp electrophysiology and 2-photon microscopy to image Ca(2+) dynamics in individual giant mossy fibre boutons. ACET consistently reduced short-term facilitation of pre-synaptic calcium transients induced by 5 action potentials evoked at 20-25 Hz. Taken together our data provide further evidence for a physiological role of GluK1-containing KARs in synaptic facilitation and LTP induction at mossy fibre-CA3 synapses. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Dargan, Sheila L.; Clarke, Vernon R. J.; Sherwood, John L.; Nistico, Robert; Bortolotto, Zuner A.; Doherty, Andrew J.; Lodge, David; Fitzjohn, Stephen M.; Jane, David E.; Collingridge, Graham L.] Univ Bristol, MRC Ctr Synapt Plast, Bristol BS8 1TD, Avon, England. [Alushin, Gregory M.; Mayer, Mark L.] NICHD, Lab Cellular & Mol Neurophysiol, Porter Neurosci Res Ctr, NIH,DHHS, Bethesda, MD 20892 USA. [Ogden, Ann M.; Bleakman, David] Eli Lilly & Co, Lilly Corp Ctr, Neurosci Res, Indianapolis, IN 46285 USA. RP Dargan, SL (reprint author), Univ Bristol, MRC Ctr Synapt Plast, Bristol BS8 1TD, Avon, England. EM sheila.dargan@bristol.ac.uk RI Mayer, Mark/H-5500-2013; Collingridge, Graham/C-4605-2015; OI Collingridge, Graham/0000-0002-9572-5359; Fitzjohn, Stephen/0000-0002-3859-7530; Sherwood, John/0000-0002-8484-1100; Nistico, Robert/0000-0003-3433-9232 FU MRC; BBSRC; U.S. Department of Energy [W-31-109-Eng-38]; NICHD; NIH; DHHS FX Research funded by the MRC and the BBSRC. Synchrotron diffraction data were collected at Southeast Regional Collaborative Access Team (SER-CAT) 22-ID beamline at the Advanced Photon Source, Argonne National Laboratory. Use of the Advanced Photon Source was supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract No. W-31-109-Eng-38. This work was supported in part by the intramural research program of NICHD, NIH, DHHS (MLM). NR 51 TC 32 Z9 33 U1 1 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD JAN PY 2009 VL 56 IS 1 BP 121 EP 130 DI 10.1016/j.neuropharm.2008.08.016 PG 10 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 396XN UT WOS:000262625500014 PM 18789344 ER PT J AU Wise, RA AF Wise, Roy A. TI Ventral tegmental glutamate: A role in stress-, cue-, and cocaine-induced reinstatement of cocaine-seeking SO NEUROPHARMACOLOGY LA English DT Review DE Cocaine; Reinstatement; Glutamate; Dopamine; Neuroadaptation ID CORTICOTROPIN-RELEASING-FACTOR; NUCLEUS-ACCUMBENS DOPAMINE; FACTOR-BINDING-PROTEIN; PREFRONTAL CORTEX; EXTRACELLULAR GLUTAMATE; ELECTRICAL-STIMULATION; IDENTIFIED NEURONS; INDUCED RELAPSE; DRUG-SEEKING; AREA AB Ventral tegmental dopamine neurons are activated by primary rewards and, when such rewards are predictable' by reward-predicting stimuli. Glutamatergic input to the ventral tegmental area contributes to this activation: in animals trained to self-administer cocaine, cocaine-predictive cues trigger ventral tegmental glutamate release and dopaminergic activation. Mild footshock stress similarly causes glutamate release and dopaminergic activation in cocaine-trained but not cocaine-naive animals. The ability of cocaine-predictive and stress-associated cues to activate the dopamine system and to trigger cocaine craving appears to be related to changes in the ability of glutamate to activate dopaminergic neurons, changes known to be caused by experience with stress or with drugs of abuse. Published by Elsevier Ltd. C1 Natl Inst Drug Abuse, Intramural Res Program, NIH, Dept Hlth & Human Serv, Baltimore, MD 21224 USA. RP Wise, RA (reprint author), Natl Inst Drug Abuse, Intramural Res Program, NIH, Dept Hlth & Human Serv, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM rwise@intra.nida.nih.gov FU Intramural NIH HHS [Z01 DA000471-04] NR 43 TC 19 Z9 19 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PY 2009 VL 56 BP 174 EP 176 DI 10.1016/j.neuropharm.2008.06.008 PG 3 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 396XO UT WOS:000262625600021 PM 18598707 ER PT J AU Koya, E Uejima, JL Wihbey, KA Bossert, JM Hope, BT Shaham, Y AF Koya, Eisuke Uejima, Jamie L. Wihbey, Kristina A. Bossert, Jennifer M. Hope, Bruce T. Shaham, Yavin TI Role of ventral medial prefrontal cortex in incubation of cocaine craving SO NEUROPHARMACOLOGY LA English DT Article DE Craving; Drug cues; ERK; Extinction; Cocaine self-administration; Prefrontal cortex; Reinstatement; Relapse ID DRUG-SEEKING BEHAVIOR; TIME-DEPENDENT CHANGES; INDUCED REINSTATEMENT; BASOLATERAL AMYGDALA; FEAR EXTINCTION; TYROSINE-HYDROXYLASE; SYNAPTIC PLASTICITY; NEUROTROPHIC FACTOR; CONDITIONED FEAR; HEROIN-SEEKING AB Cue-induced drug-seeking in rodents progressively increases after withdrawal from cocaine, suggesting that cue-induced cocaine craving incubates over time. Here, we explored the role of the medial prefrontal cortex (mPFC, a brain area previously implicated in cue-induced cocaine seeking) in this incubation. We trained rats to self-administer cocaine for 10 days (6 h/clay, infusions were paired with a tone-light cue), and then assessed after I or 30 withdrawal days the effect of exposure to cocaine cues on lever presses in extinction tests. We found that cue-induced cocaine-seeking in the extinction tests was higher after 30 withdrawal days than after 1 day. The time-dependent increases in extinction responding were associated with large (ventral mPFC) or modest (dorsal mPFC) increases in ERK phosphorylation (a measure of ERK activity and an index of neuronal activation). After 30 withdrawal days, ventral but not dorsal injections of muscimol + baclofen (GABAa + GABAb receptor agonists that inhibit neuronal activity) decreased extinction responding. After I withdrawal day, ventral but not dorsal mPFC injections of bicuculline + saclofen (GABAa 4 GABAb receptor antagonists that increase neuronal activity) strongly increased extinction responding. Finally, muscimol + baclofen had minimal effect on extinction responding after I day, and in cocaine-experienced rats, ventral mPFC injections of muscimol + baclofen or bicuculline + saclofen had no effect on lever presses for an oral sucrose Solution. The present results indicate that ventral mPFC neuronal activity plays an important role in the incubation of cocaine craving. Published by Elsevier Ltd. C1 [Koya, Eisuke; Uejima, Jamie L.; Wihbey, Kristina A.; Bossert, Jennifer M.; Hope, Bruce T.; Shaham, Yavin] NIDA, Behav Neurosci Branch, IRP, NIH,DHHS, Baltimore, MD 21224 USA. RP Shaham, Y (reprint author), NIDA, Behav Neurosci Branch, IRP, NIH,DHHS, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM yshaham@intra.nida.nih.gov RI Hope, Bruce/A-9223-2010; shaham, yavin/G-1306-2014 OI Hope, Bruce/0000-0001-5804-7061; FU Intramural NIH HHS [Z01 DA000434-08] NR 83 TC 106 Z9 108 U1 1 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PY 2009 VL 56 BP 177 EP 185 DI 10.1016/j.neuropharm.2008.04.022 PG 9 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 396XO UT WOS:000262625600022 PM 18565549 ER PT J AU Ferre, S Goldberg, SR Lluis, C Franco, R AF Ferre, Sergi Goldberg, Steven R. Lluis, Carme Franco, Rafael TI Looking for the role of cannabinoid receptor heteromers in striatal function SO NEUROPHARMACOLOGY LA English DT Review DE Local module; Receptor heteromers; Cannabinoid CB(1) receptor; Dopamine D(2) receptor; Adenosine A(2A) receptor; mu Opioid receptor; Striatum ID LONG-TERM DEPRESSION; DOPAMINE D2 RECEPTORS; RAT NUCLEUS-ACCUMBENS; MU-OPIOID-RECEPTORS; GABAERGIC SYNAPTIC-TRANSMISSION; PROTEIN-COUPLED RECEPTORS; GLOBUS-PALLIDUS; BASAL GANGLIA; CB1 RECEPTORS; NEUROTRANSMITTER RELEASE AB The introduction of two concepts, "local module" and "receptor heteromer", facilitates the understanding of the role of interactions between different neurotransmitters in the brain. In artificial cell systems, cannabinoid CB, receptors form receptor heteromers with dopamine D(2), adenosine A(2A) and mu opioid receptors. There is indirect but compelling evidence for the existence of the same CB, receptor heteromers in striatal local modules centered in the dendritic spines of striatal GABAergic efferent neurons, particularly at a postsynaptic location. Their analysis provides new clues for the role of endocannabinoids in striatal function, which cannot only be considered as retrograde signals that inhibit neurotransmitter release. Recent studies using a new method to detect heteromerization of more than two proteins, which consists of sequential BRET-FRET (SRET) analysis, has demonstrated that CB(1), D(2) and A(2A) receptors can form heterotrimers in transfected cells. It is likely that functional CB(1)-A(2A)-D(2) receptor heteromers can be found where they are highly co-expressed, in the dendritic spines of GABAergic enkephalinergic neurons. The functional properties of these multiple receptor heteromers and their role in striatal function need to be determined. Published by Elsevier Ltd. C1 [Ferre, Sergi; Goldberg, Steven R.] NIDA, Intramural Res Program, Biomed Res Ctr, NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. [Lluis, Carme; Franco, Rafael] Univ Barcelona, Dept Biochem & Mol Biol, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Inst Invest Biomed August Pi & Sunyer,Fac Biol, E-08028 Barcelona, Spain. RP Ferre, S (reprint author), NIDA, Intramural Res Program, Biomed Res Ctr, NIH,Dept Hlth & Human Serv, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM sferre@intra.nida.nih.gov RI Ferre, Sergi/K-6115-2014; Franco, Rafael/C-3694-2015 OI Ferre, Sergi/0000-0002-1747-1779; Franco, Rafael/0000-0003-2549-4919 FU National Institute on Drug Abuse; National Institutes of Health, Department of Health and Human Services FX Supported by the National Institute on Drug Abuse (intramural Research funds), National Institutes of Health, Department of Health and Human Services. NR 101 TC 42 Z9 42 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PY 2009 VL 56 BP 226 EP 234 DI 10.1016/j.neuropharm.2008.06.076 PG 9 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 396XO UT WOS:000262625600027 PM 18691604 ER PT J AU Negash, S Greenwood, PM Sunderland, T Parasuraman, R Geda, YE Knopman, DS Boeve, BF Ivnik, RJ Petersen, RC Smith, GE AF Negash, Selam Greenwood, Pamela M. Sunderland, Trey Parasuraman, Raja Geda, Yonas E. Knopman, David S. Boeve, Bradley F. Ivnik, Robert J. Petersen, Ronald C. Smith, Glenn E. TI The Influence of Apolipoprotein E Genotype on Visuospatial Attention Dissipates After Age 80 SO NEUROPSYCHOLOGY LA English DT Article DE attention; APOE; phenotype; old-old ID POSITRON-EMISSION-TOMOGRAPHY; ALZHEIMERS-DISEASE; HIPPOCAMPAL VOLUME; COGNITIVE DECLINE; SPATIAL ATTENTION; CHOLINERGIC HYPOTHESIS; FUNCTIONAL RECOVERY; LONGITUDINAL CHANGE; EPSILON-4 ALLELE; APOE EPSILON-4 AB Although it is established that apolipoprotein E (APOE) e4 allele increases the risk of Alzheimer's disease (AD), epidemiological studies indicate that genetic risk decreases late in life. This raises the question of whether the effects of APOE oil cognition that are seen in midlife arise from a cognitive phenotype of APOE or from the presence of early AD in some APOE-e4 carriers. The authors addressed this question by comparing the cognitive consequences of variation in the APOE gene between individuals over the age of 80 (old-old) and middle-aged and young-old individuals. A Spatially Cued discrimination paradigm-previously shown to be sensitive to AD and to APOE genotype-required a speeded categorization of a target letter following cues that were valid, invalid, or neutral in predicting target location. Results revealed greater costs of invalid cues in the APOE-e4 carriers of middle-aged and young-old, but not old-old, groups. The dissipation of the APOE effect in old-old individuals at lower risk of AD suggests that visuospatial attention impairments seen as early as midlife in APOE-e4 carriers may be a preclinical marker of AD. C1 [Greenwood, Pamela M.; Parasuraman, Raja] George Mason Univ, Dept Psychol, Fairfax, VA 22030 USA. [Negash, Selam; Knopman, David S.; Boeve, Bradley F.; Petersen, Ronald C.] Mayo Clin, Dept Neurol, Rochester, MN USA. [Sunderland, Trey] NIMH, NIH, Bethesda, MD USA. [Geda, Yonas E.; Ivnik, Robert J.; Smith, Glenn E.] Mayo Clin, Dept Psychiat, Rochester, MN USA. [Geda, Yonas E.; Ivnik, Robert J.; Smith, Glenn E.] Mayo Clin, Dept Psychol, Rochester, MN USA. RP Greenwood, PM (reprint author), George Mason Univ, Dept Psychol, David King Hall 2060,MSN 3F5,4400 Univ Dr, Fairfax, VA 22030 USA. EM Pgreenw1@gmu.edu RI Geda, Yonas/D-9570-2012; OI Smith, Glenn/0000-0003-1506-9484; Negash, Selam/0000-0001-7150-7181 FU NIMH [AG19653, P50 AG16574, U01 AG06786, K12 RR24151, K01 MH 69351]; Mayo Foundation FX This work was supported by NIMH Intramural Funding, Grants AG19653, P50 AG16574, U01 AG06786, AG19653, K12 RR24151, K01 MH 69351, and the Robert H. and Clarice Smith and Abigail Van Buren Alzheimer's disease Research Program of the Mayo Foundation. NR 57 TC 12 Z9 13 U1 1 U2 1 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0894-4105 J9 NEUROPSYCHOLOGY JI Neuropsychology PD JAN PY 2009 VL 23 IS 1 BP 81 EP 89 DI 10.1037/a0014014 PG 9 WC Psychology, Clinical; Neurosciences; Psychology SC Psychology; Neurosciences & Neurology GA 391CA UT WOS:000262209300008 PM 19210035 ER PT J AU Nelson, EE Winslow, JT AF Nelson, Eric E. Winslow, James T. TI Non-Human Primates: Model Animals for Developmental Psychopathology SO NEUROPSYCHOPHARMACOLOGY LA English DT Review DE rearing; mood; anxiety; social; depression; amygdala ID MONKEYS MACACA-MULATTA; CSF MONOAMINE METABOLITE; PITUITARY-ADRENAL AXIS; YOUNG RHESUS-MONKEYS; OPIOID-RECEPTOR GENE; SEROTONIN TRANSPORTER AVAILABILITY; CEREBROSPINAL-FLUID CONCENTRATIONS; EARLY ENVIRONMENTAL-REGULATION; EXCESSIVE ALCOHOL-CONSUMPTION; ORBITAL PREFRONTAL LESIONS AB Non-human primates have been used to model psychiatric disease for several decades. The success of this paradigm has issued from comparable cognitive skills, brain morphology, and social complexity in adult monkeys and humans. Recently, interest in biological psychiatry has focused on similar brain, social, and emotional developmental processes in monkeys. In part, this is related to evidence that early postnatal experiences in human development may have profound implications for subsequent mental health. Non-human primate studies of postnatal phenomenon have generally fallen into three basic categories: experiential manipulation (largely manipulations of rearing), pharmacological manipulation (eg drug-induced psychosis), and anatomical localization (defined by strategic surgical damage). Although these efforts have been very informative each of them has certain limitations. In this review we highlight general findings from the non-human primate postnatal developmental literature and their implications for primate models in psychiatry. We argue that primates are uniquely capable of uncovering interactions between genes, environmental challenges, and development resulting in altered risk for psychopathology. C1 [Winslow, James T.] NIMH, Non Human Primate Neurobiol Res Core, Intramural Res Program, Bethesda, MD 20892 USA. [Nelson, Eric E.; Winslow, James T.] NIMH, Mood & Anxiety Disorders Program, Intramural Res Program, Bethesda, MD 20892 USA. RP Winslow, JT (reprint author), Non Human Primate Neurobiol Res Core, 16701 Elmer Sch Rd,NIHAC 110-121, Dickerson, MD 20842 USA. EM jameswinslow@mail.nih.gov RI Nelson, Eric/B-8980-2008 OI Nelson, Eric/0000-0002-3376-2453 FU NIMH FX This work was supported by the NIMH Intramural Research Program. NR 211 TC 38 Z9 39 U1 6 U2 19 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JAN PY 2009 VL 34 IS 1 BP 90 EP 105 DI 10.1038/npp.2008.150 PG 16 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 386DL UT WOS:000261862400006 PM 18800061 ER PT J AU Wang, PS Heinssen, R Oliveri, M Wagner, A Goodman, W AF Wang, Philip S. Heinssen, Robert Oliveri, Molly Wagner, Ann Goodman, Wayne TI Bridging Bench and Practice: Translational Research for Schizophrenia and Other Psychotic Disorders SO NEUROPSYCHOPHARMACOLOGY LA English DT Review DE translational research; schizophrenia; psychotic disorders ID MENTAL-HEALTH-SERVICES; ATYPICAL ANTIPSYCHOTIC MEDICATIONS; CLINICAL-TRIALS; 2ND-GENERATION ANTIPSYCHOTICS; PHARMACOLOGICAL-TREATMENT; RESISTANT SCHIZOPHRENIA; CLOZAPINE TREATMENT; RANDOMIZED-TRIALS; ELDERLY-PATIENTS; NURSING-HOMES AB Translational research is urgently needed to turn basic scientific discoveries into widespread health gains and nowhere are these needs greater than in conditions such as schizophrenia and other psychotic disorders. In this article, we discuss one type of translational research-called T1-which is needed to take advantage of developments in the basic neurosciences and translate them into more efficacious diagnostic, preventive, and therapeutic interventions. However, ensuring that interventions from T1 research actually benefit patients will require a second form of translational research-called T2-to turn innovations into everyday clinical practice and health decision-making. Recent examples of T1 and T2 research in schizophrenia and other psychotic disorders as well as strategies for better linking T1 and T2 research agendas are covered. C1 [Wang, Philip S.; Heinssen, Robert] NIMH, Div Serv & Intervent Res, Rockville, MD 20852 USA. [Oliveri, Molly; Wagner, Ann] NIMH, Div Dev Translat Res, Rockville, MD 20852 USA. [Goodman, Wayne] NIMH, Div Adult Translat Res, Rockville, MD 20852 USA. RP Wang, PS (reprint author), NIMH, Div Serv & Intervent Res, 6001 Execut Blvd,Room 7141, Rockville, MD 20852 USA. EM wangphi@mail.nih.gov NR 71 TC 8 Z9 11 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JAN PY 2009 VL 34 IS 1 BP 204 EP 212 DI 10.1038/npp.2008.170 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 386DL UT WOS:000261862400013 PM 18830238 ER PT J AU Pine, DS Helfinstein, SM Bar-Haim, Y Nelson, E Fox, NA AF Pine, Daniel S. Helfinstein, Sarah M. Bar-Haim, Yair Nelson, Eric Fox, Nathan A. TI Challenges in Developing Novel Treatments for Childhood Disorders: Lessons from Research on Anxiety SO NEUROPSYCHOPHARMACOLOGY LA English DT Review DE anxiety; children; adolescents; amygdala; attention; conditioning ID LONG-TERM POTENTIATION; OBSESSIVE-COMPULSIVE DISORDER; PREFRONTAL CORTEX ACTIVATION; CONTEXTUAL FEAR MEMORY; ATTENTIONAL BIAS; GENE-EXPRESSION; D-CYCLOSERINE; EXPOSURE THERAPY; CONDITIONED FEAR; ANGRY FACES AB Alterations in brain development may contribute to chronic mental disorders. Novel treatments targeted toward the early-childhood manifestations of such chronic disorders may provide unique therapeutic opportunities. However, attempts to develop and deliver novel treatments face many challenges. Work on pediatric anxiety disorders illustrates both the inherent challenges as well as the unusual opportunities for therapeutic advances. The present review summarizes three aspects of translational research on pediatric anxiety disorders as the work informs efforts to develop novel interventions. First, the review summarizes data on developmental conceptualizations of anxiety from both basic neuroscience and clinical perspectives. This summary is integrated with a discussion of the two best-established treatments, cognitive behavioral therapy and selective serotonin reuptake inhibitors. Second, the review summarizes work on attention bias to threat, considering implications for both novel treatments and translational research on neural circuitry functional development. This illustrates the manner in which clinical findings inform basic systems neuroscience research. Finally, the review summarizes work in basic science on fear learning, as studied in fear conditioning, consolidation, and extinction paradigms. This summary ends by describing potential novel treatments, illustrating the manner in which basic neuroscience informs therapeutics. C1 [Pine, Daniel S.; Bar-Haim, Yair; Nelson, Eric; Fox, Nathan A.] NIMH, Mood & Anxiety Disorders Program, Intramural Res Program, Bethesda, MD 20892 USA. [Helfinstein, Sarah M.; Fox, Nathan A.] Univ Maryland, Dept Human Dev, College Pk, MD 20742 USA. [Bar-Haim, Yair] Tel Aviv Univ, IL-69978 Tel Aviv, Israel. RP Pine, DS (reprint author), NIMH, Mood & Anxiety Disorders Program, Intramural Res Program, 15K North Dr,MSC 2670, Bethesda, MD 20892 USA. EM Daniel.pine@nih.gov RI Nelson, Eric/B-8980-2008 OI Nelson, Eric/0000-0002-3376-2453 FU NSF GRFP FX The ideas in this report strongly reflect the pervasive influences of colleagues and collaborators. Specific viewpoints contained herein were heavily shaped by discussions with Drs Brendan Bradley, Christian Grillon, Shmuel Lissek, Donald F Klein, Rachel G Klein, and Karin Mogg. SMH is supported by an NSF GRFP. NR 81 TC 94 Z9 94 U1 11 U2 28 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JAN PY 2009 VL 34 IS 1 BP 213 EP 228 DI 10.1038/npp.2008.113 PG 16 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 386DL UT WOS:000261862400014 PM 18754004 ER PT J AU Brady, LS Winsky, L Goodman, W Oliveri, ME Stover, E AF Brady, Linda S. Winsky, Lois Goodman, Wayne Oliveri, Mary Ellen Stover, Ellen TI NIMH Initiatives to Facilitate Collaborations Among Industry, Academia, and Government for the Discovery and Clinical Testing of Novel Models and Drugs for Psychiatric Disorders SO NEUROPSYCHOPHARMACOLOGY LA English DT Review DE drug discovery; proof of concept; public-private partnership; preclinical efficacy; translational neuroscience; biomarkers ID CONSENSUS COGNITIVE BATTERY; FUNCTIONAL SELECTIVITY; SCHIZOPHRENIA; CHALLENGES; RECEPTOR; OPPORTUNITIES; PHARMACOLOGY; INHIBITION; WORKSHOP; TARGETS AB There is an urgent need to transform basic research discoveries into tools for treatment and prevention of mental illnesses. This article presents an overview of the National Institute of Mental Health (NIMH) programs and resources to address the challenges and opportunities in psychiatric drug development starting at the point of discovery through the early phases of translational research. We summarize NIMH and selected National Institutes of Health (NIH) efforts to stimulate translation of basic and clinical neuroscience findings into novel targets, models, compounds, and strategies for the development of innovative therapeutics for psychiatric disorders. Examples of collaborations and partnerships among NIMH/NIH, academia, and industry are highlighted. C1 [Brady, Linda S.; Winsky, Lois] NIMH, Div Neurosci & Basic Behav Sci, Bethesda, MD 20892 USA. [Stover, Ellen] NIMH, Div AIDS & Hlth & Behav Res, Bethesda, MD 20892 USA. [Oliveri, Mary Ellen] NIMH, Div Dev Translat Res, Bethesda, MD 20892 USA. [Goodman, Wayne] NIMH, Div Adult Translat Res & Treatment Dev, Bethesda, MD 20892 USA. RP Brady, LS (reprint author), NIMH, Div Neurosci & Basic Behav Sci, 6001 Execut Blvd,Room 7204,MSC 9645, Bethesda, MD 20892 USA. EM lbrady@mail.nih.gov FU NIMH FX The authors declare that, except for income received from the NIMH, no financial support or compensation has been received from any individual or corporate entity over the past 3 years for research or professional service and there are no personal financial holdings that could be perceived as constituting a potential conflict of interest. NR 39 TC 11 Z9 11 U1 3 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JAN PY 2009 VL 34 IS 1 BP 229 EP 243 DI 10.1038/npp.2008.125 PG 15 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 386DL UT WOS:000261862400015 PM 18800066 ER PT J AU Shippenberg, TS AF Shippenberg, Toni S. TI The dynorphin/kappa opioid receptor system: a new target for the treatment of addiction and affective disorders? SO NEUROPSYCHOPHARMACOLOGY LA English DT Editorial Material C1 NIDA, Integrat Neurosci Sect, NIH, Intramural Res Program, Baltimore, MD USA. RP Shippenberg, TS (reprint author), NIDA, Integrat Neurosci Sect, NIH, Intramural Res Program, Baltimore, MD USA. EM tshippen@intra.nida.nih.gov NR 7 TC 27 Z9 29 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JAN PY 2009 VL 34 IS 1 BP 247 EP 247 DI 10.1038/npp.2008.165 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 386DL UT WOS:000261862400019 PM 19079072 ER PT J AU Jiang, XL Xing, GQ Yang, CH Verma, A Zhang, L Li, H AF Jiang, Xiaolong Xing, Guoqiang Yang, Chunhui Verma, Ajay Zhang, Lei Li, He TI Stress Impairs 5-HT(2A) Receptor-Mediated Serotonergic Facilitation of GABA Release in Juvenile Rat Basolateral Amygdala SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE stress; 5-HT(2A) receptor; GABA; basolateral amygdala; PTSD; IPSCs ID EXCITATORY SYNAPTIC-TRANSMISSION; MOOD DISORDERS; MESSENGER-RNA; LEARNED HELPLESSNESS; NEUROTROPHIC FACTOR; POTASSIUM CHANNEL; PREFRONTAL CORTEX; DOWN-REGULATION; MODULATION; BRAIN AB The occurrence of stress and anxiety disorders has been closely associated with alterations of the amygdala GABAergic system. In these disorders, dysregulation of the serotonergic system, a very important modulator of the amygdala GABAergic system, is also well recognized. The present study, utilizing a learned helplessness stress rat model, was designed to determine whether stress is capable of altering serotonergic modulation of the amygdala GABAergic system. In control rats, administration of 5-HT or alpha-methyl-5-HT, a 5-HT(2) receptor agonist, to basolateral amygdala (BLA) slices dramatically enhanced frequency and amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs). This effect was blocked by selective 5-HT(2A) receptor antagonists while a selective 5-HT(2B) receptor agonist and a selective 5-HT(2C) receptor agonist were without effect on sIPSCs. Double immunofluorescence labeling demonstrated that the 5-HT(2A) receptor is primarily localized to parvalbumin-containing BLA interneurons. Thus, serotonin primarily acts via 5-HT(2A) receptors to facilitate BLA GABAergic inhibition. In stressed rats, the 5-HT(2A) receptor-mediated facilitative actions were severely impaired. Quantitative RT-PCR and western blot analysis showed that the impairment of 5-HT(2A) receptor signaling primarily resulted from receptor downregulation. The stress-induced effect appeared to be specific to 5-HT(2A) receptors because stress had no significant impact on other serotonin receptors, as well as histamine H(3) receptor and alpha(2) adrenoceptor signaling in the BLA. This severe impairment of 5-HT(2A) receptor-mediated facilitation of BLA GABAergic inhibition might result in an amygdala circuitry with hyperexcitability, and a lower threshold of activation, and thus be an important mechanism underlying the emergence of stress-associated psychiatric symptoms. C1 [Jiang, Xiaolong; Xing, Guoqiang; Zhang, Lei; Li, He] Uniformed Serv Univ Hlth Sci, Dept Psychiat, Ctr Study Traumat Stress, Bethesda, MD 20814 USA. [Jiang, Xiaolong; Li, He] Uniformed Serv Univ Hlth Sci, Neurosci Program, Bethesda, MD 20814 USA. [Yang, Chunhui] NIMH, Sect Neuropathol, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. [Verma, Ajay] Uniformed Serv Univ Hlth Sci, Dept Neurol, Bethesda, MD 20814 USA. RP Li, H (reprint author), Uniformed Serv Univ Hlth Sci, Dept Psychiat, Ctr Study Traumat Stress, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM hli@usuhs.mil FU DAMD [17-00-1-0110]; USUHS [RO88DC]; Henry M Jackson Foundation Fellowship; USUHS Center for the Study of Traumatic Stress FX The expert assistance of Eleanore Gamble is greatly appreciated. We thank Drs Thomas Cote, Joseph McCabe, Nelson Arispe, and Maria Braga for their comments on the paper. This work was supported by DAMD grant 17-00-1-0110 ( to HL), USUHS grant RO88DC ( to HL), Henry M Jackson Foundation Fellowship ( to XJ), and USUHS Center for the Study of Traumatic Stress. NR 72 TC 53 Z9 53 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JAN PY 2009 VL 34 IS 2 BP 410 EP 423 DI 10.1038/npp.2008.71 PG 14 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 386DN UT WOS:000261862600016 PM 18536707 ER PT J AU Lee, CEC Danielian, LE Thomasson, D Baker, EH AF Lee, Christabel E. C. Danielian, Laura E. Thomasson, David Baker, Eva H. TI Normal regional fractional anisotropy and apparent diffusion coefficient of the brain measured on a 3 T MR scanner SO NEURORADIOLOGY LA English DT Article DE Diffusion tensor imaging; Fractional anisotropy; Apparent diffusion coefficient; Brain; Normal ID APPEARING WHITE-MATTER; DISEASE AB We aim to establish norms of fractional anisotropy (FA) and apparent diffusion coefficient (ADC) in 20 different regions of the brain in healthy human volunteers. Thirty-one individuals were examined for ADC and FA in 20 regions of the brain using a single-shot, spin echo, echo planar diffusion tensor imaging sequence with 32 directions at 3 T. FA and ADC maps were computed using the Philips PRIDE tool, and regions of interest were drawn at 20 different locations in the brain. Relationships of FA and ADC with age and gender were explored. We found a negative correlation between age and FA in the inferior fronto-occipital fasciculus and forceps minor. There were no gender differences. The cerebral peduncle, the middle cerebellum, and cingulum had the highest variation in FA, while fornix, optic radiation, and optic tract had the highest variation in ADC. We provide a table of normative FA and ADC measurements in 20 brain regions of potential clinical relevance to the diagnosis and monitoring of specific neurological diseases. C1 [Lee, Christabel E. C.; Thomasson, David; Baker, Eva H.] NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. [Danielian, Laura E.] NINDS, NIH, Bethesda, MD 20892 USA. RP Lee, CEC (reprint author), NIH, Dept Diagnost Radiol, Ctr Clin, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM leechrist@mail.nih.gov; bakere@cc.nih.gov FU Clinical Center; National Institutes of Health FX This research was supported by the Intramural Research Program of the Clinical Center, National Institutes of Health. NR 15 TC 34 Z9 35 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0028-3940 J9 NEURORADIOLOGY JI Neuroradiology PD JAN PY 2009 VL 51 IS 1 BP 3 EP 9 DI 10.1007/s00234-008-0441-3 PG 7 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 385CT UT WOS:000261791400001 PM 18704391 ER PT J AU Davis, M Walker, DL Miles, LA Grillon, C AF Davis, Michael Walker, David L. Miles, Leigh A. Grillon, Christian TI Toward an operational definition of fear vs. anxiety: The role of the extended amygdala in phasic vs. sustained fear SO NEUROSCIENCE RESEARCH LA English DT Meeting Abstract C1 [Davis, Michael; Walker, David L.; Miles, Leigh A.] Emory Univ, Atlanta, GA 30322 USA. [Grillon, Christian] NIMH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 2 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PY 2009 VL 65 SU 1 BP S21 EP S21 DI 10.1016/j.neures.2009.09.1604 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 528DK UT WOS:000272421100137 ER PT J AU Hanakawa, T Hallett, M AF Hanakawa, Takashi Hallett, Mark TI Basal ganglia functions underlie both motor and cognitive agility SO NEUROSCIENCE RESEARCH LA English DT Meeting Abstract C1 [Hanakawa, Takashi] NCNP, NIN, DCFD, Kodaira, Tokyo, Japan. [Hanakawa, Takashi] JST, PRESTO, Kawaguchi, Saitama, Japan. [Hanakawa, Takashi; Hallett, Mark] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PY 2009 VL 65 SU 1 BP S193 EP S193 DI 10.1016/j.neures.2009.09.1049 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 528DK UT WOS:000272421101413 ER PT J AU Holmes, A AF Holmes, Andrew TI Phenotypic abnormalities caused by genetic loss of PSD-95 (Dlg4) reveal a potential role for MAGUKs in autism and Williams Syndrome SO NEUROSCIENCE RESEARCH LA English DT Meeting Abstract C1 [Holmes, Andrew] NIAAA, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PY 2009 VL 65 SU 1 BP S22 EP S22 DI 10.1016/j.neures.2009.09.1609 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 528DK UT WOS:000272421100142 ER PT J AU Isoda, M Hikosaka, O AF Isoda, Masaki Hikosaka, Okihide TI Superior colliculus neurons participate in switching from habitual to controlled saccades SO NEUROSCIENCE RESEARCH LA English DT Meeting Abstract C1 [Isoda, Masaki] BSI, RIKEN, Lab Symb Cogn Develop, Wako, Saitama, Japan. [Hikosaka, Okihide] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PY 2009 VL 65 SU 1 BP S59 EP S59 DI 10.1016/j.neures.2009.09.162 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 528DK UT WOS:000272421100386 ER PT J AU Jinde, S Nakazawa, K AF Jinde, Seiichiro Nakazawa, Kazu TI Role of hippocampal NR1 receptor in learning and memory impairment SO NEUROSCIENCE RESEARCH LA English DT Meeting Abstract C1 [Jinde, Seiichiro] Univ Tokyo, Dept Psychiat, Tokyo, Japan. [Jinde, Seiichiro; Nakazawa, Kazu] NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PY 2009 VL 65 SU 1 BP S8 EP S8 DI 10.1016/j.neures.2009.09.1513 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 528DK UT WOS:000272421100047 ER PT J AU Kim, H Richmond, BJ Shinomoto, S AF Kim, Hideaki Richmond, Barry J. Shinomoto, Shigeru TI Detecting a change point by a single neuron SO NEUROSCIENCE RESEARCH LA English DT Meeting Abstract C1 [Kim, Hideaki; Shinomoto, Shigeru] Kyoto Univ, Dept Phys, Kyoto 606, Japan. [Richmond, Barry J.] NIMH, Neuropsychol Lab, NIH, DHHS, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PY 2009 VL 65 SU 1 BP S133 EP S133 DI 10.1016/j.neures.2009.09.652 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 528DK UT WOS:000272421101019 ER PT J AU Koike, T Kan, S Misaki, M Miyauchi, S AF Koike, Takahiko Kan, Shigeyuki Misaki, Masaya Miyauchi, Satoru TI Rapid eye movements and waking saccades share the same brain network with different characteristics SO NEUROSCIENCE RESEARCH LA English DT Meeting Abstract C1 [Koike, Takahiko; Kan, Shigeyuki; Miyauchi, Satoru] NICT, Kobe Adv ICT Res Ctr, Kobe, Hyogo, Japan. [Koike, Takahiko; Kan, Shigeyuki; Miyauchi, Satoru] JST, CREST, Tokyo, Japan. [Misaki, Masaya] NIMH, SFIM, LBC, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PY 2009 VL 65 SU 1 BP S57 EP S57 DI 10.1016/j.neures.2009.09.148 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 528DK UT WOS:000272421100372 ER PT J AU Santos, GS Dharmaraj, EG Plenz, D Nakahara, H AF Santos, Gustavo S. Dharmaraj, Elakkat G. Plenz, Dietmar Nakahara, Hiroyuki TI Modeling instantaneous network correlations over multiple spatial scales SO NEUROSCIENCE RESEARCH LA English DT Meeting Abstract C1 [Santos, Gustavo S.; Nakahara, Hiroyuki] RIKEN BSI, Lab Integ Theor Neurosci, Wako, Saitama, Japan. [Dharmaraj, Elakkat G.; Plenz, Dietmar] NIMH, Unit Neural Netw Physiol, Lab Sys Neurosci, Bethesda, MD 20892 USA. [Nakahara, Hiroyuki] Tokyo Tech, Dept Comp Intel & Sys Sci, Yokohama, Kanagawa, Japan. RI Nakahara, Hiroyuki/N-5411-2015 OI Nakahara, Hiroyuki/0000-0001-6891-1175 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PY 2009 VL 65 SU 1 BP S133 EP S133 DI 10.1016/j.neures.2009.09.648 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 528DK UT WOS:000272421101015 ER PT J AU Toda, K Mizuhiki, T Sugase-Miyamoto, Y Inaba, K Ozaki, S Richmond, BJ Shidara, M AF Toda, Koji Mizuhiki, Takashi Sugase-Miyamoto, Yasuko Inaba, Kiyonori Ozaki, Shigeru Richmond, Barry J. Shidara, Munetaka TI Effects of reward proximity and amount on neural activity in the rostral anterior cingulate cortex SO NEUROSCIENCE RESEARCH LA English DT Meeting Abstract C1 [Toda, Koji; Mizuhiki, Takashi; Inaba, Kiyonori; Ozaki, Shigeru; Shidara, Munetaka] Univ Tsukuba, Grad Sch Comprehens Human Sci, Tsukuba, Ibaraki 305, Japan. [Sugase-Miyamoto, Yasuko] AIST, Neurosci Res Inst, Tokyo, Japan. [Richmond, Barry J.] NIMH, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PY 2009 VL 65 SU 1 BP S190 EP S191 DI 10.1016/j.neures.2009.09.1030 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 528DK UT WOS:000272421101394 ER PT J AU Wilke, M Mueller, KM Turchi, J Smith, K Zhu, C Leopold, DA AF Wilke, Melanie Mueller, Kai-Markus Turchi, Janita Smith, Katy Zhu, Charles Leopold, David A. TI Role of thalamo-cortical interactions in visual awareness SO NEUROSCIENCE RESEARCH LA English DT Meeting Abstract C1 [Wilke, Melanie] CALTECH, Pasadena, CA 91125 USA. [Wilke, Melanie; Mueller, Kai-Markus; Turchi, Janita; Smith, Katy; Zhu, Charles; Leopold, David A.] NIMH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PY 2009 VL 65 SU 1 BP S17 EP S17 DI 10.1016/j.neures.2009.09.1574 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 528DK UT WOS:000272421100108 ER PT J AU Wray, S AF Wray, Susan TI Migration and neuronal activity of GnRH-1 neurons SO NEUROSCIENCE RESEARCH LA English DT Meeting Abstract C1 [Wray, Susan] NINDS, CDNS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PY 2009 VL 65 SU 1 BP S11 EP S11 DI 10.1016/j.neures.2009.09.1536 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 528DK UT WOS:000272421100070 ER PT J AU Jagannathan, J Li, J Szerlip, N Vortmeyer, AO Lonser, RR Oldfield, EH Zhuang, ZP AF Jagannathan, Jay Li, Jie Szerlip, Nicholas Vortmeyer, Alexander O. Lonser, Russell R. Oldfield, Edward H. Zhuang, Zhengping TI APPLICATION AND IMPLEMENTATION OF SELECTIVE TISSUE MICRODISSECTION AND PROTEOMIC PROFILING IN NEUROLOGICAL DISEASE SO NEUROSURGERY LA English DT Review DE Microdissection; Proteome; Proteomics; Tumor; Vascular ID IMAGING MASS-SPECTROMETRY; 2-DIMENSIONAL GEL-ELECTROPHORESIS; HIPPEL-LINDAU DISEASE; SUBARACHNOID HEMORRHAGE; CEREBRAL VASOSPASM; PROTEIN EXPRESSION; BRAIN-DAMAGE; GLIOBLASTOMA-MULTIFORME; CELL-DIFFERENTIATION; SURGICAL-MANAGEMENT AB OBJECTIVE: Proteins are the primary components of cells and are vital constituents of any living organism. The proteins that make up an organism (proteome) are constantly changing and are intricately linked to neurological disease processes. The study of proteins, or proteomics, is a relatively new but rapidly expanding field with increasing relevance to neurosurgery. METHODS: We present a review of the state-of-the-art proteomic technology and its applications in Central nervous system diseases. RESULTS: The technique of "selective microdissection" allows an investigator to selectively isolate and study a pathological tissue of interest. By evaluating protein expression in a variety of central nervous system disorders, it is clear that proteins are differentially expressed across disease states, and protein expression changes markedly during disease progression. CONCLUSION: Understanding the patterns of protein expression in the nervous system has critical implications for the diagnosis and treatment of neurological disease. As gatekeepers in the diagnosis, evaluation, and treatment of central nervous system diseases, it is important for neurosurgeons to develop an appreciation for proteomic techniques and their utility. C1 [Jagannathan, Jay; Li, Jie; Szerlip, Nicholas; Vortmeyer, Alexander O.; Lonser, Russell R.; Oldfield, Edward H.; Zhuang, Zhengping] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. [Jagannathan, Jay; Oldfield, Edward H.] Univ Virginia, Hlth Sci Ctr, Dept Neurosurg, Charlottesville, VA 22908 USA. RP Zhuang, ZP (reprint author), NINDS, Surg Neurol Branch, NIH, Bldg 10,Room 5D37, Bethesda, MD 20892 USA. EM zhuangp@ninds.nih.gov FU Intramural NIH HHS [Z99 NS999999] NR 102 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD JAN PY 2009 VL 64 IS 1 BP 4 EP 14 DI 10.1227/01.NEU.0000335776.93176.83 PG 11 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 393MO UT WOS:000262377600002 PM 19145153 ER PT J AU Burgio, K Richter, H Brubaker, L Kraus, S Chai, T Nyberg, L Xu, Y AF Burgio, Kathryn Richter, Holly Brubaker, Linda Kraus, Stephen Chai, Toby Nyberg, Lee Xu, Yan TI PREDICTORS OF OUTCOMES OF DRUG THERAPY, COMBINED DRUG AND BEHAVIORAL THERAPY AND DRUG DISCONTINUATION IN THE TREATMENT OF URGE URINARY INCONTINENCE IN WOMEN SO NEUROUROLOGY AND URODYNAMICS LA English DT Meeting Abstract CT 6th Annual Winter Meeting of the Society-for-Urodynamics-and-Female-Urology CY FEB 25-28, 2009 CL Las Vegas, NV SP Soc Urodynam & Female Urol C1 [Burgio, Kathryn; Richter, Holly] Univ Alabama, Birmingham, AL USA. [Brubaker, Linda] Loyola Univ, Maywood, IL 60153 USA. [Kraus, Stephen] Univ Texas San Antonio, San Antonio, TX USA. [Chai, Toby] Univ Maryland, Baltimore, MD 21201 USA. [Nyberg, Lee] NIDDK, Bethesda, MD USA. [Xu, Yan] New England Res Inst, Watertown, MA 02172 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 0733-2467 J9 NEUROUROL URODYNAM JI Neurourol. Urodyn. PY 2009 VL 28 IS 2 BP 144 EP 144 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 412XL UT WOS:000263757400093 ER PT J AU Steers, W Richter, H Nyberg, L Kusek, J Kraus, S Dandreo, K Chai, T Brubaker, L AF Steers, William Richter, Holly Nyberg, Leroy Kusek, John Kraus, Stephen Dandreo, Kimberly Chai, Toby Brubaker, Linda TI Challenges of Conducting Multi-Center, Multi-Disciplinary Urinary Incontinence Clinical Trials: Experience of the Urinary Incontinence Treatment Network SO NEUROUROLOGY AND URODYNAMICS LA English DT Article DE clinical trials; urinary incontinence; Urinary Incontinence Treatment Network; Colposuspension; Slings; behavioral therapy ID STRESS-INCONTINENCE; WOMEN; STANDARDIZATION; RELIABILITY; TERMINOLOGY; PROLAPSE; IMPACT AB The Urinary Incontinence Treatment Network (UITN) was established in 2000 as a multi-disciplinary, multi-institutional network by the National Institute for Diabetes, Digestive, and Kidney Diseases (NIDDK) to investigate treatments for urinary incontinence in women. Methods: Over 8 years this network composed of urologists, urogynecologists, geriatricians, behavioral psychologists, physical therapists, nurses, epidemiologists, social scientists and statisticians from nine academic sites and a Data Coordinating Center has been effective in designing and completing prospective randomized clinical trials for treatments of urinary incontinence in women. Results: Two major clinical trials have been completed and a third has completed recruitment. The focus of the completed trials was a comparison of surgical methods to treat stress urinary incontinence whereas the third examined the potential benefit of combined behavioral. intervention and antimuscarinic drug therapy to eliminate the need for long-term use of drug therapy alone to manage urge urinary incontinence. The scientific output of the network measured by abstracts, original papers and presentations demonstrates the productivity of the network. Conclusions: Many unique challenges are posed by a multi-disciplinary team located at sites across the United States undertaking several clinical trials. This review presents some of the logistics, barriers, tactics, and strategies used to create this successful clinical trials network focused on urinary incontinence. Neurourol. Urodynam. 28:170-176, 2009. (c) 2008 Wiley-Liss, Inc. C1 [Steers, William] Univ Virginia, Dept Urol, Charlottesville, VA USA. [Richter, Holly] Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. [Nyberg, Leroy; Kusek, John] NIDDK, Bethesda, MD 20892 USA. [Kraus, Stephen] Univ Texas San Antonio, Dept Urol, San Antonio, TX USA. [Dandreo, Kimberly] New England Res Inst, Watertown, MA 02172 USA. [Chai, Toby] Univ Maryland, Dept Urol, College Pk, MD 20742 USA. [Brubaker, Linda] Loyola Univ, Dept Urol Obgyn, Chicago, IL 60611 USA. RP Steers, W (reprint author), POB 800422, Charlottesville, VA 22908 USA. EM wds6t@virginia.edu FU NIDDK NIH HHS [U01 DK058229-02S1] NR 28 TC 4 Z9 4 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0733-2467 J9 NEUROUROL URODYNAM JI Neurourol. Urodyn. PY 2009 VL 28 IS 3 BP 170 EP 176 DI 10.1002/nau.20653 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 426HL UT WOS:000264698500004 PM 19030190 ER PT S AU Kiyatkin, EA Sharma, HS AF Kiyatkin, Eugene A. Sharma, Hari Shanker BE Sharma, HS TI ACUTE METHAMPHETAMINE INTOXICATION: BRAIN HYPERTHERMIA, BLOOD-BRAIN BARRIER, BRAIN EDEMA, AND MORPHOLOGICAL CELL ABNORMALITIES SO NEW CONCEPTS OF PSYCHOSTIMULANTS INDUCED NEUROTOXICITY SE International Review of Neurobiology LA English DT Review; Book Chapter ID NORMOTENSIVE YOUNG-RATS; CENTRAL-NERVOUS-SYSTEM; SUBSTITUTED AMPHETAMINES; NEURONAL DAMAGE; C57BL/6J MOUSE; CHOROID-PLEXUS; FREE-RADICALS; HEAT-STRESS; NEUROTOXICITY; DOPAMINE AB Methamphetamine (METH) is a powerful and often abused stimulant with patent addictive and neurotoxic properties. While it is generally assumed that multiple chemical substances released in the brain following METH-Induced metabolic activation (or oxidative stress) are primary factors underlying damage of neural cells, in this work we present data suggesting a role of brain hyperthermia and associated leakage of the blood-brain barrier (BBB) in acute METH-induced toxicity. First, we show that METH induces a dose-dependent brain and body hyperthermia, which is strongly potentiated by associated physiological activation and in warm environments that prevent proper heat dissipation to the external environment. Second, we demonstrate that acute METH intoxication induces robust, widespread but structure-specific leakage of the BBB, acute glial. activation, and increased water content (edema), which are related to drug-induced brain hyperthermia. Third, we document widespread morphological abnormalities of brain cells, including neurons, glia, epithelial, and endothelial cells developing rapidly during acute METH intoxication. These structural abnormalities are tightly related to the extent of brain hyperthermia, leakage of the BBB, and brain edema. While it is unclear whether these rapidly developed morphological abnormalities are reversible, this study, demonstrates that METH induces multiple functional and structural perturbations in the brain, determining its acute toxicity and possibly contributing to neurotoxicity. C1 [Kiyatkin, Eugene A.; Sharma, Hari Shanker] NIDA, Intramural Res Program, Behav Neurosci Branch, NIH, Baltimore, MD 21224 USA. [Sharma, Hari Shanker] Uppsala Univ, Univ Hosp, Dept Surg Sci Anesthesiol & Intens Care Med, Cerebrovasc Res Lab, SE-75185 Uppsala, Sweden. [Sharma, Hari Shanker] Uppsala Univ, Univ Hosp, Dept Surg Sci Anesthesiol & Intens Care Med, Pain Res Lab, SE-75185 Uppsala, Sweden. RP Kiyatkin, EA (reprint author), NIDA, Intramural Res Program, Behav Neurosci Branch, NIH, Baltimore, MD 21224 USA. RI Sharma, Hari/G-4508-2016 FU Intramural NIH HHS [ZIA DA000445-10] NR 67 TC 38 Z9 38 U1 1 U2 10 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7742 BN 978-0-12-374504-0 J9 INT REV NEUROBIOL JI Int. Rev. Neurobiol. PY 2009 VL 88 BP 65 EP + DI 10.1016/S0074-7742(09)88004-5 PG 38 WC Neurosciences SC Neurosciences & Neurology GA BMI37 UT WOS:000272436800005 PM 19897075 ER PT S AU Cadet, JL Krasnova, IN AF Cadet, Jean Lud Krasnova, Irina N. BE Sharma, HS TI MOLECULAR BASES OF METHAMPHETAMINE-INDUCED NEURODEGENERATION SO NEW CONCEPTS OF PSYCHOSTIMULANTS INDUCED NEUROTOXICITY SE International Review of Neurobiology LA English DT Review; Book Chapter ID INDUCED DOPAMINERGIC NEUROTOXICITY; BLOOD-BRAIN-BARRIER; NITRIC-OXIDE SYNTHASE; DISMUTASE TRANSGENIC MICE; ZINC SUPEROXIDE-DISMUTASE; NECROSIS-FACTOR-ALPHA; INDUCED NEURONAL APOPTOSIS; MICROGLIAL ACTIVATION; STRIATAL DOPAMINE; GENE-EXPRESSION C1 [Cadet, Jean Lud; Krasnova, Irina N.] NIH DHHS, Mol Neuropsychiat Branch, NIDA Intramural Immunol, Baltimore, MD 21224 USA. RP Cadet, JL (reprint author), NIH DHHS, Mol Neuropsychiat Branch, NIDA Intramural Immunol, Baltimore, MD 21224 USA. FU Intramural NIH HHS NR 145 TC 82 Z9 82 U1 2 U2 12 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7742 BN 978-0-12-374504-0 J9 INT REV NEUROBIOL JI Int. Rev. Neurobiol. PY 2009 VL 88 BP 101 EP 119 DI 10.1016/S0074-7742(09)88005-7 PG 19 WC Neurosciences SC Neurosciences & Neurology GA BMI37 UT WOS:000272436800006 PM 19897076 ER PT S AU Baumann, MH Rothman, RB AF Baumann, Michael H. Rothman, Richard B. BE Sharma, HS TI NEURAL AND CARDIAC TOXICITIES ASSOCIATED WITH 3,4-METHYLENEDIOXYMETHAMPHETAMINE (MDMA) SO NEW CONCEPTS OF PSYCHOSTIMULANTS INDUCED NEUROTOXICITY SE International Review of Neurobiology LA English DT Review; Book Chapter ID BRAIN-SEROTONIN NEURONS; ORALLY-ADMINISTERED MDMA; VALVULAR HEART-DISEASE; CENTRAL-NERVOUS-SYSTEM; IN-VIVO MICRODIALYSIS; DORSAL RAPHE NEURONS; RAT-BRAIN; ECSTASY MDMA; EXTRACELLULAR SEROTONIN; INCREASED ANXIETY AB (+/-)-3,4-methylenedioxymethamphetamine (MDMA) is a commonly abused illicit drug which affects multiple organ systems. In animals, high-dose administration of MDMA produces deficits in serotonin (5-HT) neurons (e.g., depletion of forebrain 5-HT) that have been Viewed as neurotoxicity. Recent data implicate MDMA In the development of valvular heart disease (VHD). The present paper reviews several issues related to MDMA-associated neural and cardiac toxicities. The hypothesis of MDMA neurotoxicity in rats is evaluated in terms of the effects of MDMA on monoamine neurons, the use of scaling methods to extrapolate MDMA doses across species, and functional consequences of MDMA exposure. A potential treatment regimen (L-5-hydroxytryptophan plus carbidopa) for MDMA-associated neural deficits is discussed. The pathogenesis of MDMA-associated VHD is reviewed with specific reference to the role of valvular 5-HT(2B) receptors. We conclude that pharmacological effects of MDMA occur at the same doses in rats and humans. High doses of MDMA that produce 5-HT depletions in rats are associated with tolerance and impaired 5-HT release. Doses of NIMM that fail to deplete 5-HT in rats can cause persistent behavioral dysfunction, suggesting even moderate doses may pose risks. Finally, the MDMA metabolite, 3,4-methylenedioxymethamphetamine (MDA), is a potent 5-HT2B agonist which could contribute to the increased risk of VHD observed in heavy MDMA users. C1 [Baumann, Michael H.; Rothman, Richard B.] Natl Inst Hlth NIH, Clin Psychopharmacol Sec, Intramural Res Program IRP, Natl Inst Drug Abuse NIDA, Baltimore, MD 21224 USA. RP Baumann, MH (reprint author), Natl Inst Hlth NIH, Clin Psychopharmacol Sec, Intramural Res Program IRP, Natl Inst Drug Abuse NIDA, Baltimore, MD 21224 USA. FU Intramural NIH HHS [ZIA DA000562-01] NR 157 TC 19 Z9 20 U1 0 U2 5 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7742 BN 978-0-12-374504-0 J9 INT REV NEUROBIOL JI Int. Rev. Neurobiol. PY 2009 VL 88 BP 257 EP 296 DI 10.1016/S0074-7742(09)88010-0 PG 40 WC Neurosciences SC Neurosciences & Neurology GA BMI37 UT WOS:000272436800011 PM 19897081 ER PT J AU Boztug, K Appaswamy, G Ashikov, A Schaffer, AA Salzer, U Diestelhorst, J Germeshausen, M Brandes, G Lee-Gossler, J Noyan, F Gatzke, AK Minkov, M Greil, J Kratz, C Petropoulou, T Pellier, I Bellanne-Chantelot, C Rezaei, N Monkemoller, K Irani-Hakimeh, N Bakker, H Gerardy-Schahn, R Zeidler, C Grimbacher, B Welte, K Klein, C AF Boztug, Kaan Appaswamy, Giridharan Ashikov, Angel Schaffer, Alejandro A. Salzer, Ulrich Diestelhorst, Jana Germeshausen, Manuela Brandes, Gudrun Lee-Gossler, Jacqueline Noyan, Fatih Gatzke, Anna-Katherina Minkov, Milen Greil, Johann Kratz, Christian Petropoulou, Theoni Pellier, Isabelle Bellanne-Chantelot, Christine Rezaei, Nima Moenkemoeller, Kirsten Irani-Hakimeh, Noha Bakker, Hans Gerardy-Schahn, Rita Zeidler, Cornelia Grimbacher, Bodo Welte, Karl Klein, Christoph TI A Syndrome with Congenital Neutropenia and Mutations in G6PC3 SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID UNFOLDED PROTEIN RESPONSE; GLYCOGEN-STORAGE-DISEASE; SUBUNIT-RELATED PROTEIN; GLUCOSE-LEVELS; GENE; ELASTASE; APOPTOSIS; MCL-1; IDENTIFICATION; DEFICIENCY AB Background The main features of severe congenital neutropenia are the onset of severe bacterial infections early in life, a paucity of mature neutrophils, and an increased risk of leukemia. In many patients, the genetic causes of severe congenital neutropenia are unknown. Methods We performed genomewide genotyping and linkage analysis on two consanguineous pedigrees with a total of five children affected with severe congenital neutropenia. Candidate genes from the linkage interval were sequenced. Functional assays and reconstitution experiments were carried out. Results All index patients were susceptible to bacterial infections and had very few mature neutrophils in the bone marrow; structural heart defects, urogenital abnormalities, and venous angiectasia on the trunk and extremities were additional features. Linkage analysis of the two index families yielded a combined multipoint lod score of 5.74 on a linkage interval on chromosome 17q21. Sequencing of G6PC3, the candidate gene encoding glucose- 6- phosphatase, catalytic subunit 3, revealed a homozygous missense mutation in exon 6 that abolished the enzymatic activity of glucose- 6- phosphatase in all affected children in the two families. The patients' neutrophils and fibroblasts had increased susceptibility to apoptosis. The myeloid cells showed evidence of increased endoplasmic reticulum stress and increased activity of glycogen synthase kinase 3 beta (GSK-3 beta). We identified seven additional, unrelated patients who had severe congenital neutropenia with syndromic features and distinct biallelic mutations in G6PC3. Conclusions Defective function of glucose- 6- phosphatase, catalytic subunit 3, underlies a severe congenital neutropenia syndrome associated with cardiac and urogenital malformations. C1 [Boztug, Kaan; Appaswamy, Giridharan; Ashikov, Angel; Diestelhorst, Jana; Germeshausen, Manuela; Brandes, Gudrun; Lee-Gossler, Jacqueline; Noyan, Fatih; Gatzke, Anna-Katherina; Bakker, Hans; Gerardy-Schahn, Rita; Zeidler, Cornelia; Welte, Karl; Klein, Christoph] Hannover Med Sch, Dept Pediat Hematol & Oncol, D-30625 Hannover, Germany. [Schaffer, Alejandro A.] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. [Salzer, Ulrich] Univ Med Ctr Freiburg, Freiburg, Germany. [Minkov, Milen] St Anna Childrens Hosp, A-1090 Vienna, Austria. [Greil, Johann] Univ Heidelberg, Childrens Hosp, D-6900 Heidelberg, Germany. [Kratz, Christian] Univ Freiburg, Freiburg, Germany. [Petropoulou, Theoni] Univ Athens, Aghia Sophia Childrens Hosp, Athens, Greece. [Pellier, Isabelle] CHU Angers, Angers, France. [Bellanne-Chantelot, Christine] Hop La Pitie Salpetriere, Assistance Publ Hop Paris, Paris, France. [Rezaei, Nima] Univ Tehran Med Sci, Immunol Asthma & Allergy Res Inst, Tehran, Iran. [Moenkemoeller, Kirsten] Childrens Hosp Amsterdamer Str, Cologne, Germany. [Irani-Hakimeh, Noha] St Georges Univ Hosp, Beirut, Lebanon. [Grimbacher, Bodo] Royal Free & Univ Coll Med Sch, London WC1E 6BT, England. RP Klein, C (reprint author), Hannover Med Sch, Dept Pediat Hematol & Oncol, Carl Neuberg Str 1, D-30625 Hannover, Germany. EM klein.christoph@mh-hannover.de RI Rezaei, Nima/B-4245-2008; Schaffer, Alejandro/F-2902-2012; isabelle, pellier/L-5683-2015; Ashikov, Angel/N-7714-2015; Bakker, Hans/A-1787-2017 OI Rezaei, Nima/0000-0002-3836-1827; Ashikov, Angel/0000-0001-9679-7955; Bakker, Hans/0000-0002-1364-9154 FU Deutsche Forschungsgemeinschaft [KliFo 110-2]; Junior Research Group "Glycomics"; Bundesministerium fur Bildung und Forschung Bone Marrow Failure Syndromes; European Union [MEXT-CT-2006-042316]; Intramural Research Program of the National Institutes of Health; National Library of Medicine; Else Kroner Memorial Fellowship FX We thank the patients and their families for supporting our study; all colleagues referring and registering patients at the Severe Chronic Neutropenia International Registry; Francois-Loic Cosset for the kind gift of the RD114 plasmid; Edelgard Odenwald for analysis of bone marrow smears; Thomas Jack for his help with echocardiography; Jessica Pfannstiel, Maren Sievers, Marie Bohm, Marly Dalton, Martina Wackerhahn, Tanja Reinke, and Gwendoline Leroy for technical assistance; and Dr. Jean Donadieu at the Pediatric Hematology Oncology Service, Hopital Trousseau, Paris, and Dr. Roula Farah at the Department of Pediatrics, Saint Georges Hospital, Balamand University, Beirut, Lebanon, for excellent collaboration. NR 47 TC 144 Z9 146 U1 0 U2 4 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 1 PY 2009 VL 360 IS 1 BP 32 EP 43 DI 10.1056/NEJMoa0805051 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 389MI UT WOS:000262096800005 PM 19118303 ER PT S AU Arumugam, TV Okun, E Mattson, MP AF Arumugam, Thiruma V. Okun, Eitan Mattson, Mark P. BE Annunziato, L TI Basis of Ionic Dysregulation in Cerebral Ischemia SO NEW STRATEGIES IN STROKE INTERVENTION: IONIC TRANSPORTERS, PUMPS, AND NEW CHANNELS SE Contemporary Neuroscience LA English DT Article; Book Chapter ID K-CL COTRANSPORTER; APOPTOTIC VOLUME DECREASE; INDUCED NEURONAL DEATH; CELL-DEATH; IN-VITRO; POTASSIUM HOMEOSTASIS; HIPPOCAMPAL SLICE; PYRAMIDAL NEURONS; OXIDATIVE STRESS; BRAIN ISCHEMIA C1 [Arumugam, Thiruma V.] Univ Queensland, Sch Biomed Sci, Brisbane, Qld 4072, Australia. [Okun, Eitan; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Arumugam, TV (reprint author), Univ Queensland, Sch Biomed Sci, Brisbane, Qld 4072, Australia. EM t.arumugam@uq.edu.au; okune@mail.nih.gov; mattsonm@grc.nia.nih.gov RI Arumugam, Thiruma/B-4898-2011; okun, eitan/K-1314-2016 OI okun, eitan/0000-0001-8474-1487 NR 60 TC 1 Z9 1 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1061-5954 BN 978-1-60761-279-7 J9 CONTEMP NEUROSCI JI CONT NEUROS PY 2009 BP 1 EP 11 DI 10.1007/978-1-60761-280-3_1 PG 11 WC Neurosciences SC Neurosciences & Neurology GA BMQ37 UT WOS:000273345100001 ER PT B AU Juengst, ET AF Juengst, Eric T. BE Drenthen, M Keulartz, J Proctor, J TI Metagenomic Metaphors: New Images of the Human from 'Translational' Genomic Research SO NEW VISIONS OF NATURE: COMPLEXITY AND AUTHENTICITY LA English DT Article; Book Chapter ID MEDICINE; ECOLOGY; PROJECT; FUTURE; HEALTH; GENES C1 [Juengst, Eric T.] Case Western Reserve Univ, Dept Bioeth, Ctr Genet Res Eth & Law, Sch Med, Cleveland, OH 44106 USA. [Juengst, Eric T.] Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA. [Juengst, Eric T.] Penn State Univ, University Pk, PA 16802 USA. [Juengst, Eric T.] US Natl Inst Hlth, Natl Ctr Human Genome Res, Eth Legal & Social Implicat Branch, Bethesda, MD USA. RP Juengst, ET (reprint author), Case Western Reserve Univ, Dept Bioeth, Ctr Genet Res Eth & Law, Sch Med, TA 214, Cleveland, OH 44106 USA. EM eric.juengst@case.edu NR 32 TC 5 Z9 6 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-90-481-2610-1 PY 2009 BP 129 EP 145 DI 10.1007/978-90-481-2611-8_10 D2 10.1007/978-90-481-2611-8 PG 17 WC Environmental Sciences; Environmental Studies; History & Philosophy Of Science; Multidisciplinary Sciences SC Environmental Sciences & Ecology; History & Philosophy of Science; Science & Technology - Other Topics GA BKX34 UT WOS:000269522300010 ER PT S AU Berezhkovskii, AM Bezrukov, SM AF Berezhkovskii, Alexander M. Bezrukov, Sergey M. BE Macucci, M Basso, G TI Fluctuation Theorems in Biological Physics SO NOISE AND FLUCTUATIONS SE AIP Conference Proceedings LA English DT Proceedings Paper CT 20th International Conference on Noise and Fluctuations CY JUN 14-19, 2009 CL Pisa, ITALY SP Univ Pisa DE Diffusion; channel-facilitated transport; single-molecules; translocation statistics ID FACILITATED MEMBRANE-TRANSPORT; STOCHASTIC DYNAMICS; BINDING; SYSTEMS AB Recently formulated fluctuation theorems are highly relevant for interpretation of measurements performed on single molecules. One of these theorems can be applied to channel-facilitated transport of solutes through a membrane separating two reservoirs. The transport is characterized by the probability P(n)(t) that n solute particles have been transported from one reservoir to the other in time t. The fluctuation theorem establishes a relation between P(n)(t) and P(-n)(t): The ratio Pn(t)/P(-n)(t) is independent of time and equal to exp(nA/k(B)T), where A/k(B)T is the affinity measured in the thermal energy units. We show that the same fluctuation theorem is true for both single- and multi-channel transport of non-interacting particles and particles which strongly repel each other. C1 [Berezhkovskii, Alexander M.] NIH, Math & Stat Comp Lab, Div Computat Biosci, CIT, Bethesda, MD 20892 USA. RP Berezhkovskii, AM (reprint author), NIH, Math & Stat Comp Lab, Div Computat Biosci, CIT, Bldg 10, Bethesda, MD 20892 USA. NR 24 TC 1 Z9 1 U1 1 U2 1 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 978-0-7354-0665-0 J9 AIP CONF PROC PY 2009 VL 1129 BP 525 EP 530 PG 6 WC Biophysics; Physics, Applied SC Biophysics; Physics GA BJR96 UT WOS:000267057200121 ER PT J AU Kiesewetter, DO Lang, L Ma, Y Bhattacharjee, AK Gao, ZG Joshi, BV Melman, A de Castro, S Jacobson, KA AF Kiesewetter, Dale O. Lang, Lixin Ma, Ying Bhattacharjee, Abesh Kurnar Gao, Zhan-Guo Joshi, Bhalchandra V. Melman, Artem de Castro, Sonia Jacobson, Kennetb A. TI Synthesis and characterization of [Br-76]-labeled high-affinity A(3) adenosine receptor ligands for positron emission tomography SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE Adenosine A(3) receptor; G-protein-coupled receptor; Nucleoside; Purines; Receptor binding; Bromine-76 ID TUMOR-GROWTH INHIBITION; NF-KAPPA-B; RHEUMATOID-ARTHRITIS; A3 RECEPTORS; CELLS; ACTIVATION; ANTAGONISTS; AGONISTS; TARGET; INJURY AB Introduction: Bromine-76-radiolabeled analogues of previously reported high-affinity A(3) adenosine receptor (A(3)AR) nucleoside ligands have been prepared as potential radiotracers for positron emission tomography. Methods: The radiosyntheses were accomplished by oxidative radiobromination on the N-6-benzyl moiety of trimethyltin precursors. Biodistribution studies of the kinetics Of uptake were conducted in awake rats. Results: We prepared an agonist ligand {[Br-76](1'S,2'R,3'S,4'R,5'S)-4'-{2-chloro-6-[(3-bromophenylmethyl)amino]purin-9-yl}-1'-(methylaminocarbonyl)bicyclo[3.1.0]hexane-2',3'-diol (MRS3581)} in 59% radiochemical yield with a specific activity of 19.5 GBq/mu mol and all antagonist ligand {[Br-76](1'R,2'R,3'S,4'R,5'S)-4'-(6-(3-bromobenzylamino)-2-clhloro-9H-purin-9-yl)bicyclo[3.1.0]hexane-2',3'-diol (MRS5147) in 65% radiochemical yield with a specific activity of 22 GBq/mu mol. The resultant products exhibited the expected high affinity (K-i similar to 0.6 nM) and specific binding at the human A(3)AR in vitro. Biodistribution studies in the rat showed uptake in the organs of excretion and metabolism. The antagonist MRS5147 exhibited increasing uptake in testes, an organ that contains significant quantities of A(3)AR, over a 2-h time course, which suggests the presence of a specific A(3)AR retention mechanism. Conclusion: We were able to compare uptake of the [Br-76]-labeled antagonist MRS5147 to [Br-76]agonist MRS3581. The antagonist MRS5147 shows increasing uptake in the testes, an A(3)AR-rich tissue, suggesting that this ligand may have promise as a molecular imaging agent. Published by Elsevier Inc. C1 [Kiesewetter, Dale O.; Lang, Lixin; Ma, Ying; Bhattacharjee, Abesh Kurnar] NIBIB, Positron Emiss Tomog Radiochem Grp, Ctr Clin, NIH, Bethesda, MD 20892 USA. [Gao, Zhan-Guo; Joshi, Bhalchandra V.; Melman, Artem; de Castro, Sonia; Jacobson, Kennetb A.] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Kiesewetter, DO (reprint author), NIBIB, Positron Emiss Tomog Radiochem Grp, Ctr Clin, NIH, Bethesda, MD 20892 USA. EM dk7k@nih.gov RI de castro, sonia/E-7303-2012; Jacobson, Kenneth/A-1530-2009 OI de castro, sonia/0000-0002-3838-6856; Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural Research Programs of NIBIB and NIDDK; National Institutes of Health, Bethesda, MD FX This work was supported by the Intramural Research Programs of NIBIB and NIDDK, National Institutes of Health, Bethesda, MD. The authors acknowledge the technical assistance of Larry Reyes and Yinghui Shi for in vivo animal experiments and Dr. Larry Szajek, NIH/CC PET Department, for Br-76 isotope production and purification. NR 38 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0969-8051 EI 1872-9614 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD JAN PY 2009 VL 36 IS 1 BP 3 EP 10 DI 10.1016/j.nucmedbio.2008.10.003 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 407ZN UT WOS:000263402900002 PM 19181263 ER PT J AU Huang, DW Sherman, BT Lempicki, RA AF Huang, Da Wei Sherman, Brad T. Lempicki, Richard A. TI Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists SO NUCLEIC ACIDS RESEARCH LA English DT Editorial Material ID HIGH-THROUGHPUT EXPERIMENTS; MICROARRAY EXPRESSION DATA; SET ENRICHMENT; ONTOLOGY TERMS; PROTEOMIC DATA; WEB TOOL; BIOLOGICAL INTERPRETATION; STATISTICAL-ANALYSIS; GENOMIC ANALYSIS; ANNOTATION AB Functional analysis of large gene lists, derived in most cases from emerging high-throughput genomic, proteomic and bioinformatics scanning approaches, is still a challenging and daunting task. The gene-annotation enrichment analysis is a promising high-throughput strategy that increases the likelihood for investigators to identify biological processes most pertinent to their study. Approximately 68 bioinformatics enrichment tools that are currently available in the community are collected in this survey. Tools are uniquely categorized into three major classes, according to their underlying enrichment algorithms. The comprehensive collections, unique tool classifications and associated questions/issues will provide a more comprehensive and up-to-date view regarding the advantages, pitfalls and recent trends in a simpler tool-class level rather than by a tool-by-tool approach. Thus, the survey will help tool designers/developers and experienced end users understand the underlying algorithms and pertinent details of particular tool categories/tools, enabling them to make the best choices for their particular research interests. C1 [Huang, Da Wei; Sherman, Brad T.; Lempicki, Richard A.] Natl Canc Inst, Lab Immunopathogenesis & Bioinformat, Clin Serv Program, SAIC Frederick Inc, Ft Detrick, MD 21702 USA. RP Lempicki, RA (reprint author), Natl Canc Inst, Lab Immunopathogenesis & Bioinformat, Clin Serv Program, SAIC Frederick Inc, Ft Detrick, MD 21702 USA. EM rlempicki@mail.nih.gov RI Lempicki, Richard/E-1844-2012 OI Lempicki, Richard/0000-0002-7059-409X NR 93 TC 3314 Z9 3359 U1 32 U2 256 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2009 VL 37 IS 1 BP 1 EP 13 DI 10.1093/nar/gkn923 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 392XO UT WOS:000262335700001 ER PT J AU Chon, HG Vassilev, A DePamphilis, ML Zhao, YM Zhang, JM Burgers, PM Crouch, RJ Cerritelli, SM AF Chon, Hyongi Vassilev, Alex DePamphilis, Melvin L. Zhao, Yingming Zhang, Junmei Burgers, Peter M. Crouch, Robert J. Cerritelli, Susana M. TI Contributions of the two accessory subunits, RNASEH2B and RNASEH2C, to the activity and properties of the human RNase H2 complex SO NUCLEIC ACIDS RESEARCH LA English DT Article ID AICARDI-GOUTIERES-SYNDROME; YEAST SACCHAROMYCES-CEREVISIAE; DNA-REPLICATION FORK; ESCHERICHIA-COLI; MUTATIONAL ANALYSES; INTERACTION NETWORK; PROTEIN COMPLEXES; CRYSTAL-STRUCTURE; RIBONUCLEASE HII; BINDING DOMAIN AB Eukaryotic RNase H2 is a heterotrimeric enzyme. Here, we show that the biochemical composition and stoichiometry of the human RNase H2 complex is consistent with the properties previously deduced from genetic studies. The catalytic subunit of eukaryotic RNase H2, RNASEH2A, is well conserved and similar to the monomeric prokaryotic RNase HII. In contrast, the RNASEH2B and RNASEH2C subunits from human and Saccharomyces cerevisiae share very little homology, although they both form soluble B/C complexes that may serve as a nucleation site for the addition of RNASEH2A to form an active RNase H2, or for interactions with other proteins to support different functions. The RNASEH2B subunit has a PIP-box and confers PCNA binding to human RNase H2. Unlike Escherichia coli RNase HII, eukaryotic RNase H2 acts processively and hydrolyzes a variety of RNA/DNA hybrids with similar efficiencies, suggesting multiple cellular substrates. Moreover, of five analyzed mutations in human RNASEH2B and RNASEH2C linked to Aicardi-Goutires Syndrome (AGS), only one, R69W in the RNASEH2C protein, exhibits a significant reduction in specific activity, revealing a role for the C subunit in enzymatic activity. Near-normal activity of four AGS-related mutant enzymes was unexpected in light of their predicted impairment causing the AGS phenotype. C1 [Chon, Hyongi; Vassilev, Alex; DePamphilis, Melvin L.; Crouch, Robert J.; Cerritelli, Susana M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, Bethesda, MD 20892 USA. [Zhao, Yingming; Zhang, Junmei] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA. [Burgers, Peter M.] Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA. RP Crouch, RJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, Bethesda, MD 20892 USA. EM robert_crouch@nih.gov FU Intramural NIH HHS; NIGMS NIH HHS [GM32431, R01 GM032431] NR 41 TC 45 Z9 45 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 JAN PY 2009 VL 37 IS 1 BP 96 EP 110 DI 10.1093/nar/gkn913 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 392XO UT WOS:000262335700009 PM 19015152 ER PT J AU Mazan-Mamczarz, K Kuwano, Y Zhan, M White, EJ Martindale, JL Lal, A Gorospe, M AF Mazan-Mamczarz, Krystyna Kuwano, Yuki Zhan, Ming White, Elizabeth J. Martindale, Jennifer L. Lal, Ashish Gorospe, Myriam TI Identification of a signature motif in target mRNAs of RNA-binding protein AUF1 SO NUCLEIC ACIDS RESEARCH LA English DT Article ID RICH ELEMENT; 3'-UNTRANSLATED REGION; HNRNP-D; GENE-EXPRESSION; NUCLEAR IMPORT; TRANSLATION; HUR; STABILITY; TURNOVER; DECAY AB The ubiquitous RNA-binding protein AUF1 promotes the degradation of some target mRNAs, but increases the stability and translation of other targets. Here, we isolated AUF1-associated mRNAs by immunoprecipitation of (AUF1RNA) ribonucleoprotein (RNP) complexes from HeLa cells, identified them using microarrays, and used them to elucidate a signature motif shared among AUF1 target transcripts. The predicted AUF1 motif (2939 nucleotides) contained 79 As and Us, consistent with the AU-rich sequences of reported AUF1 targets. Importantly, 10 out of 15 previously reported AUF1 target mRNAs contained the AUF1 motif. The predicted interactions between AUF1 and target mRNAs were recapitulated in vitro using biotinylated RNAs. Interestingly, further validation of predicted AUF1 target transcripts revealed that AUF1 associates with both the pre-mRNA and the mature mRNA forms. The consequences of AUF1 binding to 10 predicted target mRNAs were tested by silencing AUF1, which elevated the steady-state levels of only four mRNAs, and by overexpressing AUF1, which also lowered the levels of only four mRNAs. In total, we have identified a signature motif in AUF1 target mRNAs, have found that AUF1 also associates with the corresponding pre-mRNAs, and have discovered that altering AUF1 levels alone only modifies the levels of subsets of target mRNAs. C1 [Mazan-Mamczarz, Krystyna; Kuwano, Yuki; White, Elizabeth J.; Martindale, Jennifer L.; Lal, Ashish; Gorospe, Myriam] NIA, Lab Cellular & Mol Biol, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Mazan-Mamczarz, Krystyna] Univ Maryland, Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA. [Zhan, Ming] NIA, Res Resources Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Lal, Ashish] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Lal, Ashish] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Gorospe, M (reprint author), NIA, Lab Cellular & Mol Biol, Intramural Res Program, NIH, Baltimore, MD 21224 USA. EM myriam-gorospe@nih.gov FU National Institutes of Health [Z01-AG000392] FX This research was supported entirely by the Intramural Research Program of the NIA-IRP, National Institutes of Health. Funding for open access charge: Project number Z01-AG000392. NR 58 TC 50 Z9 53 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2009 VL 37 IS 1 BP 204 EP 214 DI 10.1093/nar/gkn929 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 392XO UT WOS:000262335700018 PM 19033365 ER PT J AU Barrett, T Troup, DB Wilhite, SE Ledoux, P Rudnev, D Evangelista, C Kim, IF Soboleva, A Tomashevsky, M Marshall, KA Phillippy, KH Sherman, PM Muertter, RN Edgar, R AF Barrett, Tanya Troup, Dennis B. Wilhite, Stephen E. Ledoux, Pierre Rudnev, Dmitry Evangelista, Carlos Kim, Irene F. Soboleva, Alexandra Tomashevsky, Maxim Marshall, Kimberly A. Phillippy, Katherine H. Sherman, Patti M. Muertter, Rolf N. Edgar, Ron TI NCBI GEO: archive for high-throughput functional genomic data SO NUCLEIC ACIDS RESEARCH LA English DT Article ID MICROARRAY DATA; STANDARDS; CELLS; INFORMATION; EXPRESSION AB The Gene Expression Omnibus (GEO) at the National Center for Biotechnology Information (NCBI) is the largest public repository for high-throughput gene expression data. Additionally, GEO hosts other categories of high-throughput functional genomic data, including those that examine genome copy number variations, chromatin structure, methylation status and transcription factor binding. These data are generated by the research community using high-throughput technologies like microarrays and, more recently, next-generation sequencing. The database has a flexible infrastructure that can capture fully annotated raw and processed data, enabling compliance with major community-derived scientific reporting standards such as 'Minimum Information About a Microarray Experiment' (MIAME). In addition to serving as a centralized data storage hub, GEO offers many tools and features that allow users to effectively explore, analyze and download expression data from both gene-centric and experiment-centric perspectives. This article summarizes the GEO repository structure, content and operating procedures, as well as recently introduced data mining features. GEO is freely accessible at http://www.ncbi.nlm.nih.gov/geo/. C1 [Barrett, Tanya; Troup, Dennis B.; Wilhite, Stephen E.; Ledoux, Pierre; Rudnev, Dmitry; Evangelista, Carlos; Kim, Irene F.; Soboleva, Alexandra; Tomashevsky, Maxim; Marshall, Kimberly A.; Phillippy, Katherine H.; Sherman, Patti M.; Muertter, Rolf N.; Edgar, Ron] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Barrett, T (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, 45 Ctr Dr, Bethesda, MD 20892 USA. EM barrett@ncbi.nlm.nih.gov FU National Institutes of Health; National Library of Medicine FX Funding for open access charge: Intramural Research Program of the National Institutes of Health; National Library of Medicine. NR 12 TC 537 Z9 552 U1 2 U2 12 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 JAN PY 2009 VL 37 BP D885 EP D890 DI 10.1093/nar/gkn764 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 386TT UT WOS:000261906200155 PM 18940857 ER PT J AU Benson, DA Karsch-Mizrachi, I Lipman, DJ Ostell, J Sayers, EW AF Benson, Dennis A. Karsch-Mizrachi, Ilene Lipman, David J. Ostell, James Sayers, Eric W. TI GenBank SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DATABASE; BLAST AB GenBank (R) is a comprehensive database that contains publicly available nucleotide sequences for more than 300 000 organisms named at the genus level or lower, obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects. Most submissions are made using the web-based BankIt or standalone Sequin programs, and accession numbers are assigned by GenBank (R) staff upon receipt. Daily data exchange with the European Molecular Biology Laboratory Nucleotide Sequence Database in Europe and the DNA Data Bank of Japan ensures worldwide coverage. GenBank is accessible through the National Center for Biotechnology Information (NCBI) Entrez retrieval system, which integrates data from the major DNA and protein sequence databases along with taxonomy, genome, mapping, protein structure and domain information, and the biomedical journal literature via PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of the GenBank database are available by FTP. To access GenBank and its related retrieval and analysis services, begin at the NCBI Homepage: www.ncbi.nlm.nih.gov. C1 [Benson, Dennis A.; Karsch-Mizrachi, Ilene; Lipman, David J.; Ostell, James; Sayers, Eric W.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Sayers, EW (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. EM sayers@ncbi.nlm.nih.gov FU Intramural Research Program of the National Institutes of Health; National Library of Medicine FX Funding for open access charge: Intramural Research Program of the National Institutes of Health, National Library of Medicine. NR 13 TC 379 Z9 387 U1 1 U2 15 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 JAN PY 2009 VL 37 BP D26 EP D31 DI 10.1093/nar/gkn723 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 386TT UT WOS:000261906200005 PM 18940867 ER PT J AU Fu, W Sanders-Beer, BE Katz, KS Maglott, DR Pruitt, KD Ptak, RG AF Fu, William Sanders-Beer, Brigitte E. Katz, Kenneth S. Maglott, Donna R. Pruitt, Kim D. Ptak, Roger G. TI Human immunodeficiency virus type 1, human protein interaction database at NCBI SO NUCLEIC ACIDS RESEARCH LA English DT Article ID INTERACTION NETWORK; INFORMATION; UPDATE; HOST; GENE AB The 'Human Immunodeficiency Virus Type 1 (HIV-1), Human Protein Interaction Database', available through the National Library of Medicine at www.ncbi.nlm.nih.gov/RefSeq/HIVInteractions, was created to catalog all interactions between HIV-1 and human proteins published in the peer-reviewed literature. The database serves the scientific community exploring the discovery of novel HIV vaccine candidates and therapeutic targets. To facilitate this discovery approach, the following information for each HIV-1 human protein interaction is provided and can be retrieved without restriction by web-based downloads and ftp protocols: Reference Sequence (RefSeq) protein accession numbers, Entrez Gene identification numbers, brief descriptions of the interactions, searchable keywords for interactions and PubMed identification numbers (PMIDs) of journal articles describing the interactions. Currently, 2589 unique HIV-1 to human protein interactions and 5135 brief descriptions of the interactions, with a total of 14 312 PMID references to the original articles reporting the interactions, are stored in this growing database. In addition, all protein-protein interactions documented in the database are integrated into Entrez Gene records and listed in the 'HIV-1 protein interactions' section of Entrez Gene reports. The database is also tightly linked to other databases through Entrez Gene, enabling users to search for an abundance of information related to HIV pathogenesis and replication. C1 [Fu, William; Sanders-Beer, Brigitte E.; Ptak, Roger G.] So Res Inst, Frederick, MD 21701 USA. [Katz, Kenneth S.; Maglott, Donna R.; Pruitt, Kim D.] Natl Ctr Biotechnol Informat, Natl Lib Med, NIH, Bethesda, MD 20892 USA. RP Fu, W (reprint author), So Res Inst, Frederick, MD 21701 USA. EM fu@southernresearch.org FU National Institutes of Health; National Institute of Allergy and Infectious Diseases; Division of AIDS [N01-AI-05415, N01-AI-70042]; National Library of Medicine FX National Institutes of Health, National Institute of Allergy and Infectious Diseases, Division of AIDS (N01-AI-05415 and N01-AI-70042 to W. F., B. E. S.-B. and R. G. P.); Intramural Research Program of the National Institutes of Health, National Library of Medicine (to K. S. K., D. R. M. and K. D. P.). Funding for open access charges: Southern Research Institute. NR 17 TC 131 Z9 132 U1 2 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 JAN PY 2009 VL 37 BP D417 EP D422 DI 10.1093/nar/gkn708 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 386TT UT WOS:000261906200076 PM 18927109 ER PT J AU Galperin, MY Cochrane, GR AF Galperin, Michael Y. Cochrane, Guy R. TI Nucleic Acids Research annual Database Issue and the NAR online Molecular Biology Database Collection in 2009 SO NUCLEIC ACIDS RESEARCH LA English DT Article ID PREDICTION; GDB AB The current issue of Nucleic Acids Research includes descriptions of 179 databases, of which 95 are new. These databases (along with several molecular biology databases described in other journals) have been included in the Nucleic Acids Research online Molecular Biology Database Collection, bringing the total number of databases in the collection to 1170. In this introductory comment, we briefly describe some of these new databases and review the principles guiding the selection of databases for inclusion in the Nucleic Acids Research annual Database Issue and the Nucleic Acids Research online Molecular Biology Database Collection. The complete database list and summaries are available online at the Nucleic Acids Research web site (http://nar.oxfordjournals.org/). C1 [Galperin, Michael Y.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [Cochrane, Guy R.] EMBL European Bioinformat Inst, Cambridge CB10 1SD, England. RP Galperin, MY (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM nardatabase@gmail.com RI Galperin, Michael/B-5859-2013; OI Galperin, Michael/0000-0002-2265-5572; Cochrane, Guy/0000-0001-7954-7057 FU Intramural Research Program of the US National Institutes of Health; European Molecular Biology Laboratory FX Intramural Research Program of the US National Institutes of Health (to M. Y. G.); European Molecular Biology Laboratory (to G. R. C.). The Open Access publication charges for this article were waived by Oxford University Press. NR 32 TC 61 Z9 65 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2009 VL 37 BP D1 EP D4 DI 10.1093/nar/gkn942 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 386TT UT WOS:000261906200001 PM 19033364 ER PT J AU Harmar, AJ Hills, RA Rosser, EM Jones, M Buneman, OP Dunbar, DR Greenhill, SD Hale, VA Sharman, JL Bonner, TI Catterall, WA Davenport, AP Delagrange, P Dollery, CT Foord, SM Gutman, GA Laudet, V Neubig, RR Ohlstein, EH Olsen, RW Peters, J Pin, JP Ruffolo, RR Searls, DB Wright, MW Spedding, M AF Harmar, Anthony J. Hills, Rebecca A. Rosser, Edward M. Jones, Martin Buneman, O. Peter Dunbar, Donald R. Greenhill, Stuart D. Hale, Valerie A. Sharman, Joanna L. Bonner, Tom I. Catterall, William A. Davenport, Anthony P. Delagrange, Philippe Dollery, Colin T. Foord, Steven M. Gutman, George A. Laudet, Vincent Neubig, Richard R. Ohlstein, Eliot H. Olsen, Richard W. Peters, John Pin, Jean-Philippe Ruffolo, Robert R. Searls, David B. Wright, Mathew W. Spedding, Michael TI IUPHAR-DB: the IUPHAR database of G protein-coupled receptors and ion channels SO NUCLEIC ACIDS RESEARCH LA English DT Article ID INTERNATIONAL UNION; SEQUENCE DATABASE; GENOME DATABASE; NOMENCLATURE; PHARMACOLOGY; INFORMATION; GENE; UPDATE; KNOWLEDGEBASE; SUBUNITS AB The IUPHAR database (IUPHAR-DB) integrates peer-reviewed pharmacological, chemical, genetic, functional and anatomical information on the 354 non-sensory G protein-coupled receptors (GPCRs), 71 ligand-gated ion channel subunits and 141 voltage-gated-like ion channel subunits encoded by the human, rat and mouse genomes. These genes represent the targets of approximately one-third of currently approved drugs and are a major focus of drug discovery and development programs in the pharmaceutical industry. IUPHAR-DB provides a comprehensive description of the genes and their functions, with information on protein structure and interactions, ligands, expression patterns, signaling mechanisms, functional assays and biologically important receptor variants (e.g. single nucleotide polymorphisms and splice variants). In addition, the phenotypes resulting from altered gene expression (e.g. in genetically altered animals or in human genetic disorders) are described. The content of the database is peer reviewed by members of the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR); the data are provided through manual curation of the primary literature by a network of over 60 subcommittees of NC-IUPHAR. Links to other bioinformatics resources, such as NCBI, Uniprot, HGNC and the rat and mouse genome databases are provided. IUPHAR-DB is freely available at http://www.iuphar-db.org. C1 [Harmar, Anthony J.; Hills, Rebecca A.; Rosser, Edward M.; Dunbar, Donald R.; Greenhill, Stuart D.; Sharman, Joanna L.] Univ Edinburgh, Queens Med Res Inst, Ctr Cardiovasc Sci & Neurosci Res, Edinburgh, Midlothian, Scotland. [Jones, Martin] Univ Edinburgh, Inst Evolutionary Biol, Ashworth Labs, Edinburgh, Midlothian, Scotland. [Buneman, O. Peter] Univ Edinburgh, Sch Informat, Edinburgh, Midlothian, Scotland. [Bonner, Tom I.] NIMH, Genet Lab, Bethesda, MD 20892 USA. [Catterall, William A.] Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA. [Davenport, Anthony P.] Univ Cambridge, Clin Pharmacol Unit, Cambridge CB2 2QQ, England. [Delagrange, Philippe; Spedding, Michael] Inst Rech Servier, F-92150 Suresnes, France. [Dollery, Colin T.] GlaxoSmithKline Inc, Management Div, Harlow CM19 5AW, Essex, England. [Foord, Steven M.] GlaxoSmithKline Res & Dev Ltd, Stevenage, Herts, England. [Gutman, George A.] Univ Calif Irvine, Dept Microbiol & Mol Genet, Irvine, CA 92697 USA. [Laudet, Vincent] Inst Genom Fonct Lyon, Mol Zool Grp, Lyon, France. [Neubig, Richard R.] Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA. [Ohlstein, Eliot H.] Venuv Pharmaceut, Glenmoore, PA USA. [Olsen, Richard W.] Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. [Peters, John] Univ Dundee, Inst Neurosci, Dundee DD1 9SY, Scotland. [Pin, Jean-Philippe] Ctr Natl Rech Sci, Montpellier, France. [Ruffolo, Robert R.] Wyeth Res, Collegeville, PA 19426 USA. [Searls, David B.] GlaxoSmithKline Inc, King Of Prussia, PA 19406 USA. [Wright, Mathew W.] EMBL EBI, HGNC, Hinxton CB10 1SD, England. RP Harmar, AJ (reprint author), Univ Edinburgh, Queens Med Res Inst, Ctr Cardiovasc Sci & Neurosci Res, Edinburgh, Midlothian, Scotland. EM tony.harmar@ed.ac.uk OI Wright, Matt/0000-0002-2650-2426; Spedding, Michael/0000-0002-1248-8221; Harmar, Anthony/0000-0002-3838-9264; Sharman, Joanna/0000-0002-5275-6446; Greenhill, Stuart/0000-0002-5038-5258; Davenport, Anthony Peter/0000-0002-2096-3117 FU British Pharmacological Society (through their Anniversary Strategic Initiatives Fund); UNESCO (through the ICSU Grants Programme); Incyte; GlaxoSmithKline; Novartis; Servier; Wyeth; Oxford University Press FX British Pharmacological Society (through their Anniversary Strategic Initiatives Fund); UNESCO (through the ICSU Grants Programme); Incyte; GlaxoSmithKline; Novartis; Servier; Wyeth. Funding for Open Access Publication charges were waived by Oxford University Press. NR 41 TC 123 Z9 123 U1 1 U2 6 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 JAN PY 2009 VL 37 BP D680 EP D685 DI 10.1093/nar/gkn728 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 386TT UT WOS:000261906200121 PM 18948278 ER PT J AU Klimke, W Agarwala, R Badretdin, A Chetvernin, S Ciufo, S Fedorov, B Kiryutin, B O'Neill, K Resch, W Resenchuk, S Schafer, S Tolstoy, I Tatusova, T AF Klimke, William Agarwala, Richa Badretdin, Azat Chetvernin, Slava Ciufo, Stacy Fedorov, Boris Kiryutin, Boris O'Neill, Kathleen Resch, Wolfgang Resenchuk, Sergei Schafer, Susan Tolstoy, Igor Tatusova, Tatiana TI The National Center for Biotechnology Information's Protein Clusters Database SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ESCHERICHIA-COLI K-12; METABOLIC PATHWAYS; SEQUENCE DATABASE; GENOME; RESOURCES; FAMILIES; KEGG AB Rapid increases in DNA sequencing capabilities have led to a vast increase in the data generated from prokaryotic genomic studies, which has been a boon to scientists studying micro-organism evolution and to those who wish to understand the biological underpinnings of microbial systems. The NCBI Protein Clusters Database (ProtClustDB) has been created to efficiently maintain and keep the deluge of data up to date. ProtClustDB contains both curated and uncurated clusters of proteins grouped by sequence similarity. The May 2008 release contains a total of 285 386 clusters derived from over 1.7 million proteins encoded by 3806 nt sequences from the RefSeq collection of complete chromosomes and plasmids from four major groups: prokaryotes, bacteriophages and the mitochondrial and chloroplast organelles. There are 7180 clusters containing 376 513 proteins with curated gene and protein functional annotation. PubMed identifiers and external cross references are collected for all clusters and provide additional information resources. A suite of web tools is available to explore more detailed information, such as multiple alignments, phylogenetic trees and genomic neighborhoods. ProtClustDB provides an efficient method to aggregate gene and protein annotation for researchers and is available at http://www.ncbi.nlm.nih.gov/sites/entrez?db=proteinclusters. C1 [Klimke, William; Agarwala, Richa; Badretdin, Azat; Chetvernin, Slava; Ciufo, Stacy; Fedorov, Boris; Kiryutin, Boris; O'Neill, Kathleen; Resch, Wolfgang; Resenchuk, Sergei; Schafer, Susan; Tolstoy, Igor; Tatusova, Tatiana] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Dept Hlth & Human Serv, Bethesda, MD 20894 USA. RP Klimke, W (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Dept Hlth & Human Serv, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20894 USA. EM klimke@ncbi.nlm.nih.gov FU Intramural Research Program of the National Institutes of Health; National Library of Medicine FX Funding for open access charge: Intramural Research Program of the National Institutes of Health; National Library of Medicine. NR 24 TC 111 Z9 112 U1 0 U2 3 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 JAN PY 2009 VL 37 BP D216 EP D223 DI 10.1093/nar/gkn734 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 386TT UT WOS:000261906200040 PM 18940865 ER PT J AU Lee, TL Cheung, HH Claus, J Sastry, C Singh, S Vu, L Rennert, O Chan, WY AF Lee, Tin-Lap Cheung, Hoi-Hung Claus, Janek Sastry, Chandan Singh, Sumeeta Vu, Loc Rennert, Owen Chan, Wai-Yee TI GermSAGE: a comprehensive SAGE database for transcript discovery on male germ cell development SO NUCLEIC ACIDS RESEARCH LA English DT Article ID GENE-EXPRESSION; GENOME BROWSER; SERIAL ANALYSIS; UCSC; UPDATE AB GermSAGE is a comprehensive web-based database generated by Serial Analysis of Gene Expression ( SAGE) representing major stages in mouse male germ cell development, with 150 000 sequence tags in each SAGE library. A total of 452 095 tags derived from type A spermatogonia (Spga), pachytene spermatocytes (Spcy) and round spermatids (Sptd) were included. GermSAGE provides web-based tools for browsing, comparing and searching male germ cell transcriptome data at different stages with customizable searching parameters. The data can be visualized in a tabulated format or further analyzed by aligning with various annotations available in the UCSC genome browser. This flexible platform will be useful for gaining better understanding of the genetic networks that regulate spermatogonial cell renewal and differentiation, and will allow novel gene discovery. GermSAGE is freely available at http://germsage.nichd.nih.gov/. C1 [Lee, Tin-Lap; Cheung, Hoi-Hung; Rennert, Owen; Chan, Wai-Yee] NIH, Sect Dev Genom, Lab Clin Genom, Bethesda, MD 20892 USA. [Claus, Janek; Sastry, Chandan; Singh, Sumeeta; Vu, Loc] Eunice Kennedy Shriver NICHHD, Div Informat Technol, NIH, Bethesda, MD 20892 USA. RP Chan, WY (reprint author), NIH, Sect Dev Genom, Lab Clin Genom, Bldg 10, Bethesda, MD 20892 USA. EM chanwy@mail.nih.gov RI Lee, Tin-Lap/A-7853-2009; Cheung, Hoi-Hung/G-7605-2011 OI Lee, Tin-Lap/0000-0002-6654-0988; FU National Institutes of Health; National Institute of Child Health and Human Development FX Open access charge and this research are funded by the Intramural Research Program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 16 TC 12 Z9 13 U1 0 U2 1 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 JAN PY 2009 VL 37 SI SI BP D891 EP D897 DI 10.1093/nar/gkn644 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 386TT UT WOS:000261906200156 PM 18832368 ER EF